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Morphometry of cardiomyocytes and capillary domains in the left ventricle myocardium was performed in control rats and in rats treated with nitro-L-arginine methyl ester 50 mg/kg/day p.o. for a period of 8 weeks. The myocardial hypertrophy accompanying the NO-deficient hypertension induced by chronic inhibition of NO synthase is characterized by an increase in thickness of myocardial fibres and by relative rarefaction of the capillary bed, e.g. an alteration in myocardial structure which is typical for pressure overload hypertrophy.

Inhibition of experimental metastases of lymphosarcoma LS/BL cells by diltiazem, a calcium blocking agent, was tested. Diltiazem treatment (2 X 30 mg/kg p.o. for 12 days) resulted in a maximum of 72.8% inhibition of liver metastases. The authors suggest that diltiazem might become suitable candidate for antimetastatic treatment in humans.

The influence of previous pharmacotherapy or intra-aortic balloon counterpulsation (with thiamine infusion) on the effectiveness of reperfusion of the left anterior descending (LAD) coronary artery after 150 minutes of occlusion has been studied in dogs. The infarct size was determined by morphometric method 20 hours after the onset of ischaemia. Reperfusion 150 minutes after the occlusion of the LAD coronary artery resulted in a smaller infarct; however, no protective effect from pharmacological or mechanical heart support during the period of ischaemia was observed.

A study was carried out of a therapy supporting the anaerobic glycolysis and coronary perfusion of ischemic myocardium and preserving its potassium and magnesium contents, which consisted in combined administration of hyaluronidase, glucose, insulin, Tris, methoxamine, and potassium and magnesium aspartate. The drugs were administered to Beagle dogs between 30 minutes and 20 hours after the ligation of the left anterior descending coronary artery. The size of infarction was determined by the Nachlas method, which is based on the detection of activities of dehydrogenases in heart slices. Treated animals showed a reduced infarction size (p less than 0.001). The evidence of the favourable effect of the therapy used was brought also by hemodynamic measurements. The heart rate was slower (p less than 0.02) and the mean arterial blood pressure was higher (p less than 0.001) in treated animals than in control ones (as evaluated at the end of the experimental period). Significant correlation between the infarction size and the heart rate on the one hand and the mean arterial pressure on the other hand was found (r = 0.59, p less than 0.01; r=--0.47, p less than 0.05, respectively).

The remnant stumps of the atria in six calves surviving with the artificial TNS-Brno II methacrylate heart for up to 5 months were examined by means of the Bodian silver-impregnating technique and by the formalin-induced fluorescence technique visualizing noradrenaline in monoaminergic nerve terminals. The degeneration of the nerve terminal system detected in animals surviving for 2 days and 1 week was followed by regeneration of the vegetative nerve system in four animals surviving for greater than 1 month. Moreover, thick myelinated nerves afferent in character were detected within the atrium of one animal surviving for 5 months.

Causes of the death of four animals from the total of eight were technical failures (diaphragm perforations, disconnection of the quick-connector, and a failure of the supply of electric current which could not be prevented). Causes of the death of the remaining four animals were embolisation in the brain stem, embolisation in the superior mesenteric artery leading to diffuse peritonitis, ruptures of aorta and hemocoagulation disorder causing fatal gastrointestinal bleeding.

Over the last 2 1/2 years, eight calves with implanted total artificial hearts (from experimental group IV) have survived for greater than 1 month. In this group two subgroups were further differentiated, subgroup IVa, including three calves surviving 31, 35, and 75 days, and subgroup IVb, with five calves surviving 104, 142, 150, and 155 days and one calf still surviving greater than 160 days. Mean survival in the fourth group was greater than 106.5 days. The artificial ventricles used were the TNS-BRNO-II made of polymethylmethacrylate (seven calves) and the TNS-BRNO-III, made of segmented polyetherurethane (one calf). The controller and driving units were of our own design. The Chirasist-TN-3 and TN-4 worked without trouble over the total duration of the studies in all calves. Autoregulation of suction was used in three of these calves. All calves survived in good physiological condition; however, some common changes were observed in all of them, such as a gradual central venous pressure increase and liver enlargement. Anticoagulation therapy was used in all calves. Causes of death were technical in three cases and biological in four. Body weight gains were normal in the majority of these calves, with slight individual differences observed. Diaphragm mineralization of various degrees was observed in three cases. In one of them it was directly related to the cause of death. These results are very encouraging for further development of the total artificial heart research in our center.

The progress in the methods and techniques for surgical implantation of the TAH has progressed in parallel with the technology and design of the cardiac prosthesis. During the period from December 1974 to May 1982 the authors performed altogether 75 orthotopic implantations of eight types of TAH in calves. The Soviet TAH type KEDR I-III was implanted in 26 calves, type MODUL to one calf. The American TAH JARVIK 3 was implanted in one calf and Czechoslovak TAH type TNS BRNO I-III in 47 calves. The modification of blood pump and improved system of its control provided for the limitation of the range of surgery and to shorten the time of operation and cardiopulmonary bypass. The methods of preoperative care, anaesthesia, cardiopulmonary bypass and postoperative care in our laboratory were gradually improving in parallel. This was associated with maximum survival time of animals in the course of the research period which gradually increased from 5.5 h in 1974 to 173 days in 1982. The chief experiences acquired from all experiments performed are presented and problems associated with the investigation of the TAH in general are discussed in this paper.