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Biomedical subjects

S Mallov

Publications and source records attributed to S Mallov.

18 recordsLinked to original sources
PubMed1984

Effect of cardiotoxic concentrations of catecholamines on Na+-Ca2+ exchange in cardiac sarcolemmal vesicles.

The mechanism by which the administration of large doses of catecholamines produces myocardial necrosis in experimental animals and humans has not yet been ascertained. One of the consequences of such administration is the accumulation of high concentrations of Ca in the heart and it has therefore been suggested that this is the factor that leads to cell injury. The elevated intracellular Ca appears to be due in part to enhanced Ca influx resulting from catecholamine-induced opening of membrane Ca channels and in part to increased membrane permeability caused by membrane damage. It is not clear, however, why the myocardial cells are unable to extrude their extra load of Ca, at least initially, so as to maintain normal Ca concentrations. The effects of high concentrations of epinephrine and isoproterenol on Na+-Ca2+ exchange transport in isolated sarcolemmal vesicles prepared from hearts of Sprague-Dawley rats were determined. It was found that catecholamine concentrations of 10(-4) to 10(-2) M inhibited the exchange in a dose-related manner while choline, in the same concentrations, had no effect. It is therefore possible that cardiotoxic concentrations of catecholamines also interfere with Na+-Ca2+ exchange transport across the myocardial sarcolemma in vivo and thereby inhibit the efflux of intracellular Ca.

Animals↗
PubMed1983

Role of calcium and free fatty acids in epinephrine-induced myocardial necrosis.

A possible mechanism by which large doses of catecholamines produce myocardial necrosis was investigated. Male Sprague-Dawley rats, 275 to 325 g in weight, were injected once, sc, with 3 mg/kg epinephrine (E) or infused iv for 1 hr with E at a rate of 1.2 or 1.7 micrograms/min, and also injected iv with either 45Ca or [3H]palmitic acid (3H-PA) at the same time as or at various periods of time after E administration but exactly 0.5 or 1 hr before death. Controls were injected with saline solution. Heart/plasma ratios of radioactivity (H/P) were determined. The ratios increased in the case of both 45Ca and [3H]PA within 0.5 hr after E, reached peak values after 18 to 24 hr with 45Ca and 3 to 6 hr with [3H]PA, and remained above values for the controls for at least 72 hr with 45Ca and 48 hr with [3H]PA. The rate of 45Ca influx into heart 20 hr after E administration paralleled the severity of the myocardial damage that had been produced. When 45Ca and E were injected simultaneously, H/P increased progressively with time to 30 times control values, indicating the accumulation and retention of Ca in the heart. Under the same conditions, H/P values with [3H]PA also rose but remained constant at a level two to three times that in controls. Total cardiac free fatty acids (FFA) rose slightly and remained constant at the elevated level. It was not possible to distinguish a given point in time at which the increase in either Ca or FFA influx, initially due to the normal pharmacological effect of E, began to occur as a consequence of damage produced by the latter. It is concluded that high concentrations of catecholamines promote the deposition of Ca and FFA in myocardial cells in various forms, and that the deposition of these substances as soaps in the plasma membranes may cause permeability changes that lead to cell injury.

Animals↗
PubMed1983

Effect of amrinone on sodium-calcium exchange in cardiac sarcolemmal vesicles.

The mechanism of action of amrinone, a synthetic cardiotonic drug, is unknown. It has been postulated that it increases cardiac contractility by increasing intracellular free Ca++ concentration, in some manner. Purified cardiac sarcolemmal vesicles have been shown capable of carrying out Ca++ transport in either direction by Na+/Ca++ exchange. We have observed that amrinone inhibits Ca++ uptake by Na+/Ca++ exchange in such vesicles prepared from both guinea pig and rat hearts. The inhibitory effect is dose-dependent and maximal at a concentration of about 300 micrograms/ml. If amrinone decreases the rate of Ca++ efflux from myocardial cells in vivo during diastole by this mechanism, this action may account, at least in part, for the observed positive inotropic effect of the drug.

Aminopyridines↗
PubMed1977

Quantitative determination of stress-induced myocardial damage in rats.

The degree of myocardial damage produced in rats by exposing them to unsignalled, irregular foot-shock stress was determined in three ways: by measuring (1) enzymes (LDH, GOT and GPT) released into the circulation, (2) the rate of release of one of these enzymes (LDH) from isolated perfused hearts into the perfusate, and (3) the cardiac uptake, in vivo, of the radioactively labeled bone-seeking agents, technetium-99m-stannous pyrophosphate or technetium-99m-methylene diphosphonate. The latter two methods permitted quantitative determination of the degree of myocardial damage produced. Determination of cardiac technetium-99m uptake was found to be simple, quantitative, highly sensitive and truly indicative of cardiac damage, and therefore most suitable for studies of the effects of stress on cardiac injury.

Animals↗
PubMed1977

Drug interactions.

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Analgesics, Opioid↗
PubMed1977

Myocardial uptake of Tc-99m skeletal agents in the rat after experimental induction of microscopic foci of injury.

The cardiac uptake of Tc-99m tagged skeletal agents was studied after myocardial injury produced by subcutaneous catecholamine injection and random foot-shock stress. Rats stressed for 2 hr developed microfocal myocardial injury, without gross change, whereas those stressed for 12 hr sustained more confluent and sometimes grossly visible damage. Tc-99m MDP and Tc-99m PPi concentrations in these hearts were significantly above control (undamaged) heart levels, producing positive gamma-camera images. Subcutaneous epinephrine injections resulted in grossly visible lesions, with tracer concentrations higher than those previously reported in vasoocclusive infarcts. We postulate that the stress-induced scattered microfocal lesions may accumulate radiopharmaceutical on a per-gram basis in the same way as the larger catecholamine-induced lesions, since tracer delivery to the injured areas in each case is probably less impeded than in frankly vasoocclusive models. Such microfoci, then, could provide an explanation for some of the "false positive" myocardial scans observed clinically.

Animals↗
PubMed1977

Protective effect of ethanol against epinephrine-induced myocardial necrosis in rats.

Myocardial necrosis was produced in rats by the subcutaneous injection of a single dose of epinephrine (3 mg base/kg). The severity of the cardiac injury produced was assessed by visual inspection, determination of the release of LDH, CPK, GOT, and HBDH from isolated perfused hearts, and measurement of cardiac uptake of technetium-99m-methylene diphosphonate in vivo. Ethanol, given in doses of 0.5 to 6.0 gm/kg 15 minutes or two hours prior to epinephrine administration protected the hearts against the epinephrine-produced injury, the degree of protection increasing with dose. Investigations of possible mechanisms of action of ethanol indicated that the protective action of the latter does not appear to be due to a lowering of plasma free fatty acid levels, a reduction of cardiac contractility, a non-specific caloric effect, an interference with epinephrine-induced platelet aggregation, or ethanol-induced analgesia.

Animals↗
PubMedDate not supplied

Inhibition of epinephrine-induced myocardial necrosis in rats by administration of single doses of ethanol.

The oral administration of single doses (0.5-6.0 g/kg) of ethanol to rats, shortly before injecting them with a large dose (3.0 mg base/kg) of epinephrine subcutaneously, significantly reduced the severity of the myocardial damage produced by the epinephrine. The larger the dose of ethanol, the greater was the protective effect. The results were the same, regardless of the method used to determine the degree of cardiac injury. Experiments employing various agents to determine the mechanisms of ethanol action have tentatively suggested that a platelet de-aggregating or an osmotic effect of alcohol may be involved.

Animals↗