Activity of glucose-6-phosphate-dehydrogenase enzyme studies in calves with long--survivals with total artificial heart.

The research aimed at studying metabolic changes of erythrocytes in the calves surviving for a long period with total artificial heart of BRNO VII type. The authors studied partly the count of erythrocytes, the plasma levels of free hemoglobin and activity of glucose-6-phosphate-dehydrogenase enzyme. The changes found were compared with the levels measured in a group of 10 healthy calves. Constant decrease of erythrocyte count, slightly increased concentration of free hemoglobin in plasma and repeatedly decreased activity of the enzyme studied were found in the group of 4 experimental calves, from the 5th to 17th weeks of surviving. These changes can be explained by a long-term action of mechanical stress on the erythrocytes that pass through the pump of the total artificial heart. The cells damaged mechanically have the decreased energetic metabolism and, consequently, shortened viability. As young healthy animals with normal erythropoiesis which is stimulated by the application of drugs during the experiment are used, compensated anaemia develops, but it is not a limiting factor for the surviving of the calves with total artificial heart.

Mineralization of polyurethane membranes in the total artificial heart (TAH): a retrospective study from long-term animal experiments.

The degree of mineralization of TAH membranes in animals is directly related to the survival time of animals with a TAH. Large differences in mineralization of the membranes among individual animals have been observed. These differences can be explained by the simultaneous presence of infection on biomaterials (polyurethane) as well as by different levels of natural inhibitors of mineralization. No positive influence of applying sodium warfarin for the inhibition of the mineralization was observed.

Recent efforts in artificial heart research in Czechoslovakia.

The authors present basic information about the technical development of the total artificial heart (TAH) and TAH drivers. Long-term experiments, in which the TAH TNS-Brno-II and VII and the Rostock hearts were implanted, are described. Long-term experiments were dedicated to analysis of specific pathophysiologic problems (venous hypertension, thrombogenesis, and calcification) in order to increase survival rates. Thrombogenesis has been partially solved in the TNS-BRNO-VII device by optimal TAH construction using an asymmetric driving diaphragm, the undulating motion of which produced excellent results. Two methods for prevention of increase in central venous pressure (CVP) are verified: administration of antihypertensive drugs and atrial electrical stimulation. Of 155 calves studied, 50 long-term experiments in calves and one in a goat were done. The survival of these animals extended from 31 to 293 days of pumping (average survival, 116.9 days). To prevent driving diaphragm calcification, we have incorporated exogenic inhibitors of calcification into the diaphragm biomaterial (polyurethane). A unique long-term experiment with intrathoracic TAH implantation in the goat is also described. In addition clinical use of the TAH as a bridge to transplantation is discussed. Parallel research with the left ventricular assist device (LVAD) system was studied experimentally, and twice used in patients. The TAH TNS-BRNO-VII/80/clin/ was used in four patients. It worked faultlessly for 22 hours to 10 days. More precise and specific indications for TAH implantation when used as a bridge to transplantation are needed.

[Therapy of venous hypertension in animals with an artificial heart and long-term survival]. / K terapii zilní hypertenze u zvírat dlouhodobe prezívajících s totální náhradou srdce.

1. The authors elaborated an original concept for the interpretation of vasomotor disorders in subjects with an artificial heart. 2. This concept is based on the regeneration of nervous elements in the walls of the atria (in particular the right one) after implantation of the artificial heart and on comparison of their activity with the venous pressure which revealed the interrelationship of the two phenomena. 3. Both therapeutic methods based on this concept, the method of influencing the afferentation and efferentation of vasomotor nervous regulations leading to a reduction of the central venous pressure proved valid and effective. 4. Evaluation of the effectiveness of this therapy is based on regular assessment of the central venous pressure, on the laboratory assay of enzymes (AST, ALT, GMT and LDH), on the assessment of serum albumin and finally on the morphological and histological examination of the liver incl. assessment of the hepatic index. 5. The nervous pathogenesis is closely linked with hormonal factors. The latter are conceived as the participation of associated factors in the pathogenesis of venous hypertension in recipients with an artificial heart.

Therapy of venous hypertension in calves with total artificial heart (TAH).

Vasomotor disregulation, preponderantly expressed by a pathological increase of central venous pressure (CVP) in calves with total artificial heart (TAH), starts to be evident from about the 50th day of pumping. The main cause of this state is an imbalance in cardiac receptor areas. Ventricular vasodepressor mechanisms are eliminated with the ventricular tissue, which is replaced by the artificial blood pump. In the stumps of both atria, which remain in situ, all neural elements disappear immediately after TAH implantation, but within two months they are fully regenerated. Regenerated atrial receptors are the starting points of afferent neural stimuli, which in the vasomotor center of the brainstem, increase the activity of the vasoconstricting functional component. A general tendency to vasoconstriction, now not well counterbalanced, increases, and the progressive venous hypertension causes loss of liver function and morphology. Two therapeutic approaches were tried: afferent therapy by atrial electrical stimulation, and efferent therapy by the administration of antihypertensives. Both kinds of this therapy were sufficiently effective in reducing CVP, protecting the liver, and prolonging average survival.

Serum aldosterone studies in 10 calves living for 2-5 months with a total artificial heart (TAH).

A group of 10 experimental calves that lived for 61-147 days with a TAH was used to study serum aldosterone levels by RIA with ALDOCTK-125 CEA Kit (Sorin Biomedica, Italy). The aldosterone levels were plotted against the serum sodium and potassium, body weight, CVP, urinary sodium and potassium and with hematocrit levels. In these experiments, three types of TAH (TNS-BRNO II, VII, and Rostock) were used. The levels of aldosterone were already high before the surgery and during the entire pumping period, which indicates the development of secondary aldosteronism. The study deals with the mechanisms that participate in the development of aldosteronism in each phase of the experiment with the TAH.

Haemocompatibility of segmented polyurethanes investigated in vivo.

Samples of segmented polyurethanes differing in composition and in surface morphology were introduced into the left ventricles of hearts of goats for 72 h. After removal of the samples, their surface and the surface of the heart endothelium were evaluated visually with respect to the formation of thrombi. Differences in the interaction of the individual polyurethanes with blood were examined by XPS photoelectron spectroscopy, SEM, and by infrared (i.r.) reflexion spectroscopy. The results suggest ways for improving the haemocompatibility of the surfaces of polyurethanes used as parts of the total artificial heart.

Hematological and biochemical studies in calves living over 100 days with the polymethylmethacrylate total artificial heart TNS Brno II.

A polymethylmethacrylate total artificial heart (kinetic components made of polyetherurethane) of TNS Brno II type was implanted into seven calves (2-5 months of age) surviving for the average of 152.4 +/- 19.1 days after the implantation. During the entire post-operative period the animals received oral warfarin-sodium, acetylsalicylic acid, dipyridamole and alpha-tocopherol. Blood was taken for biochemical and hematological examinations twice a week from the jugular vein. During the experiments there were decreases in the number of red blood cells, hematocrit and hemoglobin levels. Plasma free hemoglobin and serum enzymes (alkaline phosphatase, AST, ALT, LDH) increased. Coagulation tests were abnormal because anticoagulation therapy was used. There were minimal changes in the number of white blood cells and platelets, fibrinogen, blood pH, blood glucose, serum electrolytes, bilirubin (total and direct), creatinine, blood urea, and lactate. Possible reasons for observed changes include the gradual rise in the central venous pressure and damaged function of the liver parenchyma. Other factors playing a possible role in inducing changes in laboratory findings are also discussed.

Some problems associated with the implantation of a cardiac prosthesis and with early postoperative care in animals with a total artificial heart.

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.

Reperfusion of coronary arteries after temporary occlusion in dogs.

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.

Mechanical combined heart supporting system for prevention of irreversible ventricular fibrillation after experimental cardiogenic shock.

To determine whether haemodynamic effective support of the failing heart can prevent spontaneous irreversible ventricular fibrillation (IVF) after experimental cardiogenic shock, 63 open chest dogs were assigned randomly into four groups--two control groups (combined heart failure--CHF) and two MCHSS-treated (combined heart failure and non-pulsatile bypass with intraaortic counterpulsation). The CHF was produced by occlusion of the anterior descending coronary artery (group I) or the left circumflex coronary artery (group II) and by an artificial shunt between the pulmonary artery and right atrium. IVF were observed in 10 out of 22 control dogs (group I) and im 17 out of 21 control dogs (group II). In the 20 dogs with the CHF (10 animals in each group) the MCHSS was performed in the course of two hours. During the heart support no IVF were observed in any of the dogs. The difference between the incidence of IVF in the control and treated animals is statistically significant (Chi square = 21.9767 greater than Chi square 0.005).

Suppression of the progress of necrosis after coronary artery ligation in the dog by pharmacologic interventions.

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).