[A case of scrotal bladder hernia containing bladder cancer]. A 70-year-old man had a history of total laryngectomy for laryngeal cancer and bilateral inguinal hernia repair 5 years previously. The patient had suffered from difficulty with urination since then and had been treated for prostatic hypertrophy at our department. He developed microscopic hematuria from June 1991, and was admitted because a bladder tumor was detected by cystoscopy. Cystography showed a scrotal bladder hernia with filling defects in the bladder per se and the bladder hernia as well. Cystoscopy revealed tumors in the hernia and in the vicinity of the ureteral orifice. Biopsy indicated transitional cell carcinoma. Voiding cystourethrography showed normal urination and no residual urine. Excision of the tumor-containing hernia, partial cystectomy with right ureteral orifice, and reconstruction of the right inguinal canal were performed on October 25, 1991. The postoperative course was favorable and he was discharged on the 40th postoperative day. The tumors were respectively stage as TCC, G1, and pT1a, and TCC, G1 greater than G2, and pT1b. Thirty five cases of bladder hernia that have been reported in Japan. Eight cases of accompanied by cancer have been reported in Japanese (3 cases) and foreign (5 cases) literatures. These are reviewed and discussed.


Tuberculin survey in Ethiopia.

Tuberculin survey in Ethiopia. For planning and implementation of effective national tuberculosis control programme (NTP) in Ethiopia, it is essential to know the real magnitude of tuberculosis problem. Previous tuberculin survey carried out during the period from 1953 to 1955 revealed the annual risk of infection 3.0%, and since then, there has been no survey. A new tuberculin survey was thus conducted during the period from December 1987 to April 1990. In order to get a sample of 47 previously BCG unvaccinated children, aged 6 to 10 years, selected from each 480 representative clusters of randomly selected 16 Woredas (districts), a total of 26,529 children, approximately 55 in each cluster, were given tuberculin intradermal injection, and the reaction was read in 26,269 children (99.0%). A scar survey was done, and 23,695 had no BCG scar, while 2,574 (10.1%) had BCG scar. Out of the former, 2,503 children (10.6%) were positive, and the annual risk of infection thus calculated was 1.4%. Out of the latter, 591 (23.0%) were positive. The results of these two surveys indicate that tuberculosis showed decline in the past 37 years with the annual reduction rate of 2.2%, however, the trend might change in the future due to present pandemic of HIV infection.


[The study of pulmonary tuberculosis in the elderly]. A clinical study of 52 patients diagnosed as having pulmonary tuberculosis at National Chiba-Higashi Hospital between 1988 and 1990 was performed. The cases ranged in age from 80-89 years; mean male patient age was 82.5, and mean female patient age was 84.3. Diagnosis of the cases were as follows: 19 discovered when checking into hospital because of chest symptoms; 14 diagnosed during the treatment of other diseases; 14 diagnosed during admission to the hospital for other diseases; and five cases were detected by chest X-rays. A total of 38 cases, had received primary treatment for pulmonary tuberculosis, 11 cases had received secondary treatment, and three cases were receiving treatment for tuberculosis. Upon admission to the hospital after the detection of tuberculosis, 19 cases tested positive to sputum smear examinations, six cases tested positive to culture examinations but negative to smear examinations, and culture examinations were negative in 27 cases. Regarding the chest X-ray findings, using the criterion of roentgenological classification for pulmonary tuberculosis established by the Japanese Society for Tuberculosis, two cases revealed type I, 29 cases revealed type II, and 21 cases revealed type III. Cavitary cases were observed in 60% of the chest X-ray findings. Upon hospital admission, 18 cases were observed to have circulatory diseases, 16 cases had central nervous diseases, 12 cases had digestive diseases and 11 cases had respiratory diseases. Nine cases had malignant neoplasm, five cases had diabetes mellitus and 14 cases had other diseases. A total of 18 cases ended in death; six cases died of pulmonary tuberculosis, and 12 cases died of other diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of inflammatory bronchial polyp associated with pulmonary and bronchial tuberculosis]. A 67-year-old man was admitted to our hospital because of cough and sputum. Chest X-ray revealed cavity and consolidation in the right upper lobe. Microscopical examination of stained specimens of sputum disclosed acid-fast bacilli (Mycobacterium tuberculosis). Cough and sputum resolved and cultures of sputum did not yield M. tuberculosis a month after administration of antituberculosis agents. However, a mass shadow in the right upper lobe was found 3 months later. Bronchofiberscopy revealed a polyp with a stalk at the orifice of right upper bronchus, which was elastic, soft in consistency, smooth surfaced, and movable. The pathological findings of the polyp showed non-specific inflammatory granulation which suggested to be inflammatory bronchial polyp. It was appeared in the healing process of bronchial tuberculosis.


[Short course chemotherapy and relapse in pulmonary tuberculosis in Japan]. As far as short course chemotherapy of pulmonary tuberculosis is concerned, Japan is considered to have been a little behind the trend of the world in the past. However, since 1978 the concept of the chemotherapy has begun to be adopted in some hospitals and research councils (Cooperative Study Unit of Chemotherapy of Tuberculosis of National Sanatoria, Tuberculosis Research Committees, Ryoken), and then seems to be prevailing in other hospitals as the results of their gradual understanding. This movement has likely been accelerated since Dr. W. Fox came to Japan in 1978 at the invitation of Japanese Society of Tuberculosis and gave us much information and suggestion through his special lecture on short course chemotherapy of tuberculosis. Fifteen years have past since short course chemotherapy started in Japan. At this opportunity, I would like to review the results of short course chemotherapy studies reported by Japanese investigators. Bacteriological relapse rates in cases followed-up for three years and for from five to nine years after the end of short course chemotherapy were 1.9% (20 out of 1067) and 3.3% (26 out of 783), respectively. According to the analysis of the time of relapse after completion chemotherapy, bacteriological relapses could be divided into two types. One was early relapse which occurred within one year after completing treatment, and the other was late relapse which occurred two or three years after completing treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


[Elimination of tuberculosis in Japan].

[Elimination of tuberculosis in Japan]. According to the operational definition adopted at Wolfheze Workshop held in March 1991 (Table 1), tuberculosis low incidence countries are defined as those where the incidence of all forms of tuberculosis is less than 1 per 100,000. The incidence was 41.9 in 1990 in Japan, so that Japan cannot be considered as a low incidence country. Why is the incidence of tuberculosis so high in Japan? What part of population is affected by the tuberculosis disease? To solve these questions and to make clear the mode of development of tuberculosis, a study was carried out. Fortunately, both the annual risk of tuberculosis infection and the prevalences of persons with healed and/or fibrotic lesion in the lung are known from the results of the National Tuberculosis Prevalence Surveys carried out in 1963 and 1973 as shown in Figures 1 and 2. From these data, the number of newly infected within 5 years and that of remote infections by age group were estimated. The former was divided into BCG vaccinated and non-vaccinated and the latter into persons with fibrotic lesion, with healed foci and without abnormality in the lung. (Table 2). The rates of development of tuberculosis disease according to the X-ray findings of the lung were observed at the five-years follow-up study of all the examinees at the Prevalence Survey carried out in 1968. The ratio of development of the disease in those with recent infections, remote infections with fibrotic lesion, those with healed foci and those without abnormality was estimated as 20 : 10 : 2 : 1. (Table 3)(ABSTRACT TRUNCATED AT 250 WORDS)


[Early results of surgical treatment of patients with Wolff-Parkinson-White syndrome]. Successful dissection of accessory pathways (AcP's) was performed in 19 of 20 patients. 15 pts had single, 4 double and 1 patient had 3 accessory pathways (AcP's). The patient with 3 AcP's was operated twice. During the first operation two AcP's were eliminated. The third one was revealed during the postoperative electrophysiologic study. Verapamil facilitated its manifestation and localisation. No patient had syncope or atrio-ventricular tachycardia after the operation. In 3 of 10 patients who had atrial fibrillation before the operation, episodes of AF occurred in the early postoperative period. Conduction to the ventricles was through the normal conduction system. Dissection of AcP's prevented extremely fast ventricular response and syncope. After discontinuation of amiodarone more frequent ventricular premature beats occurred in patients with long history of cardiac arrhythmias, on drugs for a long time and in patients who had heart dilatation. Several months after the operation VEB were less frequent, probably because tachycardias did not occur, left ventricle geometry improved, and cardiodepressant drugs were discontinued. Previously these patients had been treated usually with combination of 2-3 such drugs. After the successful dissection of AcP's the patients lost the feeling of illness and do not feel being imperilled. Children can attend schools normally and some adult patients resumed their professional activities.


[A case of perforation of the pericardial sac by Seldinger's catheter guide]. This is a case report of perforation by Seldinger's catheter leader into pericardial sack. The leader was inserted contrary-wise++ to the subclavian vein with the sharp end in front. The leader moved forward toward the venous system and perforated into the pericardial sack. The preceding steroid therapy which the patient had undergone due to asthmatic status resulted in mediastinitis after the primary surgery. Right technique of reoperation and intensive postoperative care led to patient recovery.


[Left coronary artery-pulmonary artery fistula. Case report]. A case of a 45-year-old male with anterior descending branch of the left coronary artery fistula to the main pulmonary trunk is reported. The patient was admitted because of a retrosternal pain. ECG showed ST-elevation in leads V2-3. This was first episode of anginal symptoms. The authors suggest that the single episode of coronary pain may have been provoked by faintness (following alcohol consumption) in the mechanism of the steal syndrome or by coronary spasm. A fistula (on coronarography) was diagnosed (the coronary arteries showed no changes). The value of the shunt calculated via Flick's method was 1.1 l/min. Exercise test, 24-hour ECG recording as well as stress thallium scintigraphy did not reveal post-exertion ischemic changes. During a 17-month post hospitalization follow-up the patient reported no anginal symptoms. Because of the small shunt and asymptomatic follow-up no surgical treatment was recommended.


[Enalapril improves hemodynamics and exercise tolerance in pulmonary heart disease caused by obstructive lung disease]. Chronic enalapril therapy was assessed in 11 patients with cor pulmonale due to chronic obstructive pulmonary disease. Enalapril was added to the maintenance dose of diuretics and digitalis and when clinical stabilisation was achieved haemodynamics, spirometry, blood gases and maximal treadmill exercise test accompanied by +pulse oximetry were performed before and after 30 days, 10-20 mg a day, enalapril therapy. Haemodynamic study showed moderate but significant decrease in mean pulmonary artery pressure, from 24 +/- 3 to 21 +/- 5 mmHg (p = 0.05). There were no substantial differences in cardiac output as well as in blood gases and spirometry after enalapril therapy. Slight decrease in oxygen delivery, on an average from 9157 +/- 3808 to 8074 +/- 3574 (p = NS), was accompanied by a concomitant fall in haemoglobin. We noted significant improvement of maximal exercise test results after enalapril therapy. Maximal workload achieved and the time of exercise increased. It was accompanied by subjective improvement as assessed by Borg scale. We observed no adverse effects of enalapril during one month therapy in patients with cor pulmonale and COPD.


[Effect of ventricular and sequential stimulation on the left- ventricular systolic function]. Left ventricular systolic function at rest was determined by echocardiography and Doppler in 20 patients after dual chamber pacemaker implantation due to second and third degree A-V block. Measurements were performed in each patient during VVI and DDD mode pacing at three different atrio-ventricular (A-V) intervals: 100, 150 and 200 ms. The essential hemodynamic superiority of DDD stimulation over VVI mode in the form of significant increase of forward stroke volume index (SVI) and cardiac index (CI) during dual chamber stimulation at identical rate stimulation was observed. Closer individual analysis of the values of CI during DDD stimulation at three different A-V intervals (100, 150 and 200 ms) gave the possibility of programming optimal A-V intervals (the highest value of CI) for each patient. The sequential atrio-ventricular stimulation as compared to right ventricular stimulation essentially improves the left ventricular systolic function at rest in patients without symptoms of heart failure. Maximum hemodynamic advantage during DDD stimulation depends on individual selection of A-V delay in each patient.


[Plasma beta-endorphin level in "silent" myocardial ischemia during Holter ECG monitoring]. The results from recent studies suggest that the endogenous opioid beta-endorphin (beta-E) is related to pain modulation. Therefore, plasma beta-E levels were studied in 23 patients with essential hypertension (EH) and in 7 patients with coronary artery disease (CAD) during asymptomatic ischemic events and in 5 patients with CAD during symptomatic ischemic events. Blood samples for beta-E were taken at the moment of silent ST depression, pointed with alarm by the real time ECG monitor "Q Med Monitor" (USA). Control blood samples were taken under the same conditions without ischemic events. Control plasma beta-E levels were significantly higher (p less than 0.01) in patients with EH as compared to that in both groups of patients with CAD (22.9 +/- 4.0 vs 7.0 +/- 1.9 and 4.5 +/- 1.6 pmol/l). At the time of silent ischemia, beta-E showed a significant increase in patients with EH (+10.1 +/- 2.1 pmol/l, p less than 0.01) and in patients with CAD (+10.7 +/- 1.3 pmol/l, p less than 0.05) as compared to the control levels. However, plasma beta-E showed no increase (+1.0 +/- 0.6 pmol/l, p greater than 0.1) during symptomatic ischemia as compared to the control levels. Thus, differences in the circulating levels of beta-E may be associated with the presence or absence of pain during myocardial ischemia.


[Clinico-genealogical characteristics of patients with ischemic heart disease and different disorders of lipid metabolism]. The paper presents a clinical and genealogical characterization of 50 probands suffering from coronary heart disease concurrent with various lipid metabolic disturbances and 211 first-degree relatives whose data have been obtained from the probands' histories while making up their pedigrees. The prevalence of atherosclerosis among the first-degree relatives has been demonstrated to be related to the nature of lipid metabolic disturbances in a proband. Some dyslipoproteinemias in the proband have been characterized by early onset of coronary heart disease, stroke, and their grave course in close relatives.


[Effect of psycho-emotional stress test on the blood coagulation system and thrombocytic hemostasis in patients with stenocardia]. A total of 101 male patients (mean age 52.3 +/- 1.7 years) with documented coronary heart disease and stable angina and 25 healthy males (mean age 49.8 +/- 2.0 years) were studied. Hemostatic parameters and catecholamine levels were determined at rest, at the peak of psychoemotional stress test and at 10 min of rest. During the test, the healthy subjects showed a protective activation of the anticoagulative hemostatic system that hindered intravascular blood coagulation. Some definite compensatory potentials of the blood anticoagulative system preserved in Type B behavior patients under the similar conditions. The patients with Type A behavior displayed enhanced intravascular coagulation and increased thrombogenic potential.


[Comparative evaluation of cardiovascular function in patients after myocardial infarction during exercise test with the optimal and sub-optimal frequency of pedalling]. Cardiovascular function was studied in 59 patients with myocardial infarction during their bicycle ergometer exercise performance at optimal and +sub-optimal pedalling rates. The total performance at the optimal rate was found to average 1.48 times more than that at the +sub-optimal rate. The efficiency of cardiovascular performance was achieved by a less increase in heart rate and systolic pressure. ECG changes resulting in exercise test cessation were observed in 7 and 30 cases at the optimal and +sub-optimal rates, respectively. It is concluded that physical training that fails to impose patients' rhythm and exercise capacity are more physiological and maximally safe.


[Crystallogenic properties of serum lipid fraction in healthy persons and in patients with ischemic heart disease]. A crystallization method was proposed to assess disturbances in the lipid system; it was based on the interaction of a serum lipid fraction with a lecithin matrix. A total of 255 invidividuals were examined. A model experiment was performed by using chemically pure cholesterol (96 samples) and 10 different cholesterol esters (240 samples). There were a great differences in the frequency of various pattern structural types (homogeneous texture, fan crystals) in the healthy persons and patients. The test results were found to be related to the ratio of esterified to non-esterified cholesterol in the serum lipid fraction. The application of rheopolyglucin, , hemosorption, quantum hemotherapy in the patients contributed to normalization of crystallization test indices.


[Effect of long-term treatment with prazosin and its combination with nadolol on the levels of blood hormones of the hypophyseal- gonadal system in patients with hypertension]. The levels of pituitary and gonadal hormones were measured by radioimmunoassay during a long-term (12-month) therapy with prazosin and its combination in 23 patients aged 30-59 years who suffered from Stage II hypertensive disease. Prazosin monotherapy resulted in a significant decrease in prolactin levels, followed by inhibited elaboration of luteinizing, follicle-stimulating, and testicular hormones in the first 6 months of therapy without changing estradiol levels. The hypoprolactinemic effect of prazosin was significantly enhanced with an increase in therapy duration and more profound in patients who had high baseline prolactin levels and in younger patients. Prazosin in combination with nadolol was found to level off the hyperprolactinemic effect of the latter without potentiating the reduction in the levels of follicle-stimulating, luteinizing, and testicular hormones which was observed during therapy with each drug alone.


[Study of myocardial perfusion in patients with hypertension]. Exercise 199Tl myocardial scintigraphic data were studied during dipyridamole test in 39 patients with Class II essential hypertension. Transient myocardial perfusion defects were revealed in 60% of patients with negative exercise test. Intraventricular administration of albumin microspheres in 8 females with normal coronary artery allowed the authors to detect areas of their accumulation at the same sites as in exercise 199Tl myocardial scintigraphy. Thus, the changes in the small vessels which are revealed by intraventricular albumin microspheres are one of the causes of impaired myocardial perfusion in patients with essential hypertension.


[Changes in the activity of antioxidant enzymes in patients with hypertension]. The authors examined the activity of the antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GP) in the blood of patients with permanent essential hypertension and hypertensive crises and changes in the activity of these enzymes when monotherapy with the calcium antagonist corinfar was used. A total of 62 patients (age 52.7 +/- 0.7 years) with hypertension and 25 apparently healthy volunteers (age 43.9 +/- 0.7 years) were examined. The activity of SOD and GP was found to be decreased by 33 and 22%, respectively, in patients with permanent hypertension and by 40 and 32%, respectively, during hypertensive crises. When hypertension was treated with corinfar, the activity of COD and GP was increased by 10 and 18%, respectively. Concurrently, these patients had subjective and clinical improvement. The findings suggest that impaired lipid peroxidation makes a great contribution to the pathogenesis of essential hypertension. It can be assumed that the use of antihypertensive agents producing effects on the level of lipid peroxidation products and the enhancements of the activity of antioxidative enzymes.


[The role of the prostaglandin system in the cardioprotective effect of adaptation to hypoxia in stress]. The adaptation to periodic altitude hypoxia is known to have cardioprotective and antiarrhythmic effects in stress-induced and ischemic lesions. The effects are assumed to be associated with the enhanced activity of the body's stress-limiting systems, including prostaglandins (PG). Wistar rats were adapted in a hypobaric chamber at an altitude of 4000 m for 6 hours during 40 days. The levels of myocardial and plasma PGE, PGE2 alpha, PGI2, thromboxane A2 were measured by radioimmunoassay and those of plasma catecholamines by enzyme radioassay. In the myocardium, the adaptation showed a 2-fold increase in PGE levels, the PGE/PGE2 alpha ratio and PGI2 levels rose by 70 and 73%, respectively, the PGI2/thromboxane A2 ratio remaining unchanged, while thromboxane A2 concentrations also rose. In adaptation, the levels of PGE and PGI2 was 78 and 60% higher, respectively. In restraint stress, myocardial and plasma PG levels proved to be substantially higher in adapted animals than in the controls, but stress-induced plasma catecholamine release, i.e. stress reaction, showed a 2-3-fold decrease that in the controls undergoing the same stress. The findings along with the data on the cytoprotective and vasodilating action of PGE and PGI2 suggest that enhanced activity of the myocardial and blood PG system is the important link in the mechanism responsible for the antistress impact of adaptation.


[Prostacyclin-thromboxane imbalance after adrenergic damage of the heart and aorta and its correction with calcium antagonist finoptin and the adaptation to high-altitude climate]. Adrenergic cardiac and aortic lesion was reproduced by using intramuscularly a stress-necrogenic epinephrine dose of 2 mg/kg. Following 24 hours, the levels of malonic dialdehyde (MDA) as a TxA2 marker, were measured in the platelets. The antiaggregability of the aortic wall where PGI2 is synthesized was also examined. The adrenergic lesion was found to impair the platelet function-vascular wall balance, creating the condition for enhancing spontaneous platelet aggregation. This led to 50% death of experimental "lowland" rats. The short-term high-altitude adaptation failed to substantially modify the death rates in adrenergic lesion, though the platelets showed a 30% decrease in MDA generation. The combination of high-altitude adaptation and the calcium antagonist finoptin completely prevented the stress-induced increase in the platelet generation of MDA, a TxA2 marker, which was followed by a drastic reduction (16.6% versus 50%) in sudden death cases among the rats during adrenergic cardiac and aortic lesion.


[Dynamics of myocardial function in the complex treatment of patients with heart failure using isolated ultrafiltration (polycardiographic data)]. Sixty patients with Stages IIB-III chronic heart failure were examined. The main group included 30 patients on complex therapy involving isolated ultrafiltration (IUF), the other 30 patients who refused to have IUF comprised the control group. The patients from the main group had improvement in the phasic pattern of a cardiac cycle, which was associated with enhanced myocardial contractility and performance due to decreased preload. Improved phasic parameters observed after IUF sessions were sustained in the post-ultrafiltration period and different from those in the control group in which their significant changes were absent during treatment.


[Comparison of the data of 24-hour ECG monitoring and the condition of the coronary bed in patients with the variants of the course of unstable stenocardia]. A total of 232 patients with various clinical types of unstable angina pectoris were examined. All the patients underwent coronary angiographic studies, 24-hour ECG monitoring. In 40.5% of the patients, 24-hour monitoring revealed transient ST segment changes which were not accompanied by pain in 47% of the cases. ST segment changes were equally encountered in patients with one-, two-, and three-vessel disease in the presence or absence of pain. Ischemic ST segment changes generally occurred with an anginal episode in patients with crescendo unstable angina, whereas in those with more prolonged and intensified pain and angina at rest in particular, silent myocardial ischemic episodes were significantly more frequently recorded, which were more common in these patients with multivessel disease.


[Myocardial catecholamine levels in patients with congenital and acquired heart defects]. Catecholamine levels were determined in the myocardial slices from 66 patients with congenital and acquired heart diseases by the trihydroxyindole++ method on a Lumilan fluorescence spectrophotometer. The patients were found to have greatly varying epinephrine and norepinephrine levels. The accumulation of catecholamine reflected, to a certain extent, the occurrence of disorders in relation to the functional load, hyperfunctions of the myocardium. Blood hypoxemia and myocardial hypoxia affected the status of the patients.


[Potential possibilities of using adrenergic beta blockers in chronic heart failure]. The study was undertaken to examine the efficacy of beta-adrenoblockers used in 26 patients with chronic heart failure which had been caused by coronary heart disease in 12 patients, by rheumatic heart disease in 8 patients, by dilated cardiomyopathy in 5 patients, and by chronic myocarditis in 1 patient. beta-Blockers such as oxprenolol, propranolol, and metoprolol were supplemented to the therapy of the patients with chronic heart failure who were resistant to cardiac glycosides, diuretics, and vasodilators. This resulted in functional class improvement by the New York Heart Association from 3.67 +/- 0.1 to 2.29 +/- 0.1. The authors defined the following predictors of the efficacy of beta-blockers in chronic heart failure: duration of the disease, diastolic pressure, cardiac rhythm, and left ventricular ejection fraction and discussed the mechanisms responsible for their positive effect in chronic heart failure.


[Effects of restored coronary circulation on nature and character of arrhythmia during attacks of angina pectoris in patients with ischemic heart disease]. The nature and frequency of cardiac arrhythmias were studied in 23 patients with coronary heart disease during anginal episodes accompanied by ECG ST-segment depression and elevation. All the ischemic episodes were divided into 2 periods: (1) that from the onset of ST-segment displacement to its maximum; (2) that from the first period to the return of ST segment to the baseline position. The predictive poor ventricular arrhythmias were more frequently recorded in the second period of ST-segment displacement. The occurrence of arrhythmias was demonstrated to be related to the degree of ST-segment elevation (depression) and the duration of the first period of ischemic episode in the second period of ST-segment displacement.


[Study of left ventricular blood filling during post-pacing ischemia: comparison of Doppler echocardiography and heart catheterization]. Left ventricular blood filling was performed in 72 patients by using pulsed Doppler echocardiography at rest and in postpacing ischemia. In 10 patients, non-invasive examination findings were compared with the values of a left ventricular pressure curve which had been obtained in frequent atrial pacing. No changes in transmitral blood flow were found in patients without coronary heart disease, whereas 2 types of abnormal transmitral blood flow were detected in those with coronary heart disease in the postpacing period. The patients with Type I abnormal transmitral blood flow exhibited prolonged isovolumetric relaxation and slightly elevated left ventricular end-diastolic pressure in the postpacing period when catheterization was conducted. Those with Type I ("pseudonormal") transmitral blood flow displayed more prolonged relaxation and significantly (greater than 20 mm Hg) elevated end-diastolic pressure. The pattern of changes in transmitral blood flow was not pathognomonic to any definite myocardial abnormality, but reflected the hemodynamics.


[Characteristics of bioelectric activity of brain structures in patients with different types of tachyarrhythmia]. The paper gives the results of study of 81 patients with various paroxysmal tachyarrhythmias. All the patients underwent transesophageal pacing and electroencephalographic examinations. There was a relationship between EEG abnormalities and various tachyarrhythmias.


[Anti-arrhythmia and hemodynamic effects of allapinin during a course therapy in patients with circulatory failure]. The antiarrhythmic effects of allapinine were studied in 57 patients with chronic circulatory failure (CCF) and cardiac arrhythmias by employing 48-hour Holter monitoring. Allapinine was found to suppress premature ventricular contraction, group premature ventricular contraction and 'runs' of ventricular tachycardia by 82.5, 88.6, and 93.1%, respectively. The antiarrhythmic activity of the agent was more pronounced in patients with coronary heart disease, Stages I-IIA CCF and left ventricular ejection fraction greater than 40%. In addition, in Stages I-IIA CCF allapinine increased myocardial contractility and left ventricular ejection fraction, whereas in Stages IIB-III CCF it showed a slight cardiodepressive effect. Thus, when given in the course therapy in patients with CCF, allapinine has a high antiarrhythmic activity and, to a lesser extent, affects central hemodynamics.


[A comparative analysis of 2 different approaches to implementing preventive measures in patients with borderline arterial hypertension]. Routine recommendations were used to prevent hypertensive disease in patients with borderline arterial hypertension without using drugs in one of the surveys. The other involved the same methods under constant control and psychological maintenance to continue preventive measures. The second approach was found to be more effective and to considerably increase the patients' compliance.


[Immediate and long-term results of thrombolytic therapy in patients with myocardial infarct: the necessity of differential treatment]. Systemic thrombolytic therapy was performed in 273 patients with large myocardial infarction: 82 on streptokinase, 25 on tissue plasminogen activator, and 166 on streptodecase. The signs of recovered coronary blood flow were observed in 68, 84, and 33% of the patients, respectively. The application of tissue plasminogen activator resulted in the maximum reperfusion. The success of thrombolytic therapy was related to the fibrinolytic system of a patient: reperfusion was achieved in 96% of patients having a high blood fibrinolytic activity and only in 31% with a low one. The clinical effect of reperfusion was most profound in patients with Killip's Class III heart failure. The patients with early recovery of coronary blood flow developed twice more frequently, which was evidenced by a 12-month follow-up. Fifty percent of patients with an ejection fraction of below 40% died within the first year of the follow-up. The authors discuss whether one can use a differential therapy, including surgical tools for myocardial revascularization.


[Clinico-functional correlations of left atrial myocardial excursions in patients with mitral valve defects]. The pre- and intraoperative drug maintenance was evaluated in 50 patients with mitral valvular disease and compared with the types of left atrial myocardial excursions. The maintenance with cardiac glycosides and diuretics was greatly different in 3 groups of patients with various types of left atrial myocardial excursions. In patients with Type I excursions the maintenance was minimal, in those with Type III excursions it was maximal, those with Type II excursions, it was intermediate. It is concluded that the functional characteristics of left atrial myocardial excursions may be used as an indicator of cardiac performance.


[Features of blood lipid spectrum in a schoolchildren's population in Kharkov]. The blood lipid and lipoprotein spectrum was biochemically studied in 580 pupils aged 12-16 years. The normal value ranges were found for total cholesterol (TC), triglycerides (T), high density lipoprotein (HDL) and low density lipoprotein in the Kharkov schoolchildren population. The upper limits of lipid lipoprotein levels enabled patients with hyperlipoproteinemias to be identified in the studied age groups. The Kharkov children were demonstrated to have high TC and T levels and relatively low HDL cholesterol, i. e. they had unfavourable characteristics as to atherogenesis. The findings suggest that the factors that influence the formation of atherogenic dyslipoproteinemias should be further studied and the preventive measures aimed at normalizing the lipid spectrum should be implemented.


[Morphometric characteristics of coronary atherosclerosis in different ethnic groups of Andizhan population]. A gross morphometric study of coronary atherosclerosis was performed in 554 native males aged 20-59 years and 142 migrant males of the same age from Andizhan according to the WHO Expert Programme (Bull, WHO, 1976, vol. 53, p. 485). The migrants over 40 years displayed a greater extent of atherosclerosis (except lipid streaks) than did the natives; but there were small differences between the comparable groups of young persons under 40 years. A histometric study of the coronary arteries was made in 81 apparently healthy males indicated that fine-dropped (mainly intracellular) lipid deposits were more common in the natives, mixed (fine- and coarse-dropped) and coarse-dropped lipid deposits occurring with cell breakdown were seen in the migrants. The thickness of atherosclerotic lesions in the coronary arteries was greater in the migrants. Varying degrees of coronary intimal hyperplasia were found in individuals from the comparable ethnic groups. The hyperplasia was more profound in the migrants. There was a direct relationship between its degree and the development of atherosclerotic lesions.


[Prognostic significance of bicycle ergometry test in patients with myocarditis]. A total of 42 patients with rheumatic carditis were examined in the acute-subacute period and following 3-5 years. Seventeen patients were diagnosed as having primary rheumatic carditis, 9 presented with tonsillogenic rheumatic carditis, and 16 had viral rheumatic carditis. The diagnosis of myocarditis was established on the basis of clinical, immunological, and virological findings. The study involved ECG, PhCG, PCG, and bicycle ergometer testing recordings. Groups of patients with good and poor prognosis were identified. Low threshold exercise, exercise-inadequate tachycardia, complex cardiac arrhythmias, phasic myocardial hypodynamic syndrome and volume exercise syndrome that are formed during performance are prognostically poor indicators. More profound electric and mechanic dysfunctions were observed in patients with tonsillogenic or viral myocarditis.


[Acute heart failure and its treatment in cardiologic drug poisoning]. The causes of sudden cardiac arrest (SCA) and its associated early death were examined in 179 patients with acute intoxications due to amitriptyline, antiarrhythmic agents and cardiac glycosides. In the first hours of intoxication, various cardiac conduction disturbances were found to occur in 39.6% of the patients, among whom 11.7% died due to SCA predominantly in complete bundle-branch block. The cause of SCA was an acute (contractile) heart failure that had run as cardiogenic shock and been associated with the specific selective action of the agents in question on cardiomyocytes. Premodulation of acute heart failure with membrane protective agents (unithiol, alpha-tocopherol, hydrocortisone), pharmacological antagonists (novodrin, alupent, isoprenaline), and the cardiotonic agent dobutamine enabled acute heart failure to be effectively treated, hemosorption to be made in early periods and cardiac events to be abolished in 80% of the patients, SCA mortality rates decreased from 11.7 to 3.2%.


[Functional significance of 2 pathways of energy transport in cardiomyocytes]. To study the relative roles of creatine kinase (CK) and adenylate systems in cardiac energy turnover, the effect of CK inhibitor, iodoacetamide- (IAA, 0.5 mM), and 2-deoxyglucose-(DOG, 2 mM) induced) 65% depletion of adenine nucleotides at slightly decreased CK flux was determined in isolated rat heart. Both substances did not substantially affect contractile parameters of the isovolumic heart. However, an augmentation of cardiac work induced by isoproterenol addition was feeble and transient in IAA-treated hearts while the response of DOG-treated hearts was well preserved. The cardiac failure after IAA treatment was associated with irreversible fall in myocardial ATP content as evidenced by 31P-NMR technique. Furthermore, these hearts were unable to perform cardiac pump function due to insufficient cardiac filling and distensibility. The DOG-treated hearts exhibited 50% reduction in the pump function and were able to increase their work in elevated resistance. The results suggest that CK pathway is extremely important for both full cardiac relaxation and maximal contractile function.


[Effects of prolonged-action nitrates on platelet aggregation and prostaglandin formation]. Platelet aggregation and prostaglandin levels were examined in 50 patients with coronary heart disease concurrent with Functional Classes II-III angina who received nitroglycerin-retard (n = 20; Group 1), corovas (n = 20; Group 2), and placebo (n = 10; Group 3). Long-acting nitrates were found to exert a positive action on thrombocytic hemostasis as decreased platelet aggregation and reverse aggregation in 25% of the corovas-treated patients. Placebo failed to have the same action. Nitroglycerin-retard caused an increase in prostacyclin concentrations. Nitroglycerin-retard and corovas produced a clear-cut antianginal effect. They promoted the reduction in the number of anginal episodes and of nitroglycerin tablets used. No antianginal effect was absent when placebo was used.


[Hemodynamic changes in bundle-branch block]. The paper gives the data on hemodynamic features in patients with bundle-branch block. Based on the data available in the literature, the authors outline hemodynamic abnormalities occurring in various bundle-branch blocks, mechanisms of their development, influences of hemodynamic changes occurring in the blocks on the general condition of patients.


[Late ventricular potentials and left ventricular performance in patients with hypertrophic cardiomyopathy]. Twenty patients with hypertrophic cardiomyopathy were examined. They were found to have late ventricular potentials in the disease, which were characterized by an increase in average QRS complex duration, a decrease in voltage, and a rise in the duration of last 40 msec of the QRS complex filtered. Such patients generally exhibited lower exercise tolerance in severe asymmetric left ventricular hypertrophy, which caused a significant deterioration of cardiac pump function.


[Cellular mechanisms of impaired cardiac energetics in patients with dilated cardiomyopathy: decrease in mitochondrial respiration and creatine kinase expression]. The mitochondrial functional characteristics were assessed in the biopsy specimens from patients with various Functional Classes dilated cardiomyopathy (DCMP). The assessment was made by using endomyocardial biopsy specimens weighing 2-4 mg which had been taken from 39 patients aged 19-64 years during coronary ventriculography and cardiac transplantation. The status of mitochondria and the efficiency of mitochondrial creatine kinase functioning were evaluated by recording the respiration of saponin-skinned muscular fibers. The maximum mitochondrial respiration rate calculated on a dry weight basis was not substantially different in all functional classes of DCMP, while the acceptor control index (Vmax/V0) and the level of creatine-activated respiration decreased with an increase in the functional class of DCMP. The findings show a good positive correlation between ejection fraction and creatine-stimulated respiration values and a linear negative correlation between this parameter and end-diastolic pressures. Thus, the respiratory parameters of mitochondria in the endomyocardial biopsy specimens may be used to assess the severity of cardias lesions.


[Comparative study of the action of Finoptin, Korinfar and Capoten in patients with stage II hypertensive disease]. The effects of Finoptin, Corinfar, and Capoten were examined in 154 patients with Stage II hypertensive disease. The calcium antagonists Finoptin and Corinfar, as well as Capoten were equal in lowering blood pressure and having a heterodirectional action on cardiodynamics: Finoptin exerted a positive inotropic effect in 46.3% and a negative one in 53.7%, corinfar in 66.7 and 33.3%, respectively, and Capoten in 37.5 and 62.5%. The baseline hemodynamic type fails to predict how the myocardium in a particular patient will respond to the antihypertensive drug. Nevertheless, Corinfar is more preferable in patients with hypertensive disease attended by hypokinetic circulation, Capoten is more preferable in those with its hyperkinetic variant. The baseline hemodynamic type makes an insignificant contribution to the activity of Finoptin.


[Significance of left ventricular structural changes in arterial hypertension for the prolongation of electric cardiac systole]. Echocardiography was used to examine 93 patients with Stages I and II arterial hypertension with a view to clarifying the impact of structural changes occurring in the left ventricle in the course of the disease on the duration of electric systole. Left ventricular muscle mass was found to become larger with an increase in corrected Q-T interval duration, the upper dependence correlating better with concentric hypertrophy. The duration of electric systole increased with deteriorated left ventricular function. It was empirically concluded that the left ventricular mass index of 200 g was associated with prolonged Q-T interval, which was more than the normal parameters.


[Methodologic features of determining renin-like activity in human arteries]. Human arterial tissue was shown to have renin-like activity. For its determination the authors propose methodological approaches. The optimum pH of renin activity in the vascular wall was found to be 5.8-6.0. The renin-like enzyme was ascertained to be present in the vascular wall as inactive and to be activated by trypsin. The renin activity was compared in the human vascular wall and human plasma. Their optimum pHs were nearly identical. The methodological features determined in this paper allowed one to differentiate the true renin-like activity from the activity of acid proteases.


[The baroreceptor reflex as a predictor of crises in arterial hypertension]. The sensitivity of baroreceptor reflex was determined by the "neck chamber" method at a pressure of 40 mm Hg in patients with mild, moderate and malignant arterial hypertension (AH). A 24-hour blood monitoring was performed in patients with mild and moderate AH. There was a negative correlation between the lowering values in blood pressure on baroreceptor stimulation and the incidence of hypertensive crises in all the groups. There was also a negative correlation between the baroreceptor sensitivity and the daily blood pressure variations in patients with moderate AH. The findings suggest that a decrease in baroreceptor sensitivity might be a predictor of the critical course of AH.


[Effect of hemosorption on microcirculation, humoral autoimmunity and lipid peroxidation in patients with stable angina pectoris]. Microhemo- and lymphocirculation, capillary permeability, humoral autoimmunity and lipid peroxidation were determined in 46 patients with Functional Classes III-IV stable angina concurrent with multiple atherosclerotic coronary lesions 24 hours following the second hemosorption session. The clinical efficiency of hemosorption was observed in 47.8% of patients with stenotic coronary atherosclerosis refractory to antianginal therapy. In this group of patients, hemosorption led to accelerated microcirculation, increased microcirculatory reserve potentials and decreased microvascular resistance at rest and in reactive postischemic hyperemia. In patients with abnormal humoral autoimmunity and lipid peroxidation, hemosorption resulted in their hormalization.


[Cardiolipin antibodies in patients with myocardial infarction and unstable angina pectoris]. The clinical value of IgG and IgM cardiolipin antibodies (CLa) was examined in 22 patients with myocardial infarction and 9 patients with unstable angina (UA). Higher IgG levels were observed in 41% of MI patients and 55% of UA patients. There was a significant correlation between the detection of IgG CLa in patients with a history of myocardial infarction and the presence of left ventricular intracavitary thrombosis. The levels of IgG CLa were increased in 78% of patients with history of MI and in 32% without MI history. In addition, those of IgG CLa was higher in 80% of IM patients with signs of intracavitary thrombosis and in 38% with cavitary thrombosis. The findings suggest that antibodies to cardiolipin (of IgG in particular) make contribution to the development of thrombotic events in patients with coronary atherosclerosis in the absence of autoimmune pathology.


[Clinical and hemodynamic effect of piracetam (Nootropil) in elderly and very old patients with coronary heart disease in the outpatient rehabilitative period]. The clinical and hemodynamic efficiency of piracetam (nootporil) used in the long-term combined therapy of elderly and senile patients with chronic coronary heart diseases was studied outpatiently. This drug led to a significant enhancement of the antianginal effect of the basic treatment, to more regression of clinical signs of chronic circulatory insufficiency, to positive central hemodynamic changes, higher exercise tolerance, lower energy consumption index per performance unit, increased adaptive potential of the circulatory system, and maintained optimal cerebral blood flow.


[Clinical course of the disease, myocardial functional status and rheological properties of blood in patients with post-infarction cardiosclerosis and angiographically documented unchanged coronary arteries]. The clinical course of the disease, myocardial functional status and blood rheological properties were examined in coronary heart disease patients with postinfarction and angiographically evidenced intact coronary arteries. This group of patients was shown to be characterized by young age, acute onset of the disease and rather favourable prognosis. The abnormalities were caused by extended postinfarction asynergies, yet there was no significant progression of circulatory insufficiency even in patients with left ventricular aneurysm during a long-term follow-up (5.2 +/- 0.2 years). A correlation was found between the level of myocardial blood flow and the degree of disturbed blood rheological properties. It is suggested that impaired blood rheology along with altered coronary tone should determine the functional component of coronary resistance and represent a main mechanism of coronary insufficiency in patients with coronary heart disease and unchanged coronary arteries, as evidenced by angiography.


[Phenotypic familial correlations of prostacyclin and thromboxane A2 levels in children and adolescents with or without hereditary predisposition to ischemic heart disease]. The familial correlations of prostacyclin and thromboxane levels were examined in 90 children and adolescents from 70 families with hereditary coronary heart disease and in 56 of the same age from 38 families without hereditary atherosclerosis and their parents. The genetic factors were demonstrated to make a significant contribution to the phenotypic dispersion of prostanoids. The familial predisposition to the disease was ascertained to modify the pattern of familial correlations of prostacyclin and thromboxane levels as compared with no predisposition. The influence of familial and environmental factors was found to be more pronounced in the families of patients with coronary heart disease, and one of the important sequelae is thromboxane hyperproduction in the patients' wives.


[Cardioprotective effects of adaptation to restraint stress and hypoxia]. Isolated rat heart experiments have revealed that restraint stress adaptation results in enhanced resistance of the isolated heart to reperfusion. There is also a higher resistance to the autolysis of the organelles isolated from the hearts of stress-adapted animals. This complex of changes is designated as a phenomenon of adaptive stabilization of structures (PhASS). The phenomenon developing in restraint stress adaptation substantially limits arrhythmias, contracture, contraction amplitude depression, and creatine kinase release into the perfusate in thermal damage to the isolated rat heart. Simultaneously, PhASS is accompanied by a multiple increase in five hsp70 isoforms with pI 5.8-6.3 in cytosol and two isoforms with pI about 6.3 in the nucleoplasm. Only two hsp70 isoforms with pI about 5.8 accumulate solely in cytosol during adaptation to intermittent hypoxia. Consistently, the resistance of Ca(2+)-pump and nuclear DNA remains unchanged and the protection against reperfusion and thermal damage are several times less pronounced.


[Effect of exogenous creatine phosphate on electrophysiologic myocardial parameters in overload heart failure]. Experiments with rats undergoing overload testing showed that exogenous creatine phosphate was likely to fail to penetrate into myocardiocytes and to affect their energy balance directly. However, during its long-term administration in energy deficiency, creatine phosphate was able to maintain cardiac pump function via activation of processes controlling sinus nodal automatism and atrioventricular conduction.


[The course of chronic circulatory insufficiency in patients with primary pulmonary hypertension]. A physical and X-ray examination and echo-, electro- and phonocardiographies were performed in 29 patients with primary pulmonary hypertension. Their central hemodynamics was also conducted by introducing a Swan-Ganz flowing balloon catheter into the right cardiac cavities. With evolving chronic circulatory insufficiency, the patients showed profound hemodynamic changes both in the right (end-diastolic pressure in the right ventricle and atrium rose and ventricular stroke index dropped) and left (heart rate increased, cardiac and stroke indices decreased in the ventricle) ventricles. There were slight changes in peripheral hemodynamics. Pulmonary pressure became lower, but this fact cannot be considered to be positive as this led to significantly lower right ventricular stroke index that indicates the critical diminution in right ventricular performance, unlike cases successfully treated with peripheral vasodilators.


[Experimental ultrasound contrast study of the myocardium]. The ultrasound contrast medium obtained by the original methods was administered into the left ventricular cavity and myocardium of 12 open-chest dogs by using a catheter. After its administration into the cavity there was its intensive contrast. When the ultrasound contrast was administered into the aortic root, the entire myocardium contrasted, on selective administrations of the contrast into the coronary arteries, the beds supplied by appropriate arteries contrasted. The ultrasound contrast study enabled the areas with impaired perfusion as echo-negative "filling defects" to be detected and mapped. The imaging of myocardial blood flow in tomographic sections and real time allows one to regard it promising for clinical use.


[Effect of high-frequency pulse ultrasound on experimental myocardial infarction]. The rat precardial region was exposed to single 30-minute and course radiations with pulse ultrasound at 2640 kHz before and after experimental myocardial infarction. Ligation of the left coronary artery caused an increase in 99mTc pirphotech accumulation by 243.4% as compared with the controls. Single and course ultrasounding after left coronary ligation substantially decreased rat myocardial isotope accumulation (by 130 and 179.1%, respectively) and reduced the number of complications, and prolonged animals' survival.


[Exercise-induced cardiodynamic changes in invalids after leg amputation]. Cardiodynamic studies by one-dimensional echocardiography were performed in 45 disabled persons with various lower limb amputations at rest and during graded bicycle ergometer exercises. The disabled included males aged 20-40 years with posttraumatic limb amputations who had no respiratory and circulatory disorders. The results of the studies were comparable with the data obtained in the control group. The handicapped were found to have significant cardiodynamic changes which were regarded as sequelae of weight and vascular bed loss. On exercise, there was loss of capacity to adequately enhance venous return and left ventricular diastolic filling, which was evidenced by concurrently decreased end-systolic and end-diastolic volumes and no increased systolic ejection. At the same time there was a regular reduction in myocardial contractility.


[Origin of the aorta and pulmonary artery from the right ventricle: anatomic and echocardiographic comparisons]. The origin of the aorta and pulmonary artery from the right ventricle is a complicated and little studied congenital cardiac malformation. The A. N. Bakulev Institute of Cardiovascular Surgery, USSR Academy of Medical Sciences, have developed anatomic and morphological criteria for the malformation. With the criteria, echocardiograms from 64 patients were retrospectively analysed and their anatomic and echocardiographic comparisons were made. The findings revealed the echocardiographic measures of the aorta and pulmonary artery from the right ventricle and determines the optimal echocardiographic projections for their estimate.


[Functional state of the heart in ventricular tachycardia as evidenced by radionuclide ventriculography]. The paper presents the results of examining the structural and functional parameters of the ventricles in 40 patients with ventricular tachycardia by radionuclide ventriculography on the first passage of a radioactivity bolus. Twenty patients had ventricular tachycardia resistant to antiarrhythmic agents. The patients with ventricular tachycardia were found to have systolic and diastolic dysfunction of the both ventricles. Lower pump function and higher volumetric parameters of the left ventricle in patients with refractory ventricular tachycardia concurrent with hyperkinesia of some right ventricular segments and abnormal velocity and time variables can be a criterion for resistance to antiarrhythmic agents in this group of patients.


[Effect of thrombolytic therapy with intravenous streptokinase on the size of myocardial infarction estimated by the ECG QRS score system]. The impact of short-term intravenous large dose streptokinase injection on the myocardial infarction size estimated by a QRS score system was studied in 57 patients with primary myocardial infarction admitted to hospital at least 6 hours following the onset of the disease. There was a lower myocardial infarction size despite its localization and the time of treatment initiation when thrombolysis was successful, as evidenced by non-invasive criteria. The reliability of the QRS score system used to estimate the myocardial infarction size increased when the patients with anterior or inferior myocardial infarction and those with successful and unsuccessful systemic streptokinase thrombolysis.


[Structural and functional parameters of the myocardium and atrial natriuretic peptide in atrial fibrillation]. The plasma level of atrial natriuretic factor and its relation to intracardiac and systemic hemodynamic parameters were examined in patients with coronary heart, rheumatic and mitral valvular diseases, neurocirculatory dystonia which were complicated by atrial fibrillation. The concentration of atrial natriuretic factor was found to vary with the left ventricular myocardial mass, left atrial contractility, antiarrhythmic therapy intensity and efficacy.


[Anaerobic threshold in patients with chronic circulatory insufficiency]. To evaluate the severity of chronic circulatory insufficiency (CCI), 12 healthy subjects and 69 patients with cardiovascular diseases underwent exercise testing. Parameters such as anaerobic threshold (AT) and peak oxygen consumption (peak VO2) were measured by respiratory gas analysis to assess the circulatory insufficiency. AT decreased with an increase in New York Heart Association functional class and amounted to 18.9 +/- 4.3, 14.5 +/- 3.5, 11.6 +/- 2.9, and 7.5 +/- 2.0 ml/min/kg in Classes 1, 2, 3, 4, respectively. The peak VO2 decreased as hCCI progressed. The findings suggest that the parameters of external respiration and gas exchange are closely associated with CCI pathophysiology. The parameters may be used as objective and valid criteria for the severity of CCI and its dynamics in the course of treatment.


[Significance of platelet membrane destruction in vasospastic angina pectoris during its exacerbation]. The parameters of the structure and function of platelet membranes were examined in 30 patients with unstable vasospastic angina in relation to the outcome of the disease (myocardial infarction stabilization or development). The fractions of phospholipids (lysophosphatidylcholine, phosphatidylserine, sphingomyelin, phosphatidylcholine, phosphatidylethanolamine), the levels of platelet membranous free and esterified cholesterol, plasma malonic dealdehyde and thromboxane B2, the activity of platelet superoxide dismutase and catalase were determined. The exacerbation of vasospastic angina was found to appear as accumulation of cholesterol (mainly of its fraction), an increase in platelet membranous levels of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin, accumulation of malonic dealdehyde. These changes were more profound in cases with subsequent myocardial infarctions. There were differences in the dynamics of the examined parameters in relation to the outcome of the disease.


[Hirudin therapy and blood coagulability]. The changes in blood coagulative properties, which occur in the treatment with medical leeches, were studied in 57 patients with coronary heart, rheumatic and chronic pulmonary diseases. Hirudin therapy was established to affect blood coagulation. The leech salina penetrated into the skin wound to block hemostasis. Having entered the circulating blood, some part of the saliva normalized its impaired coagulative properties. The correction of the above abnormalities and related bleeding indicate it beneficial to use hirudin therapy in secondary coagulopathies and circulatory decompensation.


[Hormonal aspects of the pathogenesis of cardiac arrhythmias in patients with hypertrophic cardiomyopathy]. Radioimmunoassay was used to measure thyroid, somatotropic, parathyroid hormones and cyclic nucleotides in 40 patients with hypertrophic cardiomyopathy and 14 with hypertensive disease concurrent with asymmetrical myocardial hypertrophy. In the patients with hypertrophic cardiomyopathy, the mean blood concentration of thyroid, somatotropic, parathyroid hormones and cyclic nucleotides was generally within the normal ranges and similar to that in hypertensive patients with apparently healthy individuals. The patients with hypertrophic cardiomyopathy concurrent with supraventricular arrhythmias exhibited higher blood levels of total and free thyroxine and thyroxine/thyroxine-bound globulin ration than did patients without arrhythmias. The patients with hypertrophic cardiomyopathy concurrent with arrhythmias displayed increased blood levels of cyclic nucleotides. The findings suggest that thyroid hormones and cyclic nucleotides are likely to make contribution to the pathogenesis of arrhythmias in hypertrophic cardiomyopathy.


[Effect of emotional stress on catecholamine and dopa levels in some central nervous regions and in the heart of experimental animals]. The paper presents the results of examining the levels of dopamine, norepinephrine, epinephrine and precursors of their DOPA biosynthesis in the hypothalamus, hypophysis, medulla oblongata, adrenals and heart in miniature pigs exposed to acute stress. The acute emotional stress was shown to be characterized by a significant increase in the activity of the brain hypothalamic region, adrenals, peripheral portion of the sympathoadrenal system, as evidenced by higher norepinephrine release and hence lower neurotransmitter levels in the above structures. This resulted in abnormal physiological norepinephrine/epinephrine ratios in the central nervous system and heart, predisposing to myocardial metabolic and electric instability.


[Hemodynamic effects of purine nucleosides in regional ischemia and reperfusion]. The rat hearts were subjected to 60-min ischemia by left coronary artery ligation followed by 60-min reperfusion, involving intravenous adenosine inosine or guanosine given in a dose of 1 mg/kg.min-1 in the first 30 minutes of reperfusion. Ischemia and subsequent reperfusion caused a progressive decrease in cardiac output and coronary blood flow. Adenosine was found to enhance coronary blood flow and increase cardiac and stroke outputs. Inosine produced nearly the same, but less pronounced effect. Guanosine increased cardiac output without changing coronary blood flow.


[Assessment of myocardial function and metabolism in patients during aortocoronary bypass surgery after hypoxia-reoxygenation]. The myocardial function and metabolism were assessed in 12 patients with coronary heart disease intraoperatively during aortocoronary bypass surgery. The antioxidative properties of the blood of the heart were found to become lower along with activated peroxidation after the major stage of an arrested heart operation, that correlated with depressed myocardial function.


[Atherogenesis and serum levels of apolipoprotein E]. Serum apolipoprotein (apo) E levels and their relationship with age were examined in different age groups of healthy individuals of both sexes in a Lithuanian population. The serum concentrations of apo E in patients after coronary bypass were measured and patients suffered from diabetes mellitus were also examined. The mean levels of apo E were found to be higher in healthy males than those in healthy females only in young age. Serum apo E levels were inversely associated with age (P < 0.05). Apo E levels were significantly higher in males over 45 years of age who suffered from coronary atherosclerosis and in males under 45 who had diabetes mellitus (types I and II) than those in healthy individuals (P < 0.05). There was an insignificant difference in apo E levels among healthy and diabetic females (P < 0.05). The findings demonstrated the association of increased apo E levels with atherogenesis.


[Hypoalphacholesterolemia and coronary disease (an approach using a factor analysis)]. The data obtained from a screening of 1,467 males aged 40-59 years made it possible to characterize the relation of dyslipoproteinemias, primarily hypoalphacholesterolemia, to the incidence of coronary heart disease and risk factors in males, by using factorial and multivariate analyses. The findings suggest that hypoalphacholesterolemia is closely associated with hypertriglyceridemia in its atherogenicity, thus from the clinical point of view low levels of HDL cholesterol should be used as a ground for thorough examination of lipid metabolism, with great emphasis on metabolic disturbances of triglyceride-rich lipoproteins.


[Effects of lovastatin (mevacor) on platelet function in hypercholesterolemia in patients with ischemic heart disease]. The impact of a 4-week course of lovastatin (mevacor) therapy on platelet function was examined in 26 patients with coronary heart disease concurrent with hypercholesterolemia (the baseline plasma cholesterol level was 250 mg% or more). The agent was given in a daily dose of 20-40 mg. The agent in this dose was found to have no action on the thromboxane-prostacyclin balance in plasma, on the degree of ADP-induced aggregation and lipid peroxidation in platelets, phospholipid composition and levels of ester-bound cholesterol in platelet membranes. Free cholesterol tended to increase at the end of the 4th week of treatment. Despite the effective reduction of plasma levels of total and LDL cholesterols whose action on platelets is well known, there was no estimated decrease in the activity of platelets during lovastatin therapy.


[Effects of lovastatin therapy on the level of low density lipoproteins and atherogenic potential of serum in patients with ischemic heart disease and hypercholesterolemia]. The serum atherogenic potential in patients with coronary heart disease (CHD) concurrent with hypercholesterolemia (LDL cholesterol more than 200 mg/dl), which is able to cause accumulation of intracellular cholesterol in cultured cells has been recently shown to be directly related to the level of total cholesterol and LDL cholesterol. The study was undertaken to examine how a lovastatin-induced decrease in LDL levels affects serum atherogenicity in patients with CHD and hypercholesterolemia. It was shown that the therapy of 22 patients with CHD and hypercholesterolemia led to a reduction in total and LDL cholesterol levels on an average by 24% and 32%, respectively. There were 3- and 1.5-2-fold decreases in circulatory immune complexes and the atherogenic potential, respectively. The findings suggest that the significant reduction in serum LDL cholesterol levels in patients with CHD concurrent with hypercholesterolemia who take hypolipidemic therapy is followed by a decrease in the atherogenic potential.


[Effects of laser therapy in patients with functional class II-IV effort angina (using instrumental techniques of the study)]. Infrared laser therapy using an arsenide-gallium laser was used in 54 patients aged 30-75 years who suffered from coronary heart disease. A positive clinical effect was achieved in 47 (87%) of 54 patients, as evidenced by the reduced number of nitroglycerin tablets used and improved bicycle ergometric, echo- and electrocardiographic parameters in the patients.


[Relationship of physical work capacity, blood pressure and other hypertension risk factors with the rate of erythrocyte Na/Li countertransport]. The relationship of physical working capacity (PWC), blood pressure and other arterial hypertension risk factors to the rate of red blood cell Na+/Li+ countertransport was examined in a representative sample comprising 60 individuals (22 males and 38 females) whose age was 35-54 years. Regression analyses demonstrated that there was no significant relationship between PWC and the rate of red blood cell Na+/Li+ countertransport, but a significant correlation was found between the rate of Na+/Li+ countertransport and "double product" (DP) as an indirect indicator of PWC and heart rate. Thus, there is a heart rate- and DP-mediated correlation between the rate of red blood cell Na+/Li+ countertransport and the level of PWC. The magnitude of a decrease in the rate of red blood cell Na+/Li+ countertransport depends inversely on the dynamics of heart rate in males and females and directly on the dynamics of DP in females. Hence, there is a direct relationship between the magnitude of a reduction in the rate of red blood cell Na+/Li+ countertransport and that of PWC increment during exercise.


[Comparative analysis of antiarrhythmic action and electrophysiological effects of a new benzodiazepine derivative gidazepam and ethacizin in arrhythmias of various genesis]. The antiarrhythmic and electrophysiological effects of the new benzodiazepine tranquilizer gidazepam versus ethacizin were examined in patients with cardiac arrhythmias. The antiarrhythmic effect of the agent was found during 24-day monitoring and simulated psychoemotional stress in 81% of patients with neurocirculatory dystonia and in 61% of patients with coronary heart disease. The antiarrhythmic effects developed with gidazepam-induced changes in electrophysiological properties of the cardiac conduction system. The preventive antiarrhythmic effect of gidazepam was demonstrated to be higher than that of ethacizin during stress in patients with arrhythmias of extra-ischemic genesis.


[Clinical effectiveness of cordarone in combination with other anti-arrhythmia agents in refractory atrial fibrillation and adverse effects of the drugs]. The study was undertaken to examine 105 patients with various circulatory diseases complicated by atrial fibrillation. Patients with refractory atrial fibrillation who had taken combined antiarrhythmic therapy were found to be more responsive to the combinations of cordarone + kinilentin (quinidine disulphate) and cordarone + ethacizin. The combinations of cordarone+digoxin and cordarone + finoptin were demonstrated to be less beneficial.


[Arrhythmia in athletes during length diving]. On diving at a distance of 50 m by arresting their breathing, some male athletes were shown to develop cardiac arrhythmias which occurred at min 2 of a restorative period and entirely disappeared at the end of the second-fifth min. It is essential to make further studies of the impact of diving on the cardiac rhythm in athletes in order to elucidate how these disturbances should be regarded: abnormal or physiological.


[Results of closed mitral commissurotomy after 20-25 years]. The 20-25 year results of 486 closed mitral commissurotomies were analysed. The actuarial analysis demonstrated that 25-year survival was 59%, stable good results were 38%, repeated mitral interventions were performed in 31% of the patients. The patients' survival and functional results of commissurotomies depend on early surgery which should be done in patients with severe and acute mitral stenosis prior to the development of drastic valvular changes, calcinosis, regurgitation, atrial fibrillation, cardiomegaly, atrial thrombosis and other complications. Timely mitral commissurotomy is a rather effective palliative intervention in uncomplicated mitral stenosis.


[ECG dynamics at rest and during exertion after mitral commissurotomy]. Four degrees of left atrial electrical activity were identified by ECG made before and after closed mitral commissurotomy in 70 patients with mitral stenosis and sinus rhythm. The critical electrical activity of the left atrium and hypertrophy of the right ventricle along with the typical auscultation pattern of mitral stenosis were found to cardiographically correspond to critical stenosis of the left atrioventricular ostium in most cases. The area of the mitral orifice, which was attributable to that of the body, was 0.6 to 0.8 cm2/m2. The patients with critical left atrial electrical activity were considered to be at risk for atrial fibrillation in the immediate postoperative period.


[State of coronary circulation and results of 24-hour ECG monitoring in patients with refractory angina pectoris]. The paper compares the data of selective coronary angiography and 24-hour monitoring in 39 patients with refractory angina pectoris. Transient ST-segment changes were revealed in 79% of the patients, ST-segment depression occurring in 54%, ST-segment elevation in 46%, T-wave inversion in 38%. A combination of ST-T interval changes and occurrence of ventricular premature contraction was found in a third of the examinees. There was no statistically significant correlation between the extent of major coronary lesion and the mean length of ST-segment displacements.


[Doppler echocardiography in the assessment of arteriovenous blood ejection in patients with ventricular septal defects]. To assess Doppler echocardiography used to determine blood ejection through ventricular septal defect, this procedure and cardiac catheterization were performed in 32 patients. Comparison of the findings showed a high correlation (r = 0.81; p < 0.05). To determine whether echocardiographic accesses are correctly chosen, volumetric greater circulation was measured from the suprasternal access in the ascending aorta and aortic arch, but volumetric lesser circulation was measured from the parasternal access in the pulmonary trunk and from the apical access of the projection of 4 chambers through the mitral orifice. The comparison of the findings showed a high correlation in this group. Twenty one patients were examined after plastic surgery of ventricular septal defect, who had been clinically suspected to have a residual shunting. An analysis of the findings made it possible to develop Doppler echocardiographic criteria for differential diagnosis of graft vibration due to arteriovenous blood ejection.


[Effects of adaptation to periodic hypoxia on Ca2+ pump of the cardiac sarcoplasmic reticulum and its resistance to endogenous damaging factors]. The adaptation of rats to periodic "altitude" hypoxia in the altitude chamber (6 hour daily at an altitude of 5000 m during a month) led to increased activity of the Ca2+ pump in the myocardial sarcoplasmic reticulum, which was associated with lower Kd values and higher calcium transport Vmax. When a cardiac homogenate was kept at 4 degrees C, autolysis resulted in a decrease in Ca2+ pump activity (which was more rapid in adapted animals than in the controls) and an equal increase in the levels of free calcium in the homogenates in the two series of experiments. The approximate data were obtained when a homogenate was incubated at 37 degrees C, but when it was incubated at 4 degrees C, the rate of Ca(2+)-pump inactivation decreased 20-fold. Incubation in the presence of free radical oxidative inductors (Fe2+ ascorbate) led to high resistance of myocardial Ca(2+)-pump in the adapted rats. The paper discusses the causes of myocardial Ca(2+)-pump activation in periodic hypoxic adaptation and the mechanisms for its increased resistance to active oxygen, as well as their role in the cardioprotective effect of the adaptation.


[Effects of bonnecor on transmembrane potentials of cardiomyocytes of the ventricular contractile myocardium of the intact heart and ventricular fibrillation]. The microelectrode technique has shown that bonnecor given in a dose of as many as 2 mg/kg increases the action potential amplitude, but when its dose is increased up to 3 mg/kg, the agent decreases the action potential amplitude of ventricular cardiomyocytes in the guinea-pig, the resting potential remaining steady. Administration of bonnecor prevents ventricular fibrillation after aconitine application and provokes ventricular fibrillation and flutter when the focus of ectopic automatism is formed.


[Specific features of the regulation of coronary circulation during reperfusion after coronary insufficiency of different degrees]. Coronary insufficiency of various degrees was reproduced in experiments with anesthetized dogs by using coronary artery catheterization by progressively limiting the regional blood flow by 30, 50, 70, and 90%, the dog chest being closed. The specific features of regulatory reactions of cardiac vessels were also studied under subsequent reperfusion. It was shown that regulation of coronary circulation became changed in most cases after markedly limited coronary blood flow, as manifested by impaired reperfusion hyperemia and its rapid cessation that prevented the "payment" of blood flow debt and a secondary increase of cardiac vascular resistance above the preocclusive level. There was a significant relationship between the detected disorders and the degree of prior limited coronary perfusion.


[Atherogenic properties of phenothiazine drugs manifesting in cultured cells of the human aortic intima]. The effects of phenothiazine drugs on the levels of cholesterol in smooth cells of the human aortic intima. Two antiarrhythmics (ethacizin and ethmozine) and two neuroleptics (trifluoperazine and chlorpromazine) were evaluated. The three agents ethacizin, trifluoperazine, and chlorpromazine given in concentrations of 10(-7) to 10(-5) M were ascertained to cause intracellular cholesterol accumulation, whereas ethmozine produced no effects on the intracellular levels of cholesterol. Ethacizin failed to cause cholesterol accumulation when the cells were incubated with ethacizin in the culture medium supplemented with lipid-deficient serum. Ethacizin in a concentration o 10(-5) M was shown to inhibit the synthesis of cholesterol esters and had no action on the intracellular synthesis of steroids.


[Echocardiographic assessment of cardiac pump function using afterloading characteristics]. Seventy five patients and twenty healthy individuals were investigated by using cardiac ultrasound technique, followed by mathematical simulation of changes in left ventricular pressure during contraction. The findings show that the afterload characteristics based on a wealth of evidence for cardiac and left ventricular performance, unlike the conventional central hemodynamic parameters and cardiac phasic indices, enable the occult circulatory disorders to be revealed and the cardiac compliance with the arterial system to be assessed.


[Doppler echocardiographic assessment of left atrial and left ventricular function during right bundle branch block]. Electrocardiographic, echocardiographic and Doppler echocardiographic studies were performed in 44 patients with coronary heart disease and complete right bundle branch block. The patients were found to have an impaired phase pattern of left ventricular systole and diastole as more prolonged length of its isometric relaxation and contraction, lower economic feasibility and efficiency of its contraction, moderate dilation and hypertrophy. Hemodynamic abnormalities in the left heart in these patients are closely correlate with the changes in the phase pattern of right ventricular systole and they turn out to be so greater as the degree of its hypertrophy is. In complete right bundle branch block, left ventricular pump dysfunction leads to decreased cardiac output and cardiac index, increased total peripheral vascular resistance, thus predisposing to impaired greater circulation.


[Cardiac diastolic function in children and adolescents during prompt and long-term adaptation to physical exercise]. To study the natural changes in cardiac diastolic function in ontogenesis at various stages of exercise adaptation, 65 males aged 10-17 years who go in for various kinds of sports developing primarily physical fitness have been examined. Long-term adaptation to cyclic muscular activity has been shown to result in a reduction in cardiovascular lability, an optimization of inclusion of myocardial functional reserves, and an increase in efficiency of using cardiac cycle time in response to myocardial restorative processes. High stages of exercise adaptation formed an additional mechanism responsible for diastolic filling at the expense of an atrial systole (an atrial mechanism of diastolic regulation).


[Intraoperative myocardiography, a new method of regional myocardial function evaluation during aortocoronary bypass surgery]. Excursions of the myocardium in its revascularization area were recorded in 70 patients with coronary heart disease. Myocardial dyskinesia correlated with low bypass blood flows, myocardial ischemia and infarction in the area of revascularization at any blood flow values. The evaluation of the diagnostic efficacy of myocardiographic symptoms suggested that myocardiography had some advantages. It was concluded that it was essential to include intraoperative myocardiography into the set of methods for examining patients with coronary heart disease during myocardial revascularizations.


[Role of coronary collateral circulation in the compensation of disorders of myocardial perfusion and left ventricular function in patients with newly appearing angina pectoris]. The myocardial perfusion and left ventricular function were evaluated by bicycle ergometry and myocardial scintigraphy in 23 patients with primary angina taking into account the status of coronary collateral circulation in response to stenotic and occlusive atherosclerosis. In addition to severe occlusive disease of the coronary bed, most patients had significant disturbances of myocardial perfusion and left ventricular function, which were detected during exercise tests. In patients with compensatory collateral circulation in the coronary bed, such disturbances were less marked than in those without anastomoses. However collateral coronary circulation cannot be regarded to be of real value as it compensates impaired perfusion incompletely, but in some cases it can result in impaired myocardial vascularization apparently due to the steal syndrome.


Effect of K depletion on renal K and Rb excretion: evidence for activation of K reabsorption. Prolonged potassium depletion activates tubular transport mechanisms mediating potassium absorption. To study ion specificity and factors that modulate the activity of potassium transport pathways, fractional potassium excretion (FEK) was compared with that of rubidium (FERb) in control and potassium-depleted rats subjected to various experimental maneuvers. In control rats FEK considerably surpassed FERb (FEK/FERb 1.54 +/- 0.08; mean +/- SEM), whereas in potassium-depleted rats FEK was significantly lower than FERb (FEK/FERb 0.72 +/- 0.05). Preferential retention of potassium compared to rubidium in potassium-depleted rats was accentuated (FEK/FERb 0.33 +/- 0.01) when residual potassium secretion was inhibited by amiloride and K-H exchange stimulated by increased distal buffer delivery (metabolic alkalosis). When distal fluid and buffer delivery were increased in control animals by acetazolamide, FEK and FERb rose in parallel. In potassium-depleted rats only FERb but not FEK was enhanced by acetazolamide. These data demonstrate that both potassium secretory and potassium absorptive transport pathways prefer potassium to its congener rubidium. Prolonged potassium depletion activates a potassium absorptive mechanism which is stimulated by increased distal buffer delivery and which transports potassium more effectively than rubidium.


Cultured mesangial cells from autoimmune MRL-lpr mice have decreased secreted and surface M-CSF. M-CSF has been implicated in the pathogenesis of lupus nephritis in MRL-lpr mice. We recently reported persistently high levels of serum M-CSF in MRL-lpr mice as early as one week of age, not present in normal mice including C3H mice. In addition, M-CSF transcripts in MRL-lpr renal cortex increased with an increase in the severity of nephritis. Because glomerular mesangial cells (MC) secrete M-CSF, we investigated whether cultured MRL-lpr MC secrete more M-CSF than C3H MC. Paradoxically, unstimulated MRL-lpr MC secreted substantially less M-CSF than C3H MC [26 +/- 11 vs. 109 +/- 7 colony forming units (CFU)]. We then explored whether MC could express membrane bound M-CSF. We detected a 31 kDa form of membrane M-CSF on both MRL-lpr and C3H MC. Fewer MRL-lpr MC than C3H MC (24 +/- 5% vs. 78 +/- 5%) expressed membrane M-CSF. Furthermore, the increase in the mean channel log fluorescence intensity on MRL-lpr MC was considerably less than in C3H MC, indicating a lower density of M-CSF on MRL-lpr MC. Because our prior studies established that MRL-lpr kidneys have enhanced expression of TNF alpha, we stimulated cultured MC with TNF alpha. TNF alpha increased M-CSF secretion by stimulated MRL-lpr by twofold over unstimulated MRL-lpr MC, but did not increase M-CSF in C3H MC. In addition, M-CSF secretion was modestly greater in stimulated MRL-lpr MC compared to stimulated C3H MC. In conclusion, this is the first report of membrane M-CSF detectable on cultured MC. These studies note that despite higher circulating M-CSF and renal M-CSF transcripts in MRL-lpr mice, cultured MRL-lpr MC have lower basal secreted and membrane bound M-CSF than cultured C3H MC.(ABSTRACT TRUNCATED AT 250 WORDS)


Uninephrectomy enhances urolithiasis in ethylene glycol treated rats. Uninephrectomy (uNX) usually induces compensatory hyperfunction of the remaining kidney in an attempt to preserve the homeostasis of body fluid composition. The present study used uninephrectomized Sprague-Dawley rats on a lithogenic diet (0.5% ethylene glycol, EG) to evaluate the influence on urinary stone formation and calcium oxalate crystal deposition of compensatory excretion of lithogenic substances in the remnant kidney. The results showed that there were no urinary stones or calcium oxalate crystal deposits in the intact or uNX rats fed a normal diet. In the EG feeding groups, the incidence of massive (grade 3) crystal deposits was significantly higher in the uNX rats (87.5%) than that in the intact rats (37.5%; P less than 0.05). The incidence of urinary stone formation was also higher in the uNX rats as compared to that of the intact rats, although the difference did not achieve statistical significance. The serum magnesium, phosphorus and creatinine increased significantly, whereas creatinine clearance (CCr), 24-hour urinary excretions of citrate, sodium, potassium and chloride decreased significantly in the uNX rats fed EG. These data indicate that uninephrectomy increases the vulnerability of the contralateral remnant kidney to urolithiasis and crystal deposition when the lithogenic risk factors are present. Furthermore, once the remnant kidney forms urolithiasis or massive calcium oxalate crystal deposits, the renal function is severely compromised.


NaCl transport by Madin Darby canine kidney cyst epithelial cells. The mechanism of NaCl transport across the epithelium of intact MDCK cysts grown in a collagen gel matrix was investigated. Double-barreled microelectrodes were used to measure basolateral membrane PD (Vbl), transepithelial PD (Vt), and intracellular (Cli) and intralumenal (Clcy) Cl- activities in cysts under different conditions. In a control Ringer's solution (RS), Cli (60 +/- 1 mM) and Clcy (107 +/- 2 mM) exceeded the values corresponding to electrochemical equilibrium across the basolateral membrane and epithelium, respectively. Cli was reduced by superfusing the cysts with a low Cl- RS (Cli, 20 +/- 3 mM), a low Na+ RS (Cli, 40 +/- 4 mM), or by adding amiloride to the control RS (Cli, 46 +/- 1 mM). Cli was unaffected by removal of either K+ or HCO3- from the RS or by adding furosemide or SITS to the control RS. Vbl in the control RS was -50 +/- 2 mV and was affected only by removal from the RS of K+ (Vbl, -31 +/- 3 mV) or HCO3- (Vbl, -29 +/- 4 mV) or by the addition of SITS to the control RS (Vbl, -59 +/- 5 mV). Vt in control RS was -2 +/- 0.2 mV (lumen negative), and was increased by reducing bath Na+ (Vt, -37 +/- 2 mV) but not by reducing bath Cl-. These data indicate that Cl- is secreted in a basolateral to apical direction by the cyst epithelium. Basolateral Cl- transport probably occurs mainly by an electroneutral Cl-/HCO3- exchanger. Transepithelial Na+ transport seems to occur via a paracellular route which appears to be cation selective. These experiments also support the existence, in the basolateral membrane, of a Na+/K+ ATPase, a Na+/H+ exchanger, and possibly a Na+/HCO3-/CO3(2-) transporter.


Hemodialysis related induction of interleukin-6 production by peripheral blood mononuclear cells. Interleukin-6 (IL-6) has a complex spectrum of biological activities, for example, growth and differentiation of B cells and synthesis of acute-phase proteins by the liver. To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with hemodialysis membranes, we have investigated the IL-6 synthesis and release in supernatant of 24-hour cultured peripheral blood mononuclear cells (PBMC) isolated from: (a) 10 hemodialyzed patients, (b) seven patients with advanced chronic renal failure (GFR less than or equal to 10 ml/min), and (c) eight healthy control subjects. In the same groups of subjects we evaluated the relationship between IL-6 synthesis and release and beta-2-microglobulin (beta 2m) production. Before and after dialytic treatment hemodialysis patient blood samples were drawn using the following criteria: (1) after two months of dialysis with cuprophan membranes, (2) after one and two months of dialysis with polymethylmethacrylate (PMMA) membranes, and finally, (3) after one further month of dialysis with cuprophan membranes. IL-6 was determined after 72 hours of incubation of PBMC supernatant serial dilutions with IL-6-dependent hybridoma cell line, 7TD1. Compared to IL-6 synthesis in control subjects (6.0 +/- 5.6 U/3 x 10(6) PBMC/24 hr), hemodialyzed patients, when treated with cuprophan membranes, showed significantly higher value of IL-6 production both before (23 +/- 13 U/3 x 10(6) PBMC/24 hr) and after (26.2 +/- 11.3 U/3 x 10(6) PBMC/24 hr) the dialytic session.(ABSTRACT TRUNCATED AT 250 WORDS)


Extrarenal cytokines modulate the glomerular response to IgA immune complexes. Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.


Renal effect of anti-hypertensive drugs depends on sodium diet in the excision remnant kidney model. Angiotensin converting enzyme inhibitors (ACEI) are believed to protect remnant kidney, but all previous studies used the ligation model which causes severe hypertension, and very few have compared drugs in rats having similar control of blood pressure (BP). We compared rats with uremia obtained by 70% excision of total renal mass, a model which causes mild, late hypertension. Study I compared the effects of enalapril (E), cicletanine (C) and placebo (P) in uremic (U) rats fed a 0.50% (normal-high) Na diet. Study II compared the effects of E, C, P, and guanfacine (G) in U rats fed a diet restricted to 0.25% Na (normal-low). In study I, UP rats developed progressive hypertension (140, 146, 160 and 166 mm Hg at 3, 6, 9 and 12 weeks), proteinuria (240 mg/day at 9 and 12 weeks) which were not affected by E or C. The occurrence of end-stage renal disease (ESRD) led to the sacrifice of all rats after three months. All three groups had similar severe renal lesions (over 25% sclerosed glomeruli in 5 of 10 UP, 9 of 14 UE, 7 of 14 UC rats, with huge cystic tubular dilatations). In study II, rats could be sacrificed later (6 months) and had evidence of less severe renal disease. All the drugs tested prevented hypertension throughout the study (P less than 0.001), with lowest values in UE rats. E and G, but not C, reduced proteinuria. Renal damage was reduced with E and G, but not with C, despite similar BP in C and G rats. Thus, in contrast with what was obtained in the ligation model, ACEI affected neither the BP nor the renal lesions of rats made uremic by renal excision and fed a 0.50% Na diet. Moderate Na restriction improved the consequences of nephron loss and restored the anti-hypertensive effect of drugs. However, these drugs had a different effect on renal preservation: it was dramatic with E, good with G, and undetectable with C.


Synthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease. Evidence suggests an important role for the renin-angiotensin system in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). Therefore, we studied the presence of immunoreactive renin in renal biopsies and measured the concentrations of renin in cyst fluids. Normal kidneys and kidneys with renal artery stenosis were used for comparison. In ADPKD, immunoreactive renin was present in juxtaglomerular apparatus, associated arterioles, and in some cells within the connective tissue surrounding the cysts. Vascular immunoreactive renin was less prominent than in renal artery stenosis. Increased amounts of tubular immunoreactive renin were noted in polycystic kidneys, as compared to normal kidneys and kidneys with renal artery stenosis. Cyst fluids contained renin detected by Western analysis and enzymatic activity; concentrations were greater in gradient cysts than in nongradient cysts. Seventy-four percent of the renin in gradient cysts was active as compared to 23% in nongradient cysts and 15% in plasma. To determine whether cyst epithelial cells are capable of synthesizing renin, these cells were isolated in tissue culture. Enzymatic assay of extracts from these cells revealed the presence of renin-like enzymatic activity (1.3 +/- 0.8 ng AI/mg protein/hr). The synthesis of renin by tubulocystic epithelium was confirmed by [35S]-methionine radiolabeling of cyst-derived cells, followed by immunoprecipitation and SDS-PAGE and by detection of renin mRNA by the polymerase chain reaction. These results indicate that the tubulocystic epithelium has the potential to synthesize renin. Elevated levels of active renin in renal cysts may be linked to the pathogenesis of hypertension in ADPKD. The occurrence of renin in the lining epithelium of cyst walls raises the possibility that abnormal expression of the renin-angiotensin system may, by a paracrine or autocrine mechanism, regulate epithelial hyperplasia in growing renal cysts.


Binding of serum immunoglobulins to collagens in IgA nephropathy and HIV infection. The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I (HIV) infection, and healthy controls to purified native collagen types I to VI, and to an extract of normal kidney tissue. HIV infection is an appropriate disease control because of the lack of mesangial IgA deposits, despite high serum levels of IgA and IgA1-containing immune complexes. Increased levels of IgA-binding to collagen types I and V and the kidney extract were found only in IgAN. Both IgAN and HIV-infected patients had increased IgA-binding to collagen types II, III, and VI. Preabsorption of the sera with gelatin substantially reduced the IgA-binding to collagen types I to IV, but not to types V and VI. This finding suggests that the binding to collagen type V is not fibronectin-mediated, but may reflect autoantibody formation. Thus, fibronectin-mediated IgA-collagen interactions are not specific for IgAN, and their pathogenetic role is questionable. The role of IgA anti-collagen type V antibodies requires further study.