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

(-)-Adrenaline caused concentration-dependent increases in cAMP levels and the rate of beating in eight-day-old heart cell cultures of newborn rats. Half-maximal increases in both parameters (5- and 0.2 -fold, respectively) occurred at about 10(-6)M. Following the addition of 3 X 10(-7) M adrenaline, the cellular cAMP level rose to a max imum in 30 sec. The rise was abolished by 5 X 10(-8) M (-)-propranolol and was greatly magnified by 10(-4) M 1-methyl-3-isobutylxanthine. In the presence of the latter compound, the average rate of accumulation of cAMP in thecultures during the first 10 seconds of exposure to 3 X 10(-7) M adrenaline was 8.78 pmol/mg of protein-sec, which is 230 times more rapid than the basal accumulation rate. These findings may be taken as evidence in support of the view that cAMP is involved in the positive chronotropic action of adrenaline on cardiac pacemaker cells.

Protein kinase that phosphorylated histone and lesser amounts of protamine was demonstrated in human heart. It was activated three times by 10(-6) M cyclic adenosine 3':5'-monophosphate (cAMP) and by 10(-3) M other cyclic nucleotides. Km values for cAMP, ATP, Mg2+, and Co2+ were about 2 X 10(-8) M, 4 X 10(-5) M, 2 X 10(-3)M, and 1.7 X 10(-4) M, respectively. On DEAE cellulose column, the main peak of the enzyme eluted at high NaCl concentration. On Sephadex G-200 gel filtration the majority of the holoenzyme eluted at a peak corresponding to a molecular weight of about 300,000. There was an additional peak corresponding to a molecular weight of about 400,000, with relatively high cAMP binding compared to kinase activity. Right atrium and ventricle showed significantly higher enzyme activities than left atrium and ventricle and interventricular septum. On multivariate analysis of the enzyme activity versus 12 clinical and pathological findings of 122 cases, cardiac hypertrophy and coronary sclerosis were slight but significant negative contributors to the enzyme activity. Multiple correlation coefficient was low, indicating the enzyme activity remained at a relatively stable level, despite different clinical situations. This may be suitable for control of intracellular events through the membrane adenylate cyclase system.

When isolated rat hearts are perfused with Ca2+-containing medium, after a brief Ca2+-free period, irreversible cell damage occurs (calcium paradox). This phenomenon is concomitant with a rapid consumption of myocardial high-energy phosphate stores, prior to the appearance of these compounds in the effluent perfusion medium. A possible mechanism for the origin of myocardial necrosis, caused by intracellular Ca2+ overload, is discussed.

Significant alterations in fatty acyl composition of cardiac phospholipids and neutral lipids are induced by dietary cod liver oil in the rat. Increased dietary availability of docosahexaenoic acid (22:6 omega3) leads to extensive replacement of linoleic acid (18:2omega6) and arachidonic acid (20:4omega6) in phospholipids. Dietary cod liver oil (10%) reduces isoproterenol stress tolerance and results in increased development of cardiac necrosis and mortality following isoproterenol treatment. It is suggested that diminished catecholamine stress tolerance may be related to altered synthesis of prostaglandins or related products.

The action of quinidine on heart microsomal and mitochondrial calcium binding in the presence of MgATP was studied under different experimental conditions and compared with other antiarrhythmic agents such as procaine amide and lidocaine. Quinidine stimulated microsomal calcium binding but depressed mitochondrial calcium binding. Although procaine amide stimulated microsomal calcium binding, it did not affect mitochondrial calcium binding. On the other hand, lidocaine depressed calcium binding by mitochondria without affecting calcium binding by the microsomal fraction. The stimulation of microsomal calcium binding by quinidine was not apparent at high concentrations of Mg2+, low concentrations of ATP, or low concentrations of Ca2+. The depressant action of quinidine on mitochondrial calcium binding was not observed at low concentrations of Mg2+ or ATP but was more pronounced at low concentrations of Ca2+. These results suggest that the action of quinidine on mitochondria may play a major role in eliciting cardiodepressant effect.

Left ventricular heat loss was examined by measuring the temperatures in the coronary sinus blood, in the aortic blood, and in the left atrial blood by thermistors. The temperature was highest in the coronary sinus blood, in the aortic blood next, and it was the least in the left atrial blood. However, since the aortic blood flow was naturally higher than the coronary sinus blood flow, the heat loss was larger in the left ventricular cavity than in the rest of the chambers. This heat loss was mostly proportional to the magnitude of the changes of both the arterial blood pressure and the aortic blood flow.

Two functional mitochondrial populations with different sedimentation rates (S) were obtained from homogenates of canine myocardium by rate zonal centrifugation using an iso-osmotic Ficoll gradient. To ascertain the origin of these populations, the left ventricular wall of normal myocardium was divided into subepicardial (outer one-third), intermediate (middle on-third), and subendocardial (inner one-third) layers. The slow S mitochondria comprised 75% of the mitochondrial population of the subepicardial layer. In contrast, the fast S mitochondria contributed 65% of the subendocardial population. Intermediate layer mitochondria resembled those of the subepicardium. Mitochondria isolated from the three layers had approximately the same density, as shown by isopycnic zonal centrifugation. These studies indicate that mitochondria from subepicardial and subendocardial layers of normal myocardium differ in size and shape but not in density. Electron micrographs (EM) of the subepicardium showed many mitochondria as long as 4 to 8 sarcomeres. Mitochondria from the outer and inner layers of normal myocardium had the same oxidative phosphorylation parameters. Acute myocardial infarction, lasting 1 or 2 hr, resulted in the selective loss of the fast S mitochondria. Because the fast S mitochondria are prevalent in the subendocardium, these results may explain the greater vulnerability of this layer to anoxia.

Significant uptake and release of immunoreactive insulin by the heart have been observed in man, and this is related to plasma insulin levels. Exercise and the fed state appear to affect the myocardial handling of insulin. The findings could not be related to myocardial carbohydrate metabolism, but could, during exercise, be related to myocardial lipid metabolism.