Recent advances in studies on cardiac structure and metabolism最新文献

The binding of [3H]atropine by the primary subcellular fractions and plasma membrane-enriched fractions from atria and ventricles of various species was measured by the Millipore filtration technique. Although all of the primary particulate fractions exhibited binding activities, the bulk of the total homogenate binding activity was associated with the washed particles sedimenting at the lower gravitational forces; this was observed with either atria or ventricles of dog, guinea pig, rabbit, hamster, and rat. Plasma membrane-enriched fractions isolated from the right atrium of guinea pig exhibited atropine binding activities with characteristics similar to dog atrial membranes; binding activity was moderately enriched in these membranes with respect to the starting material.

Properties of the ATP-dependent calcium transport system of heart sarcolemma are presented. Calcium accumulation (with oxalate) in sarcolemma was increased due to cAMP-dependent protein kinase and phosphorylase b kinase. Protein kinase increased the Vmax of the sarcolemmal calcium accumulation without any detectable effect on the affinity for Ca2+. Both kinases failed to stimulate calcium binding. Protein kinase catalyzed phosphorylation of membrane proteins of molecular weights of 100,000, 25,000, and 14,000. Phosphorylase b kinase also catalyzed phosphorylation of these proteins. Protein kinase stimulated ATPase activity of sarcolemma. Sarcolemma contained endogenous protein kinase and protein phosphatase activities.

Reperfusion of Ca2+-deprived rat hearts with Ca2+-containing medium results in irreversible cell damage (calcium paradox). In this study this type of cell damage was studied in the anoxic rat heart, in the presence and absence of glucose. Creatine kinase (CK) release was used to define cell damage. Hearts were perfused successively with Ca2+-containing medium (30 min), Ca2+-free medium (5 min), and Ca2+-containing medium (5 min). In the presence of glucose, myocardial ATP was maintained at a fairly high concentration. Reperfusion with Ca2+ resulted in an immediate and massive release of CK. In the absence of glucose, the ATP concentration was almost zero after 30 min. Reperfusion with Ca2+ did not result in release of CK. Massive release occurred as soon as these hearts were reoxygenated. It is concluded that this type of calcium-induced cell damage only occurs in the presence of ATP, or oxygen plus substrate. Mitochondria most likely play a major role in the occurrence of the calcium paradox because of their ability to accumulate huge amounts of Ca2+ under these conditions.

Uncoupling of oxidative phosphorylation was suggested in experiments using the infarcted myocardium, even in dogs with 15-min ligation. The same type of disturbance in mitochondrial respiration was observed in dogs with reperfusion after 45-min ligation, whereas the disturbance was recovered in dogs with reperfusion after 15-min ligation.

In the isolated blood-perfused canine ventricular tissue, antiarrhythmic agents could be classified as having: 1) positive chronotropic and inotropic effects (procainamide), 2) negative chronotropic but positive inotropic effects (quinidine), and 3) negative chronotropic and inotropic effects (lidocaine, ajmaline, diphenylhydantoin, and propranolol).

Action potential durations in premature excitations showed paradoxical prolongation at the shorter coupling intervals; this was abolished by manganous ions. Voltage-clamp experiments also disclosed a transient increase of slow inward current in premature excitations. These results indicate that prolongation of action potential durations was mainly brought about by changes in slow inward current, especially in its characteristics of recovery from inactivation.

The effect of physical training (conditioning) on myocardial circulation and myocardial damage has been evaluated in experimental myocardial necrosis in albino rats. Conditioning was done by making the animals swim in a tank of water, thermostatically controlled at 32 degrees +/- 1 degrees C, 60 minutes daily, six days a week, for eight weeks. Myocardial necrosis was produced by subcutaneous injection of isoproterenol, 85 mg/kg body weight, on two consecutive days. Investigations included ECG (lead II), SGOT, SGPT, SLDH, SCPK, histopathology of the heart, and myocardial Rubidium 84 uptake. It was observed that, in conditioned animals, elevation of serum enzymes was less, incidence of cardiac arrhythmia was lower, myocardial damage was less marked, and myocardial circulation was better after myocardial necrosis in comparison to unconditioned animals. Less myocardial damage and lower incidence of cardiac of cardiac arrhythmia are presumably associated with a better prognosis.

Based on the assumption that circulating acetaldehyde (AcH) is cardiotoxic, D-penicillamine was administered to dogs given alcohol orally, or given AcH intravenously. Paralleling the increase in plamsa norepinephrine (NE) and epinephrine (E) induced by AcH infusion, hemodynamic measurements showed a positive inotropic response with increase in pulse, blood pressure, left ventricular contractility, and cardiac output. Infusion of D-penicillamine abruptly lowered circulating levels of AcH and catecholamines, which was accompanied by an appropriate hemodynamic response.

Tension fall of frog heart contraction was analyzed under voltage-clamp conditions. It appears mostly exponential. The rate of relaxation depends upon the extracellular and intracellular Na concentrations. This suggests that the relaxation is under the control of Na-Ca exchange. The speeding up of relaxation by adrenaline in frog heart is revealed by low Na solution, while it is hidden by the primordial Na-Ca exchange in Ringer's solution.