Cardioscience最新文献

Spontaneous, sustained low frequency oscillations of pulmonary arterial pressure were observed in 8 patients with moderate to severe chronic heart failure during recordings of pulmonary arterial pressure of 8.6 to 48 hours duration. The oscillations (frequency range 0.015 to 0.035 Hz) had a distinct peak from and lower frequency range than respiration (0.2 to 0.6 Hz) and heart rate (0.8 to 1.9 Hz). They were present from 42% to 82% of the recording time with an amplitude varying from undetectable to a maximum range from 5.3 mm Hg to 19.7 mm Hg. When detectable, the mean amplitude of the low frequency oscillations of pulmonary arterial pressure ranged from 1.2 +/- 1.2(SD) mm Hg to 4.3 +/- 3.3 mm Hg. These oscillations are lower in frequency than the low frequency component usually described in recordings of systemic arterial pressure and heart rate in normal subjects, and are closer to the very low frequency rhythms described in severe chronic heart failure and Cheyne Stokes respiration.

Leukotrienes, lipid mediators derived from arachidonic acid by the 5-lipoxygenase pathway, have been implicated in a variety of myocardial ischemic events including myocardial infarction and coronary spasm. We have examined the comparative effects of leukotriene C4 in isolated human non-atherosclerotic and atherosclerotic coronary arteries to gain an insight into the role of leukotrienes in coronary heart disease. Human coronary arteries, obtained from recipient hearts at the time of cardiac transplantation, were cut into rings and examined in an isolated organ bath. In atherosclerotic arteries leukotriene C4 (1nM-100nM) produced a maximal contractile response of 54.9 +/- 7.98% KCI (n = 7) and the mean EC50 value was 11.1nM (95% confidence interval: 9.4-13.0). The leukotriene receptor antagonist ICI-198,615 (3 x 10(-8)M) produced an approximate 50-fold rightward shift of the leukotriene C4 dose-response curve (n = 5). In contrast, non-atherosclerotic arteries were either non-responsive (n = 5) or only weakly responsive (n = 2) to leukotriene C4 (1nM-100nM), producing an average maximum response of 3.65 +/- 3.05% KCI (n = 7; p < 0.01 atherosclerotic vs non-atherosclerotic). In the presence of indomethacin and in vessels denuded of endothelium, non-atherosclerotic arteries remained unresponsive to leukotriene C4 (n = 3). In addition, leukotriene C4 did not relax preconstricted vessels (n = 7). In vitro autoradiography showed specific [3H]-leukotriene C4 binding to smooth muscle in both non-atherosclerotic and atherosclerotic arteries, with no evidence of endothelium-dependent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocytes prepared from perfused rat heart were studied spectroscopically using a photodiode array spectrophotometer adapted to a rapid mixing stopped-flow apparatus. The isolated cells were found to be viable for 3 to 4 hours, i.e. over the total time of the experiments. Sodium ascorbate and tetramethyl-para-phenylenediamine were used as exogenous reductants. Cytoplasmic and mitochondrial membranes were found to be freely permeable to tetramethyl-para-phenylenediamine. The use of singular value decomposition proved to be powerful in resolving the spectral contributions of the chromophoric components within the overall absorption spectrum. Spectral resolution was improved by adding carbon monoxide at a concentration that kept myoglobin fully saturated without affecting the activity of cytochrome c oxidase. The redox state of cytochrome c and cytochrome a was observed during the steady-state consumption of oxygen and during the reduction following the exhaustion of oxygen. The redox state of the two chromophores was found to be approximately equal and close to 25-30% oxidized during steady-state respiration; during the final reduction they changed simultaneously. These experiments suggest that in living cells, as in the purified enzyme, the rate limiting step of the turnover of cytochrome oxidase is the internal transfer of electrons from cytochrome a to cytochrome a3.

Hypertrophic cardiomyopathy is characterized by an unexplained hypertrophy of the left ventricle, particularly the interventricular septum. Although point mutations in the beta-myosin chain gene have been found in several US families in familiar hypertrophic cardiomyopathy, the pathogenetic pathways leading to myocyte hypertrophy, the most important feature, are still not clear. To examine whether activation (expression) of nuclear proto-oncogenes may play a role in hypertrophic cardiomyopathy, endomyocardial biopsies from 13 patients with hypertrophic cardiomyopathy were examined using monoclonal antibodies against c-myc, c-fos and c-jun. The nuclear proto-oncogenes c-fos, c-jun and c-myc were expressed in 53, 60, and 50%, respectively, of patients with hypertrophic cardiomyopathy. In control biopsies, c-myc was detectable in only 10% of the patients, while c-fos and c-jun were always undetectable. These results show that nuclear proto-oncogenes are induced in patients with hypertrophic cardiomyopathy, although the triggering mechanisms remain unknown.

The heart rate is modulated from beat to beat by efferent vagal and sympathetic fibers, the former being the predominant mediators of the chronotropic influence of arterial baroreceptors and respiration and the latter being important in the cardiac responses to physical and mental stress. Cardiac vagal influences are modulated by a number of factors. These can be grouped as: 1) neural factors, such as the wakefulness-sleep cycle, the alerting reaction, and exercise; 2) humoral-pharmacological factors, such as angiotensin II, atrial natriuretic factor, cardiac glycosides; 3) normal aging; 4) a number of cardiovascular and other diseases, such as arterial hypertension, coronary artery disease, congestive heart failure and diabetes mellitus. The mechanisms underlying modulation of cardiac vagal control are not completely understood, the range of the possibilities including structural or functional alterations in baroreceptor afferents, in central and efferent vagal pathways and in cardiac responsiveness to neural stimuli. Irrespective of the mechanisms involved, the modulation of cardiac vagal control may have important implications for normal cardiovascular homeostasis, as well as for the pathophysiology, diagnosis and prognosis of various diseases.

Calcitonin gene-related peptide, the main transmitter released from capsaicin-sensitive sensory-motor fibers, has positive inotropic and chronotropic effects on the heart and causes vasodilatation in the coronary arteries and elsewhere in the peripheral vasculature. We review some aspects of the cardiovascular actions induced by exogenous calcitonin gene-related peptide and by release of the peptide following activation of capsaicin-sensitive nerves. The efferent function of cardiac sensory-motor neurones is modulated by a number of endogenous substances of physiopathological interest, including opioid peptides, norepinephrine and adenosine. The receptors involved in the prejunctional regulation due to these substances have been characterized. Studies on the mesenteric bed of the rat have shown that, at least in such a resistance vascular bed, the relaxing effect of calcitonin gene-related peptide is mediated by a direct mechanism independent of endothelium-derived nitric oxide release. In cultured human endothelial cells from the umbilical cord vein, calcitonin gene-related peptide, at nM concentrations, stimulates cell growth in a dose-dependent manner. The possible implications of calcitonin gene-related peptide in the physio-pathological regulation of the cardiovascular system and in the trophism of vascular tissues are discussed.

In several species, xanthine oxidoreductase activity seems to be a major source of free radicals in myocardial tissue. Its activity changes during development and aging, at least in the rat heart. Hardly any data are available about its activity in two important diseases, hypertension and hypercholesterolemia, in which the production of free radicals induced by xanthine oxidoreductase activity could play a role. Therefore we measured the activity of xanthine oxidase and dehydrogenase in myocardial tissue of spontaneously hypertensive. Wistar (control hypertensive), Yoshida (hypercholesterolemic) and Brown Norway (control hypercholesterolemic) rats of various ages. Cytosolic fractions were incubated at 30 degrees C, pH 8.3, with 60 microM xanthine, and the formation of urate was measured with high performance liquid chromatography. In the Wistar group, xanthine oxidoreductase activity was relatively constant during aging (about 1.8 U/g protein). In the hypertensive group, the activity increased gradually from 1.7 to 2.3 U/g at 18 months (p < 0.05 compared with Wistar at 18 months). Xanthine oxidase was about twice as high in both groups at 18 months (p < 0.001 compared with 2 and 6 months). The ratio of xanthine dehydrogenase to xanthine oxidase had decreased 42% at this age (p < 0.001). In the Yoshida and Brown Norway groups, xanthine oxidoreductase activity was similar, with a peak at 6 months. These data suggest that the hypercholesterolemic state does not influence xanthine oxidoreductase activity. In contrast, in hypertrophied myocardium, xanthine oxidoreductase activity was higher than in the control, suggesting a different potential for free-radical generation.(ABSTRACT TRUNCATED AT 250 WORDS)

Positron emission tomography is a non-invasive radionuclide imaging technique which enables in vivo assessment of regional cardiac function. When used with appropriate radiotracers and kinetic models, it can provide quantitative measurements of myocardial perfusion, metabolism and pharmacology. The development of quantitative measurements should help to decrease much of the ambiguity in the interpretation of data that often occurs. The short half-life of the radionuclides used allows the imaging of more than one function to be performed conveniently within the same scanning session with a low radiation dose to the subject. This integrated approach provides a means for investigating in vivo the physiology and pathophysiology of the human heart.

Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive rats. Cells from spontaneously hypertensive rats have a higher basal ATP synthase capacity than those from normotensives, but lack the normal up-regulation in response to an increased energy demand. After treatment of spontaneously hypertensive rats with captopril (60 mg/kg per day for 12 weeks), cellular hypertrophy characteristic of the hypertensives was abolished and the cardiomyocytes showed a normal ATP synthase capacity. Normal up-regulation of this enzyme was also restored. All cells showed a normal down-regulation of the synthase in response to cyanide. Experiments with the calcium antagonists, verapamil and ruthenium red, suggest that abnormal ATP synthase regulation observed in the untreated spontaneously hypertensive rats results from an alteration of Ca2+ handling in cardiac cells under chronic high workload, which is reversed by captopril treatment.

The physiological role of atrial natriuretic factor in the regulation of cardiovascular homeostasis has not yet been defined. The principal mechanisms that control biosynthesis, secretion and clearance of the peptide, however, are well characterized. In addition, several biological functions of the peptide, originally identified by studying the results of exogenous administration, have been confirmed in humans and in experimental animals at physiological blood levels, as well as with the help of pharmacological tools such as clearance inhibitors and monoclonal antibodies. This article reviews the principal biological actions of atrial natriuretic factor in the context of their physiological significance.