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Biomedical subjects

P Anversa

Publications and source records attributed to P Anversa.

At least 163 records · Page 9Linked to original sources
PubMed1990

Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart.

To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this small change was not statistically significant. These estimations of myocyte cellular hyperplasia, however, were complicated by the fact that cell loss continued to take place with age. The volume fraction of collagen in the tissue, in fact, progressively increased from 8% and 7% at 4 months to 16% and 22% at 29 months in the left and right ventricles, respectively. In conclusion, myocyte cellular hyperplasia tends to regenerate the ventricular mass being lost with age in the adult mammalian rat heart.

Aging↗
PubMed1990

Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster.

The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.

Animals↗
PubMed1990

Hypertensive cardiomyopathy. Myocyte nuclei hyperplasia in the mammalian rat heart.

To determine whether long-term hypertension leads to hyperplasia of myocyte nuclei in the heart, a phenomenon suspected to occur in humans, renal hypertension was produced in rats and the animals were killed 8 mo later. Arterial blood pressure remained elevated for approximately 5 mo, but decreased progressively in the last 3 mo so that at 8 mo this parameter was practically identical to that found in controls. Moreover, left ventricular end diastolic pressure was markedly increased in experimental animals in association with a substantial decrease in left ventricular dP/dt. The alteration of these physiological measurements was indicative of severe ventricular dysfunction. Quantitative analysis of the transmural distribution of myocyte nuclei in the left ventricle showed 36 and 23% increases in myocyte nuclei concentration in the epimyocardium and endomyocardium, respectively. These changes in nuclei were accompanied by 25 and 16% reductions in myocyte cell volume per nucleus in the outer and inner layers of the wall. In conclusion, long-term hypertension leads to impairment of ventricular function and proliferation of nuclei in myocytes.

Animals↗
PubMed1990

Noncoordinate regulation of alpha-1 adrenoreceptor coupling and reexpression of alpha skeletal actin in myocardial infarction-induced left ventricular failure in rats.

To determine the effects of myocardial infarction-induced left ventricular failure on the regulation of surface alpha-1 adrenoreceptors and signal transduction, large infarcts were produced in rats and the animals killed seven days later. After the documentation of impaired left ventricular pump performance, radioligand binding studies of the alpha-1 adrenoreceptor, norepinephrine-stimulated phosphoinositol turnover, and ADP ribosylation of 41 kD substrate by pertussis toxin were examined in the hypertrophying unaffected myocardium. Moreover, the expression of sarcomeric actin isoforms was analyzed by Northern blots and hybridization with specific oligonucleotide probes. Alpha-1 adrenoreceptor density was found not to be altered in membranes obtained from the spared left ventricular tissue, whereas phosphoinositol turnover was increased 3.1-fold in the viable myocytes of infarcted hearts. Furthermore, pertussis toxin substrate was augmented 2.5-fold in membranes prepared from the surviving left ventricular myocardium. Finally, an upregulation of the skeletal actin isoform was detected in the tissue of the failing left ventricle. In conclusion, the possibility is raised that in the presence of severe myocardial dysfunction and ongoing reactive hypertrophy, effector pathways linked to the alpha-1 adrenoreceptor may stimulate the myocyte hypertrophic response which would tend to normalize cardiac hemodynamics. The reexpression of alpha skeletal actin may be a molecular indicator of the persistance of an overload on the myocardium.

Actins↗
PubMed1989

Global myocardial hypertrophy in conscious dogs with chronic elevation of plasma norepinephrine levels.

Chronically elevated plasma norepinephrine is associated with many disease states in which myocardial hypertrophy is also found, yet whether the hypertrophy results from the hemodynamic actions of catecholamines or a trophic effect is still unknown. The goal of our study was to determine the extent of hypertrophy following 28 days of norepinephrine infusion and the role of altered hemodynamics as the stimulus for the hypertrophy in conscious dogs. In a retrospective study gross cardiac weights were examined in 25 control instrumented dogs (controls) and in 41 instrumented dogs with elevated norepinephrine (NE). In the NE dogs LV (94 +/- 2.8 g), septum (33 +/- 1.5 g) and total heart weights (172 +/- 4.5 g) were greater than in controls (85 +/- 5.0, 31 +/- 1.9, and 158 +/- 9.0 g, respectively). The LV (3.95 +/- 0.10 g/kg), RV (1.91 +/- 0.06), septum (1.38 +/- 0.06) and total weight (7.23 +/- 0.15) to body weight ratios were also significantly greater (3.32 +/- 0.12, 1.73 +/- 0.08, 1.24 +/- 0.06, and 6.28 +/- 0.23 g/kg). The dry/wet weight ratios were not different in the two groups. After cutting the hearts into 1 cm rings, the planimetered area of each ring showed that the wall thickness increased at all levels, e.g. at the base by 25 +/- 3.2%. The chamber internal diameter was significantly increased only near the apex in the NE dogs making the heart more cylindrical in shape. There was no obvious sign of fibrosis in any layer of the myocardium. In physiologic studies, no index of contractility was altered including: LV dP/dt, LV dD/dt, shortening, LV dWT/dt and there was also no change in preload. Heart rate was significantly reduced throughout the 28 days of study. Cardiac output was reduced and there were no significant changes in cardiac work. Thus in these dogs NE caused a 19% and 10% increase in LV and RV to body weight ratios, respectively, without any obvious hemodynamic stimulus.

Animals↗
PubMed1989

Morphometric analysis of the infarcted heart.

To determine whether left ventricular hypertrophy following myocardial infarction leads to a complete or incomplete reconstitution of myocardial mass, the left coronary artery in rats was ligated and the animals sacrificed 30 days later. Infarcts affecting an average 43% of the ventricle were characterized by a 90% hypertrophic growth of the remaining myocardium that was inadequate for a full restoration of ventricular tissue. Myocyte hypertrophy, evaluated by changes in mean cell volume per nucleus, was again insufficient for a total recovery of the myocyte compartment of the ventricle. These observations suggest that infarcts comprising nearly 50% of the ventricle produce a sufficiently large stress on the spared myocytes to stimulate their maximal hypertrophic reserve capacity. Cardiac muscle cells, however, appear to be unable to offset by cellular hypertrophy alone the loss of mass induced by infarcts of this size. The inadequate compensatory response of the myocytes could be the underlying structural mechanism responsible for impaired ventricular function in large infarcts.

Animals↗
PubMed1989

ACE inhibitors in acute and chronic ischaemia: current status and future promise.

1. Myocyte loss, reactive hypertrophy, dynamic ischaemia with 'stunning', and ventricular wall remodelling are all involved in the initiation and progression of myocardial failure which is ischaemic in origin. 2. The effects of ACE inhibitors to reduce preload and afterload has potentially salutary effects in these settings. Moreover, sulphyl containing ACE inhibitors may have further actions in reducing free radicals and their damage in the acute phases of these events. 3. These promising initial studies warrant further exploration.

Acute Disease↗
PubMed1989

Alterations of coronary blood flow and reserve with aging in Fischer 344 rats.

To determine whether aging affects the coronary circulation, left and right ventricular coronary blood flow and vascular resistance at rest and after maximal vasodilation were measured by left atrial injection of radioactive microspheres in conscious, unrestrained male Fischer 344 rats at 4, 12, and 20 mo of age. As a function of age, maximal coronary blood flow per 100 g of tissue decreased by 43% in the left ventricle at both 12 and 20 mo, whereas a 44 and a 47% reduction was found in the right side of the heart at the same time intervals. Minimal coronary vascular resistance per 100 g of myocardium increased by 56 and 36% in the left ventricle and by 48 and 44% in the right at 12 and 20 mo, respectively. No change was found in total minimal coronary resistance for either ventricle despite an increase in myocardial mass. Maximal coronary blood flow per 100 g to the endocardium was depressed more than epicardial flow, leading to a 24% reduction in the endocardial-to-epicardial flow ratio at 20 mo. Coronary vascular reserve per 100 g, expressed as the increase in coronary blood flow during maximal coronary vasodilation, was greater in the right than in the left ventricle at all ages. It is concluded that the changes in coronary hemodynamics associated with maturation and aging are comparable with those seen in pressure overload hypertrophy with an increased vulnerability potential of the myocardium to ischemic episodes, particularly of the subendocardial region of the left ventricle.

Aging↗
PubMed1989

Effects of age on mechanical and structural properties of myocardium of Fischer 344 rats.

To determine whether the mechanical and structural characteristics of the myocardium from the left and right ventricles are comparable in the adult rat and whether aging affects the two ventricles in a similar manner, the left and right posterior papillary muscles of rats at 10-11 and 19-20 mo of age were studied in terms of function and quantitative morphology. At 10-11 mo of age, the duration of isometric contraction was shorter and resting tension higher in the right muscle than in the left muscle. Isotonic velocity of shortening and relengthening were quicker in the left, but time-to-peak shortening was faster in the right. With aging (19-20 mo), velocity of shortening fell in the left ventricle while duration of contraction became prolonged. No such age-related effects were found in the right papillary muscle. On a structural basis, myocardial damage in the form of replacement scarring was present in the left and right muscles at 10-11 mo of age. However, the left muscle was more severely injured, and this difference persisted with age because a comparable increase in replacement fibrosis occurred in both muscles. It was concluded that cardiac performance is distinctly different in the left and right papillary muscles and aging exerts its detrimental impact on the left more than in the right myocardium, an observation that is further supported by the magnitude of tissue injury.

Aging↗
PubMed1989

Long-term pressure-induced cardiac hypertrophy: capillary and mast cell proliferation.

To determine whether a prolonged duration of mechanical load on the ventricular myocardium leads to capillary proliferation, constriction of the pulmonary artery was produced in rats at 3 mo of age, and the hearts were examined 200 days later. Functionally, elevations of right ventricular systolic pressure, from 30 +/- 12 to 67 +/- 11 mmHg, and right ventricular end-diastolic pressure, from 2.4 +/- 1.4 to 8.6 +/- 2.4 mmHg, were found. Anatomically, a 69% enlargement in right ventricular mass was observed, and this hypertrophic growth was characterized by a 78% thickening of the wall with no change in ventricular wall area, the latter calculated from the quotient of ventricular volume and wall thickness. Morphometric data showed a 44% increase in the capillary-to-myocyte ratio, a 66% augmentation of the total length of capillaries in the whole ventricle, and a 77% greater number of capillaries across the ventricular wall. Furthermore, these indexes of neogenesis of capillary units were associated with a more than three fold increase in the numerical density of mast cell profiles in the myocardium. In conclusion, capillary proliferation occurs in the adult rat heart, and this process appears to be coupled with mast cell hyperplasia.

Animals↗
PubMed1989

Mechanical and electrical properties of cardiomyopathic hearts of Syrian hamsters.

To determine whether the cardiomyopathy that develops in the Syrian hamster before the occurrence of congestive heart failure is associated with mechanical and electrical alterations consistent with myocardial dysfunction, left ventricular posterior papillary muscles of control and cardiomyopathic animals at 120 days of age were studied in vitro. Moreover, the electrocardiographic response to ouabain was investigated in vivo to analyze the arrhythmogenic potential of the cardiomyopathic heart to glycoside exposure. Results showed a decreased tension-generating ability of the myocardium in the diseased animals, which was accompanied by a prolongation of the timing parameters of contraction and an increase in the duration of the repolarization phase of the transmembrane action potential. Furthermore, the velocity of isotonic muscle shortening and relengthening was depressed at all physiological loads. Glycoside infusion elicited premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation in diseased hamsters much earlier in time than in healthy controls. The impairment in mechanical performance in association with the abnormality in membrane electrical activity may be responsible for the progression of the disease process and the occurrence of lethal arrhythmias in this animal model.

Action Potentials↗
PubMed1989

Ventricular remodeling induced by acute nonocclusive constriction of coronary artery in rats.

To determine the consequence of acute nonocclusive constriction of the epicardial coronary artery on the adaptation of the left ventricle and its impact as a function of age, the left main coronary artery was narrowed in rats 4 and 12 mo of age, and the animals were killed 45 min later. Similar reductions in the luminal diameter, averaging 4%, were obtained in both groups of animals, and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative change in pressure overtime (dP/dt) and in peak-developed ventricular pressure. Left ventricular volume increased by 66% and 56% at 4 and 12 mo because of increases in both the longitudinal and transverse chamber diameters. In contrast, wall thickness decreased by 27% and 35%, whereas sarcomere length increased only by 8.0% and 6.0%, respectively. These changes implied the occurrence of side-to-side slippage of myocytes within the wall to accommodate the larger chamber volume. The alterations in myocardial performance combined with the variations in ventricular size and wall thickness produced a marked elevation in diastolic and systolic wall stress. Moreover, myocyte cell damage in the form of contraction bands and disorganization of the intercalated disc region was seen. No consistent difference was found in any of the parameters measured as a function of age. Measurements of resting coronary blood flow across the left ventricular wall before coronary artery narrowing were comparable with those obtained 45 min after constriction. In conclusion, acute nonocclusive coronary artery stenosis has profound detrimental effects on the function and structure of the myocardium in the absence of an impairment of resting coronary blood flow.

Aging↗
PubMed1989

Capillary growth in anemia-induced ventricular wall remodeling in the rat heart.

To determine whether anemia-induced cardiac hypertrophy affects ventricular size and shape and the component structures of the capillary network of the left and right ventricles, young male rats were fed an iron- and copper-deficient diet for 7 weeks. By that time, blood hemoglobin content fell to 5 +/- 1 g/dl, and packed cell volume fell to 18 +/- 3%. To further characterize the implications of anemia, red blood cell number, hemoglobin corpuscular content, systemic arterial pressure, heart rate, and blood viscosity were measured. Moreover, the changes in ventricular weights were analyzed in terms of the alterations in ventricular wall area and ventricular wall thickness to establish the impact of the elevation in load associated with a high cardiac output state on ventricular remodeling. The quantitative properties of the capillary circulation were also examined biventricularly by low power electron microscopic morphometry to evaluate the adaptive growth potential of the coronary microcirculation in this form of cardiac hypertrophy. Anemia was found to interfere with the production of red blood cells and their mean corpuscular hemoglobin content and resulted in a 40% reduction in blood viscosity and a 12% and 27% decrease in systolic and diastolic blood pressure, respectively. The changes in heart rate were not statistically significant. In comparison with control animals, heart weight increased by 50%, but the enlargement in right ventricular mass (65%) was greater than that of the left ventricle (47%). Ventricular hypertrophy occurred with increases in wall area and wall thickness although the former increased consistently more than the latter in either ventricle. Tissue growth was accompanied by a 60% lengthening of the capillary network, which in combination with an increase in capillary diameter resulted in a 65% and 34% expansion in capillary luminal volume and 56% and 20% larger luminal surface density in the left and right sides of the heart, respectively. In conclusion, hypochromic microcytic anemia leads to eccentric ventricular hypertrophy with a significant amount of capillary proliferation that may tend to protect the myocardium from the increased potential for ischemic injury.

Adaptation, Physiological↗
PubMed1989

Differences in load dependence of relaxation between the left and right ventricular myocardium as a function of age in rats.

To determine whether the variation in the magnitude of work load sustained by the left and right ventricles during adulthood and senescence affects the load-dependent aspect of relaxation, posterior papillary muscles from the left and right ventricles of rats at 4, 10, and 20 months of age were studied under variably loaded conditions in vitro. Because of differences between the life spans of Fischer and Sprague-Dawley rats, the functional characteristics of relaxation were investigated to evaluate the possibility of a differential age-associated response in these two strains of animals. The kinetic performance of the diastolic phase of myocardial contraction was measured by assessing the relative time during which load bearing occurred in a series of afterloaded isotonic twitches. This measurement was expressed as the ratio of the duration of afterloaded isotonic shortening and relengthening to the time required for isometric force to decline to the same level during isometric relaxation. A ratio of less than unity identified a load-dependent state whereas a value greater than one reflected a load-independent condition. Results showed that the right myocardium was completely load independent whereas the left myocardium was fully load dependent at all physiological afterloads. Aging reduced the load independence of the right ventricle and the load dependence of the left ventricle in Fischer rats. In contrast, no aging effect on the properties of afterloaded isotonic relaxation was seen in Sprague-Dawley rats. In conclusion, distinct differences exist in the mechanical dynamics of inactivation between the left and right ventricular myocardium. Aging reduced these variations in Fischer rats but had no apparent influence in Sprague-Dawley animals up to 20 months after birth.

Aging↗
PubMed1989

Alterations in collagen cross-linking impair myocardial contractility in the mouse heart.

A number of genetic disorders in humans are associated with defects in the synthesis and metabolism of collagen, which are accompanied by multiple cardiovascular disease processes. To determine whether genetically determined cross-linking abnormalities of collagen may alter cardiac function, left ventricular papillary muscles of mice with a genetic defect in the cross-linking of collagen (Movbr) were studied in vitro. With respect to controls, increases in time to peak tension, from 102 +/- 1.4 to 125 +/- 5.4 msec (p less than 0.001), and time to one-half relaxation, from 76 +/- 3.0 to 98 +/- 6.1 msec (p less than 0.05), were measured. Moreover, resting tension at the length associated with maximum developed isometric force (L) was elevated, from 11.1 +/- 1.7 to 19.3 +/- 1.1 mN/mm2 (p less than 0.001), and a similar difference was also seen throughout the physiological range of muscle lengths. In contrast, developed tension was depressed at 93-97% of L. Peak rate of tension rise and decay were diminished whereas time to peak rate of tension rise was prolonged. Isotonically, a decrease in the magnitude of peak shortening at L, from 4.0 +/- 0.5 to 2.0 +/- 0.2% (p less than 0.04), and an increase in time to peak shortening, from 100 +/- 2.3 to 129 +/- 2.8 msec (p less than 0.001), were seen. In addition, peak velocities of shortening and relengthening were diminished in the Movbr mouse heart. In conclusion, the impairment in collagen cross-linking alters cardiac mechanics by a reduction in force-generating ability and a prolongation of the timing parameters of the systolic and diastolic phases of contraction in vitro.

Animals↗
PubMed1989

Morphometric analysis of coronary capillaries during physiologic myocardial growth and induced cardiac hypertrophy: a review.

The quantitative structural properties of the ventricular myocardium with respect to its capillary concentration and distribution have been measured morphometrically during postnatal physiologic growth and later in life in the rat, and compared with those accompanying an increased load in the adult heart to determine whether induced cardiac hypertrophy is a pathologic condition or a form of accelerated myocardial growth. The following morphometric parameters of the capillary microvasculature were examined: 1. Capillary luminal volume density; 2. Capillary luminal surface density; and 3. The average diffusion distance for oxygen. The expansion of the ventricular myocardium during maturation shows a remarkable degree of well balanced compensatory response, because the capillary microvasculature and myocytes grow in proportion to the increase in cardiac mass. In older rats parenchymal cells increase more than the capillary network resulting in a reduction of the oxygenation potential of the tissue and local ischemic damage. Cardiac hypertrophy produced by pressure overload, volume overload and by a combination of both may also show alterations affecting capillary luminal volume and surface densities and the path length for oxygen molecular transport, which indicate an inadequate growth adaption of the component structures responsible for tissue oxygenation. In conclusion, myocardial enlargement that develops with age or as a result of an increased work load on the heart may lead to a conditioned state of the myocardium that can be expected to increase its vulnerability to ischemia as in pathologic cardiac hypertrophy.

Aging↗
PubMed1988

Effects of alcohol on isoproterenol-induced ventricular fibrillation in adult rats.

To determine whether the pattern of alcohol consumption, intake, and withdrawal modulates the incidence of malignant ventricular arrhythmias and sudden cardiac death due to beta-adrenergic stimulation in a species susceptible to administration of isoproterenol alone, a regimen was formulated in which both continuous and interrupted alcohol ingestion was obtained. After alcohol treatment of fully mature, adult rats for 7 weeks, a single subcutaneous injection of 150 micrograms/kg of isoproterenol was given to control (non-alcohol-treated), alcoholic (continuous consumption), and alcohol withdrawal (interrupted) rats. The incidences of malignant ventricular arrhythmias and related deaths were compared. The results revealed that arrhythmias and arrhythmic deaths were highest in the "alcohol withdrawal group," 92% and 54%, respectively. As judged from baseline studies, withdrawal of alcohol produced a 16% decrease in serum K+ concentration compared with controls, whereas continuous alcohol ingestion resulted in a 20% elevation in magnesium concentration. These electrolyte changes were further affected by isoproterenol and may have contributed to the differential response to beta-adrenergic stimulation as a result of the pattern of alcohol intake.

Animals↗