A confocal microscopic evaluation of the interface between Syntac adhesive and tooth tissue.

The aim of this study was to microscopically evaluate the effect of dentine smear layer thickness, tubular orientation and immediate stress application on a modern dentine bonding agent. Eighty mesial and distal wedge-shaped cavities were cut into dentine/cementum cervically in 40 extracted human lower third molars. The thickness of the dentine smear layer was reduced by polishing the cavity surface in half the samples. Each component of the bonding agent (Syntac: Ivoclar Vivadent) was labelled with a fluorescent dye, the unfilled resin being light cured for 30 s with the composite restoration placed in one increment and light cured for 40 s. The samples were longitudinally sectioned using a slow speed diamond saw underwater, either immediately or 24 h post placement. The sectioned surfaces were then viewed using a confocal optical microscope. The thickness of the smeared layer only effected the penetration of adhesive in dentine tubules which were separated from the pulp chamber by the cavity design. These areas were well filled with adhesive; however, areas communicating with the pulp chamber showed no penetration differences due to smear layer reduction by polishing. The interdependence of the adhesive components was illustrated by failure to achieve a well-impregnated tooth/adhesive hybrid layer when the materials were incorrectly handled. The Syntac/dentine interface was generally able to withstand the stress of sectioning immediately post placement, but showed signs of failure in the cavity line angle when the applied stresses were greatly increased.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of doughing and manipulation times of acrylic resin denture base material and a proposal for a specification for a packing plasticity test.

The doughing and manipulation times of a range of acrylic resin denture base polymers are presented in this study. The methods evaluated were: (i) probing following American Society for testing materials specification, F451-76; (ii) hole penetration following British Standard, 2487: 1989 and International Standard Organisation, 1567: 1988; (iii) probing using a penetrometer employing a 20 g load and 1 mm diameter needle; (iv) oscillating rheometer apparatus used at a fixed frequency of 1 Hz by sweeping through a programmed linear increase in strain. The results indicate that each of the methods is capable of evaluating the doughing and manipulation times of the unprocessed polymers. It is concluded that the Bohlin VOR Oscillating Rheometer is excellent for investigating the flow properties of denture base polymers but it cannot be recommended for a standards specification test because of the high cost. The penetrometer method has been shown to be superior to the current standards specification test and would be ideal for a packing plasticity standards test.


Intraligamentary anaesthesia.

The introduction of specialized syringes in the late 1970s and early 1980s has led to an increase in the use of intraligamentary anaesthesia as a means of pain control in dentistry. This paper reviews the technique and its efficacy and considers the advocated advantages and disadvantages of the method in the light of the published scientific evidence. It is concluded that intraligamentary anaesthesia has a role to play in modern dental local anaesthesia but it does not fulfil all the requirements of a primary technique.


Tooth wear and facial morphology.

This review sets out to explore the relationship between tooth wear and facial morphology, with particular reference to the occlusal vertical dimension. Evidence from anthropological and archaeological investigations suggests that severe tooth wear may not only affect the teeth and occlusion, but may also have more wide ranging effects on overall dentofacial morphology. Studies on contemporary subjects confirm this finding, and the literature on the nature of these effects is reviewed. It is concluded that the adult dentofacial complex is not a static entity, but can compensate for the dental effects of wear. The consequences of this with respect to reconstruction of the worn dentition are discussed, and it is proposed that the dynamic nature of this complex may be employed to help simplify the treatment of severe tooth wear.


Titanium nitride coatings in clinical dentistry.

Titanium and its alloys are increasingly important in dentistry. Thin titanium nitride (TiN) coatings improve properties of metallic material for industrial purposes. Recently TiN coatings have been advocated in dentistry. In a survey of the literature, aspects of biological, mechanical and corrosive behaviour are assessed. Moreover, specific problems for clinical application are indicated. It is concluded that as long as the integrity of the TiN coating is not guaranteed under critical conditions, one should be cautious with its clinical application, and in no situation can it be used to improve deficient dental alloys.


GDPs' and specialists' decisions in the management of fissure caries.

As part of a continuing education programme in dentistry, four specialists and 27 selected general dental practitioners were asked to rate 58 clinical management options relating to fissure caries in six simulated patient management problems called challenges. Their ratings are presented and the advantages and disadvantages of the approach are discussed. Areas of agreement and disagreement are highlighted and possible reasons for these explored.


An analysis of multiple failures of resin-bonded bridges.

A clinical trial involving 203 resin-bonded bridges (RBBs) was undertaken to investigate the influence of several variables on the survival of these prostheses. This article presents the experiences with rebonded and replacement RBBs after failure of the originally bonded RBBs. A total of 62 dislodged and rebonded RBBs was included in this study and evaluated using Kaplan-Meier estimates. Rebonded RBBs that dislodged for a second time were replaced by another type of RBB ('replacement' RBBs, n = 32). The study revealed that rebonded RBBs were more susceptible to dislodgement than originally bonded RBBs. Fifty per cent survival was reached 2.1 years after rebonding. The sooner the first dislodgement occurred, the lower the retention rate of the rebonded RBB (PH-model, beta = 0.78, P = 0.02). Also some failure characteristics were evaluated. Failure characteristics (i.e. fracture site and partial versus complete dislodgement) of first and second dislodgement were not correlated (Chi-square, P values > 0.25). The survival of 'replacement' RBBs was significantly better than the survival of multiply failure RBBs (median survivals respectively 1.6 years and 1.0 year, P = 0.03). From the results of this study it may be concluded that the survival rates of rebonded and replacement RBBs were unacceptable.


In vivo confocal microscopy in clinical dental research: an initial appraisal.

Until recently, the in vivo microscopic investigation of intraoral tissues at high resolution has been virtually impossible. Confocal microscopy enables high-resolution imaging to be achieved below semitransparent surfaces in intact living specimens, but this may still be impractical for intraoral applications because of the need to stabilize the sample. The development of a steadying objective (x 240 overall mag.) which is held against the sample surface and is focused by moving internal elements, avoids the need for fine adjustment of the living sample under the microscope to achieve a change of focus. It is therefore more comfortable and also reduces the problems of movement due to the pulse. The objective was used with a tandem scanning microscope, with images recorded via a SIT video camera. Using this system internal tooth structure (e.g. enamel prisms/adhesive restoration interfaces) and the lining cells of the gingival crevice through to the junctional epithelium may be examined. It is also possible to image the oral mucous membrane, focusing to the capillary loops in the basal layers, where streaming red blood cells can be seen. Access is limited to the anterior regions as far back as the premolar teeth. Applications could include caries research, soft and hard tissue responses to biomaterials (e.g. implants), wound healing and monitoring the effect of periodontal treatment regimens. This new technique offers numerous exciting opportunities for the microscopic investigation of many clinical operative procedures in vivo, allowing the response of the tissues to be non-destructively monitored, over time, at high resolution.


Surface pH of resin-modified glass polyalkenoate (ionomer) cements.

The recently developed group of materials known as light-activated, or resin-modified, glass polyalkenoate (ionomer) cements have been produced in response to clinical demands for a command set cavity base material. This study monitored the surface pH of three commercially available resin-modified glass ionomer cements over a 60-min period following either mixing alone or mixing followed by a 30-s exposure to a curing lamp. The results indicate that each material behaves in a unique manner. For all materials and conditions the pH reached after a 60-min period was significantly (P < 0.001) higher than the initial value. Light curing the materials significantly increased (P < 0.01) the surface pH of two of the materials (Baseline VLC and Vitrebond) as compared to the same materials in the uncured state. In the case of XR-Ionomer, however, no significant (P > 0.05) effect of light curing upon the surface pH was apparent. The precise clinical consequences of a low surface pH are unclear but may be an aetiological factor in postoperative pulpal sensitivity. It is therefore recommended that a sublining of a proprietary calcium hydroxide lining material should be placed routinely beneath these materials and every effort made to ensure effective light curing.


Microleakage of three generically different fluoride-releasing liner/bases.

Three generically different fluoride-releasing materials that function as a liner or base were assessed for their microleakage performance on enamel and dentine. Group 1 (light-cured liner/base) showed much more leakage, but less bulk absorption of tracer, than Group 2 (traditional glass ionomer) or Group 3 (light-cured glass ionomer). The response of the three materials to tracer penetration was consistent with what is known about their chemistry. The Group 2 and 3 materials are probably the materials of choice at the caries-vulnerable margins, which are not easily visible for inspection.


Effect of the curing cycle on residual monomer levels of acrylic resin denture base polymers.

It has been shown previously that high levels of residual monomer have a deleterious effect on the properties of denture base polymers. Levels of residual monomer were determined on a homopolymer and a copolymer using gas-liquid chromatography. A wide range of recommended and 'short cut' curing cycles were then investigated which produced values ranging from 0.56 to 18.46%. From the ranges examined an optimum cycle of 7 h at 70 degrees C and 1 h at 100 degrees C was established which was used to polymerize 23 currently available synthetic denture base polymers. Only small differences were found between the materials tested with a range from 0.54 to 1.08% of residual monomer.


Selection of dental procedures for antibiotic prophylaxis against infective endocarditis.

A dental source of infection remains the most common identifiable risk factor in infective endocarditis and this may be particularly important in patients at 'high risk'. We therefore performed a questionnaire survey of dental practitioners to assess acceptance of The British Society of Antimicrobial Chemotherapy (BSAC) recommendations, especially with regards to selection of dental procedures for antibiotic prophylaxis. The results showed that the dental practitioners surveyed treated the 'high risk' patient group differently by extending the range of dental procedures covered by antibiotics but the BSAC only recommend that they be treated differently by hospital treatment and/or parenteral antibiotics. This must be an area of concern and deserves further attention, especially with regards to the need for wider publicity and the range of dental procedures that should be covered in the 'high risk' group where morbidity and mortality from infective endocarditis are higher.


The fit of gold-alloy full-crown castings made with pre-wetted casting ring liners.

Measurements were made of the fit of full-crown gold-alloy castings produced with two types of pre-wetted ring liner (asbestos and cellulose) and a typical gypsum-bonded investment (Cristobalite Inlay, Sybron/Kerr Products, Romulus, MI; W/P = 0.40). Laboratory measurements were made of the effects of the liners on potential investment expansion, and properties of the lining materials considered relevant to casting accuracy were also measured. There was a wide variation in values for mean dimensional inaccuracy. One liner produced a series of castings all of whose inaccuracies lay within the range +/- 0.1%, with a mean value of + 0.01%. With the other five liners, all or most castings were undersize. With three, all or most castings showed inaccuracies worse than -0.2%. The values for casting inaccuracy with the various liners showed a probable correlation with potential investment expansion (p < 0.05); however, no correlation was found between casting inaccuracy and any apparently relevant liner properties, alone or in combination. In casting techniques which use a pre-wetted ring liner, the choice of a specific lining material is an important factor which has a significant effect on casting inaccuracy. With at least three of the six liners tested, a higher investment expansion was needed for accurate full-crown castings to be ensured.


The fit of gold-alloy full-crown castings made with ceramic casting ring liners.

Measurements were made of the fit of gold-alloy full-crown castings produced with dry ceramic ring liners. When used with vacuum investing, these liners absorb relatively large amounts of water from the investment mix (thereby reducing its original W/P ratio) and then function as wet liners, thus increasing the investment's potential expansion and giving castings which are consistently larger than when air investing is used. With four of the five liners tested, investing in air produced many castings which were unacceptably undersized (inaccuracy worse than -0.2%). The fifth liner, an industrial material 2 mm thick, gave only one casting out of 12 which was outside this limit, although all castings were undersized to a lesser extent. Vacuum investing gave improved casting accuracy; with four of the five liners, the improvement was highly significant (p < 0.001), and with the fifth, probably significant (p < 0.05). Even with vacuum investing, however, with only two of the liners did all castings show inaccuracies within +/- 0.2%. With the other three liners, some castings (ranging from 2/10 to 7/9) had inaccuracies worse than -0.2%. With both air and vacuum investing, changing from one liner to another caused changes in relative casting accuracy which were often significant (p < 0.01) or highly significant (p < 0.001). In casting techniques where a ceramic ring liner is used, the choice of specific lining material and the choice between investing in air or under vacuum are important factors which can have a major effect on the fit of castings.


The effect of using layered specimens for determination of the compressive strength of glass-ionomer cements.

Compressive strength is widely used as the criterion of strength of glass-ionomer dental cements, despite the difficulties in interpretation of the findings. With the introduction of light-cured glass-ionomer cements, which can be used only in thin layers, the question arises of how test specimens should be prepared for the measurement of compressive strength. A suggested method has been to prepare test pieces by building them up in layers, an approach which is examined critically in the current paper. Two different conventional (acid-base) glass-ionomers were studied with the use of layered and unlayered specimens of dimensions 6 mm (height) x 4 mm (diameter) and 12 mm (height) x 6 mm (diameter). While smaller samples gave the same value of compressive strength as larger specimens, layered specimens gave significantly lower values of compressive strength for both sizes. In view of these findings, and since the layered specimens are tedious to prepare, we conclude that compressive strength is unsatisfactory as a criterion of strength for light-cured glass-ionomer cements.


Association between salivary flow rate and the use of systemic medication among 76-, 81-, and 86-year-old inhabitants in Helsinki, Finland.

The aim of this study was to examine salivary flow rate and its association with the use of medication in a representative sample of 76-, 81-, and 86-year-old subjects, totaling 368. In this study, 23% (n = 80) of the subjects were unmedicated. From one to three daily medications were used by 47% (n = 168) and more than four medications by 30% (n = 104). The most commonly used medications were nitrates, digitalis or anti-arrhythmic drugs (47.7%), analgesics and antipyretics (32.6%), and diuretics (29.5%). The mean number used daily was significantly higher in 86-year-olds than in the two younger age groups (p < 0.01). No significant differences in this respect were found between genders. Among the unmedicated subjects, 76-year-olds had significantly higher stimulated salivary flow rates than did the 81-year-olds (p < 0.05). Unmedicated women showed significantly lower unstimulated (p < 0.01) and stimulated flow rates than did men (p < 0.05). Stimulated salivary flow rate was also significantly higher in the 76-year-old medicated subjects than in the medicated 86-year-old subjects (p < 0.05). No statistically significant differences were found in unstimulated salivary flow rates among the three age groups. Medicated women showed significantly lower unstimulated salivary flow rates than men (p < 0.001), although the difference in stimulated saliva flow was not significant. A statistically significant difference in unstimulated and stimulated salivary flow rates was found between unmedicated persons and those who took from four to six, or more than seven, prescribed medications daily.


Immunocytochemical localization of cathepsins B and G in odontoclasts of human deciduous teeth.

For clarification of the mechanisms by which odontoclasts resorb deciduous teeth during physiological root resorption, cysteine-proteinases such as cathepsins B and G were immunocytochemically localized in odontoclasts at the ultrastructural level. Extracted human deciduous teeth undergoing root resorption were fixed with a mixture of formaldehyde and glutaraldehyde and processed for immunocytochemical detection of these enzymes. Sheep antisera, raised against either human cathepsin B or G, were used as primary antibodies. In odontoclasts, specific immunogold labeling of both anti-cathepsin B and G was clearly localized in lysosomes and pale vacuoles of various sizes, and in a portion of the extracellular canals of odontoclastic ruffled borders. In the presence of either antibody, the cytoplasmic matrix, mitochondria, and nuclei were minimally labeled by immunogold particles. The presence of these proteolytic enzymes in odontoclasts suggests that, during odontoclastic root resorption, these enzymes are involved in the formation of resorption lacunae by means of intra/extracellular degradation of collagen and other non-collagenous matrix proteins of deciduous teeth.


Effects of sialagogues on ornithine decarboxylase induction and proto-oncogene expression in murine parotid gland.

The mechanism of a sialagogue-induced increase in ornithine decarboxylase (ODC) activity and the expressions of proto-oncogenes in murine parotid gland were investigated by use of isoproterenol (IPR), carbachol (CC), and methoxamine (MTX). The results were as follows: (1) The three sialagogues had similar effects on the parotid in vivo (mouse parotid after a single injection of IPR) and/or in vitro (rat parotid explants cultured on siliconized lens paper floating on 199 medium containing IPR, CC, or MTX), the order of their effectiveness being IPR > CC > MTX. (2) Northern/dot and Western blot analyses revealed that the sialagogues elevated the steady-state levels of ODC mRNA and ODC protein to maxima at two h and six h, respectively, after stimulation. The increases were roughly proportional to those in ODC activity, suggesting that sialagogue-dependent enzyme induction is regulated at the transcriptional level. (3) The mRNAs of four of nine proto-oncogenes examined showed sialagogue-dependent increases to maxima at 30 min (c-fos) or 60 min (c-jun, c-myc, and c-src) after the beginning of stimulation. These increases were all transient, with the levels returning to the control values (without sialagogue) within 60 min. (4) The IPR-dependent elevations of ODC activity and the mRNAs of ODC, c-fos, and c-jun were inhibited by monensin, but not by polymyxin B. On the other hand, the CC-dependent increases in these parameters were inhibited by polymyxin B but not by monensin.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of age on immunoglobulin content and volume of human labial gland saliva.

Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p < 0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18-20-year-old group (n = 46) secreted at least 10 microL of labial saliva in a 7-10-minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 microL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as microgram/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age.


The effect of chewing gum use on in situ enamel lesion remineralization.

Two independent cross-over studies investigated the possibility of enhanced early enamel lesion remineralization with the use of chewing gum. The first study involved a sorbitol-containing chewing gum, and the second, which had an identical protocol, tested a sucrose-containing chewing gum. In each study, 12 volunteers wore in situ appliances on which were mounted enamel sections containing artificial caries lesions. Subjects brushed twice daily for two min with a 1100-ppm-F (NaF) dentifrice (control and test) and in the test phase chewed five sticks of gum per day for 20 min after meals and snacks. Microradiographs of the enamel lesions were made at baseline and at the end of the seven-week experimental period. In the sugar-free gum study, the weighted mean total mineral loss (delta z) difference [(wk7-wk0) x (-1)] was 788 vol.% min. x micron for the gum, corresponding to remineralization of 18.2%, vs. the control value of 526 vol.% min. x micron, 12.1% remineralization (p = 0.07). There were no significant differences for the surface-zone (p = 0.20) and lesion-body (p = 0.28) values. In the sucrose-containing gum study, the delta z difference was 743 vol.% min. x micron for the gum, corresponding to a remineralization of 18.3%, vs. the control value of 438 vol.% min. x micron, 10.8% remineralization (p = 0.08). The surface-zone values were not significantly different (p = 0.55). For the lesion body, however, the sucrose-containing gum value of 6.11 vol.% min. was significantly different (p = 0.01) from that of the control (2.81 vol.% min.).


Characterization of fibroblast clones from periodontal granulation tissue in vitro.

Connective tissues are known to be composed of heterogeneous fibroblast subpopulations. The significance of this heterogeneity in different physiological and pathological conditions is poorly understood. Granulation tissue is formed in connective tissue during wound healing, chronic inflammation, and certain pathological conditions. In this study, heterogeneity of fibroblasts from granulation tissue was investigated by cell-cloning techniques. Granulation-tissue fibroblasts (GTFs) from both chronically inflamed periodontal lesions and healing wound granulation tissue behaved similarly. GTFs showed a more pronounced decrease in proliferative capacity with increasing cumulative population doubling levels (CPDLs) and 30-40% lower cloning efficiency compared with normal gingival fibroblasts (HGFs). Morphologically, cells in GTF cultures were mainly large, whereas HGFs were mainly small in size. Both cell-line types showed heterogeneity in cell morphology. Clones composed of large stellate-like cells predominated in GTF cultures, whereas clones composed of small spindle-shaped or epithelioid cells predominated in HGF cultures. In both cell-line type the proportion of clones composed of large cells increased without increasing CPDL. These findings show that the properties of the fibroblasts changed during their in vitro life spans. The finding that normal connective tissue and granulation tissues contain morphologically distinct fibroblast clones in different proportions suggests that local factors could stimulate local fibroblasts to differentiate into GTFs. Alternatively, local factors could select some fibroblast subpopulations to overgrow the others to form granulation tissue.


Histomorphometric study of the periodontal vasculature of the rat incisor.

This study assessed quantitatively the vascular system in the cementum-related periodontal ligament (PDL) along the rat incisor. The lower left incisors of six rats (+/- 200 g) were subjected to routine histological procedures and cross-sectioned serially (2 microns), and the distance between each section and the apex was computed. The PDL of five sections at different levels along the tooth was divided into mesial, lingual, and lateral parts. The number and area of small and terminal arterioles, capillaries (C), sinusoids (S), post-capillary venules (PCV), and connecting venules, as well as the area of the PDL, were established. Blood vessels (BV) occupied 47 +/- 2% of the PDL area in the apical half and 4 +/- 2% at the incisal end. Of the total BV area, 41%, 32%, and 27% were located on the lingual, mesial, and lateral tooth sides, respectively. The majority of BV belonged to the venous system (98.5 +/- 0.6% and 82.5 +/- 3.0% in the apical and incisal parts, respectively). The apical venous system comprised 95.4 +/- 1.6% S and 3.2 +/- 1.0% PCV, reversing to 27.2 +/- 14.2% S and 55.2 +/- 11.3% PCV in the incisal half. The number of arterial profiles increased gradually from 6.8 +/- 1.5 at the apex to 25.3 +/- 2.4 in the incisal part and that of C from 9.0 +/- 1.18 to 25.0 +/- 4.3. The extensive vascularization in the apical half of the PDL is consistent with the high metabolic demands and with the need for protective cushioning of the constantly growing dental and periodontal tissues.2+_


The vascularity of dental pulp in cats.

The fraction of the volume of the coronal pulp of cat canines that is occupied by blood vessels was estimated by measurement of the cross-sectional areas of all the vessels in a complete transverse section of the pulp from each of four teeth. The sections were taken 0.5 mm from the pulp cornu. Overall, 14.4% of the area of the pulp was occupied by vessels. In the core of the pulp, the average value was 42.9%, and superficially, near the odontoblast layer, it was between 5 and 10%. The average capillary density was 1402/mm2, which is higher than in most other tissues. Laser Doppler flow meters can be used for recording blood flow from the coronal pulp of intact teeth, but these instruments are linear only if the moving blood cells occupy no more than 1% of the tissue volume. The present results suggest that this figure is exceeded in pulp.


Suppressor cell function in oral lichen planus.

Oral lichen planus (OLP) is a common inflammatory condition of the oral mucous membranes which affects between one and two percent of the general population. In accordance with the protracted clinical course of OLP and its association with known auto-immune diseases, the level of self-tolerance is questionable and possibly diminished in patients with this disorder. Normal suppressor T lymphocyte function is reputedly an essential element in the maintenance of self-tolerance, and deficient cell-mediated suppressor activity is implicated in the pathogenesis of auto-immune diseases. For assessment of in vitro cell-mediated suppressor activity in OLP, peripheral blood mononuclear cells (PBMC) from ten patients with OLP and from 11 control subjects were activated with the plant mitogen concanavalin A (Con A), followed by co-culture with autologous responder cells. The ability of irradiated Con A-activated cells to suppress the proliferation of Con A-stimulated responder cells was determined. Con A-induced suppressor activity of PBMC in the OLP patients was significantly less than that in control subjects (p = 0.001). Results of the present investigation complement previous in vitro findings which provided indirect evidence of deficient cell-mediated suppressor activity in OLP, particularly a decreased proportion of circulating CD4+CD45RA+ lymphocytes and reduced Con A-stimulated PBMC proliferation. The depressed Con A-induced suppressor activity of PBMC in the OLP patients provides direct evidence of deficient in vitro cell-mediated suppressor function in OLP, and suggests that defective cell-mediated suppressor circuits and reduced self-tolerance may be involved in the pathogenesis of this disorder.


Effect of a pulsing electromagnetic field on demineralized bone-matrix-induced bone formation in a bony defect in the premaxilla of rats.

A 2-mm non-healing bony defect was prepared in the premaxilla of male Wistar rats weighing about 180 g as a simulation of an alveolar cleft, for determination of whether a pulsing electromagnetic field (PEMF) could promote regeneration of bone induced by demineralized bone matrix (DBM). The defect was either treated with 7 mg DBM or was left as a non-grafted control. The rats were exposed to a PEMF with a frequency of 100 Hz, a 10-ms-wide burst with 100 microseconds-wide quasi-rectangular pulses, repeating at 15 Hz, and magnetic field strength of 1.5-1.8 G. Alkaline phosphatase activity increased significantly from day 7 in the DBM-graft-plus-PEMF group and from day 10 in the DBM-graft group, reaching a maximum on day 14. A greater-than-two-fold rise in alkaline phosphatase activity and a three-fold rise in the amount of 45Ca incorporation in the DBM-graft-plus-PEMF group were attained compared with those of the DBM-graft group. The DBM-graft-plus-PEMF group produced more bone with almost complete osseous bridging in the defect sites than did the group treated with DBM only on day 35. The findings indicate that PEMF had an enhancing effect on the bone-inductive properties of the DBM through the stimulation of osteoblast differentiation induced by DBM.


Dental predictors of high caries increment in children.

A comprehensive set of dental variables was investigated to find the "best" combination of predictors for high caries increment in 7/8-year-old and 10/11-year-old children. Four populations with widely different caries prevalence were studied. Logistic regression analysis supplied multiple-input models by stepwise selection of predictors. A "low number of sound primary molars" was the best and most consistent predictor of high caries increment. The second best predictors were "high numbers of pre-cavity lesions on permanent first molars" (discolored pits and fissures in the younger age group and white spots on the smooth parts of buccolingual surfaces in the older age group). Inclusion of radiological variables did not substantially increase the quality of prediction. For practical application, models with various multiple inputs selected by stepwise procedures were compared with "fixed" three-input models. These three-input models resulted in predictive quality nearly equal to those of the multiple models. Traditional one-input models, containing DMFT or dmft, were inferior to the three-input models, particularly in the older age class. The lower the caries prevalence of the source data, the better was the prediction. As a summary measure characterizing the predictive performance of a model, we used the index "area under the receiver operating characteristic curve" A. For the 1984 data and the three-input models, the area was approximately 80%, and for the 1972 data, the area was 65-70%.


Accuracy of visual inspection, fiber-optic transillumination, and various radiographic image modalities for the detection of occlusal caries in extracted non-cavitated teeth.

Occlusal caries lesions may progress into the dentin without this resulting in a macroscopic breakdown of the enamel surface. Imaging methods may therefore be needed to aid in the visual detection of occlusal caries. It was the aim of this study to evaluate diagnostic accuracy in a laboratory set-up of visual inspection (VI), fiber-optic-transillumination (FOTI), conventional radiography (CR), and two digital radiographic image modalities (DRm and DRr) for detection of occlusal caries in clinically non-cavitated teeth. Eighty-one extracted third molars from 18-20-year-old males were assessed by four observers on a five-rank confidence scale by the five methods. Ground sections (500-600 microns) served as validation for true state of disease: 1 = no caries in dentin, 2 = caries just beyond dentino-enamel junction, or 3 = deep dentinal caries, halfway or more to the pulp. ROC analysis was performed on the basis of the confidence rank scale data on two diagnostic thresholds, T1 = caries in dentin (disease state 2+3) and T2 = caries deep in dentin (state 3). On the T1 level, use of the FOTI method gave on average the most accurate diagnosis, closely followed by VI, both performing better than use of radiography. On the T2 level, all five diagnostic methods performed equally well.


Robustness of the t test applied to data distorted from normality by floor effects.

In calculus, plaque, and gingivitis trials, measures are taken on subjects both prior to the use of an active treatment and after its use. When the trial is short-term, or when a cleaning of the mouth takes place after the baseline measurement, distributions of such measures (e.g., the Volpe-Manhold score or the Löe and Silness scale) are approximately normally distributed above zero but also can have a proportion of subjects who attain scores of zero. When the effects of an active treatment are compared with those of a control, the two-independent-sample t test can be applied to outcome scores or to differences between the baseline and outcome scores. Robustness of these t tests, in the presence of distributions "distorted" from normality as described, was investigated by computer simulation. In general, both t tests produced actual significance levels which were close to nominal significance levels, even in the presence of small samples and distributions in which as many as 50% of the subjects attained scores of zero.


[The action of low doses of nitrosomethylurea on a stationary cell population. An experiment and modelling].

The change of stationary cell population (murine spleen) following an exposure to low doses of methylnitrosourea (10(-11)-10(-5) g/kg of mouse weight) was investigated and modelled mathematically. The suggested model is based on the idea that the effect of cytotoxic agent in low doses has nondestructive "signal" character, changing dynamic balance between cells in proliferating and quiescent compartments.


[The effectiveness of ultralow doses and concentrations of biologically active compounds].

Numerous data of literature are analysed on the biological activity of ultra-low (10(-12)-10(-19) M) concentrations and corresponding doses of same bioregulators. Our own data are presented on the modulation of lymphatic vessel contractility by peptides (thyroliberin, defensin, and tuftsin) in concentrations ranging from 10(-13) to 10(-16) M. Hypothetic mechanisms of these phenomena are discussed.


[The MB1 family of repeats in clones from the genomes of mammals].

Members of MB1 family repeats are revealed in genomes of many mammals (cow, rabbit, opossum, horse, ...). The MB1 repeats from cow and rabbit genomes are mirror-reflected about the SINE families repeats from cow and rabbit genomes. The life time of MB1 repeats are no less than 100 million years. Classification of MB1 repeats from human genome using the information similarity was performed. This classification has revealed two subfamily MB1 repeats in human genome. Possible processes of creation of MB1 family repeats common for many mammals are discussed.


[The suppression of the chemiluminescence of mammalian cells by the metabolites of Crithidia oncopelti].

Effect of water-soluble (polypeptides) fraction (PF) of Crithidia oncopelti on the chemiluminescence of human blood cells and murine splenocytes was studied. The study has shown that PF possessed a capacity to inhibit oxygen-dependent killer system of polymorphonuclear leucocytes in dose-dependent manner. This effect was of a complex nature. The inhibitory effect of PF was demonstrated also in respect to murine mononuclear phagocytes and splenocytes. It was suggested that, in this case, the suppressor effect was related with the influence on membranous cytokines.


Papillon-Lefèvre syndrome.

Papillon-Lefèvre syndrome, also known as hyperkeratosis palmaris et plantaris or hyperkeratosis palmoplantaris, is a devastating dermatological disease characterized by a thickening of the stratum corneum of the skin on the palms of the hands and soles of the feet. In addition, some patients manifest excessive sweating (hyperhidrosis), the growth of fine body hair and the development of dirty-colored skin on the affected parts. Calcification of the falx cerebri of the dura mater, as well as other areas of the brain, have been reported. From a dental standpoint, young patients with Papillon-Lefèvre syndrome have juvenile or precocious periodontosis, with severe destruction of the alveolar bone in both deciduous and permanent dentitions. Bone loss has been observed as early as two years of age, with premature exfoliation of the teeth. There is usually gingival enlargement, gingival ulceration and the formation of deep periodontal pockets; but in some cases, there is no inflammatory reaction and only the periodontium of the secondary teeth is affected. This disease eludes all known forms of therapy and results in edentulousness after only a few years.


Advertising and the dental profession. Retrospective and prospective.

"Advertising" has become a very controversial topic, not just among dentists, but among all professionals. That controversy focuses on three questions. First, what are the legal issues surrounding dental advertising and how are these issues being resolved? Second, what are the attitudes toward advertising among practicing dentists and how are these attitudes changing? Finally, how many dentists advertise and what are those advertising dentists actually doing? The purpose of this paper is to neither praise nor excoriate advertising, but to refer to the law and to published research in order to provide dental practitioners with a broader understanding of this topic.


Invasive versus conservative strategy after thrombolytic therapy for acute myocardial infarction in patients with antecedent angina. A report from Thrombolysis in Myocardial Infarction Phase II (TIMI II).

This study was designed to assess the possibility that a subgroup of patients at high risk for recurrent ischemia and reinfarction after thrombolytic therapy might benefit from early intervention. The Thrombolysis in Myocardial Infarction Phase II (TIMI II) study recently concluded that an obligatory invasive strategy after thrombolytic therapy offered no advantage over a more conservative strategy. Data from the 3,534 patients enrolled in the TIMI II trial were analyzed to determine whether a history of antecedent angina before myocardial infarction identifies patients at high risk for subsequent ischemia and whether these patients might benefit from an invasive strategy. Within the TIMI II population, antecedent angina identified patients at increased risk for recurrent chest pain in the hospital (32.3% vs. 22.1%, p < 0.001) and recurrent infarction during the 1st year of follow-up (11.2% vs. 7.9%, p = 0.001) compared with that of patients without antecedent angina. Among patients assigned to the invasive strategy, coronary arteriography revealed that those with antecedent angina had a more severe residual stenosis of the infarct-related artery after thrombolytic therapy (77.1 +/- 0.7% vs. 73.0 +/- 0.9%, p < 0.001) and more multivessel disease (37.9% vs. 26.4%, p < 0.001). The clinical outcome of the patients with antecedent angina assigned randomly to either the invasive or the conservative strategy were compared. The invasive strategy patients had a slightly lesser incidence of recurrent chest pain in the hospital (29.9% vs. 34.8%, p = 0.13) and more negative (normal) findings on exercise tolerance tests (24.7 vs. 18.9%, p = 0.003), but there was no difference between the treatment strategies in the end point variable of recurrent myocardial infarction or death. These data demonstrate that antecedent angina identifies patients at increased risk for recurrent ischemic events after thrombolytic therapy. However, similar to the results for the overall population, the invasive strategy does not alter the risk of reinfarction or death compared with the conservative approach.


Long-term survival in 618 patients from the Western Washington Streptokinase in Myocardial Infarction trials.

The aim of this study was to determine whether streptokinase treatment improves long-term survival in patients with acute myocardial infarction. Thrombolytic treatment for acute myocardial infarction reduces early mortality and improves the 1-year survival rate, but the long-term (3 to 8 years) survival benefits of treatment and the relation between survival and baseline clinical characteristics, infarct size and ventricular function have not been established. We assessed survival status at a minimum of 3 and a mean of 4.9 +/- 2.3 years in 618 patients randomized between 1981 and 1986 to receive conventional treatment (n = 293) or thrombolysis with streptokinase (n = 325) in the Western Washington Intracoronary (n = 250) and Intravenous (n = 368) Streptokinase in Myocardial Infarction trials. The relation between long-term survival and thrombolytic treatment, admission baseline clinical characteristics and late radionuclide tomographic thallium-201 infarct size and ejection fraction was assessed in a subset of patients. Survival at 6 weeks was 94% in patients who received streptokinase versus 88% in the control group (p = 0.01). However, survival at 3 years was 84% in the streptokinase group and 82% in the control group and for the total period of follow-up, there was no significant survival benefit (p = 0.16). Analysis by infarct location showed a higher survival rate at 3 years for patients treated with anterior infarction (76% vs. 67% for the control group), but no overall survival benefit (p = 0.14). Survival at 3 years for patients with an inferior infarction was 89% in the streptokinase group and 91% in the control group (p = 0.62). By stepwise Cox regression analysis, admission clinical variables associated with decreased long-term survival were anterior infarction, advanced age, history of prior infarction and the presence of pulmonary edema or hypotension. Although streptokinase therapy was associated with improved survival, it was not an independent determinant of survival (p = 0.069). Ejection fraction and thallium-201 infarct size measured approximately 8 weeks after enrollment had a strong association with long-term survival. Univariate analysis in a subgroup of 289 patients with complete data selected infarct size, ejection fraction, age and history of prior infarction as predictors of survival. In the multivariate model, only ejection fraction (p < 0.0001), age (p = 0.008) and prior myocardial infarction (p = 0.02) remained strong predictors. In these early trials of thrombolytic therapy for acute myocardial infarction, streptokinase improved early survival, but there was little long-term survival benefit. This failure to show an improvement in the 3- to 8-year survival rate may also reflect the need to study a larger group of patients or to initiate treatment earlier after symptom onset.


Additional ST segment elevation during the first hour of thrombolytic therapy: an electrocardiographic sign predicting a favorable clinical outcome.

The aim of this study was to investigate the significance of further ST elevation that occurs during the 1st h of thrombolytic therapy before the expected resolution. Early resolution of ST segment elevation is commonly accepted as a marker of clinical reperfusion during thrombolytic therapy for acute myocardial infarction. Using frequent electrocardiographic recordings, we observed in some patients further ST elevation that occurred during hour 1 of thrombolysis before the expected resolution. To investigate the significance of this pattern, we classified 177 consecutive patients with a first acute myocardial infarction into two groups: Group A, 98 patients with ST elevation > or = 1 mm above the initial ST elevation during the 1st h of thrombolytic therapy, and Group B, 79 patients without this finding. Although the presence or absence of additional ST elevation was not associated with a clinical or prognostic difference in patients with a first inferior or posterior acute myocardial infarction, its presence indicated a more favorable clinical outcome and prognosis in patients with anterior infarction. Among the patients with anterior infarction the 65 patients in Group A had a higher ejection fraction (44 +/- 9% vs. 35 +/- 11%, p < 0.01), less heart failure (15% vs. 35%, p = 0.02) and a lower in-hospital mortality rate (0% vs. 8%, p = 0.04) than did the 37 patients from Group B. Additional ST elevation early during thrombolytic therapy in patients with anterior infarction suggests a favorable clinical outcome and thus may be indicative of successful reperfusion.


Relation of deep arterial resection and coronary artery aneurysms after directional coronary atherectomy.

The aims of this study were to document the frequency of coronary artery aneurysm formation in patients undergoing directional coronary atherectomy and to determine the relation of such aneurysms to the depth of arterial resection. Deep arterial injury is relatively frequent with the use of directional coronary atherectomy, but the potential for subsequent coronary artery aneurysm formation is unknown. Results in a consecutive series of 64 successfully treated patients (a total of 69 lesions; mean angiographic follow-up at 5 months) treated with directional coronary atherectomy were retrospectively analyzed with use of quantitative angiographic and histologic data. Coronary aneurysms (ratio of dilated vessel segment to the adjacent reference segment > 1.2:1) occurred in seven patients (10%). The only significant clinical correlate of aneurysm formation was a relatively shorter duration of angina. There were no significant preprocedural angiographic predictors of aneurysms, although 6 (86%) of the 7 aneurysmal lesions arose from restenosis lesions compared with 30 (48%) of 62 lesions with no subsequent aneurysm development (p = 0.06). Histopathologic examination of 414 specimens from 68 treated lesions showed no significant difference in the occurrence of subintimal resection (media +/- adventitia) between those with and without subsequent aneurysm (29% vs. 22%). Media alone was found in 14% of specimens from lesions that later became aneurysmal versus 15% of those that did not; adventitial resection was found in 14% and 7% of specimens, respectively (p = 0.08), with relatively more adventitia per specimen from those with aneurysm (55% vs. 30% without aneurysm, p = 0.08). Aneurysms occur relatively frequently after directional coronary atherectomy. Although there was no statistically significant correlation with the depth of arterial resection, the evidence from this study suggests that the role of adventitial resection in the occurrence of late aneurysm development should be explored further.


Prognosis in cardiogenic shock after acute myocardial infarction in the interventional era.

The purpose of this study is to describe the outcome in cardiogenic shock treated with aggressive reperfusion therapy and to identify factors predictive of in-hospital and long-term mortality. Cardiogenic shock is the most common cause of death in patients admitted to the coronary care unit. Although studies have reported lower mortality rates in shock treated with angioplasty, few studies have described a cohort of patients with shock who were not selected because they were most likely to benefit from reperfusion therapy. A consecutive series of 200 patients admitted with acute myocardial infarction complicated by cardiogenic shock were studied. The in-hospital mortality rate was 53%. Variables with significant univariable association with in-hospital death included patency of the infarct-related artery, patient age, lowest cardiac index, highest arteriovenous oxygen difference and left main coronary artery disease. The most important independent predictors of in-hospital death were patency of the infarct-related artery, cardiac index and peak creatine kinase, MB fraction. The mortality rate in patients with patent infarct-related arteries was 33% versus 75% in those with closed arteries and 84% in those in whom arterial patency was unknown. Patients who survived to hospital discharge were followed up for a median of 2 years, with a mortality rate of 18% after 1 year. The best descriptors of the relation between these variables and postdischarge mortality included age, peak creatine kinase, ejection fraction and patency of the infarct-related artery. In a large consecutive series of patients with cardiogenic shock with complete follow-up, patency of the infarct-related artery was most strongly associated with in-hospital and long-term mortality. This finding supports an aggressive interventional strategy in patients with cardiogenic shock.


Effects of acute, transient coronary occlusion on global and regional right ventricular function in humans.

The aim of this study was to investigate the changes in right ventricular function during acute coronary occlusion produced by inflating a coronary angioplasty balloon catheter. Alterations in right ventricular function are well known to occur in patients with acute myocardial infarction or ischemic cardiomyopathy. However, the changes in right ventricular function resulting from acute, transient coronary occlusion of each of the major coronary arteries have been scantily studied, perhaps because of serious limitations of currently available technology. A newly designed, mobile, multiwire gamma camera, in combination with generator-produced tantalum-178, affords high count rate first-pass radionuclide angiography and is thus ideal for studying right ventricular function at the bedside. Accordingly, 46 patients underwent first-pass radionuclide angiography at baseline and during transient coronary occlusion induced by a coronary angioplasty balloon catheter. A significant, albeit modest, decrease in global right ventricular ejection fraction occurred during occlusion of the left anterior descending (from 42.9 +/- 9.3% to 39 +/- 8.7%, p < 0.05) and left circumflex (from 44 +/- 9.1% to 38.8 +/- 7.9%, p = 0.03) coronary arteries, but diagonal artery occlusion caused no significant change in right ventricular ejection fraction. Occlusion of the right coronary artery proximal (but not distal) to the acute marginal branch caused a significant decrease in right ventricular ejection fraction (from 42.6 +/- 4.7% to 35.7 +/- 7.2%, p < 0.01). Although occlusion of the left anterior descending, left circumflex and proximal right coronary arteries all caused significant deterioration in regional right ventricular function, only proximal right coronary occlusion caused right ventricular dilation (p < 0.005). Significant impairment of right ventricular function occurs during transient occlusion of the left anterior descending, left circumflex and proximal right coronary arteries, but only occlusion of the latter causes acute right ventricular dilation, probably as a result of ischemia.


Relation between stimulation site of cardiac afferent nerves by adenosine and distribution of cardiac pain: results of a study in patients with stable angina.

The purpose of this study was to establish whether stimulation of cardiac sensory receptors in different myocardial regions results in different distributions of cardiac pain. Previous studies have shown that adenosine provokes cardiac pain through stimulation of sensory receptors in the absence of myocardial ischemia. In this study adenosine was used to obtain a regional stimulation of cardiac sensory receptors. Increasing doses of adenosine (0.25, 0.5 and 1 mg/min) were selectively infused into the right and then into the left coronary artery in 26 patients with stable angina. No patient developed ischemic electrocardiographic changes during either adenosine infusion. Eighteen patients experienced cardiac pain during both infusions. Despite the stimulation of sensory receptors in different myocardial regions, 13 patients experienced cardiac pain in the same body area. Adenosine-induced pain was always similar to the anginal pain. By contrast, the remaining five patients experienced adenosine-induced cardiac pain in different body areas. In two of these patients, the distribution of anginal pain was similar to that experienced during one of the two adenosine infusions. In the remaining three patients, the distribution of anginal pain was similar to that experienced during adenosine infusion into the right coronary artery during some anginal episodes and to that experienced during adenosine infusion into the left coronary artery during other episodes. During stimulation by adenosine of sensory receptors in different myocardial regions, the majority of patients experience cardiac pain in the same body area; only a few experience pain in different areas. These differences might be caused by different organizations of the ascending neural pathways to the cortex. Our results suggest that in the same patient different distributions of pain during anginal attacks are probably due to ischemia in different myocardial regions.


Comparison of transthoracic and transesophageal echocardiography in evaluation of 47 Starr-Edwards prosthetic valves.

Our objectives were to characterize by transesophageal echocardiography the normal appearance of the Starr-Edwards prosthetic heart valve and to compare the utility of transesophageal and transthoracic echocardiography in detection of valve abnormality. The Starr-Edwards prosthetic heart valve, the first mechanical valve to be used, has demonstrated excellent durability. Fifty transthoracic and transesophageal echocardiographic studies on 37 patients with 47 Starr-Edwards prosthetic valves were analyzed retrospectively. Six cases of surgically confirmed infective endocarditis were studied. Vegetation or abscess formation, or both, was identified by transesophageal echocardiography in all six cases of infective endocarditis but was found in only one of these cases by transthoracic echocardiography. Thrombus was detected by transesophageal echocardiography in 9 of 11 patients with transient ischemic attacks or stroke and in 2 patients by transthoracic echocardiography with 3 confirmed at surgery. In 26 of the 30 patients with a mitral Starr-Edwards valve, the valve demonstrated a trivial or mild "closing volume" early systolic or holosystolic leak on transesophageal echocardiography alone. Transthoracic evaluation identified significant mitral regurgitation in six of the eight patients who had this finding on transesophageal echocardiography. Serial studies were performed to assess response to treatment or need for surgical intervention in eight patients. Seventeen valves have been implanted for 12 years; six of these had significant leakage without apparent cause, a finding not observed more recently implanted valves. These observations demonstrated the unique utility of transesophageal echocardiography in patients with Starr-Edwards prosthetic valve dysfunction, endocarditis or thrombus formation, and of the clear superiority of transesophageal echocardiography over transthoracic echocardiography in these situations.


Aortic valve replacement in octogenarians with aortic stenosis: a case-control study.

This study was designed to compare the results of aortic valve replacement in patients greater than or equal to 80 years old with those in patients 65 to 75 years old. Aortic valve replacement may be potentially more complicated and require the use of more resources when performed in octogenarians rather than in younger patients. Few hard data on this possibility are available. The study group comprises all 44 patients greater than or equal to 80 years old (mean age 82 years) who underwent aortic valve replacement at our institution between January 1981 and July 1989. A control group of 83 patients with a mean age of 70 years was matched with the study group for gender and approximate date of valve replacement. Before operation, 86% of the older patients versus 36% of the younger patients were in New York Heart Association functional class III or IV (p less than 0.001). Data were retrospectively collected from hospital records and a self-assessment telephone interview was conducted. The early mortality rate was 14% in the older group versus 4% in the younger group (p = 0.045). The duration of respirator support, intensive care and the total duration of the hospital stay did not differ significantly between groups. The incidence of postoperative low cardiac output syndrome was higher in the older group (p = 0.049), but the incidence of late valve-related complications was similar in the two groups. The 2-year survival rate (including data on patients who died early) was 73% in the older group and 90% in the younger group (p = NS). Six months postoperatively all patients but one were in functional class I or II. Although the patients greater than or equal to 80 years old had a poorer preoperative status than that of younger patients, aortic valve replacement in this group did not require more use of hospital resources and resulted in a clinical improvement comparable to that of younger patients.


Aortic valve resistance as an adjunct to the Gorlin formula in assessing the severity of aortic stenosis in symptomatic patients.

This study was conducted to determine the utility of aortic valve resistance in assessing the severity of aortic stenosis. Assessment of the severity of aortic stenosis has traditionally employed hemodynamic data and the Gorlin formula to calculate the area of the aortic valve. Recently, flow dependence of the Gorlin formula has been identified and the accuracy of the formula challenged. Aortic valve resistance, the quotient of gradient and cardiac output, has been advanced as potentially useful in assessing the severity of valve stenosis. We studied 48 symptomatic patients with an initial diagnosis of severe aortic stenosis based on a calculated aortic valve area of less than or equal to 0.8 cm2 by the Gorlin formula. Forty of these patients (Group I) were confirmed to have severe aortic stenosis, whereas 8 (Group II) were subsequently proved not to have severe aortic stenosis. The 18 patients in Group I with a valve area of 0.6 to 0.8 cm2 (Group IA) were directly compared with Group II patients who had a similar valve area. Aortic valve area was nearly identical in Group IA and Group II patients (0.69 +/- 0.05 and 0.71 +/- 0.06 cm2, respectively, p = NS). However, aortic valve resistance was much less in Group II patients (212 +/- 6 vs. 316 +/- 11 dynes.s.cm-5, p less than 0.0001). In this small cohort, aortic valve resistance achieved nearly complete separation of patients in Groups IA and II. In some patients with relatively mild aortic stenosis, the calculated valve area may indicate that the stenosis is severe. The use of aortic valve resistance in conjunction with the Gorlin formula helps separate patients with truly severe aortic stenosis from those with milder disease.


Diastolic function of the nonfilling human left ventricle.

To investigate an early-diastolic left ventricular suction effect in humans, tip-micromanometer left ventricular pressure recordings were obtained in patients with mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon, which fits tightly in the mitral orifice. When mitral inflow was impeded in anesthetized dogs, left ventricular pressure decayed to a negative asymptote value. This negative asymptote value was consistent with an early diastolic suction effect. Tip-micromanometer left ventricular pressure recordings were obtained in 23 patients with symptomatic mitral stenosis at the time of balloon inflations during percutaneous mitral valvuloplasty performed with a self-positioning Inoue balloon. The left ventricular diastolic asymptote pressure (P(asy)) was determined in 47 nonfilling beats with a sufficiently long (greater than 200 ms) diastolic time interval (that is, the interval from minimal first derivative of left ventricular pressure to left ventricular end-diastolic pressure) and equaled 2 +/- 3 mm Hg for beats with normal intraventricular conduction and 3 +/- 2 mm Hg for beats with aberrant intraventricular conduction. Left ventricular angiography was performed in five patients during the first inflation of the Inoue balloon at the time of complete balloon expansion. Left ventricular end-diastolic volume of the nonfilling beats averaged 38 +/- 14 ml and was comparable to the left ventricular end-systolic volume (39 +/- 19 ml) measured during baseline angiography before mitral valvuloplasty. Time constants of left ventricular pressure decay were calculated on 21 nonfilling beats with a diastolic time interval greater than 200 ms, normal intraventricular conduction and peak left ventricular pressure greater than 50 mm Hg. Time constants (T0 and TBF) derived from an exponential curve fit with zero asymptote pressure and with a best-fit asymptote pressure were compared with a time constant (T(asy)) derived from an exponential curve fit with the measured diastolic left ventricular asymptote pressure. The value for T(asy) (37 +/- 9 ms) was significantly smaller than that for TBF (68 +/- 28 ms, p less than 0.001) and the value for the measured diastolic left ventricular asymptote pressure (2 +/- 4 mm Hg) was significantly larger than that for the best-fit asymptote pressure (-9 +/- 11 mm Hg, p less than 0.001). T0 (44 +/- 20 ms) was significantly (p less than 0.01) different from TBF but not from T(asy). During balloon inflation of a self-positioning Inoue balloon, left ventricular pressure decayed continuously toward a positive asymptote value and left ventricular cavity volume was comparable to the left ventricular end-systolic volume of filling beats. In these nonfilling beats, the best-fit asymptote pressure was unrelated to the measured asymptote pressure and T0 was a better measure of T(asy) than was TBF. Reduced internal myocardial restoring forces, caused by different extracellular matrix of the human heart, reduced external myocardial restoring forces caused by low coronary perfusion pressure during the balloon inflation and inward motion of the balloon-occluded mitral valve into the left ventricular cavity could explain the failure to observe significant diastolic left ventricular suction in the human heart.


Quantitation of chronotropic response: comparison of methods for rate-modulating permanent pacemakers.

The aim of this study was to develop a technique for quantitating chronotropic response. Although the importance of chronotropic response for optimizing cardiac output during exercise is widely recognized, methods for quantitating the rate-modulating behavior of permanent pacemakers have not been developed. For a method of quantitating chronotropic response to be clinically useful, the rate-modulating characteristics of a pacing system should be defined at the onset of exertion, over a variety of exercise work loads and during recovery. Three methods for quantitation of rate modulation were assessed in 10 patients during treadmill exercise testing using the chronotropic assessment exercise protocol with expired gas exchange analysis. To compare the observed chronotropic response with a standard, the "expected" heart rate throughout exercise was calculated by using the concept of heart rate reserve as described by Wilkoff. The pacing rate observed during exercise was analyzed with 1) standard linear regression analysis, 2) comparison of observed and expected pacing rates at the midpoint and end of each quartile of exercise, and 3) integration of the area under the rate-response curve with comparison with the area under the expected curve. With use of a normalized scale relating change in heart rate to change in metabolic work load, with values of heart rate and metabolic work load at rest set to 0 and those at maximal exertion set to a value of 1, the mean y intercept for the study group was 0.10 +/- 0.20 (range -0.14 to +0.45), with a mean slope of 0.81 +/- 0.25 (range 0.31 to 1.19). The correlation coefficient relating change in heart rate to change in exercise work load was a mean of 0.90 +/- 0.09 (range 0.63 to 0.98). Integration of the area under the rate-response curve observed during exercise yielded a mean area that was 101 +/- 36% of that expected. When the range of exercise work loads was divided into quartiles, the area under the observed rate-response curve was 151 +/- 114% of that expected during the first quartile of exercise, 113 +/- 70% during the second, 96 +/- 38% during the third and 92 +/- 20% during the fourth. The mean area under the curve during recovery was 93 +/- 29% of that expected. Although calculation of the observed heart rate as a percent of that expected at the midpoint and end of each quartile of exercise used fewer observations, it provided similar results. Quantitation of the rate-response curve with comparison with the expected heart rate curve provides accurate methods for quantitation of chronotropic response. Adoption of this method would facilitate comparisons of artificial sensors and provide a framework to address issues of optimal rate modulation.


Flosequinan, a new vasodilator: systemic and coronary hemodynamics and neuroendocrine effects in congestive heart failure.

The aim of this study was to evaluate the immediate and long-term systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan in patients with congestive heart failure. Preliminary studies have shown that this new long-acting oral systemic vasodilator may have beneficial effects in patients with heart failure. Thirteen patients with congestive heart failure were studied. Systemic and coronary hemodynamic, metabolic and neurohormonal effects of flosequinan were assessed acutely with repeat systemic hemodynamic studies after 6 weeks of treatment. The administration of flosequinan acutely and after long-term treatment, resulted in a significant increase in cardiac index, stroke work index and stroke volume index with a reduction in systemic and pulmonary vascular resistances. The improvement in ventricular function was associated with an improvement in left ventricular efficiency without a change in myocardial oxygen consumption or coronary sinus blood flow. Myocardial oxygen extraction and net myocardial lactate extraction also did not change significantly with flosequinan therapy. Systemic catecholamine levels and myocardial catecholamine balance did not change. Plasma arterial and coronary sinus atrial natriuretic factor concentrations were elevated at baseline; the latter concentrations at the level of the great cardiac vein were significantly higher than those of arterial concentrations, indicating increased left ventricular release of atrial natriuretic factor in congestive heart failure. Both arterial and coronary sinus atrial natriuretic factor levels were significantly reduced with the administration of flosequinan at peak effect in association with an improvement in systemic hemodynamics. Flosequinan therapy in patients with congestive heart failure results in a sustained beneficial hemodynamic action and improved cardiac performance without an increase in metabolic demand or activation of the sympathetic nervous system.


Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure.

This study was undertaken to determine if a standard dose of aspirin interacts relevantly with the circulatory effects of enalapril in severe heart failure. The frequent association of heart failure with coronary artery disease confers potential for combined treatment with an angiotensin-converting enzyme inhibitor and the prostaglandin synthesis inhibitor aspirin, the pharmacodynamic actions of which are, in part, mutually opposed. In 18 patients, on 3 consecutive days, hemodynamic measurements were performed at baseline and 4 h after administration of a double placebo, enalapril (10 mg) plus placebo and enalapril plus aspirin (350 mg) according to a double-blind, randomized, crossover protocol. Enalapril given before aspirin led to significant decreases in systemic vascular resistance, left ventricular filling pressure and total pulmonary resistance together with a significant increase in cardiac output. When given with or on the day after aspirin, enalapril did not elicit significant changes in any of these variables. There was a clear tendency to lower values for pulmonary artery pressure on all regimens, and slowing of the heart rate was incurred whether or not aspirin had been given. Chi-square analysis of the individual responses showed that the probability of effecting a decrease in systemic vascular resistance > or = 300 dynes.s.cm-5 was six times greater when enalapril was given without aspirin (p < 0.01). In severe heart failure, the prostaglandin synthesis inhibition by aspirin counteracts the systemic arterial vasodilation of angiotensin-converting enzyme inhibition with enalapril and substantiates its dependence on the integrity of prostaglandin metabolism. Trends toward reductions of pulmonary artery pressure and slowing of the heart rate were still observed, presumably subsequent to lowered norepinephrine concentrations indicating maintenance of prostaglandin-independent actions of angiotensin-converting enzyme inhibition.


Amiodarone therapy does not compromise subsequent heart transplantation.

The objective of this study was to determine the frequency of pulmonary complications, feasibility of early hospital discharge and requirements for postoperative inotropic and chronotropic support in patients receiving amiodarone therapy before heart transplantation. Although many patients waiting for heart transplantation will die of arrhythmias before a donor heart is found, the use of amiodarone has been limited by concern about increased complications in the perioperative period. The 29 patients receiving amiodarone at the time of heart transplantation at University of California, Los Angeles Medical Center between October 1986 and September 1990 were compared with 29 control recipients to evaluate postoperative morbidity. Patients were receiving amiodarone for recurrent ventricular tachyarrhythmias (n = 11), atrial fibrillation (n = 2) or complex ventricular ectopic activity (n = 16). The average daily dose was 360 +/- 230 mg/day for an average of 11 +/- 22 months before transplantation. Amiodarone and control groups had a similar ejection fraction (0.18 +/- 0.07 vs. 0.20 +/- 0.08), frequency of coronary disease, age and gender. There were three more status I patients in the control group. OKT3 was given to only two patients receiving amiodarone and 12 control patients at high risk for renal dysfunction. Postoperatively, the duration of assisted ventilation was 21 +/- 19 h after amiodarone therapy versus 26 +/- 2 h in the control group (20 +/- 18 h vs. 15 +/- 9 h after excluding patients receiving OKT3), discharge arterial oxygen saturation was > 95% in both groups. Two patients in the amiodarone group with a smoking history of > 100 pack-years developed bilateral pulmonary infiltrates of brief duration. Although patients receiving amiodarone required atrial pacing more frequently (eight vs. two patients) and had a lower heart rate at discharge (75 +/- 18 vs. 86 +/- 11 beats/min), the duration of inotropic support (2.1 +/- 1.5 vs. 3.5 +/- 2.5 days) and of hospital stay (10 +/- 3 vs. 15 +/- 10 days) was not higher in the amiodarone than in the control group. The mortality rate at 30 days was similar in the two groups (6.8% vs. 3.4%, p = NS). Amiodarone therapy before heart transplantation may contribute to occasional pulmonary complications but does not significantly increase perioperative morbidity or mortality with the regimens used in this retrospective study.


Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries.

The effects of hypertension and diabetes on the physical properties of large arteries were compared in men. Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension. Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject. Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05). Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension.


Pressure overload-induced cardiac hypertrophy with and without dilation.

The present study was designed to produce a small animal model showing compensated hypertrophy followed by congestive heart failure within a reasonable time period. Although there are various large animal experimental models of hypertrophy and heart failure, the occurrence of these two stages within a reasonable time period has not been shown very successfully in small animals. A mildly constricting band was placed around the ascending aorta of very young guinea pigs (mean age 25 +/- 3 days) to impose a gradually increasing pressure overload. The animals were examined at different postoperative intervals up to 20 weeks. At 10 weeks, there was a 56% increase in ventricular weight/body weight ratio, a 33% increase in left ventricular wall thickness and a significant increase in left ventricular systolic pressure. The animals with 20 weeks of banding had developed various clinical symptoms of congestive heart failure including dyspnea, cyanotic appearance of the extremities, hydrothorax and ascites. Although at this stage there was 86% hypertrophy, the increase in wall thickness was only 20%, indicating cardiac dilation. Depressed left ventricular systolic pressure and increased left ventricular end-diastolic pressure and the increase in wet weight/dry weight ratio in the lungs and liver at 20 weeks also indicated the occurrence of heart failure. The collagen content in the heart of animals with banding for 10 and 20 weeks was 160% and 240%, respectively, of that in corresponding sham control animals. The data suggest that the heart was in a stage of compensated hypertrophy for up to 10 weeks, whereas heart failure was seen at 20 weeks. The two functional stages, compensatory hypertrophy followed by prolonged failure, make this model appropriate for studies on the transition of heart hypertrophy to congestive heart failure.


Pressure recovery in aortic stenosis: an in vitro study in a pulsatile flow model.

This study was designed to study pressure recovery in various models of aortic valve stenosis by performing hemodynamic measurements under physiologic conditions in a pulsatile aortic flow circuit. The results were used to validate calculations of pressure recovery based on theoretic considerations derived from fluid dynamics. Pressure recovery in aortic stenosis has not been systematically analyzed. Stenoses varying in size, shape (circular, Y-shaped, slitlike) and inlet configuration (sharp-edged, nozzle-shaped inlet, artificially stenosed bioprostheses) were used. Aortic pressures were measured at multiple sites distal to the stenotic orifice to determine pressure gradients and recovery. With decreasing orifice area (2, 1.5, 1 and 0.5 cm2) pressure recovery increased (5, 7, 10 and 16 mm Hg, respectively) and the index pressure recovery to maximal peak to peak gradient decreased (56%, 37%, 24% and 14%, respectively). For a given orifice size of 0.5 cm2, this index ranged between 12% for a Y-shaped orifice and 15% for a circular orifice with a nozzle (cardiac output 4 liters/min). Increasing the cardiac output increased pressure recovery, whereas the ratio of pressure recovery to maximal pressure gradient remained constant. The index pressure recovery to transvalvular pressure gradient, which expresses the hemodynamic relevance of pressure recovery, decreases with increasing severity of aortic stenosis but is independent of transvalvular flow. Thus, pressure recovery is of minor importance in severe aortic stenosis but may account for discrepancies between Doppler and manometric gradients observed in patients with mild to moderate aortic stenosis or a prosthetic valve in the aortic position.


Left ventricular shape is the primary determinant of functional mitral regurgitation in heart failure.

The aim of this study was to examine the temporal association between the onset of functional mitral regurgitation and the development of changes in left ventricular shape, chamber enlargement, mitral anulus dilation and regional wall motion abnormalities during the course of evolving heart failure. Despite extensive characterization, the exact etiology of functional mitral regurgitation in patients with chronic heart failure remains unknown. Heart failure was produced in seven dogs by multiple sequential intracoronary microembolizations. Serial changes in left ventricular chamber volume and shape were evaluated from ventriculograms. Changes in mitral anulus diameter and ventricular regional wall motion abnormalities were evaluated echocardiographically. The presence and severity of mitral regurgitation were determined with Doppler color flow mapping. Measurements were obtained at baseline and then biweekly until mitral regurgitation was first observed. No dog had mitral regurgitation at baseline but all developed mild to moderate regurgitation 12 +/- 1 weeks after the first embolization. The onset of mitral regurgitation was not associated with an increase in left ventricular end-diastolic volume relative to baseline (58 +/- 3 vs. 62 +/- 3 ml), mitral anulus diameter (2.4 +/- 0.1 vs. 2.4 +/- 0.1 cm) or wall motion abnormalities of left ventricular wall segments overlying the papillary muscles. In contrast, the onset of mitral regurgitation was accompanied by significant changes in global left ventricular shape evidenced by increased end-systolic chamber sphericity index (0.22 +/- 0.02 vs. 0.30 +/- 0.01) (p < 0.01) and decreased end-systolic major axis/minor axis ratio (1.71 +/- 0.05 vs. 1.43 +/- 0.04) (p < 0.001). These data indicate that transformation of left ventricular shape (increased chamber sphericity) is the most likely substrate for the development of functional mitral regurgitation.


Early and rapid prediction of patency of the infarct-related coronary artery by using left ventricular wall thickness as measured by two-dimensional echocardiography.

The aim of this study was to determine whether echocardiography can distinguish between persistent coronary occlusion and reperfusion. There are no adequate clinical or noninvasive laboratory markers to accurately predict successful reperfusion in an acute myocardial infarction. In a closed chest swine model, the effect of reperfusion on myocardial wall thickness was studied by comparing a 150-min total coronary artery occlusion (group 1) with 120 min of occlusion followed by 30 min of reperfusion (group 2) in the area of risk as measured by echocardiography. Wall thickness was measured at baseline and at 90 and 150 min. In group 1 (n = 4), there was no appreciable change in mean wall thickness from 90 min to 150 min of occlusion at either end-diastole or end-systole (0.54 +/- 0.02 to 0.52 +/- 0.03 cm, 0.55 +/- 0.03 to 0.54 +/- 0.03 cm, respectively; p = NS). In contrast, in group 2 (n = 6), an increase in mean wall thickness from 0.53 +/- 0.02 to 0.97 +/- 0.05 cm at end-diastole and from 0.56 +/- 0.04 to 1.04 +/- 0.07 cm at end-systole was found from 90 min of occlusion to 30 min of reperfusion (p < 0.001). Reperfusion resulted in an increase in wall thickness of 83 +/- 11% at end-diastole and 92 +/- 17% at end-systole. In contrast, persistent coronary occlusion showed minimal changes of -3.0 +/- 5% at end-diastole and -2.0 +/- 6% at end-systole. This study confirms the hypothesis that an increase in wall thickness can accurately distinguish between reperfusion and permanent coronary occlusion.


Comparison of single-photon emission computed tomographic (SPECT) myocardial perfusion imaging with thallium-201 and technetium-99m sestamibi in dogs.

The purpose of the present study was to compare single-photon emission computed tomographic (SPECT) myocardial images of technetium-99m (Tc-99m) sestamibi and thallium-201 (Tl-201) isotopes in the same dog undergoing partial coronary occlusion during pharmacologic vasodilation. To date, no controlled study has been reported comparing SPECT Tc-99m sestamibi with SPECT Tl-201 imaging during stress with anatomic and physiologic standards. Mongrel dogs were anesthetized with chloralose and instrumented to record left anterior descending coronary blood flow and aortic pressure. Partial coronary occlusion with a hydraulic cuff reduced coronary vascular conductance, which is equal to the coronary blood flow normalized to aortic pressure during peak vasodilation with intravenous adenosine. Each dog received 5 mCi of Tl-201, then 30 mCi of Tc-99m sestamibi during partial coronary occlusion at peak vasodilation. Tomographic myocardial imaging was performed in a 180 degrees anterior arc scan for 33.5 min, first with Tl-201, and later, without moving the dog, for 33.5 min with Tc-99m sestamibi. Postmortem staining defined the region underperfused because of its dependence on the artery that was partially occluded. In seven dogs with moderate reduction in coronary blood flow, coronary vascular conductance decreased with partial coronary occlusion (47 +/- 12%) during Tl-201 imaging and (47 +/- 8%, p = NS) during Tc-99m sestamibi imaging. The underperfused region was 23.9 +/- 6.4% of total left ventricular mass. Counts in the defects were 39% higher (0.86 +/- 0.08 of normal counts) for Tc-99m sestamibi than for Tl-201 (0.64 +/- 0.09 of normal counts, p < 0.001), and the defect on SPECT Tc-99m sestamibi images occupied only a fraction (0.37 +/- 0.30) of the area of the defect on the Tl-201 images of the same dog. Bull's-eye displays constructed from the pathologic slices showed that the Tl-201 defect size was closer to the underperfused region of the left ventricular mass determined pathologically than was the Tc-99m sestamibi defect size. In four additional dogs a severe, near total coronary occlusion was created during Tl-201 and Tc-99m sestamibi administration. In these dogs, similar defect contrast (0.55 +/- 0.12 vs. 0.62 +/- 0.09, p = NS) and areas (0.18 +/- 0.07 vs. 0.18 +/- 0.11, p = NS) were observed with Tl-201 and Tc-99m sestamibi, respectively. Tomographic myocardial imaging with Tc-99m sestamibi during moderately severe partial coronary occlusion underestimated the area of the defect relative to Tl-201 or to the pathologic reference standard in dogs. Defect contrast was sharper with tomographic myocardial Tl-201 than with tomographic myocardial Tc-99m sestamibi during moderately severe partial coronary occlusion.


Marked systemic hypotension depresses coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator.

This study was designed to test the hypothesis that the level of aortic blood pressure affects the rate and extent of coronary thrombolysis induced by intracoronary administration of recombinant tissue-type plasminogen activator (rt-PA). Although many studies have confirmed the efficacy of thrombolytic therapy in the treatment of acute myocardial infarction, the effects of altered blood pressure on coronary thrombolysis have not been studied. Because the aortic pressure represents the coronary artery inflow pressure, first principles predict that changes in blood pressure will affect the delivery of the thrombolytic agent and thus affect thrombolysis. The effects of large changes in blood pressure on coronary thrombolysis were studied in a canine model. Coronary thrombosis was induced by injection of radioactive blood clot through a catheter placed in the left anterior descending coronary artery. Subsequently, 24 dogs were classified into three groups of 8 dogs each: Group 1 dogs underwent phlebotomy to adjust systolic blood pressure to 130 mm Hg; Group 2 dogs underwent phlebotomy to decrease systolic blood pressure to 75 mm Hg. Dogs in Group 3 also underwent phlebotomy to achieve a systolic blood pressure of 75 mm Hg and then received norepinephrine to increase this pressure to 130 mm Hg. After adjustment in blood pressure, all dogs received an infusion of rt-PA (0.25 mg/kg body weight) over 30 min through the left anterior descending artery catheter. In a fourth group of six dogs, the effect of altered blood pressure on the rate of coronary thrombolysis was assessed. In dogs in Groups 1 and 3, the rate and extent of coronary thrombolysis were significantly increased compared with values in Group 2. In each of the six Group 4 dogs the rate of coronary thrombolysis increased when norepinephrine increased systolic blood pressure from 75 to 130 mm Hg. These results indicate that a moderate increase in coronary inflow pressure increases the rate and extent of coronary thrombolysis compared with values during marked systemic hypotension.


Delineation of acute myocardial infarction with dysprosium DTPA-BMA: influence of dose of magnetic susceptibility contrast medium.

The contrast enhancement of acutely infarcted myocardium produced by the nonionic magnetic susceptibility-enhancing agent dysprosium diethylenetriamine pentaacetic acid-bis-methylamide (DyDTPA-BMA [S-043 Injection]) was assessed in the current study to establish the lowest dose that would yield optimal contrast between normal and acutely infarcted myocardium. Magnetic susceptibility contrast agents enhance differences between normal and ischemic tissue by reducing the signal of the normally perfused tissue to which they distribute. Acute myocardial infarctions were produced by ligation of the left coronary artery. At 3 to 4 h after occlusion, a dose of 0.1, 0.3 or 0.5 mmol/kg of DyDTPA-BMA was injected intravenously into eight rats each in group 1, 2 or 3, respectively; a fourth group of seven rats served as a control group. Nuclear magnetic resonance (NMR) transverse relaxation time (T2)-weighted images (electrocardiographically gated to every 5th beat, echo delay time [TE] = 60 ms) were acquired before and for 1 h after administration of contrast agent. Images obtained before the injection of contrast agent showed moderate differences in signal intensity between normal and infarcted myocardium (p < 0.05). The contrast enhancement and the duration of delineation between infarcted and normal myocardium produced by this agent were dose dependent. At doses of 0.1, 0.3 and 0.5 mmol/kg, DyDTPA-BMA produced signal loss in normal myocardium: 63 +/- 5%, 41 +/- 4% and 28 +/- 4% of the baseline values, respectively, without any significant reduction in signal intensity of the infarcted region. The reduction in signal of normal myocardium and delineation of the infarct persisted for 5 min at a dose of 0.1 mmol/kg, for 20 min at a dose of 0.3 mmol/kg and for 40 min at a dose of 0.5 mmol/kg. No change in signal intensity or signal intensity ratio between normal and infarcted myocardium was observed in the control group during the same observation period. These results suggest that low doses of this agent, comparable to those of longitudinal relaxation time (T1)-enhancing agents, can delineate acutely infarcted myocardium. A dose of 0.3 mmol/kg of DyDTPA-BMA (S-043 Injection) provides reasonably persistent demarcation of acute myocardial infarction. Because this dose dramatically suppresses the NMR signal of normal myocardium, it shows the infarcted region as a region of high intensity (bright spot) on NMR images.


Effect of Buckberg cardioplegia and peripheral cardiopulmonary bypass on infarct size in the closed chest dog.

To simulate a human catheterization laboratory setting of controlled reperfusion during myocardial infarction, regional infusion of commercially available Buckberg cardioplegic solution and peripheral vented bypass were administered in the closed chest dog. Studies in open-chest dogs have demonstrated a significant reduction in infarct size and improvement in regional wall motion with a similar controlled reperfusion method using infusion of substrate-enriched (Buckberg) cardioplegic solution during cardiopulmonary bypass coupled with left ventricular venting. After 100 or 180 min of balloon occlusion of the proximal left anterior descending artery, controlled reperfusion was performed with cardioplegic infusion and vented bypass. Dogs matched for occlusion time underwent balloon deflation without bypass or cardioplegia (uncontrolled reperfusion groups). Microspheres were used to quantify coronary ischemia during balloon inflation. All four groups (n = 8 to 9 per group) were followed up at 1 week to determine regional wall motion and infarct size. Qualitative echocardiographic analysis demonstrated no significant difference among groups in recovery of regional wall motion at 1 week; however, wall motion improved significantly in all groups between the ischemia and 1-week recovery periods. The histologic infarct size compared with the area at risk for dogs with uncontrolled versus controlled reperfusion, respectively, was 17.9 +/- 10.5% versus 31.9 +/- 8.3% (p < 0.05) for dogs with 100 min of occlusion and 40.1 +/- 11.7% versus 46.2 +/- 8.4% (p = NS) for dogs with 180 min of occlusion. A greater rate-pressure product in the dogs with controlled reperfusion after 100 min of occlusion (p < 0.05) may explain the larger infarct size observed for that group. These results demonstrate that regional infusion of substrate-enriched cardioplegic solution in combination with peripheral vented bypass does not further reduce infarct size after prolonged ischemia in the closed chest dog (compared with uncontrolled reperfusion).


Effect of chronic supraventricular tachycardia on left ventricular function and structure in newborn pigs.

The purpose of this study was to examine the effects of supraventricular pacing tachycardia on left ventricular function and myocardial structure in newborn, immature pigs and to determine whether immature pigs respond to supraventricular tachycardia differently from adults. Previous studies have shown that supraventricular tachycardia causes dilated cardiomyopathy in adult animals; however, in humans, supraventricular tachycardia-induced congestive heart failure occurs most frequently in children and newborns. Because some clinical diseases may cause myocardial failure in adults but rarely do so in children, it was hypothesized that the effects of supraventricular tachycardia in newborns may be different from those in adults. In two groups of newborn swine (3 weeks of age), left ventricular volume, mass and function were assessed with simultaneous echocardiography and cardiac catheterization and myocardial structure was examined with light and electron microscopy. Six piglets underwent 3 weeks of left atrial pacing tachycardia (240 beats/min) and six littermates served as a control group. Both groups were followed up for 3 weeks. At the end of the protocol, left ventricular dimensions increased in the piglets with supraventricular tachycardia compared with values in the control group, but there were no differences in left ventricular mass. Systolic function, assessed by fractional shortening, peak ejection rate and maximal rate of pressure development, was decreased in the group with supraventricular tachycardia. The fractional shortening-end-systolic stress relation in the piglets with supraventricular tachycardia decreased below normal values. Left ventricular diastolic function assessed by the relaxation time constant was prolonged, the peak filling rate was decreased and left ventricular stiffness was increased in the supraventricular tachycardia group. The morphologic data demonstrated that supraventricular tachycardia did not change total myocyte volume but did decrease total myofibrillar volume. Supraventricular tachycardia caused dilated cardiomyopathy in immature pigs. These changes in left ventricular function were associated with a decrease in cellular contractile proteins. Thus, the effects of supraventricular tachycardia on left ventricular function and structure in immature animals were comparable to previous findings in mature animals.


Echocardiographic "smoke" is produced by an interaction of erythrocytes and plasma proteins modulated by shear forces.

This study was designed to determine the blood elements responsible for spontaneous echocardiographic contrast. Spontaneous contrast or "smoke" is an echocardiographic image usually found in low flow conditions. Two blood elements, erythrocytes and platelets, have been related to the generation of smoke. The echogenicity of porcine blood products was assessed in static and flow conditions and was graded on a digitized videodensity computer program that assigned a score of 0 for black and 100 for white images. Blood elements were circulated from a small tube (4-mm diameter) into a larger cylindric chamber (30-mm diameter) under controlled flow rate conditions. The following blood products were studied: whole blood, platelet-depleted blood, platelet-rich plasma, platelet-poor plasma, erythrocytes suspended in saline solution, adenosine diphosphate (ADP) added to platelet-rich plasma, and saline solution as a control medium. As blood flow was increased in 30 ml/min increments from 0 to 180 ml/min, whole blood echo videodensity (scale 0 to 100) progressively decreased in the larger tube from 38 and 42 to 20, 12, 14, 16 and 14, respectively. When flow increased from 0 to 30 ml/min in the smaller tube, corresponding to a wall shear rate of 0 to 80 s-1, the blood entering the chamber was completely echolucent. The echogenicity of blood products in the larger tube was for static flow (0 ml/min) and high flow (180 ml/min), respectively: platelet-depleted blood = 36 and 14; platelet-rich plasma = 2 and 2; platelet-poor plasma = 0 and 0; erythrocytes in saline solution = 8 and 12; ADP added to platelet-rich plasma = 0 and 15; saline solution = 0 and 0. Because platelets alone were nonechogenic but platelet-depleted blood produced a flow-dependent echogenicity similar to that produced by whole blood, platelets may not be involved in the production of smoke. However, when platelets were aggregated by ADP, they were echogenic but in dense clumps and in a flow-independent pattern not typical of the smokelike images. Erythrocytes suspended in saline solution had an intermediate density image. Echogenic smoke appears to be due primarily to the interaction of red blood cells and plasma proteins at low flow and low shear rate conditions.