Cardioscience最新文献

The aims of this study were to develop a model of left ventricular hypertrophy in the guinea pig using the technique of aortic banding below the level of the renal arteries, and to characterize any cardiac electrophysiological changes induced. Female guinea-pigs were either sham operated or the abdominal aorta was partially occluded by banding around a 23 or 25 G needle. Following recovery, animals were monitored for 10 weeks. The left ventricular dry weight to body weight ratio was similar in sham (0.326 +/- 0.01 mg/g, n = 12) and aortic banded guinea pigs (0.308 +/- 0.1 mg/g, n = 11). Conscious mean arterial blood pressure was also not modified by the aortic banding 10 weeks after operation (72 +/- 16 (sham) vs 71 +/- 1 mmHg). The action potential characteristics measured in isolated superfused left papillary muscle stimulated at 1 Hz were similar in sham and aortic banded groups. The action potential duration measured at 50 and 90% of repolarization tended to be longer in muscle from aortic banded (122.4 +/- 10 ms ADP50 and 155.2 +/- 9.5 ms APD90) than sham operated animals (105.8 +/- 8.4 and 142.2 +/- 6.2 ms) but these differences were not statistically significant. Hypoxia abbreviated the cardiac action potential to a similar degree in muscle from sham and aortic banded animals. It is concluded that sub-renal aortic banding with a 23 or 25G needle fails to develop left ventricular hypertrophy in the guinea pig 10 weeks after operation.

Many studies have shown that the contractile response of the rat left ventricle is impaired in diabetes mellitus. Few studies have examined the acute in vivo effects of catecholamines on the right ventricle of diabetic rats. The present study investigates the acute in vivo effects of norepinephrine (100 micrograms.kg-1.h-1 continuous intravenous infusion for 15 minutes) on the function of the right and left ventricle of diabetic rats. The effects of isoproterenol (25 mg.kg-1, subcutaneously) on the activity of glucose-6-phosphate dehydrogenase, the first and rate limiting enzyme of the oxidative pentose phosphate pathway, and on adenine nucleotide biosynthesis of the diabetic heart were also examined. Diabetes mellitus was induced by a single intravenous injection of streptozotocin (60 mg.kg-1) 4 weeks before measurements. The hemodynamic measurements were made on intact, anesthetized rats with Millard ultraminiature pressure tip catheters. The basal hemodynamic measurements (left ventricular systolic pressure, diastolic aortic pressure, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax) as well as glucose-6-phosphate dehydrogenase activity and adenine nucleotide biosynthesis were the same in the diabetic animals as in the controls. Heart rate was slower in the diabetics. Norepinephrine, after 15 minutes of intravenous infusion, induced a marked increase in heart rate, left ventricular dP/dtmax, right ventricular systolic pressure and right ventricular dP/dtmax; whereas left ventricular systolic pressure and diastolic aortic pressure remained unchanged. Isoproterenol caused a pronounced stimulation of both cardiac glucose-6-phosphate dehydrogenase activity (after 24 hours) and adenine nucleotide biosynthesis (after 5 hours).(ABSTRACT TRUNCATED AT 250 WORDS)

This study was undertaken to assess whether the converting enzyme inhibitor lisinopril, and the long-acting nitrate, isosorbide-5-mononitrate, affect left ventricle dysfunction and anatomical remodelling in rats with myocardial infarction. Lisinopril, isosorbide-5-mononitrate or vehicle were given to rats (n = 10-14 per group) immediately after coronary artery occlusion (by an intravenous bolus) and then for nine weeks (in drinking water). At the end of the study, left ventricular pressures were measured, the heart arrested in diastole, and infarct size, left ventricular chamber volume and wall thicknesses measured. Lisinopril significantly lowered systemic blood pressure and left ventricular systolic pressure in rats with small (< 15% scarred tissue of the left ventricle) and large (> 15%) infarcts; the weight of the left ventricle (including the septum) was reduced by 24% and 28% in animals with small and large infarcts, respectively. Lisinopril lowered left ventricular end-diastolic pressure (by 33% and 39%) and chamber volume (by 4% and 34%) in rats with small and large infarcts, respectively, compared with controls (NS). The combined anatomical and hemodynamic changes led to a reduction of the circumferential wall stress by 20% and 44% in lisinopril-treated rats with small and large infarcts, respectively (NS). No significant changes were seen in the nitrate-treated hearts compared with controls. Lisinopril, given early after myocardial infarction and continued for nine weeks, significantly affected cardiac hemodynamics and ventricular weights in rats with infarcts of different sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

The remodeling of the spared non-ischemic left ventricular myocardium after different time intervals from the occlusion of the left coronary artery was examined in rats. In the presence of large infarcts, ventricular failure developed two to three days after surgery, because of chamber dilation and thinning of the wall, resulting in an average 7.5-fold increase in diastolic stress on the surviving myocardium. Mural thinning of the ventricular wall remote from and bordering the infarction occurred through side-to-side slippage of myocytes and capillaries within the wall. Although an average hypertrophic growth of 22% of the spared myocytes has been found, this amount of hypertrophy was insufficient to restore normal myocardial function. Long-term cardiac restructuring after infarction was characterized by the persistence of chamber dilatation and thinning of the ventricular wall. In addition to the side-to-side slippage, lengthening of the myocytes was an important cause of ventricular changes. As the reactive hypertrophy of the unaffected ventricle was insufficient to re-establish the ratio of ventricular mass to chamber volume, the diastolic stress remained elevated and decompensated eccentric ventricular hypertrophy developed. The anatomical remodeling of the spared left ventricular myocardium is an important conditioning factor in the short- and long-term outcome of ischemic cardiomyopathy.

We have investigated the incorporation of cholesterol oxidation products into cardiomyocyte lipids and related this to changes in cell proliferation, evaluated by measuring cellular protein content. Primary cultures of neonatal rat ventricular cells were supplemented with scalar concentrations of several cholesterol oxidation products (cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5 alpha-cholestane-3 beta, 5, 6 beta-triol, 5-cholesten-3 beta, 4 beta-diol, 5-cholesten-3 beta-ol-7-one, and 5-cholesten-3-one). Although all the cholesterol oxidation products were incorporated into the cardiomyocyte lipids when added to the medium at a concentration higher than 0.5 microM, the extent of the incorporation of the different cholesterol oxidation products differed, depending on the concentration in the culture medium and on the chemical structure of the compound. The effects of the cholesterol oxidation products on the cellular protein content were also different: 5 alpha-cholestane-3 beta, 5, 6 beta-triol was shown to be the most potent inhibitor of cell proliferation, followed by cholestan-5 alpha, 6 alpha-epoxy-3 beta-ol, 5-cholesten-3 beta, 4 beta-diol and 5-cholesten-3 beta-ol-7-one. 5-Cholesten-3-one did not affect the cellular protein content. The ability of cholesterol oxidation products to inhibit cell proliferation, and their capacity to increase the permeability of the plasma membrane to calcium, could be deleterious for cardiac cells.

To determine the effects of chronic constriction of the left coronary artery on the function and structure of the heart, coronary artery narrowing was surgically induced in rats and ventricular pump performance, extent and distribution of myocardial damage, and the hypertrophic and hyperplastic response of myocytes were examined. Alterations in cardiac hemodynamics were found in all rats, but the characteristics of the physiological properties of the heart allowed a separation of the animals into two groups which exhibited left ventricular dysfunction and failure, respectively. Left ventricular hypertrophy occurred in both groups and was characterized by ventricular dilatation and wall thinning which were more severe in the failing animals. Multiple foci of myocardial damage across the wall were seen in all animals but tissue injury was more prominent in the endomyocardium and in failing rats. The anatomical and hemodynamic changes resulted in a significant increase in diastolic wall stress which paralleled the depression in ventricular performance. Myocyte cell loss and myocyte cellular hypertrophy were more severe with ventricular failure than with dysfunction. Finally, diastolic overload appeared to be coupled with activation of the DNA synthetic machinery of myocytes and nuclear mitotic division. In conclusion, a fixed lesion of the left coronary artery leads to abnormalities in cardiac dynamics with marked increases in diastolic wall stress and extensive ventricular remodeling in spite of compensatory myocyte cellular hypertrophy and hyperplasia in the remaining viable tissue.

The distribution of binding sites for substance P labeled with [125I]-Bolton-Hunter-reagent was studied in a mixed cell culture preparation from newborn guinea-pig atria and interatrial septum. A relatively small subpopulation of intracardiac neurons expressed substance P binding sites. These neurons exhibited a range of densities of labeling and could be heavily, moderately or lightly labeled with autoradiographic grains. In most cases, the autoradiographic grains were restricted to the neuronal cell body and more proximal regions of the neurites in culture. Intracardiac neurons expressing substance P binding sites were seen in close association with unlabeled neurons. The density of labeling and the distribution of autoradiographic grains over individual intracardiac neurons did not appear to be related to whether they were mono- or binucleate or their associated cell types. The possibility that the substance P binding sites demonstrated here represent functional receptors on intracardiac neurons and their potential role in the heart is discussed.

Previous studies in anesthetized animals showed that distension of the stomach or the descending colon primarily caused decreases in mean coronary blood flow. Whether these responses occurred during systole or diastole was not investigated. The present work was planned to study the primary effects of the distension of the two viscera on phasic coronary blood flow in the anesthetized pig. In ten animals, the stomach and the descending colon were distended at constant volume by injecting warm Ringer solution into intravisceral balloons (0.8 and 0.25 l respectively) while preventing changes in heart rate and arterial blood pressure. Distensions of the stomach or the descending colon caused a decrease in mean coronary blood flow in each pig. However, the decrease elicited by gastric distension occurred only during diastole, while the decrease caused by descending colon distension involved both systolic and diastolic coronary blood flows. The same effects on phasic coronary blood flow were observed during experiments in which the decreases in mean coronary blood flow elicited by distension of the stomach or the descending colon were further augmented by adding the distension of the second viscerum. The results indicate that the coronary vasoconstriction caused by gastric distension mainly involves the vessels which supply the subendocardial layers of the myocardium, while that caused by descending colon distension also involves the vessels which supply the subepicardial layers. The vasoconstrictor effect on the subendocardial coronary circulation is enhanced by the combined distension of the two viscera.

The aim of the present study was to investigate stable left ventricular dysfunction resulting from severe myocardial ischemia in conscious dogs, in order to evaluate the action of cardiotonic agents under pathological conditions mimicking moderate cardiac failure. Mongrel dogs with a catheter implanted in the left ventricle were trained on a treadmill and subjected to a standardized exercise before and after a Harris-type ligation of the anterior descending branch of the left coronary artery in two stages. Two weeks later the lower third of the left circumflex coronary branch was also occluded, and the exercise test repeated for at least two additional weeks to evaluate the changes in the left ventricular function indicated by left ventricular systolic pressure, end-diastolic pressure, heart rate, positive and negative dP/dtmax and dP/dt/P. Noninvasive radionuclide investigations of the left ventricular function and myocardial perfusion were done before and after the development of cardiac failure. Following occlusion of the anterior descending and circumflex coronary arteries, the baseline end-diastolic pressure increased from 7.6 +/- 2.3 mmHg to 23.3 +/- 3.0 mmHg (p < 0.05) and increased even further during exercise (to 49.2 +/- 3.5 mmHg, p < 0.05). After the development of cardiac failure, no substantial change occurred in the end-diastolic pressure, either during rest or repeated exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)