Cardioscience最新文献

Mitochondria extracted from the hearts of Wistar rats aged 6 and 24 months showed similar values for the respiratory control index (RCI), state 3 oxygen consumption (QO2) and ADP/O measured using glutamate or succinate as substrates; with the exception that the QO2 of the aged rats was lower than that of the young rats in the presence of glutamate. The consumption of O2 induced by 2-oxoglutarate and ADP was similar in both age groups. Concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM produced an increase in O2 consumption and ATP formation in the young mitochondria, with a maximum effect at 0.2 microM external free Ca2+. Little or no change in O2 consumption and ATP formation was evident in aged mitochondria following incubations in concentrations of external free Ca2+ ranging from 0.2 to 0.8 microM. The continuous rate of formation of ATP, measured in the presence of 0.2 microM external free Ca2+ using a luminescence method, confirmed the previous results. This study indicates that the cardiac mitochondrial phosphorylating system of aged rats is poorly sensitive to variations in external free calcium.

Techniques suitable for the isolation of human cardiac cells have previously been reported. However, there are difficulties concerning the reliability and reproducibility of the available methods. In the present study, a technique developed for the isolation of canine cardiocytes was successfully applied to allow isolation of human atrial and ventricular myocytes from small samples of myocardium. Application of this method allowed a direct comparison of the ionic currents recorded from human atrial and ventricular myocytes with those recorded from other mammalian preparations.

The monoclonal antibodies TT-1 against troponin T and TI-1 against troponin I of cardiac muscle, together with Western blots and immunofluorescence techniques, were used to evaluate the presence of troponin-like antigens in the smooth muscle cells of bovine coronary arteries. The walls of the left coronary artery before the bifurcation, its circumflex and descending branches, the right coronary artery, and the small branches of coronary arteries and the intramural arterial vessels were found to be homogeneously stained by the TT-1 antibody. Conversely, with the TI-1 antibody, differences were observed in the distribution of the TnI-like antigen among the smooth muscle cells of extramural and intramural vessels. Heterogeneity of the smooth muscle cells of the coronary artery was also evident in the medial layer of large vessels near the branching points, where an intimal thickening was consistently observed. Double immunofluorescence assays with anti-troponin antibodies in vivo and in vitro indicated a distinct intracellular localization of troponin T and troponin I immunoreactivities in vascular smooth muscle cells. The data are compatible with the existence of distinct troponin-like antigens in smooth muscle cells of bovine coronary arteries whose distribution is in part related to the extramural or intramural localization of blood vessels.

The influence of [Mg2+] on the basal or stimulated activity of adenylate cyclase from the hearts of young (1 month old) and aged (24 months old) rats has been investigated in vitro. The basal activity of cardiac adenylate cyclase, and its responsiveness to stimulatory or inhibitory effectors, declined with age. This is probably due to alterations at the catalytic moiety of the signal transduction system, such as an impairment in the affinity of the catalytic moiety for ATP and a lower capacity of the catalytic moiety to bind activated stimulatory (Gs) or inhibitory (Gi) guanine nucleotide binding proteins. Compared to the enzyme from the heart of aged rats, unstimulated adenylate cyclase from the heart of young rats was more sensitive to an increase in [Mg2+] in the incubation mixture, as shown by a greater increase in basal activity and in the affinity of the enzyme for ATP. An increase in [Mg2+] counteracted the inhibitory effect of spermine on adenylate cyclase more effectively in young rats than in aged rats. On the other hand, an increase in [Mg2+] facilitated the stimulation of adenylate cyclase by Gpp(NH)p, isoproterenol and forskolin more in aged rats than in young rats. GDP beta S prevented the positive effect of high [Mg2+] on the stimulation of adenylate cyclase by forskolin, suggesting that an increased [Mg2+] favors the activation of Gs or the formation of functional complexes between the catalytic moiety and Gs. We suggest that aging leads to a higher requirement for Mg2+ at the allosteric site on the catalytic moiety whose occupancy is essential for the full expression of stimulated activity.

In a variety of mammalian species, thyroid hormone regulates the contractile properties of the heart as well as the expression of the alpha and beta heavy chains of myosin. We have previously shown that the plasma levels of thyroid hormone reach a peak immediately after birth in guinea pigs and decline with maturation. We therefore studied age-related changes in the expression of the myosin heavy chains in the guinea pig ventricle in relation to the ventricular mechanical properties and the levels of thyroid hormone. The composition of the myosin heavy chains was characterized by gel electrophoresis and immunoblotting. Anti-beta-chain antibody stained equally myosins from newborns (0-5 days) and adults (75-90 days), while anti-alpha-chain positively decorated only the myosins of euthyroid newborns or of hyperthyroid adults, but not myosins of embryos, hypothyroid newborns or hypothyroid adults. Myosin of euthyroid adults was faintly stained by anti-alpha-chain. The alterations in the composition of myosin corresponded with the "thyroid state" of these groups. The plasma levels of total T3 were 24.3 +/- 2.7, 9.04 +/- 1.2 and 139.0 +/- 9.3 ng/dl (mean +/- SEM) in the euthyroid, hypothyroid and hyperthyroid adults, respectively. In euthyroid and hypothyroid newborns, the plasma levels of T3 were 56.5 +/- 11.9 and 26.5 +/- 9.8 ng/dl, respectively. Within each age group the thyroid state corresponded with maximal twitch tension (Tmax), rates of development of tension and relaxation, time to peak tension and rate of activation.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the relation between age and the heart's ability to tolerate ischemia. Groups of 5-7 isolated Langendorff perfused hearts from neonatal (5 days old), immature (11-44 days old), and adult (54 days old) rats, were subjected to 60 minutes of global ischemia and 60 minutes of reperfusion at 37 degrees C. Pre-ischemic left ventricular developed pressure was 54 +/- 1, 56 +/- 2, 59 +/- 4, 80 +/- 3, 91 +/- 9, 91 +/- 8, 94 +/- 3, 101 +/- 10, 107 +/- 8 and 132 +/- 4 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively. Left ventricular developed pressure recovered to 65 +/- 13, 69 +/- 4, 103 +/- 14, 84 +/- 10, 81 +/- 3, 59 +/- 11, 42 +/- 10, 34 +/- 6, 34 +/- 6 and 25 +/- 7% respectively. Ischemia-induced contracture was greater in adult hearts and the time-to-onset and the time-to-peak contracture decreased with increasing age. Leakage of creatine kinase after ischemia correlated poorly with the recovery of contraction. Left ventricular end-diastolic pressure, at the end of 60 minutes of reperfusion, increased in an age-dependent manner from a pre-ischemic value which was set at 2-8 mmHg to 14 +/- 4, 22 +/- 2, 21 +/- 5, 27 +/- 3, 47 +/- 16, 52 +/- 7, 71 +/- 7, 81 +/- 9, 73 +/- 5, and 82 +/- 8 mmHg in the 5, 11, 14, 18, 23, 26, 33, 40, 44, and 54 day old groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The responses in coronary blood flow and the relative myocardial extraction of oxygen to atrial pacing (causing mainly an increase in heart rate) and isometric handgrip (causing mainly an increase in pressure) were studied in patients with angina and in young and middle-aged healthy men. The myocardial extraction of oxygen and coronary sinus flow were measured by catheterizing the coronary sinus, using a catheter with thermistors for the measurement of flow by thermodilution and electrodes for atrial pacing. In the healthy men the increase in the consumption of oxygen was covered entirely by an increased coronary blood flow during both provocations, with no change in the arteriovenous oxygen difference during handgrip and a decrease during pacing. There was no significant difference in the reaction between younger and older men. In the patients with angina the increased consumption of oxygen during pacing was covered by an increased coronary blood flow with an unaltered arteriovenous oxygen difference, while during handgrip both the coronary blood flow and arteriovenous oxygen difference increased. It is concluded that during handgrip, compared to the artificial increase in heart rate, the myocardium is more dependent upon an increased relative extraction of oxygen to cover an increase in the requirement for oxygen. This may be due to a higher intramyocardial pressure. Patients with coronary heart disease are more dependent than healthy men on an increase in the relative myocardial extraction of oxygen. This may be related to a lower effective perfusion pressure because of the coronary arterial obstructions or to an increased intramyocardial pressure and a relatively shorter duration of diastole because of the impaired cardiac function.

To see whether the hypertrophic response of the surviving myocardium after infarction leads to a complete reconstitution of ventricular mass, the left coronary artery was ligated in rats and the animals killed one month later. In infarcts affecting an average of 38% of the free wall of the left ventricle, the ratio of wall thickness to chamber radius remained essentially constant. On the other hand, the ratio decreased significantly in the presence of infarcts involving an average of 60% of the ventricular wall. In addition, inadequate growth adaptations were detected in both groups of infarcts with respect to myocyte volume and length and to capillary volume and length. These defects in the regeneration of myocardial structures were associated with elevations in diastolic wall stress which were more prominent in the larger infarct group. The limited growth reaction of the myocyte and vascular compartments may be implicated in the persistence of cardiac dysfunction and failure late after infarction.

We have studied the functional and molecular changes of mitochondrial FoF1 ATP synthase of cardiac muscle during aging. ATP hydrolase activity was lower in sonic submitochondrial particles prepared from hearts of senescent rats (24 months) than in those prepared from hearts of adult rats (12 months). Oligomycin-sensitive proton conduction of cardiac submitochondrial particles was greater in senescent rats than in adult rats. The beta subunit of F1, detected immunologically in submitochondrial particles, was less in senescent rats than in adult rats. Exposure of cardiac submitochondrial particles from adult rats to free radicals, generated by 60Co, resulted in inactivation of ATP hydrolase activity and a decreased content of F1. The structural and functional alterations of mitochondrial FoF1 ATP synthase during aging may be expected to affect energy metabolism, and our results suggest that they could originate from the action of free radicals generated in the inner mitochondrial membrane.

In the myocardial cell, stimulation of the K opioid receptor is involved in the modulation of cytosolic calcium and pH homeostasis, as well as in the regulation of myofilament responsiveness to calcium. In the present study, we found that prodynorphin mRNA, which encodes for the synthesis of a common precursor of opioid peptides interacting with K sites, is synthesized both in atrial and ventricular tissue of the rat heart. In adult cultured rat ventricular cardiomyocytes, the level of prodynorphin mRNA did not differ from that detected in the original ventricular tissue. This finding indicates that the myocardial cell is a source for prodynorphin gene expression and has the potential for an intrinsic synthesis of dynorphin-related peptides.