Sodium excretion in normal conscious dogs.

Bitches maintained on a low Na intake, were given doses of saline (0.125 mol.litre(-1) NaCl, 0.025 mol.litre(-1) NaHCO3, 0.004 mol.litre(-1) KCl) by stomach tube. Doses of 100 and 200 cm3 produced only minor increases in Na excretion; after 300 cm3, Na excretion rose from about 2 to about 60 micromol.min(-1). Plasma protein fell by 1.8 litre(-1) for each 100 cm3 of saline retained. Within normal ranges of Na excretion there is a threshold of plasma protein concentration above which Na is retained and below which Na is excreted. Changes in exogenous creatinine clearance were measured allowing calculation of the filtered load of Na, which shows that the absolute tubular reabsorption of Na and water is increased in volume expansion by isotonic saline. Meat produced large increase in glomerular filtration rate without much increase in Na excretion and mechanisms are discussed by which Na reabsorptin is more effective after meat than after doses of saline. Creatinine cleaerance increased by 0.67 cm3.min(-1) for each fall of 1 g.litre(-1) in plasma protein; this is predicted by a theory that the glomerular capillary blood pressure is 9.3 kPa (70 mmHg) rather than 6.7 kPa (50 mmHg).


Cardiovascular responses to lower body negative pressure in normal subjects and in patients with diabetes mellitus.

The cardiovascular responses of non-diabetic and diabetic subjects to lower body negative pressure at 1.3, 2.7, and 5.3 kPa (10, 20, and 40 mmHg) were measured. The diabetics fell into two groups--those showing little change in systolic blood pressure with lower body negative pressure at 5.3 kPa (40 mmHg) and those showing falls greater than 2.7 kPa (20 mmHg). The patterns of response in the former group of diabetics and in the non-diabetics were similar. The diabetics who showed a fall in systolic blood pressure with lower body negative pressure nonetheless responded with a forearm vasoconstriction indicating that the vasomotor dysfunction was localised to some other vascular bed. In one subject forearm vasodilatation occurred with lower body negative pressure at 5.3 kPa (40 mmHg) although his response to milder levels of lower body negative pressure appeared normal. It is suggested that the integrity of vasomotor reflexes is most reliably tested by exposure to stepped increases in lower body negative pressure.


Noninvasively and invasively measured pulsatile haemodynamics with graded arterial stenosis.

Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respectively. Pulsatile blood pressure was measured 0.6 cm proximal and 3.7 cm distal to the stenosis. With increasing severity of stenosis there were progressive increases in the femoral artery hydraulic input impedance moduli and in the ratio of the impedance moduli to the zero harmonic impedance (or total resistance). This resulted in: a) a progressive reduction in the Fourier harmonic moduli and pulsewave amplitudes of flow, velocity, and distal pressure; b) a progressive increase in the fifth-seventh proximal pressure harmonic moduli; but c) little change in mean proximal pressure or its first 4 harmonic moduli. The data confirm the well known phenomena of a 'critical stenosis' in that there is little decrease in resting mean blood flow until there is a 70 to 80 stenosis (area reduction). Also the oscillatory portions of the femoral artery data were more sensitive to the changes in stenosis than were the nonoscillatory parameters, which confirms previously reported findings from the thoracic aorta. However, the femoral artery haemodynamics exhibited a greater amount of frequency dependent behaviour than the thoracic aorta which is probably the result of a more complex interaction of reflections from the stenosis and from the periphery in the femoral artery than in the thoracic aorta. The sensitive changes in oscillatory haemodynamics may provide a useful basis for noninvasive and invasive physiological assessment of human peripheral atherosclerotic stenosis and of experimental stenosis in animals.


Effects of methylprednisolone on ventricular arrhythmias during acute myocardial ischaemia.

The effects of methylprednisolone (50 mg.kg-1) on the incidence of ventricular tachycardia and fibrillation and on ventricular fibrillation threshold were studied during acute coronary occlusion in anaesthetised dogs. Ventricular tachycardia and/or ventricular fibrillation occurred in 11 of the 16 animals (69%) both before and after methylprednisolone pretreatment. The mean ventricular fibrillation threshold of 10 dogs was 10.1 +/- 1.8 mA before methylprednisolone and it increased slightly to 13.3 +/- 2.3 mA after the drug. This difference was not statistically significant (P greater than 0.2).


Occurrence of nucleolar material in the cytoplasm of plant cells.

This paper deals with the induction of cytoplasmic nucleolar bodies in meristematic Allium cepa L. cells after treatment with drugs which interfere with nucleolar functionality. The drugs which interfere with protein synthesis failed to produce these bodies. The ultrastructure origin and physiological significance of these bodies are discussed here, as well as their relation with the mitotic prenucleolar bodies (Moreno-Díaz de la Espina et al., 1976).


Proliferative index estimated by chromatin pattern analysis.

Chromatin pattern analysis at different density thresholds in Feulgen-stained meristems stimulated to proliferate by water inbibition, allows to estimate a proliferative potential index (PPI) which is a much earlier indicator of changes in proliferation than conventional labelling and mitotic indices. The PPI is but the ratio G1 cells to total 2C cells (or G2 to 4C cells, when cells also digress from the post-replicative stage of the cycle). The method is based in the fact that G1 and G2 cells have larger projected nuclear area and smaller dense chromatin area than their conterpart non-proliferating G0 and G0,2 cells.


Cell surface protein kinases in Dictyostelium: are they artifacts?

Evidence for cell surface protein kinases as possible regulatory factors of cell interaction in Dictyostelium discoideum was examined by incubating intact cells with gamma 32P-ATP in the presence and absence of histone. No significant incorporation of 32P was detected in the absence of histone. In its presence strong phosphorylation not only of the histone but also of endogenous proteins was obtained. This was due to the fact that histone made the cell membranes permeable for substrates and proteinkinases. Histone also preserved protein kinase activities which were otherwise lost during homogenization. The total protein kinase activity in histone treated cells was 5 fold higher than in sonicated cells.


Quantitative assessment of the amount and the activity of trypsin associated with trypsinized cells.

The present investigation has demonstrated that when cell layers are trypsinized with 125I-trypsin and washed under strictly standardized conditions, the amount of trypsin which remains associated with the cell suspension can be accurately determined. This amount is more than 10 times greater than would be expected from dilution only and is dependent on the density of the cell layers. On plating of the cells, less than 10% of the carry-over trypsin remains associated with the cells and suggestive evidence for a mainly intracellular localization was obtained with a quantitative immunoperoxidase technique. This carry-over trypsin was further shown to maintain proteolytic activity by its ability to remove significant amounts of macromolecular material from a cell layer prelabeled with 3H-Leucine.


Red cell-mediated microinjection of macromolecules into monolayer cultures of mammalian cells.

Phytohemagglutinin has been used to enhance the red cell-mediated microinjection of macromolecules into monolayer cultures of mammalian cells. The simple procedure described should promote the wider use of this microinjection technique.


Histones biosynthesis and turnover in epithelial lens cells cultured in vitro.

"Histone synthesis was compared in epithelial lens cells during exponential growth and in the stationary phase brought by contact inhibition. Double labelling experiments with 3H-lysine and 14C-lysine show a net turnover of histone H1 independent of DNA replication. The nucleosome core histones seem to turn over also, but much more slowly than H1".


Effect of alpha-tocopherol incorporation of glucose permeability and phase transition of lecithin liposomes.

Liposomes were prepared from dipalmitoyllecithin, dimyristoyllecithin, dioleoyllecithin, egg lecithin, and soybean lecithin, and the effects of incorporation of various quantities of alpha-tocopherol or its analogs on permeability of the liposomes to glucose were studied at various temperatures (4--40 degrees C). Results showed that increase in the quantity of alpha-tocopherol incorporated into dipalmitoyllecithin and dimyristoyllecithin liposomes lowered the transition temperature for marked release of glucose and also decreased the maximum rate of temperature-dependent permeability, alpha-Tocopherol also had similar but less marked effects on the permeability of dioleoyllecithin and egg lecithin liposomes, but little effect on those of soybean lecithin, which has a higher degree of unsaturation. In dipalmitoyllecithin liposomes phytol showed a similar effect of permeability to that of alpha-tocopherol, but phytanic acid caused a different pattern of temperature-dependent permeability. With analogs of alpha-tocopherol, the regulatory effect on permeability decreased with shortening and disappearance of the isoprenoid side chain. The significance of these observations is discussed in relation to the physiological functions of tocopherols in natural membranes.


Cholestryl-phosphoryl-choline in lipid bilayers.

Cholesteryl-phosphoryl-choline (CPC), a hybrid between cholesterol and lecithin, is incorporated into sonicated liposomes and erythrocyte membranes similarly to cholesterol. The effect of CPC on lipid microviscosity and degree of order is smaller, but not significantly than that of cholesterol. It is proposed that CPC may be employed as an efficient modulator of lipid dynamics.


Renin secretion in the chronically perfused pulseless calf. Evidence for failure of stimulation by decreased pulse pressure.

To study the influence of arterial pulse pressure on renin release, a chronic pulseless calf preparation was developed using a centrifugal left ventricular bypass blood pump. After pump implantation and recovery, control measurements of renal vein and arterial plasma renin activity, arterial pressure, and renal artery flow were obtained. The centrifugal bypass pump rate then was increased to capture cardiac output completely, and nine conscious calves were perfused in a nonpulsatile manner (pulse pressure less than 5-10 mm Hg) for 48 hours. Nonpulsatile perfusion was well tolerated and serum sodium, potassium, creatinine, and blood urea nitrogen were unchanged during bypass. Mean arterial pressure remained relatively constant [114 +/- 3 (SE) mm Hg] during bypass, and was not significantly changed from control. Although renal blood flow decreased slightly from control (667 +/- 84 ml/min) during the nonpulsatile perfusion period (555 +/- 73 ml/min), renin secretion did not increase significantly from control (482 +/- 81 ng angiotensin I/ml per hr per min) during the bypass period (531 +/- 99). A diurnal cycle of renin secretin was observed during the pulseless perfusions. These data document the lack of any significant stimulatory influence of decreased pulse pressure on renin secretion in a chronic awake calf model.


Correlative electrophysiological and anatomical studies concerning the site of origin of escape rhythm during complete atrioventricular block in the dog.

Complete heart block was produced in eight dogs by the selective perfusion of physostigmine or neostigm into the atrioventricular (AV) node artery. A characteristic escape AV junctional rhythm emerged in each dog. After reversal of the cholinesterase paralysis with atropine, in each dog partial heart block was produced by an incision into the AV nodal region. In three of these eight dogs, a second incision placed slightly more anteriorly produced complete AV block which was followed by the emergence of an escape AV junctional rhythm similar to the one produced pharmacologically. Hearts of these three dogs were examined histologically with serial sections to determine the exact location of the incisions and their relationship to the AV node and His bundle. In each dog the incision that produced complete heart block passed directly through the junction of AV node with His bundle. In this region previous studies had demonstrated numerous P cells, which are thought to be the site of origin of normal cardiac automaticity. In each of the three hearts there were abundant P cells in continuity with the His bundle distal to the cut producing heart block. Significance of these findings is discussed relative to the locus of action of acetylcholine within the AV junction, the site of origin of AV junctional rhythm, and sme aspects of the experimental and therapeutic production of heart block.


Prostaglandin control of the renal circulation in response to hypoxemia in the fetal lamb in utero.

We studied the effects of 10-minute periods of hypoxemia in unanesthetized fetal lambs in utero instrumented for measurements of arterial pressure and renal and iliac blood flows. Fetal hypoxemia, induced by delivering a hypoxic gas mixture to the ewe, was characterized by a reduction in fetal PaO2 from 20.1 +/- 1.4 to 8.8 +/- 1.0 mm Hg (mean +/- SE). The fetus responded with bradycardia and persistent vasoconstriction in the iliac bed throughout the 10-minute period. In contrast, renal resistance rose significantly only at the end of the hypoxemic period. After 5-7 minutes of hypoxemia, when iliac flow had fallen by 40 +/- 4% and iliac resistance had risen by 86 +/- 13%, renal flow and resistance were not changed significantly from control; in fact, we found that renal flow rose substantially at this time in several fetal lambs. After blockade of prostaglandin synthesis with either indomethacin or meclofenamate, renal flow fell after 5-7 minutes of hypoxemia by 36 +/- 5%. The reduction in renal flow and increases in renal resistance were significantly greater than was observed prior to blockade of prostaglandin synthesis. Thus, fetal hypoxemia elicits bradycardia and intense peripheral vasoconstriction reflected by the changes in the iliac bed, with relative sparing of the reanl bed. The relative protection of the renal bed during fetal hypoxemia appears to be related to a mechanism involving prostaglandins, since after blockade of prostaglandin synthesis, hypoxemia results in intense renal vasoconstriction.


The effects of cocaine and metanephrine on the cardiac responses to sympathetic nerve stimulation in dogs.

The effects of infusions of cocaine (COC) and metanephrine (MET) on the inotropic and chronotropic responses to cardiac sympathetic nerve stimulation were studied in open-chest, anesthetized dogs. COC blocks the neuronal uptake of norepinephrine (NE), whereas MET blocks the extraneuronal uptake. Both blocking agents slightly enhanced the inotropic but not the chronotropic responses. COC prolonged the cardiac responses significantly, particularly the chronotropic responses, whereas MET had no appreciable effect on the durations of these responses. Hence, it appears that the neuronal uptake mechanism plays a major role in the dissipation of neurally released NE in the heart, but that the extra-neuronal uptake mechanism plays only a minor role in its dissipation. In contrast to the results in certain other tissues, the combined effects of COC and MET on the cardiac responses were no greater or more prolonged than the sum of the effects produced by each agent acting alone.


Extracellular potentials related to intracellular action potentials during impulse conduction in anisotropic canine cardiac muscle.

This paper considers a quantitative description of intracellular and transmembrane currents in anisotropic muscle, with emphasis on the factors that determine the extracellular potentials. Although Vmax of the intracellular action potential had no relation to changes in conduction velocity in anisotropic tissue with constant membrane properties, the extracellular waveforms were quite sensitive to velocity changes. Large amplitude biphasic deflection occurred in the fast areas, and in the slow areas the waveforms were of lower amplitude and triphasic in shape; i.e., negative potentials preceded the biphasic positive-negative deflection. The extracellular potentials were simulated on the bases of a model of intracellular currents, and the theoretical and measured results showed good agreement. In tissue with anisotropic conductivity, the relationship between the spatial intracellualr potential gradient and the magnitude of the extracellular potential of the excitation wave was opposite to the classical relationship in isotropic tissue. Due to the influence of the effective intracellular conductivity on the spread of intracellular currents and on conduction velocity, in anisotropic tissue the extracellular potential decreased as the intracellular potential gradient increased. The peak values of the positive and negative potentials and the spatial distribution of the potential gradients varied considerably along the activation front. These findings were accounted for by differences in the distribution and spatial extent of the transmembrane currents, which were determined by the intracellular currents. The theoretical analysis showed that intracellular and transmembrane currents were proportional to the local conduction velocities of the wavefront. Thereby, it was not possible to have a "uniform layer" of current when there were differences in conduction velocity along the length of the excitation wave. The implications of the analysis are considerable, since the gratifying agreement between the theoretical and measured results indicates that the details of the extracellular waveforms can be explained on the basis of the distribution of intracellular currents; i.e., extracellular potentials provide a sensitive index of intracellular current flow.


Heart adaptation to acute pressure overload: an involvement of endogenous prostaglandins.

The purpose of this investigation was to study the relationships between the contractile behavior of the heart and myocardial prostaglandins. Using an open-chest model in rabbits, we assayed the left ventricular tissue content to prostaglandins (PG) E and F2 alpha at various intervals following acute pressure overload created by graduated aortic stenosis. The results suggest that the rabbits could be divided into two distinct groups based on specific hemodynamic changes following coarctation (systolic and diastolic pressure, dP/dt, and contractility index). The first  group included rabbits whose adaptation to pressure overload was expressed as a gradual increase in the contractility index. The second group was comprised of rabbits that developed heart failure following coarctation. The increase in contractility in response to overload in the first group was paralleled by an increase in the content of PGE and PGF 2 alpha in the left ventricle, whereas, in rabbits with heart failure, the prostaglandin level did not rise above that of the control hearts. It is suggested that an increased endogenous prostaglandin content may be an important factor in adaptation to acute overload.


Biochemical determinations of cholinergic innervation in cerebral arteries.

Endogenous choline acetyltransferase (ChAT) activity and high affinity (HA) 3H-choline uptake can be assayed specifically and used to quantify cholinergic neuronal mechanisms. In general, arteries at the base of the brain in the cat and rabbit were distinguished by high and in the dog by lower ChAT activity and 3H-choline levels of uptake. There was a linear relationship between the mean values of the observations from of the two assays on given cerebral arteries from the three species (r = 0.871,P less than 0.001). Since ChAT activity and HA 3H-choline uptake essentially are confined to cholinergic nerve terminals, our results imply that the Circle of Willis and its main branches in the cat, rabbit, and dog are cholinergically innervated.


Relationship between adenine nucleotide metabolism and irreversible ischemic tissue damage in isolated perfused rat heart.

The relationship between energy metabolism and the extent of irreversible ischemic damage was examined in an isolated perfused working rat heart. The amount of cardiac work recovered after reperfusion of hearts exposed to severe global ischemia was dependent upon both the duration of ischemia and the type of substrate provided (either 5 mM glucose or 5 mM glucose + acetate). There appear to be two distinct phases in the ability to recover mechanical function in the reperfused ischemic heart. The second phase corresponds to the onset of severe irreversible tissue damage. Irreversible mitochondrial damage was not found to correspond with the onset of heart failure since the ATP/ADP ratio remained constant in the reperfused myocardium. Furthermore, there does not appear to be a direct correlation between the total ATP content and the extent of irreversible damage, either during ischemia or following reperfusion. However, the total adenine nucleotide content during ischemia showed dramatic changes which correspond temporally with the initiation of the second phase of damage. The observation that the adenine nucleotide pool becomes further depleted during reperfusion suggests that alterations in the salvage pathway for adenine nucleotide synthesis have occurred. Loss of adenine nucleotides appears to be an excellent marker for irreversible heart failure. Acetate provides some protection the the ischemic myocardium. The mechanism by which acetate mediates this protective effect is discussed.


Electrophysiological study of the action of angiotensin II on the rat myometrium.

Angiotensin II (A II) produces a contraction of visceral and vascular smooth muscles of different species. The accompanying electrophysiological changes were measured on strips of rat myometrium at 35 degrees C using the double sucrose-gap technique. A II at concentrations from 5 x 10(-10) to 10(-6)M produces a depolarization and an increase in membrane conductance. This increase in membrane conductance is not membrane potential dependent since it is observed even when the membrane potential is maintained at the resting level. When all Na + in the test solution is replaced by either Li + or Mg (2+), the depolarizing effect of 10(-6)M A II is either markedly reduced or abolished. Under these conditions, A II produces a small initial hyperpolarization, which is modified by external potassium concentration changes and abolished by tetraethylammonium chloride. When all Cl- is replaced by either NO (-3) or cyclohexanesulfamate, A II (10(-6) M) still produces a 20-m V depolarization. The removal of extracellular Ca (2+) or K+ does not have any effect on the depolarizing action of A II, which also is not changed by 10(-3) M ouabain. In conclusion, A II produces a depolarization of the uterine smooth muscle membrane through an increase in the membrane conductance to Na+. The membrane conductance to potassium is increased simultaneously. The contraction induced by A II shows two components: a phasic component triggered by the Ca (2+) entry associated with spike production and a tonic component due to the release of Ca(2+) from intracellular stores.


Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats.

We studied alterations in structural and mechanical properties of mesenteric arterial resistance vessels from young (6-week) and old (50-week) spontaneously hypertensive (SHR)and matched normotensive Wistar-Kyoto (WKY) rats. Emphasis was placed upon relating the active tension capabilities of these vessels to their smooth muscle cell content. Cylindrical segments, 0.7 mm long with internal diameters of 150 micrometer, were mounted in a myograph capable of recording circumferential vessel wall tension and dimensions. Comparisons of vessel morphology and mechanics were performed at a normalized internal circumference, L1,where active tension (delta T1) is near maximum. Arterial wall and medial hypertrophy were observed in young and old SHR. Since the percent smooth muscle cells within the media for SHR was similar to that of WKY, both increased smooth muscle cell and connective tissue content account for the medial hypertrophy. These differences in SHR vessels were reflected directly in their passive and active mechanical properties. Fully relaxed vessels from SHR were less compliant, and upon activation at L1 (high potassium depolarization), delta T1 was not different for young SHR and WKY, but values for old SHR were 35% greater (P less than 0.05) than for WKY. When relating the active force generation of the vessel to the actual smooth muscle cell area, values for smooth muscle cell stress (force/area) were similar for SHR and WKY at both ages. In addition, similarities were observed for active dynamic mechanical measurements of Young's modulus and half response time. Genetic hypertension in rats therefore appears to be associated with the development of increased vessel contractility determined by a greater number of smooth muscle cells which possess contractile properties similar to those of normotensive vessels.


Age-related cardiovascular effects of catecholamines in anesthetized piglets.

We studied cardiac and peripheral circulatory effects of graded doses of catecholamines (0.05-1.0 microgram/kg) in piglets aged less than or equal to 1 day, 2--4 days, 1 wweek, 2 weeks, and 2.5-3 months, under anesthesia with pentobarbital. We evaluated cardiovascular function from simultaneous recordings of aortic pressure, ventricular pressure and its first derivative, heart rate, and phasic carotid and femoral blood flows. We calculated vascular resistance as the ratio of mean aortic pressure to mean flow. The age of onset of a given cardiovascular response was determined, and magnitudes of each type of response were compared among the age groups. Norepinephrine elevated the blood pressure at all doses in piglets of all ages, elicited reflex bradycardia only in older piglets, and increased carotid resistance. Epinephrine elevated the blood pressure at all doses in piglets less than 1 week old, but low doses lowered the blood pressure in piglets older than 1 week of age; resistance changes in the femoral and carotid circulations were variable except in the 2.5-3 month age group. Isoproterenol increased cardiac contractility at all doses in piglets of all ages and increased heart rate at low doses in piglets older than 2 days of age; however, blood pressure and femoral resistance decreases were age and dose dependent. There were age-related differences in the catecholamine dose required to elicit a given cardiac or peripheral circulatory effect and age-related differences in the direction and magnitude of such effects. These results provide evidence for differing rates of postnatal maturation of cardiovascular alpha- and beta- adrenergic mechanisms in swine.


Mechanical and structural correlates of contracture induced by metabolic blockade in cardiac muscle from the rat.

We performed morphological studies of myocardial contracture to define its nature and relationship to mechanical changes occurring during metabolic blockade. Isolated rat papillary and trabecular muscles were stretched to the apices of their length-tension curves and stimulated to contract isometrically 12 times a minute at a temperature of 28 degrees C. Incomplete and total metabolic blockade were induced by 1 hour of hypoxia (95% N2, 5% CO2) or by hypoxia plus glycolytic blockade with iodoacetic acid, 10-4M, respectively. In oxygenated control preparations, mechanical performance was stable for the 60-minute experimental period. In preparations exposed to hypoxia, developed tension fell to 7 +/- 2% of prehypoxia values at 60 minutes. Contracture tension increased progressively to 2.5 +/- 0.4 g/mm2. With total metabolic blockade, developed tension declined to zero by 10 minutes, contracture tension rose to an average peak value of 5.3 +/- 0.4 g/mm2 by 15 minutes, and subsequently slowly declined. All preparations were fixed at Lmax in the muscle bath. Light and electron microscopic studies revealed focal irregularities of A, I, and Z bands with sarcomere malalignment, hypercontraction, and fiber disruption, which increased in severity with increasing metabolic blockade. Linear densities appeared in mitochondria following total metabolic blockade, but mitochondria appeared normal otherwise. Thus, myocardial contracture after metabolic blockade is a focal process beginning within the sarcomere; morphological alterations in the contractile apparatus correlate with mechanical changes and are more severe than those in the mitochondria.


An essential view in coronary arteriography.

A significant stenosis of the left main coronary artery is associated with a significant mortality and is one of the major indications for aortocoronary bypass surgery. The diagnosis of this lesion on clinical grounds is inconsistent and should be established by angiography. All routine projections during coronary arteriography cause foreshortening of the left main coronary artery. Well-collimated anteroposterior and shallow right and left anterior oblique views show the main segment best. These views also show the proximal segments of circumflex and anterior descending branches, and should be routinely used during every coronary arteriogram.


Quantitative coronary angiography: measurement of the "critical" stenosis in patients with unstable angina and single-vessel disease without collaterals.

Quantitative angiographic assessment of proximal coronary artery stenosis was performed in 15 patients with consecutive presentations in two categories defined by clinical and angiographic criteria. Group 1 consisted of 10 patients who had new onset of refractory rest angina and ischemic ST-T changes, but no infarction, single-vessel coronary disease without collateralization, and normal left ventricular (LV) angiograms. Group 2 consisted of five patients who were similar to patients in group 1, but had subendocardial infarction (SEI). Quantitative coronary arteriography, using paired perpendicular angiographic views and digital computation, yielded statistically different lesion dimensions and hemodynamic predictions for the two groups. Minimum stenosis diameters were 0.88 +/- 0.14 (SD) and 0.64 +/- 0.08 mm, respectively, for groups 1 and 2. This corresponded to 72% and 78% diameter reduction and 92% and 95% cross-sectional area reduction for the two groups. These small dimensional differences among lesions in the two groups resulted in large differences in their hemodynamic impact as predicted from classic fluid mechanics theory. We conclude that there are characteristic lesion dimensions for the isolated "critical" stenosis in these selected patients with rest angina. Further small increases in lesions severity result in SEI. Certain practical applications and limitations of these observations are discussed.


Exercise and human collateralization: an angiographic and scintigraphic assessment.

The effect of exercise on the development of intercoronary collaterals and on left ventricular function is controversial. Twenty male patients (mean age 48 years, range 36-54 years) who had suffered an acute myocardial infarction were randomly allocated to an exercise group (10 patients) and a control group (10 patients). Both groups underwent coronary angiography, left ventricular function studies and myocardial perfusion studies with labeled microspheres, before and after the 7-month experimental period. Both groups had similar extent of disease as measured angiographically and both had mild progression of disease. Neither group showed changes in extent of callateralization, myocardial perfusion or left ventricular function. The exercise group had a significant increase in anginal threshold and a significant (p less than 0.01) decrease in heart rate at a given work load. Exercise, therefore, does not appear to affect progression of disease, myocardial perfusion, extent of collateralization, or left ventricular function in patients with coronary artery disease.


Regional left ventricular function assessed by contrast angiography in acute myocardial infarction.

The relationship of segmental left ventricular (LV) wall motion abnormalities to LV function 2-6 days after acute transmural myocardial infarction (MI) was investigated in 45 patients by quantitative contrast ventriculography. Patients were divided into four classes according to the MIRU criteria. Segmental wall motion was assessed by determining the percentage of systolic shortening (deltaS) along nine hemiaxes and the extent of akinetic or dyskinetic abnormally contracting segments (% ACS) expressed as a percentage of end-diastolic perimeter. When compared with that in 17 normal control-subjects, the LV end-diastolic volume was increased only in patients in class III and class IV; the LV end-systolic volume increased progressively from normal through class IV. Ejection fraction had a negative linear correlation with %ACS (r = 0.97). The size of ACS was larger in anterior (34 +/- 14%) than in inferior MIs (23 +/- 7%), resulting in greater LV dysfunction. However, for a comparable size of ACS, infarct location alone did not influence LV function parameters. In the noninfarcted zone, deltaS was increased when the size of ACS was less than 25% and reduced when the size of ACS was greater than 25%. Thus, the size of ACS is a major determinant of LV dysfunction in acute MI. The compensatory mechanisms operate either through an augmented mechanical function of residual myocardium when the infarct is small, or through the Frank-Starling mechanism when the infarct is large.


Oxygen consumption and hemodynamic response of exercises used in training of patients with recent myocardial infarction.

We investigated oxygen consumption (ml/kg/min) and hemodynamic response (peak heart rate-systolic blood pressure product) to individual exercise activities before and after exercise training in 22 male postmyocardial infarction patients (PMIP). Activities included swimming, walk/jogging, volleyball, calisthenics and exercise dance routines. Oxygen consumption was determined immediately after exercise by the Douglas bag gas collection procedure and, in selected patients, by a Max Planck respirometer during exercise. Hemodynamic data were obtained by pulse count and cuff sphygmomanometer. The increase in oxygen consumption and the decrease in rate-pressure product after each activity were significant (p less than or equal to 0.01). There were no differences in oxygen consumption between the Max Planck respirometer technique and collection (Douglas bag method) immediately after exercise. The oxygen consumption obtained for PMIP compared with available cumulative data on normal subjects is significantly variable, suggesting the need for caution when prescribing exercise for the PMIP based on energy costs of standard exercise measurements in normals. This was particularly relevant because of the significantly high oxygen consumption incurred during swimming.


Effect of extension of infarction on serial CK activity.

The effects of extension of myocardial infarction by reduction of regional myocardial blood flow (RMBF) to an ischemic region on serum CK activity was examined in 14 awake dogs. Initial infarction was effected by occlusion of the distal left circumflex coronary artery (LCCA) and subsequent extension was produced by occlusion of the proximal LCCA 6, 12 or 18 hours after distal occlusion. Extension was verified by serial measurements of RMBF using radioisotope-labeled microspheres before and after proximal occlusion. Serum CK activity increased initially 2-4 hours after distal coronary occlusion and then increased rapidly and reached peak values 12 hours after occlusion. When the infarction was extended at 6, 12 or 18 hours after initial occlusion, CK appearance was immediately reduced in the 6- and 12-hour experiments, but not in the 18-hour experiments. Extension of infarction at each interval caused delayed increases in CK activity beginning 2-5 hours after proximal occlusion, with peak values occurring 12 hours later. The immediate effects of extension of infarction by reducing blood flow on CK activity are a function of whether the infarcted myocardium continued to release CK, e.g., at 6 and 12 hours after occlusion, or CK release was completed, e.g., 18 hours. The immediate effects of extension of infarction were the result of perfusion on myocardium that is infarcted and continues to release CK, and do not necessarily indicate alterations in the extent of myocardial injury. The delayed effects of proximal and distal occlusion on CK activity were comparable, suggesting that delayed and not immediate alterations in CK activity represent extension of infarction.


Venous admixture in human septic shock: comparative effects of blood volume expansion, dopamine infusion and isoproterenol infusion on mismatching of ventilation and pulmonary blood flow in peritonitis.

A hemodynamic study with blood gas analysis was performed so we could observe changes induced by blood volume expansion, dopamine infusion and isoproterenol infusion in 20 adult patients suffering from peritonitis complicated with septic shock and acute respiratory failure. Blood volume expansion increased cardiac index (from 2.6 +/- 1.21/min/m2 to 3.4 +/- 1.31/min/m2; p less than 0.001), but also enhanced venous admixture (QS/QT) from 27 +/- 14% to 36 +/- 13%; p less than 0.01). Dopamine infusion increased cardiac index (from 2.6 +/- 0.9 1/min/m2 to 3.4 +/- 1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 25 +/- 11% to 31 +/- 12%, p less than 0.001). Isoproterenol infusion increased cardiac index (from 2.6 +/- 0.9 l/min/m2 to 3.6 +/- 1.1 l/min/m2; p less than 0.001), but also enhanced venous admixture (from 27 +/- 12% to 33 +/- 11%; p less than 0.001). This worsening in mismatching of ventilation and blood flow is correlated with the enhancement in pulmonary blood flow obtained by these three therapeutic procedures.


The extraction of circulating catecholamines by the lungs in normal man and in patients with pulmonary hypertension.

We directly measured the net pulmonary extraction of circulating norepinephrine, epinephrine and dopamine in control patients and patients with primary or secondary pulmonary hypertension. Mixed pulmonary artery norepinephrine, epinephrine and dopamine were 314 +/- 13 pg/ml, 102 +/- 9 pg/ml, 51 +/- 5 pg/ml, respectively, for the control group; values were similar in patients with pulmonary hypertension. The pulmonary extraction of norepinephrine was 25.4 +/- 2.6% (clearance 266 +/- 62 ng/min) in control patients; epinephrine and dopamine were not extracted. There was no net extraction or production of any of the three catecholamines by the lungs in any of the patients with pulmonary hypertension. We conclude that the lungs play a significant role in the inactivation of circulating norepinephrine in man. This metabolic function of the lungs appear to be lost in pulmonary hypertension.


Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area.

The dynamics of acute mitral regurgitation were studied in six open-chest dogs in whom a portion of the anterior leaflet was excised. Phasic mitral and aortic flows were measured electromagnetically and left ventricular filling volume, regurgitant volume (RV) and forward stroke volume (SV) were calculated. The systolic pressure gradient (SPG) between the left ventricle (LV) and left atrium (LA) was obtained from high-fidelity pressure transducers. The effective mitral regurgitant orifice area (MRA) was calculated from the hydraulic equation of Gorlin. Volume infusion resulted in significant increases in both left atrial and left ventricular pressures; thus, the SPG was unchanged and the increase in RV was due primarily to the increase in MRA. Angiotensin infused to raise arterial pressure resulted in greater increments in left ventricular than left atrial pressure, so that SPG rose significantly. The increase in RV was due to increases in both MRA and SPG. Norepinephrine infusion increased systolic left ventricular pressure and SPG, while left ventricular end-diastolic pressure and left atrial pressure diminished. Despite a significant increase in SPG, RV did not increase, due to a substantial decrease in MRA. Thus, angiotensin and volume infusion induced a substantial increase in regurgitation due to the increase in MRA, while augmentation of contractility after norepinephrine infusion resulted in a decrease in regurgitation through reduction of MRA. These findings support the clinical view that maintaining a small LV with sustained myocardial contractility will reduce mitral regurgitation. Alternatively, left ventricular dilatation can enhance mitral regurgitation by increasing the effective regurgitant orifice independent of SPG.


Dynamic geometry of the left atrium and left ventricle in acute mitral regurgitation.

The instantaneous transverse diameter of the left atrium, left ventricular free wall segment length (SEG), and the long axis of the anterior papillary muscle (APM) length were measured throughout the cardiac cycle, using ultrasonic dimension gauges together with left atrial and left ventricular pressures in 12 open-chest dogs. During atrial contraction, left atrial diameter decreased from 19.7 to 18.7 mm, while left ventricular dimensions increased simultaneously. During ventricular ejection, percent shortening was 26% in SEG and 10% in APM, while atrial diameter increased continuously to 20.5 mm, with a concomitant rise in the v  wave of left atrial pressure. After normal mitral valve opening, left atrial diameter decreased rapidly simultaneously with the y descent of atrial pressure. Graded mitral regurgitation was then produced by sectioning the chordae tendineae. With moderate mitral regurgitation, end-diastolic length of the SEG increased by 27%, while extent of shortening (delta L) was augmented by 96%. End-diastolic length of the APM increased by 7%, and delta L was augmented by 60%. Left atrial pressure was sharply elevated, with a distinct a wave followed by the more prominent v wave. End-diastolic diameter of the left atrium was enlarged to 22.9 mm with increased atrial shortening and expansion. As mitral regurgitation was increased to a severe degree by additional chordal rupture, end-diastolic length and delta L continued to increase both in SEG and APM. Left atrial pressure was further elevated (a wave 25 mm Hg and v wave 47 mm Hg). Left atrial end-diastolic diameter further increased in 24.9 mm. However, the amplitude of left atrial shortening and expansion decreased remarkably. In severe mitral regurgitation, isoproterenol and nitroprusside decreased left atrial pressure and diameter, restoring more forceful atrial shortening.


Scaling current and energy with body weight: requirements for the transthoracic ventricular defibrillation of calves as they grow from 50 to 150 kg.

To test the hypothesis that the effectiveness of a shock in achieving ventricular defibrillation is relatively independent of body weight if electrode diameter is proportional to the one-third power and current is proportional to the two-thirds power of weight, we studied defibrillation rates in 10 calves as they increased weight. At 50 kg, each calf was subjected to 20 fibrillation-defibrillation episodes using 10.3-cm diameter electrodes and 32-amp, 4-msec rectangular pulses for defibrillation. Two days after the original study, each calf underwent 20 additional episodes involving 44-amp pulses. With the specified scaling of electrode diameter and pulse amplitude, the two studies were repeated at weight intervals of 25 kg as the animals grew. Six calves survived. In the study that started with 32-amp pulses, first-shock success values of 28%, 49%, 66%, 51% and 23% were found in the six surviving calves at 50, 75, 100, 125 and 150 kg, respectively. The corresponding values were 93%, 96%, 93%, 94% and 91% in the study that started with 44-amp pulses. While the results of the 32-amp study fail to support our initial hypothesis, those obtained in the 44-amp current study appear compatible with the hypothesis.


Evolution of QRS-T relationship from birth to adolescence in Frank-lead orthogonal electrocardiograms of 1492 normal children.

Patterns of evolution of QRS-T relationship were investigated by determining statistical distributions of QRS and STT integral vectors and the ventricular gradient vector in 1492 normal children divided into 12 age groups from birth to the age of 16 years. From birth to the age of 4 days, the ventricular gradient vector shifts posteriorly and to the left due to posterior shift of the STT integral vector and an increase in the spatial angle between QRS and STT integral vectors to a mean value of 103 degrees. These early neonatal changes in QRS-T relationship probably reflect the sudden reduction of hemodynamic load and the subsequent postnatal atrophy of the right ventricle while the left ventricular load slowly increases. The magnitude of the ventricular gradient vector increases from age 3 weeks until about 7 years. The increase appears to be related to a gradual increase in the magnitude of the QRS and STT integral vectors and a drastic decrease in the spatial angle between them. The spatial angle between QRS and STT integral vectors reaches it minimum (22 degrees) in the age group 1.5--4.5 years, suggesting that at that age the average direction of ventricular excitation and repolarization wavefronts are nearly opposite to each other. In addition to the shifting balance between the left and right ventricular hemodynamic load, other factors, such as the maturation of the sympathetic nervous system, may be important in determining spatial gradients in the duration of action potentials, thus influencing the relationship between ventricular excitation and repolarization.


Right sinus of Valsalva-right atrial fistula secondary to nonpenetrating chest trauma: a case report with description of noninvasive diagnostic features.

A sinus of Valsalva-right atrial fistula secondary to nonpenetrating chest trauma is described. Echocardiogrpahy demonstrated diastolic fluttering of the anterior tricuspid valve, suggesting a left-to-right shunt at the level of the right atrium. External jugular venous pulse tracings revealed large alpha waves and attenuation of the y descent. Cardiac catheterization disclosed a fistulous communication between the right sinus of Valsalva and right atrium. After surgical repair of the fistula, the ultrasonic recording and external pulse tracing reverted to normal. We believe this is the first description of such a shunt after blunt thoracic trauma.


Left anterior hemiblock obscuring the diagnosis of right bundle branch block in acute myocardial infarction.

Thirty cases in which transient left anterior hemiblock (LAHB) obscured the diagnosis of right bundle branch block (RBBB) appearing during the first days of an acute myocardial infarction (AMI) are presented. Twenty-eight of the patients with AMI had a clear septal wall involvement, while the remaining two had an anterolateral and lateral wall AMI, respectively. These intraventricular conduction defects developed 2-120 hours (mean 64.9 +/- 26 hours) after the acute event, and persisted for 24 hours to 7 days (mean 63.1 +/- 35 hours). The ECG was characterized by a pure LAHB with wide QRS complexes and the presence of RBBB was shown by recording high V1 and right-sided chest leads. The vectorcardiogram was also useful in several cases. The clinical course of this type of bifascicular block was transient and benign, with an in-hospital mortality of 6.7%. No patient developed trifascicular or complete atrioventricular block and, therefore, we conclude that prophylactic installation of a temporary pacemaker is not indicated in this type of bifascicular block. The possible role of extracellular potassium released during acute myocardial necrosis in the pathophysiological mechanism of these blocks is discussed.


Significance of chronic bifascicular block without apparent organic heart disease.

Eighty-six of 452 patients (19%) with chronic bifascicular block were found to have no clinically apparent associated organic heart disease (OHD) and were defined as having primary conduction disease (PCD). Comparison of patients with PCD and OHD revealed a significantly lower incidence of the following clinical variables in the PCD patients (p less than 0.001): exertional angina, dyspnea, congestive heart failure, cardiomegaly, functional class I (all by study design), left bundle branch block and premature ventricular contractions. Both mean AH and HV intervals were significantly shorter in patients with PCD (p less than 0.01). The incidence of HV prolongation was 21% in PCD and 41% in OHD patients (p less than 0.001). All patients were prospectively followed for 21-2998 days with a mean +/- SEM of 1209 +/- 66 days for PCD and 1172 +/- 36 days for OHD. Atrioventricular (AV) block developed in three patients from the PCD group and 26 from the OHD group (NS), with spontaneous block occurring in one (1%) PCD patient and 19 (5%) OHD patients (p less than 0.05). Annual mortality due to sudden death as well as total cardiovascular mortality (including sudden death) for the 5-year follow-up was significantly lower in patients with PCD. Patients with PCD have significantly lower incidence of electrophysiologic abnormalities and subsequent spontaneous AV block as well as cardiovascular and sudden death mortality. The diagnosis of PCD based on clinical criteria probably underestimates the presence of underlying OHD, as suggested by a small but definite risk of cardiovascular mortality.


Platelet survival time and thromboembolism in patients with mitral valve prolapse.

Thromboembolism (TE) occurs in about 20% of patients with rheumatic mitral valve disease, and platelet survival time in these patients has correlated with TE. In patients with mitral valve prolapse, TE appears to occur very infrequently. Platelet survival (autologous labeling with chromium-51) was performed in 26 patients with mitral prolapse. Five patients had a history of stroke, as well as normal cerebrovascular arteriography and shortened platelet survival (average half-time +/- SEM 2.3 +/- 0.18 days; normal half-time 3.7 +/- 0.03 days; n = 26; p less than 0.01). Platelet survival was shortened in seven of 21 patients without TE (33%) (3.3 +/- 0.06 days; p less than 0.01 vs patients with TE). In 138 patients with rheumatic heart disease, platelet survival was shortened in 40 of 41 (98%) with a history of TE (2.3 +/- 0.08 days) and in 76 of 97 (78%) without TE (2.9 +/- 0.07 days; p less than 0.001 vs patients with TE). In patients with mitral prolapse, sulfinpyrazone increased platelet survival (2.4 +/- 0.16 to 2.7 +/- 0.19 days; n = 7; p less than 0.05). Our results suggest that platelet survival time is shortened in patients with mitral prolapse and rheumatic heart disease who have had TE. Of those without TE there is an increased frequency of shortened platelet survival in patients with rheumatic heart disease (78%) compared with those with mitral prolapse (33%), consistent with the infrequency of TE in mitral prolapse.


Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Björk-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fraction and postoperative LVMI, EF, MNSER and PSWS. We attributed this to a marked improvement of left ventricular function in patients with preoperative impaired ventricular function. Six patients with paravalvular leak to restudy has a significantly lower EF and MNSER, and a higher PSWS than patients without leak. Patients without leak had normal EF, MNSER and PSWS when compared with 10 normal persons, but LVMI remained moderately elevated. Postoperative transprosthetic gradient was 11.9 mm Hg (range 0-64 mm Hg). We conclude that impaired cardiac function is completely restored after aortic valve replacement by Björk-Shiley valve, if valve function is good. Patients with impaired cardiac function preoperatively did not have a poorer prognosis after operation than patients with normal function.


Status of patients 5 or more years after correction of coarctation of the aorta over age 1 year.

In this retrospective study, we reviewed the records of patients who had coarctectomies at the University of Virginia Hospital after 1 year of age. Follow-up data for 5 years or more after surgery were available for 52 patients. Data from 23 similar patients from the Medical College of Virginia brought the total postoperative sample size to 75. The blood pressure of this group of patients did not differ significantly from that of the population at large. We conclude that successful repair of coarctation of the aorta in childhood or early adolescence does not lead to a higher-than-expected incidence of resting hypertension in childhood.


Subxiphoid two-dimensional imaging of the interatrial septum in infants and neonates with congenital heart disease.

The interatrial septum (IAS) was studied by subxiphoid two-dimensional echocardiography (S2DE) in 88 infants under 12 months of age who weighed 1.2-9.1 kg. The IAS was adequately displayed in 87 of 88 patients. The morphology, presence and localization of defects in the IAS were evaluated by S2DE and retrospectively related to the findings at cardiac catheterization. In seven patients with no interatrial communication at cardiac catheterization, the IAS was straight, with an area of central thinning corresponding to the veil-like cover of the septum primum over the foramen ovale. The morphology of the IAS with a stretched, patent foramen ovale (56 patients) indicated the coexistence of a right or left ventricular volume or pressure overload, and was readily distinguishable from the IAS with a secundum type communication (13 patients). In patients with a stretched, patent foramen ovale and left ventricular overload lesions, the IAS was a nearly homogenous, curvilinear structure bowing into the right atrium, with a small area of septal dropout at the superior rim of the septum primum. In the presence of right ventricular overload lesions, the central defect of the foramen ovale was associated with a redundant flap valve of the septum primum billowing into the left atrium. In secundum type communications, the centrally located defect represented a deficiency rather than a redundancy of the septum primum. Balloon atrial septostomy (BAS) in 17 patients produced a secundum-type defect bordered by the flail remnants of the torn septum primum. Blalock-Hanlon septectomy (two patients) resulted in a large, posterior, sinus venosus-type communication which incorporated the preexisting BAS. Ostium primum defects (seven patients) were distinguished from the secundum lesions by their eccentric position in the IAS adjacent to the atrioventricular ring.


Determination of right atrial and right ventricular size by two-dimensional echocardiography.

No data are available on determining right atrial and right ventricular size by two-dimensional echocardiography. We performed two-dimensional echocardiograms on eight human right-heart casts obtained at autopsy and on 50 patients who underwent complete left- and right-heart catheterization. Measurement of individual dimensions of the long and short axes of the right atrium and ventricle from right heart casts closely correlated with the volume of these structures as determined by water displacement. Further, individual dimensions by cross-sectional echo correlated well with actual casts dimensions. Subsequently, echocardiographic measurements of right atrial and ventricular long and short axes were obtained in the apical four-chambered view in a group of normals and compared with a group of patients with right ventricular volume overload states. Mean values for right atrial short-axis and long-axis measurements were greater in right ventricular volume overload patients than in normals: 6.5 +/- 0.3 vs 3.6 +/- 0.1 cm, and 6.0 +/- 0.3 vs 4.2 +/- 0.1 cm, respectively (both p less than 0.001). In addition, measurements of both individual dimensions as well as planed area of the right ventricle were greater in right ventricular volume overload patients than in normals: maximal short axis 6.1 +/- 0.3 vs 3.5 +/- 0.2 cm, mid-short axis 6.1 %/- 0.4 vs 2.8 +/- 0.2 cm, and area 40 +/- 2.6 vs 18 +/- 1.2 cm2 (all p less than 0.001). There were no differences in right ventricular long-axis measurement. Two-dimensional echocardiography provided better separation of normals from right ventricular volume overload patients than did M-mode techniques. Thus, two-dimensional echocardiography, with the apical four-chambered view, enables accurate visualization of the right atrium and ventricle in almost all patients. Futher, measurements of right atrial and right ventricular size by two-dimensional echocardiography readily distinguish normal patients from those with right ventricular volume overload.


Factors influencing the success of ventricular defibrillation in man.

To define the factors influencing the success of emergency ventricular defibrillation, we identified 52 patients defibrillated at the University of Iowa Hospital during 1974--1976. Thirty-eight patients were successfully defibrillated at least once; 14 could not be defibrillated, despite multiple attempts. Comparisons between these groups revealed no significant differences in body weight, heart weight, energy per kilogram of body weight and energy per gram of heart weight. Factors that militated against successful defibrillation included a prolonged delay before the first defibrillatory shock (successful 7 +/- 7 minutes (SD); unsuccessful 17 +/- 13 minutes, p less than 0.001), acidosis (successful pH 7.36 +/- 0.22; unsuccessful pH 7.23 +/- 0.12, p = 0.05) and hypoxia (successful PO2 100 + 98 torr; unsuccessful PO2 40 +/- 67 torr; p = 0.06). These three conditions tended to occur together in individual patients. Metabolic factors are important in determining defibrillation success; however, the role of high-energy doses is uncertain.


Determinants of ventricular defibrillation in adults.

Conventional defibrillators which stored no more than 400 J and used damped sine wave pulses defibrillated 240 of 253 (95%) episodes of ventricular fibrillation (VF) in 94 prospectively assessed resuscitations in 88 adults. Shocks of 80--240 J (under 3 J/kg) delivered to the chest wall defibrillated more often than higher energy levels. Defibrillation rate did not correlate with weight. Defibrillation was determined by the diagnosis and setting in which VF occurred. Patients with acute myocardial infarction (AMI) and primary VF or with coronary disease and no AMI defibrillated more easily than patients with AMI and secondary VF or with no coronary disease. VF in a terminal patient (agonal VF) defibrillated less often than VF in other clinical situations. Age, weight, delivered energy, duration of pulse wave, and duration of VF had little, if any, influence on rate of defibrillation. These data fail to support the use of more expensive, high-output defibrillators sold by 11 or 14 American manufactures.


Emergency coronary artery revascularization: a possible therapy for acute myocardial infarction.

Cardiac muscle death caused by coronary artery occlusion is a dynamic process that often takes hours or days. Emergency revascularization (saphenous vein bypass graft (SVBG) during acute myocardial infarction (MI) can interrupt myocardial necrosis, salvage ischemic myocardium and revascularize vessels with obstructive lesions not involved in the MI. In this report we describe a preliminary experimental study of 75 patients in which emergency SVBG was the therapy for acute MI. Group 1, 16 patients, required vasoactive medications and/or intraaortic balloon pumping to maintain their blood pressure preoperatively. There was one operative death and two late deaths. Group 2 consisted of 59 hemodynamically stable patients. There were no deaths. The average preop CPK in group 1 was 892 vs 504 in group 2 (p greater than 0.05). Surgical techniques were routine. The average time from the onset of chest pain that continued to surgery was 6.5 hours. Forty patients were restudied. Post- vs presurgical hemodynamics revealed ejection fraction increased by 34% (p greater than 0.05), left ventricular end-diastolic pressure reduced by 40% (p greater than 0.01). End-systolic and end-diastolic volume reduced by 30% (p greater than 0.05), and 15% (p greater than 0.01), and stroke volume improved 25% (p greater than 0.05). Operative mortality was 1.3% and late mortality 2.8%. These results suggest that cautious continued trial of emergency SVBG in patients with evolving MI is warranted.


Evaluation of myocardial ischemic damage of various ages by computerized transmission tomography. Time-dependent effects of contrast material.

The potential role of computerized transmission tomography (CTT) in the detection and quantitation of acute myocardial ischemic damage was assessed in 42 excised canine hearts at 2 hours, 8 hours, and 48 hours after coronary occlusion. The CTT scan detected by myocardial damage that was 2-48 hours old each time the presence of regional ischemia was confirmed by histochemical straining or epicardial electrocardiographic mapping. Intravenous administration of contrast material enhanced the x-ray attenuation of areas of ischemic damage of 8 and 48 hours duration compared with normal myocardium, but enhanced only normal myocardium in those of 2 hours duration. Volumetric estimation of the extent of damage from the CTT scans in dogs with ischemia of 48 hours duration showed a close linear relationship with the morphometric volume in the absence of contrast material. Quantitation of the area of ischemic damage from the CTT scan after contrast administration resulted in substantial underestimation of the volume of damaged tissue.


Technetium-99m stannous pyrophosphate myocardial scintigraphy after cardiopulmonary resuscitation with cardioversion.

Thirty consecutive patients underwent technetium-99m stannous pyrophosphate myocardial scintigraphy 48--72 hours after successful cardiopulmonary resuscitation and direct current cardioversion. Five patients with transmural myocardial infarctions by ECG and enzyme determinations were correctly identified by scintigraphy. Myocardial scans were positive in five of nine patients with nontransmural infarction. Of 16 patients without evidence of myocardial infarction, only two (13%) had false-positive myocardial scans. The overall accuracy of imaging in this series was 80%. We conclude that false-positive scans after cardiopulmonary resuscitation with electrical cardioversion are infrequent, and do not significantly detract from the value of myocardial scintigraphy in the diagnosis of myocardial infarction.


Imaging experimental myocardial infarction with indium-111-labeled autologous leukocytes: effects of infarct age and residual regional myocardial blood flow.

The external imaging patterns and the kinetics of infiltration of indium-111 labeled polymorphonuclear leukocytes (PMNs) occurring in the course of the inflammatory response associated with myocardial infarction were studied in dogs subjected to closed-chest anterior wall infarction. The effects of infarct age and regional residual myocardial blood flow upon PMN infiltration were investigated and quantified, and the capacity of indium-111 PMNs to image the experimental infarction was evaluated qualitatively. The epicardial accumulation of indium-111 PMNs occurred primarily in infarct zones with residual blood flow of 0.6 times normal and was maximal (14.8 +/- 3.8 times normal) in the lowest blood flow zone (less than 0.1 times normal). PMN accumulation in the endocardial infarct zones occurred in the regions with blood flow less than 0.6 times normal and was maximal (26.8 +/- 4.9 times normal) in the lowest blood flow zone. However, contrary to the maximal epicardial infiltration period, which occurred within the first 24 hours after infarction, the maximal endocardial infiltration occurred at 72 hours after infarction. In both endocardium and epicardium, PMN uptake was minimal at 120 hours after infarction. In vivo cardiac images were abnormal and revealed discrete, anatomically distinct areas of increased myocardial radioactivity uptake in the anterior wall of all dogs studied within 24--96 hours after infarction. All images obtained 120 hours after infarction were negative. Thus, indium-111 PMNs provide a noninvasive means of in vivo imaging of the inflammatory response to myocardial infarction and allow quantification of this response at a tissue level.


Measurement of aortic and mitral regurgitation by gated cardiac blood pool scans.

A simple, noninvasive radionuclide technique which measures the severity of valvular regurgitation has been developed. The technique compares right and left ventricular stroke volume indices (change in counts between diastole and systole over the left and right ventricles) from 45 degrees LAO gated cardiac blood pool scans. In 14 control subjects, the left-to-right ventricular stroke index ratio was near unity (1.15 +/- 0.15 [SD]). In 26 patients with mitral and/or aortic regurgitation it was larger (range 1.36--5.30, mean 2.44). Comparison between the stroke index ratio and qualitative angiographic estimates of regurgitation revealed good agreement (F = 45.5, p less than 0.001). Gated cardiac blood pool scans permit noninvasive assessment of the severity of valvular regurgitation.


Accurate volume determination in the isolated ejecting canine left ventricle by two-dimensional echocardiography.

Two-dimensional echocardiography can provide serial cross-sectional images of the left ventricular cavity. We examined whether such serial images from steady-state ejecting hearts would allow three-dimensional reconstruction and accurate volume estimation without major geometric assumptions. Cross-circulated, paced dog hearts were suspended in a blood-filled tank. Serial cross-sectional images were taken at 3-mm intervals along the vertical axis. Left ventricular cavity and muscle areas of each image were planimetered with a light-pen system and summated for volume: total volume = sigma (areas x 3 mm). Direct left ventricular volume was measured through the cardiac cycle with a volumetric chamber connected to a balloon in the ejecting left ventricle. In six hearts, 67 separate direct volume measurements (range 9.5--54.7 ml) from various points in the cardiac cycle were compared with the simultaneous echo volume measurements. By least squares linear regression, echo volume = 1.01 (direct volume) - 0.44 ml; r = 0.972, SEE = 2.93 ml. Provided accurate cross-sectional localization is available, these studies suggest that extremely accurate steady-state left ventricular volume can be determined noninvasively in the ejecting heart from multiple cross-sectional images.


Morphologic development of the pulmonary vascular bed in experimental coarctation of the aorta.

Although electrocardiographic evidence of right ventricular hypertrophy is considered common in newborn infants with coarctation of the aorta, the reason for this finding is not well established. Investigations of the pulmonary vascular bed of these infants have resulted in variable findings, probably due to the differences in morphometric techniques, coexisting cardiac defects, and variable postnatal age at time of death. To study more carefully the pulmonary vascular bed, we produced coarctation of the aorta in fetal lambs at 103--126 days gestation. Twelve to 32 days later the fetuses were reoperated on and systemic and pulmonary arterial blood pressures, and arterial blood gas tensions were determined to be normal. At autopsy, juxtaductal coarctations extended a mean of 2.8 mm into the aortic lumen and occupied 9.5 mm of the aortic circumference. The fifth-generation pulmonary resistance vessels had increased medial width (p less than 0.01), decreased external diameter (p less than 0.001), and increased medial width/external diameter ratios (p less than 0.001) compared with vessels from control fetuses. The number of small muscular pulmonary vessels/cm2 lung tissue was significantly reduced (p less than 0.01) in the study animals compared with the control animals. These alterations of the pulmonary vascular bed were not due to fetal pulmonary arterial hypertension or fetal hypoxemia. These pulmonary vascular changes may explain the occurrence of pulmonary hypertension and right ventricular hypertrophy in newborn infants with coarctation of the aorta.


Noninvasive detection of pulmonary hypertension in patent ductus arteriosus by pulsed Doppler echocardiography.

Twenty-five patients with proven patent ductus arteriosus were examined by pulsed Doppler echocardiography (PDE) before invasive assessment. Ten patients had normal pulmonary artery pressures, and by PDE, pandiastolic ductal flow. Fifteen patients had elevation of mean pulmonary artery pressure, and by PDE, all had abbreviations of diastolic ductal flow. PDE correctly distinguished between patients with normal pressure and those with evidence of pulmonary hypertension; the ECG did not allow such differentiation. Detection by PDE of pulmonary hypertension complicating patent ductus arteriosus appears to be clinically useful.


Hemodynamic, pulmonary vascular, and myocardial abnormalities secondary to pharmacologic constriction of the fetal ductus arteriosus. A possible mechanism for persistent pulmonary hypertension and transient tricuspid insufficiency in the newborn infant.

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in a significant rise in the fetal pulmonary-to-systemic arterial mean blood pressure difference across the ductus arteriosus, presumably secondary to constriction of the ductus arteriosus. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of prostaglandin E1 (PGE1) into the fetal inferior vena cava. Fetal lungs from study and control animals were fixed by perfusion at measured pulmonary arterial mean blood pressure, and fifth-generation resistance vessels were studied. The medial width/external diameter ratio was significantly increased in the study vs the control lungs due to increased smooth muscle and decreased external diameter. In addition, study fetuses had acute degenerative myocardial changes in the tricuspid valve papillary muscles, the right ventricular free wall and the interventricular septum. Similar changes were not seen in control fetuses. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus, fetal pulmonary arterial hypertension, and right ventricular damage. If severe, this may cause rapid fetal death. If less severe, in the newborn infant, this mechanism may be one cause of persistent pulmonary hypertension due to vasoconstriction and increased pulmonary arterial smooth muscle and/or tricuspid insufficiency due to papillary muscle infarction.


An evaluation of the left atrial/aortic root ratio in children with ventricular septal defect.

Echocardiograms were performed in 80 infants and children with isolated ventricular septal defect (VSD) who underwent cardiac catheterization. The pulmonary-to-systemic flow ratio (Qp/Qs) was correlated with the echocardiographic left atrial-to-aortic root diameter ratio (LA/Ao), and a relatively poor correlation (r = 0.62) was found. The end-systolic diameters of the left atrium and aorta at the level of the aortic root, obtained from lateral cineangiograms of 55 of the 80 patients, were compared with the corresponding echocardiographic dimensions. To assess the possible effect of transducer beam angulation upon the echocardiographic determinations, the angiographic measurements were made at 0 degrees position (perpendicular to the frontal plane) and at angles of 5 degrees, 10 degrees, 15 degrees and 20 degrees from zero, using the aortic root center as the point of intersection. The echocardiographic and angiographic aortic root measurements were comparable (r = 0.95), and the angiographically derived aortic diameter did not vary with different angle projections. However, the left atrial angiographic dimensions were significantly influenced by the angle of projection. We conclude that the echocardiographic LA/Ao ratio cannot reliably estimate the severity of the shunt flow in VSD.


Routine primary repair vs two-stage repair of tetralogy of Fallot.

Fifteen of 194 patients (7.7%) with tetralogy of Fallot operated upon since January 1, 1972 under a protocol of routine primary repair despite young age died in-hospital. Most deaths were from low cardiac output. Young age and smallness of size increased the risk of operation. No deaths occurred among patients older than 4 years. High hematocrit was also a risk factor. Transannular patching has an independent effect in increasing risk. The post-repair ratio of peak pressure in the right ventricle to that in the left did not exert an independent effect. To project current risks of a two-stage approach, we determined that five of 158 patients (3.2%) died in-hospital after secondary intracardiac repair after a previous Blalock-Taussig or Waterston anastomosis between 1967--1978. Using these data and those we have published on the risk of shunting, we project that except in very small babies, the risks of hospital death of a two-stage approach are not less than those of primary repair done without a transannular patch, except when body surface area is less than about 0.35 m2. When a transannular patch is used in the primary repair, the two-stage approach is projected to be safer when the child has a body surface area of about 0.48 m2 or smaller.


Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model.

The time course of ventricular arrhythmias in the early period (0--30 minutes) after ligation of the left anterior descending coronary artery was studied in 41 open-chest mongrel dogs anesthetized with pentobarbital sodium (Nembutal). ECGs and seven single and composite electrograms from various regions in and around the ischemic zone were recorded throughout the experiments. Two periods of ventricular arrhythmias were clearly seen. The first occurred 2--10 minutes after coronary ligation, peaking at 5--6 minutes, and was designated as immediate ventricular arrhythmias (IVAs). There was a distinct correlation between incidence, severity, onset and termination of IVA and the degree of local delay and fragmentation of the normal sinus activation spread in the ischemic subepicardial zone. The second wave of ventricular arrhythmias occurred 12--30 minutes after ligation independently of the previous increased delay and fragmentation of activation in the ischemic subepicardium. Delayed ventricular arrhythmias (DVAs) were as severe as IVAs--there were nine instances of ventricular fibrillation during DVA and seven during IVA. While the mechanism of IVA is most probably related to reentry accompanied by delay and fragmentation of ischemic subepicardial activation, the mechanism of DVA remains unclear. Our evidence suggests that DVAs are also reentrant, with the reentry pathways located in deep myocardial structures or involving microscopic pathways at the Purkinje muscle junction.


Noninvasive recording of His-Purkinje activity in patients with complete atrioventricular block. Clinical application of an "automated discrimination circuit".

In seven patients with complete atrioventricular (AV) block, His bundle electrograms (HBEs), standard ECG recordings, bipolar esophageal ECGs and highly amplified, filtered, bipolar chest lead ECGs were simultaneously recorded. The filtered chest lead ECG was averaged to determine His-Purkinje activity (HPA). A simplified device, the "automated discrimination circuit," was used to selectively eliminate the superimposed atrial and ventricular potentials that are characteristic of complete AV block and unsuitable for signal averaging. The processed chest lead ECG was amenable to conventional techniques of signal averaging. In four patients with block proximal to the AV node diagnosed by HBE, there was no activity after the P wave in the surface-averaged ECGs. HPA was consistently recorded before the QRS in the surface-averaged ECG. The measurements of the HV and HPA-V intervals were very close, with a difference of less than 2 msec. Three patients with block distal to the His bundle by HBE showed a loss of electrical potential before the QRS in the surface-averaged ECG, but had a consistent HPA after the P waves. The P-HPA intervals coincided well with PH intervals, with a maximal difference of 5 msec.


Reentry within the atrioventricular node: surgical cure with preservation of atrioventricular conduction.

Paroxysmal supraventricular tachycardia (PSVT) is commonly caused by reentry within the atrioventricular (AV) node. This arrhythmia was abolished by operative dissection of the AV junction in a patient with disabling tachycardia that was not controlled by drugs. The operation was intended to create complete AV block, but AV conduction persisted after surgery. An electrophysiologic study 1 year after the operation revealed that the operation changed AV conduction in both the antegrade and retrograde directions, which may explain the absence of tachycardia. The patient has been free of arrhythmias for 18 months.


Early closure of the tricuspid valve in a case of Ebstein's anomaly with type B Wolff-Parkinson-White Syndrome.

Echocardiographic studies of a 19-year-old female with Ebstein's anomaly and type B Wolff-Parkinson-White syndrome showed an earlier closure of the anterior tricuspid leaflet (ATL) than of the anterior mitral leaflet (AML), contrary to the previous reports. The interval between the closure of the ATL and the AML was 20 msec and 30 msec, respectively, before and after administration of edrophonium chloride. However, closure of the AML preceded that of the ATL after administration of atropine sulfate and during supraventricular tachycardia by 10 msec and 60 msec, respectively, concomitant with the shortening of the duration of the QRS complex. We conclude that early closure of the ATL may depend on preexcitation of the right ventricle.


Multivessel coronary artery spasm.

A 60-year-old patient with variant angina was shown to have myocardial ischemia in two different regions supplied by separate major coronary arteries. Neither artery had significant coronary atherosclerotic obstruction. Ventricular fibrillation was noted during ST-segment elevation in anteroseptal leads. The attacks of pain and arrhythmias disappeared during nifedipine therapy.


Effects of nitroprusside and dopamine on pulmonary arterial vasculature in children after cardiac surgery.

The hemodynamic effects of nitroprusside and dopamine were studied in 28 children early after intracardiac repair. Children were placed in six groups, five according to their anatomic lesion and one made up of those who had postoperative pulmonary artery hypertension, to evaluate the possible differences in response of the pulmonary arterial vasculature to the drugs. Seven children had repair of an atrial septal defect; six, repair of tetralogy of Fallot; four, repair of ventricular septal defect; five, surgery for pulmonary stenosis; one, closure of a left ventricular to right atrial tunnel; and five, postoperative pulmonary artery hypertension. Dopamine was infused at 8 microgram/kg/min, and nitroprusside at 3 microgram/kg/min. With dopamine, the heart rate increased an average of 10% and the cardiac index 11%; both increases were statistically significant. Changes in systemic and pulmonary vascular resistance, however, were not. With nitroprusside, the heart rate increased an average of 9% and the cardiac index 5%, while there was a significant decrease in both systemic (-20%) and pulmonary (-27%) vascular resistance. With the combination of dopamine and nitroprusside, both the cardiac index (+13%) and heart rate (+20%) increased significantly while systemic vascular resistance fell an average of 23% from control, and the pulmonary vascular resistance decreased 21%. Drug response among all five anatomic subgroups tended to be similar. We conclude that an afterload-reducing agent, such as nitroprusside and an inotropic drug such as dopamine, may have potential clinical advantages when used together in children providing heart rate does not become excessive.


Modified Shumacker repair of transposition of the great arteries.

Seven infants weighing from 6.4 to 10.3 kg underwent correction of transposition of the great arteries by the venous transposition operation as described by Shumacker. In this operation, a new atrial septum is constructed using a bipedicled right atrial flap, and the lateral atrial wall is constructed using a viable pericardial flap. Three of the patients had an associated ventricular septal defect. Six of the seven patients survived and have had an excellent clinical result. Although atrial arrhythmias were common in the early postoperative period, all patients are now in sinus rhythm. Two patients have had postoperative cardiac catheterization and cineangiography, which showed excellent hemodynamic results. The modified Shumacker operation preserves two of the three internodal pathways, provides a compliant, viable atrial septum, and permits fabrication of a generous-size physiological left atrium. This appears to offer advantages not present in the Mustard procedure.


Subclavian arterioplasty for the ipsilateral subclavian-to-pulmonary artery shunt.

A new technique is described to avoid kinking and improve flow in the ipsilateral subclavian-to-pulmonary artery shunt. Experience with this procedure is reviewed in 35 infants and children with a variety of cyanotic congenital heart disease, including 10 with tricuspid atresia. Of these, 17 had had previous shunts: a Waterston shunt in six, a Glenn shunt in six, and a contralateral Blalock-Taussig shunt in five. The mean age was 5.6 years (range, 1 day to 16 years), and the mean follow-up was 24 months (range, 11 months to 4.5 years). There were no early deaths (less than 30 days), but there were two late deaths. There were three shunt failures at 2 weeks, 1 month, and 10 months; two of the failures were in infants aged 1 day and 4 days at operation. There were no late shunt failures. The patency by the life table method was 91.4% at 6 months, 88.5% at 1 year, with no further drop-off. It is concluded that subclavian arterioplasty can be performed safely and offers improved shunt patency in comparing to the ipsilateral Blalock-Taussig shunt.


Femoral artery pressure measurement during aortography.

Femoral artery pressure (FAP) measurements were carried out to evaluate the hemodynamic significance of aorto-iliac occlusive disease in 150 patients (173 limbs) at the time of transfemoral angiography. Clinical assessment based upon traditional criteria of claudication level, pulse examination, and monoplane angiography were at variance with the results of this physiologic testing in approximately one-third of the patients. Results were most variable, and FAP testing most helful in evaluating patients with moderate diffuse disease on angiography, who are usually difficult to evaluate clinically. Strong correlation existed between FAP evaluation and the results of arterial reconstructive surgery. Of the patients with a positive FAP result who underwent proximal vascular reconstruction, 96% had satisfactory relief of ischemic symptoms despite uncorrected distal disease in the majority. In contrast, 57% of the patients undergoing proximal operation despite a normal FAP result were unrelieved of symptoms and required subsequent distal procedures. Similar correlation existed with results of femoro-popliteal and femoro-femoral grafting. This simple physiologic test has been found of great value in selecting the proper level of arterial reconstruction and in accurately predicting the results of surgery.


The elderly patient with severe arterial insufficiency of the lower extremity: limb salvage by femoro-popliteal reconstruction.

To determine the feasibility of limb salvage in elderly patients in whom severe ischemia of the lower extremity is present, the results of femoro-popliteal reconstruction done primarily for limb salvage were reviewed. Of 310 femoro-popliteal bypasses, 72 were performed on patients 70 years of age or older. In the over-70 group, ischemic necrosis was present in 70.8% rest pain in 22.2%, and claudication in 7.0%. Initial limb salvage patients 70 years of age or older was 71.4%. Cumulative limb salvage at 5 years was 51.1% and at 10 years was 44.8%. Operative mortality, including mortality of subsequent amputation, when required, was 8.3%. Appreciable limb salvage can be achieved by femoro-popliteal arterial reconstruction in lieu of primary amputation in elderly patients in whom severe arterial insufficiency of the lower extremity is present.


Asymptomatic coronary artery disease managed by myocardial revascularization: results at 5 years.

A consecutive series of 17 patients surgically treated for asymptomatic coronary artery disease was surveyed for survival, clinical status, and graft patency after a mean follow-up of 75 months. Documented myocardial infarction (MI), 14 transmural and 3 subendocardial, was the major indication for catheterization. All patients were asymptomatic for at least 4 months prior to surgery. Six patients had greater than 70% obstruction in one vessel, seven in two vessels, and four in three vessels. The indication for revascularization was critical stenoses in vessels supplying large areas of viable myocardium. All patients received left internal mammary artery (LIMA) grafts to the left anterior descending coronary artery; seven patients also received saphenous vein grafts (SVG) to other vessels. There was no operative or late mortality.  In 12 patients, postoperative angiography (mean interval, 12 1/2 months) showed 11/12 LIMA and all SVG patent. One incompletely revascularized patient with an occluded LIMA is symptomatic. All others are fully active without symptoms or interval MI after a minimum follow-up of 5 1/2 years. The safety and long-term results of myocardial revascularization warrant its consideration for selected asymptomatic postinfarction patients.


Comparison of myocardial protection with nifedipine and potassium.

Nifedipine, a slow-channel calcium blocker, is thought to provide useful myocardial protection during prolonged total ischemia and reperfusion. An isolated, isovolumic, feline heart model was used to asses the effectiveness of nifedipine in both cardioplegic (100 microgram/10 ml) and noncardioplegic (10 microgram/10 ml) doses for providing myocardial preservation during 90 minutes of hypothermic ischemic arrest and 45 minutes of normothermic reperfusion. Use of nifedipine was compared to hypothermia (27 degrees C) alone and to hypothermia with potassium cardioplegia. Ventricular function was assessed by recovery of isovolumic left ventricular developed pressure and dP/dt. Myocardial carbon dioxide tension (PCO2) and myocardial oxygen tension (PO2) were measured by mass spectrometry. Potassium cardioplegia and the higher dose of nifedipine resulted in immediate asystole. The rates of rise of PCO were greatest in the group receiving 10 microgram nifedipine and in the control group. The rates of rise in the two cardioplegic groups were significantly lower. Recovery of ventricular function was significantly lower with low-dose nifedipine than with potassium cardioplegia. Higher dose nifedipine resulted in a return of function, which was no different than with potassium cardioplegia. Morphologic protection was better with higher dose nifedipine and potassium cardioplegia than with either low-dose cardioplegia or hypothermia alone. These results demonstrate that nifedipine in a cardioplegic dose results in preservation of myocardial structure and function that is similar to that obtained with potassium cardioplegia. In lower noncardioplegic dose, nifedipine does not appear to offer additional protection compared to hypothermia alone. Whether persistent depression of ventricular contractility will limit nifedipine's clinical usefulness as a myocardial protection agent will require further study.


Unstable angina pectoris: an examination of modes and costs of therapy.

Debate exists over the most appropriate form of treatment for patients with unstable angina pectoris. This study examined 106 patients randomized at the University of Alabama in Birmingham as part of the National Cooperative Study Group and focuses on the phenomenon of patients who fail medical therapy and thus require late surgery, and the costs of therapy. Discriminant function analysis revealed that the significant predictors (p less than 0.01) of patients who would later require surgery were: total number of vessels diseased, angina severly, presence of congestive heart failure, hypertension, and number of years that the patient had had angina. By means of this analysis, 85% of the late surgery patients were correctly predicted. Late surgery patients averaged 2.4 diseased vessels vs 1.5 for persistent medical patients (p less than 0.01). Mean charges for the first 2 years in the study were $6,226 (SD $2,967) for persistent medical patients, $10,416 (SD $2,146) for surgery patients, and $20,059 (SD $10,748) for late surgery patients (p less than 0.001). These data indicate that surgery is clearly an expensive procedure; but that it is more expensive for late surgery patients, who have total costs that are twice as high as surgical costs and 3.5 times as high as persistent medical costs.


A new cardiac prosthesis: the St. Jude Medical cardiac valve: in vivo results.

The St. Jude Medical cardiac valve prosthesis is a low profile, lightweight, bi-leaflet, central-flow device constructed entirely of pyrolytic carbon. In vivo testing was performed in 24 cows in which the tricuspid valve (n = 14) or mitral valve (n = 10) was replaced by a St. Jude Medical prosthesis with a 26 mm tissue annulus diameter. Eight animals died in the operative period. The 16 surviving animals were sacrificed at 4, 8, 12, or 18 weeks. There were no valve-related deaths nor mechanical valve failures. Anticoagulation was not used in the postoperative period during which time monthly laboratory parameters were obtained including hemoglobin, hematocrit, white cell count, red cell count and indices, lactic acid dehydrogenase, serum haptoglobin, and, additionally at sacrifice, platelet and red cell morphology. Values indicated this prosthesis did not cause hemolysis. At sacrifice the pulmonary arterial tree and peripheral organs showed no evidence of thromboemboli. There was smooth endocardial ingrowth on all valve sewing rings. One valve had thrombus formation on the valve sewing ring. Nine animals were anesthetized prior to sacrifice and underwent open cardiac catheterization. Ventriculography (n = 6) showed minimal transvalvar reflux, and atriograms (n = 6) demonstrated central flow. Transvalvar gradients were 0 to 22 mm Hg (n = 9). One valve of an 18-week tricuspid implant was examined for wear; valve life was calculated to be greater than 2500 years. These data in conjunction with in vitro test results justify clinical trial of the St. Jude Medical prosthesis.


Primary clinical experience with the Hall-Kaster valve in the aortic position: results at 3 months including hemodynamic studies.

The Hall-Kaster pivotal disc prosthetic heart valve was introduced in 1977. The primary goal of the design was to obtain the least possible obstruction to flow. Toward this end, innovations in the tilting axis, disc guidance mechanisms, and disc translational freedom combine to improve flow through both orifice segments of the open valve. The present study reports the primary clinical and hemodynamic findings in 28 patients (mean age, 53.8 years) with aortic valve disease, examined 3 months after insertion of the Hall-Kaster pivotal disc valve. The hemodynamics findings displayed low gradients and high calculated orifice areas. Satisfactory flow was observed through both the major and minor openings of the prosthesis. There were no arterial thromboembolic episodes. The increase in serum lactate dehydrogenase activity was moderate, indicating a slight-to-moderate intravascular haemolysis.


In vitro hydrodynamic comparison of mitral valve bioprostheses.

With the use of the pulse duplicator built in our laboratory, the hydrodynamic characteristics of three sizes of the four commercially available mitral bioprostheses, Hancock, Carpentier-Edwards, Angell-Shiley, and Ionescu-Shiley, were studied and compared. A wide range of performance was found: for example, during pulsatile testing, at peak flow of 15 1/min (corresonding to a normal resting cardiac output) transvalvular gradients varied from as high as 20 mm Hg (Angell-Shiley) to 5 mm Hg(Ionescu-Shiley) in the 25 mm mounting diameter size. Effective orifice areas (EOA) are significantly different in valves of the same mounting size, e.g., at peak flows of 20 1/min, the Ionescu-Shiley 25 provides an EOA of 1.7 cm2 while the Angell-Shiley provides only 1.17 cm2. The EOAs of all bioprostheses have been found to increase with increasing flow (e.g., from 10--30 1/min peak flow, the Hancock 25 changed from 1.25 cm2 to 1.50 cm2). The Gorlin formula, as constituted for calculating the area of stenotic mitral valves, is inappropriate for prosthetic valves. But the discharge coefficients of the bioprostheses have been found to be around 1 when the planimetered area of the open valve orifice is determined at a given flow. By using this discharge coefficient, the Gorlin formula will give an excellent estimate of the true orifice area of mitral bioprostheses.


Preoperative evaluation of subvalular fibrosis in mitral stenosis. A predictor factor in conservative vs replacement surgical therapy.

To assess the degree of mitral subvalvular fibrosis (SVF) in patients with mitral stenosis, left ventriculograms were reviewed, and a mitral subvalvular distance ratio (DR) was determined by dividing the distance from the papillary muscle tips to the closed mitral leaflets in systole by the distance from the aortic valve to the left ventricular apex in diastole. In 15 patients with normal ventricles, the mean DR was 0.244 +/- 0.017. In nine patients with minimal SVF, the mean DR was 0.181 +/- 0.025. In 10 patients with moderate SVF, the mean DR was 0.148 +/- 0.033. In 5 patients with severe SVF, the mean DR was 0.087 +/- 0.009. All mean DRs were mutually distinguishable at p less than 0.01. The clinical results and preoperative DR of 28 patients who had mitral commissurotomy were reviewed. A DR of less than 0.140 precluded a good longterm result from mitral commissurotomy alone. The DR reliably predicts the degree of SVF preoperatively and identifies patients with mitral stenosis who require valve replacement or a direct surgical attack on the subvalvular mechanism.


Surgery in active infective endocarditis.

Controversy persists concerning the role of early surgical intervention in severe infective endocarditis (IE). We therefore reviewed 163 episodes of well-documented IE in which 32 cardiac operations were performed during the active phase of IE. Congestive heart failure (CHF) was the principal indication for surgery in 88% (28/32); systemic emboli, 1/32; and persisting sepsis, 3/32. Staphylococcus and enterococcus were the most common infecting organisms in the operative group (44% and 16% respectively). Surgical mortality (11/32,37%) did not differ (p greater than 0.05) from medical mortality (26/131,20%). All 11 operative deaths occurred in patients moribund prior to surgery, including three with preoperative cardiac arrest. Surgical patients undergoing preoperative cardiac catheterization demonstrated marked CHF: a mean left ventricular end-diastolic pressure of 25.3 mm Hg. The mean cardiac index in 8/11 surgical deaths was lower (p less than 0.05) vs surgical survivors: 2.21/min/m2 vs. 3.21/min/m2. Postoperative complications were rare in the 21 surgical survivors. There were no episodes of continued infection, prosthetic dehiscence, or advanced heart block; only one paravalvular leak; and one systemic embolus. These findings emphasize the high medical and surgical mortality in patients with IE, suggest that delayed operative intervention may be a major causative factor resulting in a high surgical mortality, and justify an aggressive surgical approach in patients with valve dysfunction and heart failure. These data indicate that survivors of surgical intervention during active IE have eradication of infection and few postoperative complications.