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Biomedical subjects

D Novitzky

Publications and source records attributed to D Novitzky.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate after ischemia and cardiopulmonary bypass. An experimental study in baboons.

Cardiopulmonary bypass is associated with a reduction in plasma free triiodothyronine in patients undergoing cardiac operations. A previous experimental study in pigs demonstrated a marked inotropic effect when triiodothyronine was administered after a period of myocardial ischemia and cardiopulmonary bypass; this was associated with a significant reduction in mortality compared with the mortality in control pigs. To clarify the effect of triiodothyronine on myocardial high energy phosphate stores and lactate, a series of experiments was done in baboons undergoing 3 hours of myocardial ischemia while supported by cardiopulmonary bypass. Seven baboons received no triiodothyronine and six received 6 micrograms of triiodothyronine at the end of the ischemic period. Seventy minutes after cardiopulmonary bypass, the myocardial adenosine triphosphate level was significantly higher (p less than 0.01) in the treated animals. In untreated animals, a steady increase in myocardial lactate occurred after cardiopulmonary bypass; by 120 minutes after ischemia (70 minutes after cardiopulmonary bypass) there was a significant difference in lactate levels between the two groups (p less than 0.01). We postulate that a combination of global ischemia and depletion of triiodothyronine results in reduced mitochondrial function, inhibition of the tricarboxylic acid cycle, and increased anaerobic metabolism and depletion of myocardial phosphates. Triiodothyronine replacement therapy leads to improved mitochondrial function and increased aerobic metabolism, which results in increased synthesis of myocardial phosphates. We suggest that there may be a place for the administration of triiodothyronine in patients undergoing cardiac operations with a prolonged myocardial ischemic period or in whom there is any evidence of low cardiac output after discontinuation of cardiopulmonary bypass.

Adenosine Triphosphate↗
PubMed1988

Heterotopic thyroid tissue in the heart.

Heterotopic thyroid tissue, presumably due to an embryological developmental abnormality, was discovered incidentally within the right atrial wall of an elderly woman who underwent coronary arterial aortic saphenous vein bypass grafting. As far as we are aware, this is only the third patient with thyroid heterotopia of the heart to be documented.

Choristoma↗
PubMed1988

Catecholamine-associated smooth muscle contraction bands in the media of coronary arteries of brain-dead baboons.

In the brain death baboon model, the baboon experiences an autonomic storm with release of catecholamines both from the adrenal glands and from intracardiac sympathetic nerve endings. Since catecholamines may induce coronary arterial spasm, we looked for morphologic evidence of smooth muscle damage in the coronary arteries of 11 baboons that underwent induction of brain death under general anesthesia. Nine (82%) of the 11 animals showed coronary arterial smooth muscle contraction bands, and 9 (82%) of the 11 baboons also showed focal myocardial contraction bands and myocytolytic necrosis. Focal coronary arterial smooth muscle cell necrosis with intracytoplasmic calcium deposits were observed in three (33%) of the nine contraction band-positive cases. This study provides further support for the concept that medial smooth muscle contraction bands may be a morphologic marker of antemortem coronary arterial spasm.

Animals↗
PubMed1987

Heart transplantation at Groote Schuur Hospital, Cape Town. Twenty years' experience.

Human allogeneic heart transplantation was started at Groote Schuur Hospital in Cape Town in 1967. Since then 110 hearts (61 heterotopic and 49 orthotopic) and 12 heart-lung transplantations have been performed in the unit. Ten procedures were retransplantations including 2 third interventions. The patients fall into three groups according to their immunosuppressive therapy: group A (N = 55) from 1967 to 1982 received the so-called 'conventional treatment' (azathioprine, methylprednisolone and antithymocyte globulin (ATG)); group B (N = 15) from 1983 to 1984 received cyclosporin A in high dosage, together with methylprednisolone; and group C (N = 30) received quadruple drug therapy of low-dose cyclosporin A, together with azathioprine, methylprednisolone in lower dosages and antithymocyte globulin (for the first 4-6 days and rescue-ATG for severe rejection). The results have improved significantly over the years. The actuarial survival rate after heart transplantation within the last 12 months is 94%. Several important steps have been inaugurated: in 1973 heterotopic heart transplantation was initiated and in 1984 hormonal therapy of brain-dead organ donors was started. Radionuclide scanning, in combination with endomyocardial biopsies, has proved to be a very sensitive means of monitoring rejection.

Cyclosporins↗
PubMed1987

Improved cardiac function following hormonal therapy in brain dead pigs: relevance to organ donation.

Deterioration of function in brain dead baboons is associated with depletion of both myocardial energy stores and certain circulating hormones, notably thyroxine, cortisol, and insulin. We have therefore investigated the effect of the administration of these three hormones to the brain dead pig; their value has been assessed on both the freshly excised and stored donor heart. Brain death was induced by ligation of the two arteries to the upper part of the body which arise from the aortic arch. Storage of selected hearts was by continuous hypothermic perfusion for 20 to 24 hr. Hearts were biopsied for estimation of adenosine triphosphate, creatine phosphate, lactate, and glycogen, and were subsequently functionally tested. Six groups of pigs were studied. Hearts were tested from control pigs which had not undergone brain death (A1), from brain dead pigs which had received intravenous fluid and inotropic support for 4 hr (B1), and from brain dead pigs which had in addition received 2 hr of hormonal therapy (thyroxine 2 micrograms cortisol 100 mg, and insulin 5-10 IU hourly) (C1). A further 3 groups (A2-C2) underwent management identical to A1-C1, but in addition the hearts were stored for 24 hr. Brain death in pigs was followed by a consumption of myocardial energy stores, despite anaerobic glycolysis; this was associated with reduced myocardial function. The administration of hormones to the brain dead pig led to some replenishment of myocardial energy and glycogen reserves and reduction in lactate, with associated improvement in hemodynamic function. A period of hypothermic perfusion storage appeared to reverse the anaerobic metabolism occurring in the heart in the nonhormonally treated brain dead animal, though not in the hormonally treated animal, and led to replenishment of glycogen reserves in nontreated animals. The observation that both better function and an increase in myocardial energy stores occurred in hormonally treated, stored hearts, even though perfusate lactate dehydrogenase rose to significantly higher levels during hypothermic perfusion storage, and tissue lactate levels remained high, suggests that thyroxine promotes both aerobic and anaerobic metabolism in brain dead animals.

Animals↗
PubMed1987

Prevention of myocardial injury by pretreatment with verapamil hydrochloride prior to experimental brain death: efficacy in a baboon model.

Systemic and pulmonary hemodynamics were studied in two groups of Chacma baboons following the induction of brain death. Group A was a control group of 11 animals who underwent brain death. They showed significant increments of mean systemic arterial, left atrial, and pulmonary arterial pressures; of systemic vascular resistance, heart rate, and pulmonary artery blood flow; and a reduction in aortic blood flow during the induction of brain death. As a result of increased sympathetic nervous system activity, areas of myocardial cell necrosis occurred in 73% of the animals and pulmonary edema in 36%. Group B consisted of five animals that were pretreated with verapamil hydrochloride infused over a period of 30 minutes prior to the induction of brain death (mean dosage, 0.26 mg/kg). Except for a rise in heart rate, no significant changes occurred in systemic or pulmonary hemodynamics, and no myocardial or pulmonary histopathological changes were seen. These findings would indicate that verapamil hydrochloride prevents both the peripheral and central hemodynamic changes that result from increased sympathetic activity associated with the induction of brain death, and thus prevents myocardial structural damage, which may be associated with increased calcium uptake by the myocyte.

Animals↗
PubMed1987

Pathophysiology of pulmonary edema following experimental brain death in the chacma baboon.

Systemic and pulmonary hemodynamics have been studied during the induction of brain death in the chacma baboon. In 11 animals brain death was induced by acute intracranial hypertension. Continuous recording of blood flow through both the pulmonary artery and the aorta was obtained by electromagnetic flow meters placed around these vessels. Mean arterial, central venous, pulmonary arterial, and left atrial pressures were recorded continuously. Systemic and pulmonary vascular resistances were calculated. During the agonal period marked sympathetic activity occurred, with significant increases in circulating catecholamines and systemic vascular resistance. The great increase in systemic resistance resulted in acute left ventricular failure. Mean left atrial or pulmonary capillary wedge pressure rose above the mean pulmonary arterial pressure in 9 animals. As the systemic vascular resistance rose, a significant difference between pulmonary artery and aortic blood flows occurred, leading to blood pooling within the lungs. A mean of 72% of the total blood volume of the animal accumulated within these organs. The increase of left atrial pressure to levels higher than pulmonary artery pressure indicated a state of pulmonary capillary blood flow arrest. This, associated with the blood pooling within the lungs, almost certainly resulted in disruption of the anatomic integrity of the pulmonary capillaries (blast injury); 4 animals developed pulmonary edema, with alveolar septal interstitial hemorrhage.

Animals↗
PubMed1987

Loss of myocardial viability following hypothermic perfusion storage from contaminating trace elements in the perfusate.

Two groups (A and B) of isolated baboon hearts were preserved by continuous hypothermic perfusion storage for 48 hours using perfusates that, according to the manufacturers, differed only in the concentrations of the contaminating trace elements iron, lead, and arsenic. Storage with the perfusate containing the higher concentration of these elements (perfusate B) led to significantly less gain in heart mass, a greater reduction in coronary flow, coronary sinus effluent lactate, and myocardial arteriovenous oxygen difference and a greater increase in coronary sinus effluent lactate dehydrogenase, when compared with perfusate A. Group B hearts totally failed to support the circulation following orthotopic transplantation, whereas group A hearts showed excellent function. Group B hearts had undergone the typical changes of enhanced resting myocardial tension during the storage period (before warm blood reperfusion); we proposed that these changes were brought about by the production of superoxide anions and radicals by the higher relative concentration of iron, or a combination of contaminating trace elements, in perfusate B. To confirm that these perfusates did differ significantly in the concentration of these trace elements, in particular with regard to iron, the superoxide anion activity in both solutions was measured and was found to be significantly higher in perfusate B. The addition of superoxide dismutase to both solutions inhibited superoxide anion activity by more than 80%.

Animals↗
PubMed1987

Hemodynamic and metabolic responses to hormonal therapy in brain-dead potential organ donors.

An evaluation of the beneficial effects of hormonal therapy, consisting of T3 2 micrograms, cortisol 100 mg, and insulin 20 units, administered at hourly intervals intravenously, was assessed in brain-dead patients referred for organ donation. Twenty-six conventionally treated donors (group A) showed a progressive hemodynamic deterioration requiring significant increments of inotropic support in order to maintain cardiovascular stability, necessitating a significant increase in bicarbonate requirements in order to maintain a normal acid-base balance. Of this group, 20% of the donors were considered unsuitable as cardiac donors due to progressive cardiovascular deterioration or sudden ventricular fibrillation. Hormonal therapy was administered to 21 donors (group B) resulting in a significant improvement of cardiovascular status, requiring less inotropic support and significantly less bicarbonate. A significant reduction of serum lactate-pyruvate followed the initiation of the hormonal therapy. In group B, organs from all donors (heart, heart and lungs, and kidneys) were suitable for transplantation, with excellent organ function following implantation of the graft.

Acid-Base Equilibrium↗