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

Evidence is summarized indicating that mitochondrial respiration and citric acid cycle activity in the intact heart are controlled by the cytosolic phosphate potential and mitochondrial NAD oxidation-reduction state. Data are presented showing that the effect of respiratory acidosis is greater than that of metabolic acidosis in inhibiting left ventricular pressure development in the perfused rat heart, because of a greater fall of intracellular pH under the former conditions. Respiratory acidosis is shown to be readily associated with tissue hypoxia as a result of an increased vascular resistance and diminished flow rate through the coronary circulation. In nonischemic respiratory acidosis, the rate of ATP production is well balanced by the rate of ATP utilization, and tissue ATP and creatine-P levels remain approximately normal. Partially ischemic respiratory acidosis was associated with low tissue levels of ATP and creatine-P and high tissue levels of lactate and NADH. Ischemic areas with sharp border zones were visualized during and after an abrupt decrease of perfusion fluid pH by directly photographing NADH fluorescence from the surface of perfused hearts. Reversal of the hypodynamic state with partially ischemic respiratory acidosis could not be achieved by augmenting the coronary flow by means of an external pump. The demonstration of the existence of sharp zones of high pyridine nucleotide fluorescence adjacent to normal zones indicates a great heterogeneity of coronary perfusion and the existence of steep oxygen gradients in the intact heart.

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.

Sixty-two autopsied hearts, with left ventricular hypertrophy (LVH) caused by mitral regurgitation (MR), aortic failure (AR), combined valvular disease (CVD), hypertension (HHD), or ischemia (IHD), and 23 control hearts with normal left ventricles were studied morphologically for analysis of modes of hypertrophy and for ECG-pathology correlation. Basic disorders modify the mode of hypertrophy; that is, elongated AR-type LV makes muscle fiber orientation in the outer layer more vertical, and globular MR-type LV makes it more horizontal than normal. High-voltage QRS correlates with hypertrophy of the outer layer which is often associated with that of the inner layer. ST depression and T changes correspond to relative deterioration of the inner and median layers, respectively.

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.

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.

Normal or elevated levels of ATP and phosphocreatine (PCr) were observed from the subepicardium to the subendocardium of the canine left ventricle after five and 20 minutes of left circumflex artery occlusion followed by 20 minutes of blood reflow. However, after two or four hours of occlusion, followed by reflow, ATP and PCr levels were markedly depressed, and a significant decreasing decreasing subepicardial to subendocardial gradient appeared, suggestive of inhibition of oxidative metabolism during extended periods of ischemia but not during short periods of ischemia.

[3H] Glucosamine-labeled glycopeptides synthesized by hearts from stage 14-16 chick embryos were separated on DE-52 by ion-exchange chromatography and compared to those synthesized in other parts of the embryo at the same stage. Relatively few molecular species were present in all tissues, and they appeared closely homologous. There were no glycopeptides unique to any embryonic region examined, suggesting that tissue specificity may result from quantitative rather than qualitative differences in glycopeptides.