Cardioscience最新文献

The weights of the individual carotid bodies and cardiac ventricles were obtained at necropsy in five series of subjects. The first comprised 10 cases free of cardiopulmonary disease to act as controls. The second consisted of 10 cases of pulmonary emphysema. The third was composed of 8 cases characterized by sustained alveolar hypoxia due to causes other than pulmonary emphysema. The fourth comprised 10 cases of systemic hypertension or severe left ventricular failure. The fifth was made up of 10 cases of diseases of the liver or alimentary canal. The study confirmed that enlargement of the carotid bodies is common in cases of pulmonary emphysema or sustained alveolar hypoxia with right ventricular hypertrophy. It is also common in cases of systemic hypertension with left ventricular hypertrophy. It was also revealed that enlargement of the carotid bodies may occur in cirrhosis of the liver. We believe this to be the first report of that association.

The effect of thyroid status on myocardial function and accompanying alterations in the expression of specific genes has been well defined in animals. However, the effects of thyroid hormones on the basal phosphorylation of key cardiac regulatory proteins, which may also contribute to alterations in myocardial function, have not been defined. The present study concerns the phosphorylation status of myofibrillar proteins in hearts from hyperthyroid, euthyroid and hypothyroid rats. Hyperthyroidism was produced by daily subcutaneous injections of L-triiodothyronine, while hypothyroidism was induced with an iodine-deficient diet and KClO4. Two different approaches were used to study changes in the basal phosphorylation levels of troponin I and C protein: 1) direct measurement of the 32P-label associated with these proteins, using intact, beating hearts perfused with [32P]orthophosphate-labeled Krebs buffer; 2) indirect measurement by the back-phosphorylation technique with [gamma-32P]ATP and the catalytic subunit of cAMP-dependent protein kinase in vitro. Measurements of left ventricular contraction (+dP/dt and -dP/dt) were significantly higher in hyperthyroid than in euthyroid animals and this was associated with increases in basal phosphorylation levels of both troponin I and C protein in the myofibrils. In hypothyroid animals, both +dP/dt and -dP/dt were significantly lower than in euthyroid animals and this was associated with decreases in basal phosphorylation levels of troponin I and C protein. The changes in the phosphorylation status of troponin I or C protein correlated with the changes in the speed of myocardial relaxation (-dP/dt) in response to the altered thyroid states.(ABSTRACT TRUNCATED AT 250 WORDS)

The shape of the cardiac myocyte is complex; but, in general, it resembles that of an elliptical cylinder. Quantitative data, however, are lacking and adaptive changes in cross-sectional shape are unknown. The major and minor transverse diameters of myocytes from adult rats were measured using three independent methods: profile tracings of intact isolated myocytes, sectioned isolated myocytes, and whole-sectioned tissue. Values for major and minor diameters were virtually identical with all three methods. Using profile tracings of intact isolated myocytes, major and minor diameters were examined in isolated myocytes from freshly explanted human hearts. Five were non-failing donor hearts regarded as unsuitable for transplantation, of which 2 were normal hearts and 3 had concentric hypertrophy. Six were dilated, failing human hearts with ischemic cardiomyopathy. Major and minor diameters from the normal hearts were similar to those from normal rats. Although the number of patients was limited, the minor diameter was largest in myocytes from patients with concentric hypertrophy while the major diameter was greatest in cells from patients with ischemic cardiomyopathy. We conclude that the cross-sectional shape of structurally-intact myocytes is not altered by cell isolation. The data suggest that the transverse shape of normal human cardiac myocytes is similar to that found in rats, and that it may be altered in hypertrophy and failure.

Experiments were done on anesthetized and curarized cats to see whether the increase in blood pressure caused by electrical stimulation of group I afferent fibers is related to a direct reflex effect on the heart. The reflex effect of electrical stimulation of group I afferent fibers from the gastrocnemius-soleus muscles on the arterial pressure, the left ventricular pressure, the inotropic state of the left ventricle (dP50/dt) and the heart rate were compared before and after beta-blockade with propranolol (0.1 mg/kg intravenously) to reduce a possible direct effect on the heart. The same comparison was made before and after alpha-blockade with phentolamine (2.5 mg/kg intravenously) to keep the peripheral resistance constant. Electrical stimulation of group I afferent fibers caused an increase in the blood pressure, the left ventricular pressure and, to some extent, the inotropic state of the left ventricle and the heart rate. The beta-blockade had no significant effect on these increases, while the alpha-blockade abolished the increase in blood pressure. It is concluded that the effect of stimulation of group I afferent fibers on the blood pressure is not dependent on a direct reflex effect on the heart, but can be better explained by a reflex increase in the peripheral resistance.

The pattern of endocardial regeneration was studied in bovine parietal pericardial patch-grafts implanted in canine hearts. The grafts consisted of fibrous tissue without a cellular lining. They were implanted with either the thoracic or the cardiac surface facing the lumen of the canine ventricle to evaluate the effect on endocardial regeneration. The grafts were retrieved 7, 21, 45 and 60 days after implantation and were examined using scanning electron microscopy. At 7 days, both the thoracic and the cardiac aspect exhibited connective tissue fibers, focally covered by fibrin, platelets and blood cells. The cardiac aspect showed finer and more highly intermingled filamentous fibers than the thoracic aspect. At 21-60 days, the thoracic surface displayed a continuous network of connective fibers with a few blood cells and isolated groups of spindle-shaped cells resembling fibroblasts. At 21-60 days, the cardiac surface showed a diffuse growth of cells on the connective fiber substratum. Regenerating cells first lined the periphery of the grafts (21 days) and then proliferated towards the centrum (45-60 days). These cells varied in size and shape, were mostly closely packed, exhibited numerous microvilli or longer cytoplasmic projections, and resembled regenerating endothelial cells and mature endocardial cells. The topographic arrangement of the new lining cells suggests that they were the result of a per continuitatem regeneration (endothelial re-endothelialization) and that they they originated from the healthy endocardium of the host surrounding the implantation site. The arrangement of the connective fibers, finer on the cardiac than on the thoracic aspect, probably facilitated the development of a cellular lining.(ABSTRACT TRUNCATED AT 250 WORDS)

The membrane fluidity of the cardiac sarcoplasmic reticulum in rabbit was monitored by measuring changes in steady-state fluorescence anisotropy (rs) using diphenylhexatriene as a probe. The Ca(2+)-ATPase activity of the sarcoplasmic reticulum was measured by assaying the amount of inorganic phosphate released from ATP. Hydrogen peroxide caused damage to the sarcoplasmic reticulum, as reflected by decreases in membrane fluidity and Ca(2+)-ATPase activity. The damage caused by hydrogen peroxide was completely prevented by 20 micrograms/ml catalase. Cicaprost (240 nM) provided an effective protection against injury to the sarcoplasmic reticulum caused by exposure to hydrogen peroxide. The rs value was significantly decreased from 0.154 +/- 0.014 to 0.122 +/- 0.005 (p < 0.01). Ca(2+)-ATPase activity was increased from 3.1 +/- 1.31 to 18.87 +/- 2.11 microM phosphate/mg protein/hour (p < 0.01). The protection given by cicaprost was dose dependent. We conclude that cicaprost protects against damage produced by hydrogen peroxide in cardiac sarcoplasmic reticulum in the rabbit. The mechanism of the effect of cicaprost remains to be elucidated.

Female Sprague-Dawley rats were given magnesium orotate (100 mg/kg/day) by gavage for 7 days. The effects on left ventricular, right ventricular, and circulatory function were measured using Millar ultraminiature catheter pressure transducers and thermodilution. In another series, rats were pretreated for 4 days with magnesium orotate. Then they received an intravenous infusion of norepinephrine (0.2 mg/kg/h) for 3 days while magnesium orotate treatment was continued. Thereafter, left ventricular function was examined. Magnesium orotate given for 7 days in control rats induced an increase in heart rate from 380 +/- 18 (n = 7) to 415 +/- 9 beats/min (n = 8); in left ventricular systolic pressure from 165 +/- 8 to 183 +/- 10 mmHg; in left ventricular dP/dtmax from 11486 +/- 1082 to 13300 +/- 909 mmHg/s; and in cardiac output from 386 +/- 38 to 429 +/- 16 ml/kg/min. The pressure-rate product was significantly elevated by magnesium orotate from 54956 +/- 4260 to 66094 +/- 3703 mmHg/min (p < 0.05). Right ventricular systolic pressure was also significantly increased from 34 +/- 1 to 41 +/- 3 mmHg (p < 0.05), and right ventricular dP/dtmax was increased from 2233 +/- 167 to 2857 +/- 489 mmHg/s. Infusion of norepinephrine for 3 days induced an increase in heart rate by 34%, in left ventricular systolic pressure by 10%, in left ventricular dP/dtmax by 88%, in right ventricular systolic pressure by 147%, and in right ventricular dP/dtmax by 100%. Magnesium orotate treatment did not significantly affect the changes induced by norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Brief periods of ischemia, induced either by complete coronary artery occlusion or by rapid ventricular pacing, greatly reduce the severity of those live-threatening ventricular arrhythmias that occur during a subsequent more prolonged occlusion of a major branch of the left coronary artery. The increased tolerance achieved by brief ischemia, either regional or global, has been termed ischemic preconditioning. This was originally defined as the reduction in ultrastructural changes and infarct size resulting from coronary artery occlusion and reperfusion by prior, brief, usually multiple ischemic periods. The reduction in the severity of arrhythmias by preconditioning, which has been described in several different species using both in vivo and in vitro models, depends on the duration and number of the short preconditioning occlusions and also on the time between the preconditioning period and the subsequent prolonged coronary artery occlusion. Under optimal conditions the antiarrhythmic effect of ischemic preconditioning is as pronounced as that with standard antiarrhythmic drugs. Unfortunately, the protection if also short-lived (usually less than 1 hour). If, however, we understood the precise mechanisms involved, we might be able to exploit them to ultimate therapeutic advantage. At least in the dog, the evidence suggests that the protection involves the release (from coronary vascular endothelial cells?) of endogenous myocardial protective substances such as bradykinin, nitric oxide and prostacyclin.

The influence of global ischemia on myocardial nucleotide catabolite production and contraction was studied in Langendorff-perfused rat hearts. Hearts in the "ischemic" group were subjected to a 25 minute period of global ischemia at 30 minutes from the start of perfusion, and to two 30 s periods of global ischemia at 20 and 80 minutes of perfusion. Control hearts were subjected to three 30 s periods of ischemia at 20, 45 and 80 minutes of perfusion. Left ventricular developed pressure and concentrations of total nucleotide catabolites and adenosine in the coronary effluent were measured throughout. The concentration of nucleotide catabolites increased transiently by 2.1 +/- 0.5 microM in the control group and 2.2 +/- 0.8 microM in the "ischemic" group, immediately after 30 s ischemia at 20 minutes; while the concentration of adenosine increased transiently by 0.17 +/- 0.08 microM in the control group and 0.13 +/- 0.09 microM in the "ischemic" group. The next 30 s ischemic period in control hearts caused nucleotide catabolites to increase by 1.7 +/- 0.5 microM and adenosine by 0.12 +/- 0.06 microM. In the "ischemic" group, massive purine release was observed after 25 minutes of ischemia, the release decreasing to below pre-ischemic levels after 10 minutes of reperfusion. The increases in effluent nucleotide catabolites and adenosine in response to 30 s ischemia at 80 minutes were 1.4 +/- 0.4 microM and 0.13 +/- 0.1 microM, respectively, in the control group. In contrast, in the "ischemic" group, nucleotide catabolites increased by only 0.3 +/- 0.2 microM and adenosine by 0.011 +/- 0.008 microM after 30 s ischemia at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)