Advances in myocardiology最新文献

In the ischemic heart, high-energy phosphates are rapidly broken down. We studied the release of AMP catabolites from the isolated perfused rat heart which was temporarily made ischemic or anoxic. We measured the concentration of purine nucleosides and oxypurines with a novel high-pressure liquid chromatographic technique. The postischemic working heart released adenosine, inosine, hypoxanthine, and also substantial amounts of xanthine. The latter could indicate that xanthine oxidase is present in rat heart. Further evidence for the myocardial occurrence of this enzyme was obtained from experiments with hearts perfused retrogradely with allopurinol, an inhibitor of xanthine oxidase. This drug greatly enhanced the release of hypoxanthine, both during normoxic and anoxic perfusions. We conclude that xanthine oxidase could play an essential role in the myocardial breakdown of AMP catabolites.

The degradation of cardiac proteins is known to be altered by many physiological and pathological interventions, but the precise intracellular processes that regulate proteolysis and the relative roles of different proteolytic pathways in degrading different classes of protein remain poorly understood. Agents that interfere with lysosomal function produce major decreases in total protein breakdown; thus, lysosomes and lysosomal proteinases seem to be important in proteolysis. However, these same agents cause no change in the degradation of myofibrillar proteins, suggesting that this class of proteins is not dependent on lysosomal pathways for its turnover.

The effect of exogenous glutamic acid and arginine on the contractility of isolated perfused rat heart and on the metabolism of some nitrogenous compounds was studied. Sixty-minute anoxic perfusion (95% N2 + 5% CO2) led to a fall in developed isovolumic pressure and an elevation in diastolic pressure, to an increase in the production of alanine, glutamine, and ammonia, and to a decrease in the tissue content of aspartate and glutamate. The total pool of free amino acids and taurine under these conditions remained unchanged. Subsequent 40-min reoxygenation partially restored the contractile function. Addition of 3.5 mM glutamic acid or 5 mM arginine into the perfusate before anoxia resulted in a higher level of developed pressure and a lower level of diastolic pressure during anoxia and almost complete recovery of cardiac function after subsequent reoxygenation. Both amino acids had no effect on ammonia formation by the anoxic heart but enhanced its binding in myocardial tissue via formation of glutamine and urea. It is suggested that the exogenous amino acid effect on anoxic heart is mediated by activation of substrate phosphorylation rather than the ability to bind tissue ammonia.

It was previously shown that beta-adrenergic blockers exert a protective action on the development of heart necrotic changes in cardiomyopathic hamsters. To further investigate the possible role of catecholamines in the pathogenesis of the hamster hereditary cardiomyopathy, the ventricular adrenergic nerve terminals were visualized by fluorescence histochemistry, and NE uptake and turnover were determined after i.v. injection of labeled NE. It was found that the fluorescent nerve endings strongly proliferate with the occurrence of heart necrotic changes. With healing of the myocardial lesions, the difference between control and myopathic hearts is less apparent, and NE nerve endings are literally absent in the terminal stage of the disease. There was a marked increase in NE uptake during the necrotic stage and, at the same time, a considerable rise in elimination rate constant with a maximum level at terminal state, suggesting that the NE turnover is related to the progression of the disease. In light of the present findings, it can be surmised that NE plays a permissive role in the genesis of the hamster disease by promoting the heart necrotic changes.

The relationships among isometric tension development, the oxidation-reduction states of pyridine nucleotides and cytochrome c, and the oxygenation state of myoglobin have been assessed using the arterially perfused rabbit interventricular septum under different conditions of contraction rate, perfusate [Ca2+] and pH, catecholamine stress, and hypoxia. Hypoxia was produced either by decreasing oxygen availability with maintained flow (high-flow hypoxia) or by decreasing the flow rate (ischemia). Under normoxic conditions, increased work caused a fall of the cytosolic adenine nucleotide phosphorylation potential, delta G(ATP)c, an oxidation of the pyridine nucleotides, and a reduction of cytochrome c; the opposite occurred with decreased work. Thus, the redox potential span from NADH to cytochrome c, delta Eh, varied with the energy demand such that delta Eh and delta G(ATP)c changed in the same direction. Under hypoxic conditions, all respiratory components became more reduced, and myoglobin was partially deoxygenated. The percentage change of developed tension under hypoxic conditions was approximately proportional to the percentage change of oxidized cytochrome c. When high-flow hypoxia and ischemia were compared at the same rates of oxygen delivery, the developed tension at any level of cytochrome c reduction was always lower with ischemia than with high-flow hypoxia. This difference was attributed to the low intracellular pH of ischemic tissue. Myoglobin deoxygenation was linearly related to cytochrome c reduction under all conditions of hypoxia, indicating steep oxygen gradients. The results support the concept of heterogeneous oxygenation of the tissue with mixed populations of aerobic and anaerobic mitochondria in the hypoxic state. In the full aerobic state, the control of mitochondrial respiration in situ appears similar to that of isolated mitochondria.