Advances in myocardiology最新文献

Previously, we reported that amrinone increases isometric twitch force but relaxes K+-induced contracture in muscles from normal cat right ventricle. This study evaluated its effects on diseased cardiac tissue. Right-ventricular papillary muscles were obtained from cats with subacute right-ventricular failure (3-14 days after partial pulmonary-artery ligation) and studied in vitro during stimulation (0.5 Hz) and exposure to high-K+ Tyrode solution. Active isometric twitch force and rate of force development (dP/dt) were significantly lower in muscles from hearts with right-ventricular failure compared to control muscles. In addition, while time to peak force was not different, duration of the twitch was significantly longer. In contrast to its positive inotropic actions in control muscles, amrinone (5.3 X 10(-4) M) had no significant effects on twitch force and dP/dt in muscles from failed ventricles. Time to peak force was not changed by amrinone in either group, but unlike its action in control muscle, duration of the twitch was reduced in failed muscle. Amrinone reduced K+-contracture force similarly in both control and failed muscles. Isoproterenol (10(-6) M) significantly increased twitch force and dP/dt and reduced K+-contracture force in both muscle groups. Since amrinone appears to be a phosphodiesterase inhibitor, our data indicate that cyclic AMP (cAMP)-related relaxation processes, but not cAMP-related contractile processes, can be enhanced by phosphodiesterase inhibitors in experimental heart failure. Furthermore, amrinone's reduced positive inotropic effect in failed myocardium suggests that its improvement of ventricular function in patients reflects, in part, enhancement of relaxation.

The paraformaldehyde-fixed hearts of adult rats were embedded in paraffin. Serial sections throughout the interatrial septum and the atrioventricular junction were examined in the optical microscope after having been silver stained. The density and the distribution of different nervous elements in the perinodal nerve plexus were studied and the results compared with the electron-microscopic data. These data confirm that at the level of the atrioventricular junction, a dense terminal network can be seen. It is composed of both terminal nerve fibers and ganglionic cells forming a small ganglion adjacent to the lower edge of the bundle of His and a thin ganglionic lamina in the interatrial septum. Apart from small neurons, previously described as cholinergic, large neurosecretory cells could also be demonstrated in some of the serial thin sections through the Hissian ganglion. The neuromuscular junctions between the terminal nerve fibers and specialized cells exhibit regional specialization. While the distal portion of the atrioventricular node and the bundle of His receive essentially efferent fibers, afferent coiled endings prevail in the reticular portion of the atrioventricular node and in the adjacent interatrial septum. Similar structures, larger in diameter, can also be seen around the muscular fibers and around the capillaries of the interventricular septum. The functional significance of the aforedescribed regional specialization of the terminal innervation of the atrioventricular junction is briefly discussed.

Conversion of phosphatidylethanolamine to phosphatidylcholine through sequential transmethylation reactions was studied in rat cardiac sarcolemmal membrane prepared by the hypotonic shock-LiBr treatment method. Three catalytic sites were identified on the basis of their requirement for divalent cations and kinetic parameters. Site I (Km = 0.1 +/- 0.01 microM) required Mg2+ as a cofactor and had a very high affinity for [3H]-S-adenosyl-L-methionine (AdoMet). Sites II (Km = 2.9 +/- 0.3 microM) and III (Km = 112 +/- 6 microM) did not require any divalent cation and showed comparatively lower affinities for AdoMet. Developmental-related differences were found to exist among these three catalytic sites when phospholipid methylation was carried out in 1- to 12-week-old rats. The results suggest that three distinct methyltransferase sites are involved in cardiac sarcolemmal phospholipid methylation.

When oxidative metabolism is inhibited in heart muscle, developed tension often increases slightly before decreasing below control. We have examined the possible mechanisms underlying these changes in developed tension in two series of experiments. In the first series of experiments, the photoprotein aequorin was used to monitor intracellular free [Ca2+] [( Ca2+]i) in papillary muscles during inhibition of oxidative phosphorylation, using either cyanide or hypoxia. The observed changes of developed tension were independent of changes in [Ca2+]i. It was therefore possible that these changes of tension were due to changes of intracellular pH (pHi). We tested this idea in a second series of experiments, using 31P nuclear magnetic resonance to monitor pHi, [ATP], and phosphocreatine concentration [( PCr]) in Langendorff-perfused ferret hearts. During the application of cyanide, pHi increased transiently before decreasing to below control. [PCr] decreased throughout this period, but [ATP] did not change. It is concluded that the observed changes of pHi could account for most of the observed changes of developed tension. It is suggested that the initial increase of pHi is due to PCr breakdown and the subsequent decrease of pHi to accelerated anaerobic glycolysis.

Isolated muscle cells from adult rat heart have been used to study the relationship between myocardial glucose transport and the activity of the Na+, K+ pump. 86Rb+ uptake by cardiac cells was found to be linear up to 2 min, with a steady state reached by 40-60 min, and was used to monitor the activity of the sodium pump. Both the ouabain-sensitive and ouabain-insensitive 86Rb+ uptake by cardiac cells were found to be unaffected by insulin treatment under conditions in which a significant stimulation of 3-O-methylglucose transport occurred. 86Rb+ uptake was markedly reduced by the presence of calcium or magnesium or both, but remained unresponsive toward insulin treatment. Inhibition of the sodium-pump activity by ouabain and a concomitant shift in the intracellular Na+/K+ ratio did not affect basal or insulin-stimulated rates of 3-O-methylglucose transport in cardiac myocytes. The data argue against a functional relationship between the myocardial Na+, K+ pump and the glucose-transport system.

With the use of tetrazolium staining and risk-zone analysis, flurbiprofen has previously been shown to limit infarct size at 6 hr but not at 24 hr following coronary embolization in the dog heart. This study was designed to assess whether this delay in the development of a histologically defined infarct was real or an artifact arising from the effect of the drug on tetrazolium staining characteristics. With the use of a closed-chest bead-embolization model with a capability for reperfusion, hearts were made ischemic for 4 hr by injecting a 2.5 mm bead attached to a silk thread through a special cannula into the coronary vasculature. Immediately following occlusion, radioactive microspheres (141Ce) were administered to define the zone at risk of infarction. Hearts were divided into treatment (flurbiprofen, 1 mg/kg every 6 hr, N = 7) and control (saline, N = 7) groups. Following 4 hr of ischemia, the ischemic area was reperfused by withdrawing the thread and attached bead. Twenty hours later, the hearts were removed and transverse sections (3 mm) were prepared. The area of necrosis was visualized by tetrazolium staining and the risk zone by microsphere autoradiography. In control hearts, 24.7 +/- 5.0% of the zone at risk deteriorated to necrotic tissue; in the flurbiprofen-treated hearts, 17.4 +/- 4.3% of the risk zone became necrotic (NS, p greater than 0.10). Thus, despite earlier findings, these results suggest that the apparent delay in the development of tissue injury may be artifactual.

The mechanisms and regulatory factors involved in cardiac proteolysis are incompletely understood. Agents that interfere with lysosomal function (e.g., chloroquine, leupeptin, methyladenine) cause a 25-30% reduction in the overall rate of protein degradation. In the same hearts, however, the rate of myosin breakdown remains unchanged. Disaggregation of micro-tubules with colchicine is accompanied by a 15% reduction in the rate of degradation of total protein and of myosin. In the same hearts, the degradation of "organellar" protein, including mitochondrial cytochromes, is reduced by over 30%. Thus, it appears that the degradation of different classes of cardiac proteins may be accomplished and regulated by different processes. Lysosomes are important in overall proteolysis, but appear not to be involved in the regulation of myosin breakdown. Microtubules are also involved in the proteolytic process, and appear to be especially important for the breakdown of proteins from mitochondria and perhaps other organelles.