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Biomedical subjects

P Anversa

Publications and source records attributed to P Anversa.

At least 109 records · Page 6Linked to original sources
PubMed1994

Efficacy of angiotensin-converting enzyme inhibition and AT1 receptor blockade on cardiac pump performance after myocardial infarction in rats.

To determine whether cardiac unloading by inhibition of angiotensin I (AI) to AII conversion by captopril or blockade of the AII receptor (AT1) by losartan was more effective in prevention of the detrimental hemodynamic consequences of myocardial infarction (MI), inhibition of metabolic production of AII by captopril was compared with blockade of AT1 with losartan in Sprague-Dawley rats with large MI. Infarcts were created by surgical occlusion of the left main coronary artery and oral drug therapy initiated immediately and continued until hemodynamic evaluation seven days later. Heart weight was unchanged in untreated infarcted animals, whereas captopril reduced heart weight in control animals and losartan increased heart weight in infarcted animals. Left ventricular (LV) peak systolic blood pressure (SBP) was lower in treated and untreated infarcted animals. Although captopril reduced end-diastolic pressure (EDP) to a greater degree than losartan, all infarcted group showed an increase in this parameter with respect to similarly treated controls. LV peak rates of pressure increase and decay in infarcted hearts were decreased significantly more by captopril than by losartan administration. Captopril also impaired right side cardiac function more than losartan when peak rate of pressure increase was evaluated. Thus, inhibition of the effects of AII during cardiac failure improved but did not normalize cardiac pump performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1994

Length-dependent modulation of ANG II inotropism in rat myocardium: effects of myocardial infarction.

To determine whether changes in sarcomere length affect the inotropic response of the heart to angiotensin II (ANG II) differently in dilated and failing myocardium, papillary muscles were removed 2 days after infarction, and the effects of ANG II were studied at various muscle lengths. Myocardial infarction, which averaged 52% of the left ventricle inclusive of the interventricular septum, was characterized hemodynamically by left ventricular failure and right ventricular dysfunction. ANG II administration at 100% the muscle length where force development is maximal (Lmax) produced a 12% depression of developed tension in papillary muscles from noninfarcted ventricles and a 37% decrease in developed tension in the viable myocardium of infarcted rats. In contrast, at 85 and 92.5% Lmax and in the presence of ANG II, control muscles increased active tension by 16 and 1.0%, whereas muscles from coronary occluded hearts augmented developed tension by 13 and 22%, respectively. In conclusion, ANG II exerted a positive inotropic effect on rat myocardium at muscle lengths on the ascending limb of the Starling curve but a negative inotropic action at the muscle length normally associated with maximum force development. This phenomenon emphasizes that hormonal influences on the contractile state of the diseased heart may be modulated by the interaction of end-diastolic pressure, sarcomere length, and ventricular size and shape.

Amino Acid Sequence↗
PubMed1994

Effects of aging on quantitative structural properties of coronary vasculature and microvasculature in rats.

To determine whether the alterations in coronary vascular resistance with aging have a structural basis, the quantitative properties of the intramural branches of the coronary circulation and capillary network were measured in Fischer 344 rats at 4, 12, 20, and 29 mo. Physiological measurements demonstrated that a severe impairment in cardiac pump function developed with age, leading to the occurrence of ventricular failure at 29 mo. Morphometrically, the length densities of resistance vessels from 6 to 20 microns in luminal diameter markedly decreased at 12 mo, and this change persisted at 20 and 29 mo. This phenomenon affected the inner, middle, and outer layers of the left ventricular wall. In contrast, capillary luminal volume percentage, capillary numerical density, and average diffusion distance for oxygen in the left and right myocardium were altered only at 20 mo, whereas values comparable to those at 4 mo were found at 12 and 29 mo. The preservation of these capillary characteristics in the heart was due to a significant amount of capillary proliferation. In conclusion, aging effects lead to rarefaction of coronary arterioles in the myocardium, which may impair coronary resistance and reserve without altering the capillary microvasculature and the oxygenation potential of the old and senescent heart.

Aging↗
PubMed1994

Cilazapril treatment depresses ventricular function in spontaneously hypertensive rats.

The purpose of this study was to characterize the effect of chronic treatment with an angiotensin-converting enzyme (ACE) inhibitor on left ventricular function in spontaneously hypertensive rats (SHR). Cilazapril (5 mg/kg) was administered in the drinking water continuously for 11 wk, beginning at 4 wk of age. Systolic arterial pressure (SAP) was monitored weekly. At the end of the 11-wk period, left ventricular function was quantified using the perfused working heart preparation. Cilazapril exerted a rapid, complete, and persistent antihypertensive effect in the SHR in vivo but had no effect on SAP in the normotensive Sprague-Dawley (S-D) group. Nevertheless, the drug reduced left ventricular weight to the same extent in both strains. Function of untreated SHR hearts was not different from that of the untreated S-D hearts. Cilazapril treatment depressed heart performance (28-35%) in SHR but had no effect in the S-D group. The decline in pump performance in SHR hearts was associated with diminished tension development and velocity of shortening of papillary muscles. These results demonstrate that an ACE inhibitor, administered to young SHR, produces a reduction in left ventricular contractile function, which may be due to a decline in muscle contractility and which cannot be explained exclusively by the reduction in left ventricular mass.

Aging↗
PubMed1994

Structural basis of end-stage failure in ischemic cardiomyopathy in humans.

BACKGROUND: Ischemic cardiomyopathy is characterized by myocyte loss, reactive cellular hypertrophy, and ventricular scarring. However, the relative contribution of these tissue and cellular processes to late failure remains to be determined. METHODS AND RESULTS: Ten hearts were obtained from individuals undergoing cardiac transplantation as a result of chronic coronary artery disease in its terminal stage. An identical number of control hearts were collected at autopsy from patients who died from causes other than cardiovascular disease, and morphometric methodologies were applied to the analysis of the left and right ventricular myocardium. Left ventricular hypertrophy evaluated as a change in organ weight, aggregate myocyte mass, and myocyte cell volume per nucleus showed increases of 85%, 47%, and 103%, respectively. Corresponding increases in the right ventricle were 75%, 74%, and 112%. Myocyte loss, which accounted for 28% and 30% in the left and right ventricles, was responsible for the difference in the assessment of myocyte hypertrophy at the ventricular, tissue, and cellular levels. Left ventricular muscle cell hypertrophy was accomplished through a 16% and 51% increase in myocyte diameter and length, whereas right ventricular myocyte hypertrophy was the consequence of a 13% and 67% increase in these linear dimensions, respectively. Moreover, a 36% reduction in the number of myocytes included in the thickness of the left ventricular wall was found. Collagen accumulation in the form of segmental, replacement, and interstitial fibrosis comprised an average 28% and 13% of the left and right ventricular myocardia, respectively. The combination of cell loss and myocardial fibrosis, myocyte lengthening, and mural slippage of cells resulted in 4.6-fold expansion of left ventricular cavitary volume and a 56% reduction in the ventricular mass-to-chamber volume ratio. CONCLUSIONS: These results are consistent with the contention that both myocyte and collagen compartments participate in the development of decompensated eccentric ventricular hypertrophy in the cardiomyopathic heart of ischemic origin.

Cardiomyopathy, Dilated↗
PubMed1994

Myocyte cellular hyperplasia and myocyte cellular hypertrophy contribute to chronic ventricular remodeling in coronary artery narrowing-induced cardiomyopathy in rats.

To determine whether cardiac failure produced by chronic coronary artery stenosis was associated with the activation of myocyte cellular hyperplasia in the myocardium, the changes in number and size of left ventricular myocytes were measured in rats 3 months after surgery. The hypertrophied left ventricle was found to possess 44%, 32%, 49%, and 48% fewer mononucleated, binucleated, trinucleated, and tetranucleated myocytes, respectively. In contrast, the hypertrophied right ventricle contained 1.49 x 10(6) more myocytes as a result of a 2.1-fold, 1.4-fold, and 1.4-fold increase in mononucleated, binucleated, and tetranucleated myocytes. Myocyte cell volume was seen to increase 49% and 21% in left and right ventricular myocytes, respectively. The process of myocyte cellular hyperplasia in the right ventricular myocardium was accompanied by capillary proliferation, and these events were responsible for the parallel addition of newly formed cells and capillaries within the wall and mural thickening. Moreover, the in-series insertion of new myocytes contributed to right ventricular dilatation after coronary artery stenosis. In view of the fact that extensive myocardial damage and cell loss may have masked the phenomenon of myocyte cellular hyperplasia in the left ventricle, the presence of DNA synthesis in myocyte nuclei was evaluated at 3 days, 1 week, 2 weeks, 1 month, and 3 months after coronary artery stenosis. Bromodeoxyuridine (BrdU) labeling markedly increased in myocyte nuclei of both ventricles, reaching its peak at 1 and 2 weeks. BrdU labeling of nonmyocyte nuclei also increased but mostly at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

End-stage cardiac failure in humans is coupled with the induction of proliferating cell nuclear antigen and nuclear mitotic division in ventricular myocytes.

Proliferating cell nuclear antigen (PCNA) is a late growth-regulated gene that is expressed at the G1-S boundary of the cell cycle and is required for DNA synthesis and cell proliferation. Since quantitative results suggest that myocyte hyperplasia occurs in the decompensated human heart, we postulated that induction of the PCNA gene may be present in the failing heart in humans. PCNA protein was detected in myocardial samples obtained from the left and right ventricles of patients with congestive heart failure. Endomyocardial biopsies collected from donor subjects were used as control tissue. The percentage of positively stained myocyte nuclei in the ventricles was established by using PCNA monoclonal antibody and the immunoperoxidase technique. The localization of PCNA in myocytes was confirmed by alpha-sarcomeric actin antibody staining. PCNA labeling was present in left ventricular myocytes of 29 of the 32 hearts examined. In the right ventricle, 24 of the 29 samples showed positive staining. In a subset of 25 patients, the percentage of PCNA-labeled myocyte nuclei was measured and found to constitute 49 +/- 22% of left ventricular myocytes. A similar analysis for the right ventricle, conducted in 21 patients, showed that 49 +/- 19% of the myocyte nuclei exhibited PCNA protein. In addition, mitotic figures in myocytes were documented. A quantitative analysis of this cellular process revealed that 11 myocyte nuclei per 1 million cells exhibited mitotic images in chronic heart failure. Immediately after myocardial infarction, two cells per million showed mitotic division, and this phenomenon was restricted to the region adjacent to the necrotic tissue. No PCNA labeling or nuclear mitotic images were detected in the ventricular myocardium of control subjects. Thus, the observation that diffuse PCNA labeling and myocyte mitotic division are present in hearts with end-stage failure strongly suggests that adult ventricular myocytes are not terminally differentiated cells and that myocyte cellular hyperplasia may constitute a growth reserve mechanism of the diseased heart.

Adult↗
PubMed1993

Myocyte DNA synthesis with aging: correlation with ventricular loading in rats.

To determine whether the detrimental mechanical and anatomical changes that occur biventricularly with aging are associated with activation of DNA synthesis, flow cytometric analysis was performed on myocyte nuclei prepared from the left and right ventricles of rats at 4, 12, 20, and 29 months of age. Heart weight increased significantly with age, and this growth adaptation was associated with the development of left ventricular failure and right ventricular dysfunction. These phenomena were coupled with marked elevations in diastolic wall stress and increases in the percentage of myocyte nuclei in S+G2M in both ventricles. Linear regression analyses revealed a direct correlation between the fraction of myocytes that entered the cell cycle and diastolic pressure and wall stress. An inverse relation was found between the percentage of myocyte nuclei in S+G2M and +dP/dt and systolic wall stress. Thus the depression of hemodynamic performance coupled with alterations in the loading conditions contributes, at least in part, to increased DNA synthesis in cardiac myocytes with age.

Aging↗
PubMed1993

Impairment of myocyte contractility following coronary artery narrowing is associated with activation of the myocyte IGF1 autocrine system, enhanced expression of late growth related genes, DNA synthesis, and myocyte nuclear mitotic division in rats.

To determine whether the alterations in ventricular loading and myocyte cellular contractile performance produced by short-term coronary artery constriction were associated with the activation of genes implicated in myocyte DNA synthesis including changes in the expression of insulin-like growth factor-1 (IGF1) and insulin-like growth factor-1 receptors (IGF1-R), nonocclusive coronary artery narrowing (CAN) was induced in rats. Animals were examined 2 and 7 days after coronary constriction. Following the in vivo documentation of severe impairment of ventricular performance, estimations of single-cell mechanics in vitro showed that peak shortening was decreased in left and right myocytes of coronary stenosed rats. Moreover, time to peak shortening was prolonged whereas velocity of shortening was decreased. These defects in myocyte contractility were accompanied by increases in cell length and width, indicative of myocyte enlargement biventricularly. In addition, CAN led to an enhanced expression of proliferating cell nuclear antigen (PCNA) and histone-H3 genes in myocytes at 2 and 7 days after surgery. PCNA protein was also detected in these stressed cells. These molecular responses were associated with increases in mRNA for IGF1 and IGF1-R in combination with enhanced DNA synthesis and appearance of myocyte nuclear mitotic division. In conclusion, cardiac myocytes may respond to the elevation in wall and myocyte stress by activating an IGF1-IGF1-R autocrine system which may modulate the induction of late growth related genes which are essential for DNA replication and myocyte cellular hyperplasia.

Animals↗
PubMed1993

Myocyte loss and left ventricular failure characterise the long term effects of coronary artery narrowing or renal hypertension in rats.

OBJECTIVE: The aim was to determine the effects of chronic coronary artery narrowing and two kidney, one clip renal hypertension alone and in combination on ventricular function and myocardial morphology. METHODS: Left coronary stenosis and renal artery clipping were surgically induced in rats and pump dynamics, systolic and diastolic wall stress, cardiac anatomy, and the changes in number and size of left ventricular myocytes were examined 11-13 weeks later. RESULTS: Ventricular failure evolved with each intervention: left ventricular end diastolic pressure was raised, whereas +dP/dt, -dP/dt, stroke volume, cardiac output, and cardiac index were reduced. Calculated ventricular systolic wall stress increased nearly 70% in the three experimental conditions. By contrast, diastolic wall stress was augmented 6.1-fold with coronary stenosis, 4.0-fold with hypertension, and 4.4-fold with combined treatment. These differences were due to variable preservations of wall thickness between the groups. Left ventricular weight expanded 26%, 35%, and 32% with stenosis, hypertension, and a combination of the two, whereas diastolic cavitary volume increased 57%, 35%, and 49%. Corresponding increases in systolic chamber volumes were 156%, 122%, and 154%. Finally, myocyte loss in the ventricle was 25%, 25%, and 37% in coronary narrowing, renal hypertension and a combination of the two with concomitant enlargements of the unaffected myocytes of 47%, 63%, and 65%. CONCLUSIONS: Decompensated eccentric ventricular hypertrophy developed as a result of coronary artery narrowing, renal hypertension, or the two in combination. Coronary artery narrowing, however, may have a greater maladaptive effect on ventricular function than systemic hypertension, and coronary stenosis and hypertension combined because of the more extensive chamber and wall remodelling which sustained greater increases in diastolic wall stress.

Animals↗
PubMed1993

Effects of genetic hypertension and nutritional anaemia on ventricular remodelling and myocardial damage in rats.

OBJECTIVE: In order to determine whether alterations in cardiac function and structure occur early in life in spontaneously hypertensive rats (SHR) and whether the addition of a volume load would affect myocardial growth and haemodynamic performance, SHR were exposed to an iron and copper deficient diet for 12 weeks (SHR-A) and compared with untreated SHR and Wistar Kyoto controls (WKY). RESULTS: Systolic arterial blood pressure increased in SHR, whereas nutritional anaemia prevented the rise of blood pressure in SHR-A. The diet employed provoked a severe hypochromic microcytic anaemia with a marked reduction in blood viscosity and increased volume load on the heart in SHR-A. Genetically determined hypertension alone induced a 16% increase in left ventricular weight and an increase in left ventricular peak systolic pressure (LVPSP) and +dP/dt. The superimposition of anaemia resulted in a 43% expansion in left ventricular weight with a decrease in LVPSP and +dP/dt, and an increase in left ventricular end diastolic pressure. Wall thickening and a preservation of chamber volume occurred in SHR, while SHR-A had a degree of ventricular dilatation which exceeded the extent of wall thickening. However, genetic hypertension was accompanied by myocardial tissue injury which was fully prevented by the addition of nutritional anaemia. Moreover, the capillary volume was decreased in SHR and increased in SHR-A. CONCLUSIONS: Genetically determined hypertension in combination with anaemia results in eccentric ventricular hypertrophy and cardiac dysfunction in spite of an increase in capillary luminal volume and limited structural damage.

Anemia, Hypochromic↗
PubMed1993

ANG II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure.

To determine the relationship between reactive cardiac hypertrophy and the expression of angiotensin II (ANG II) receptors in surviving myocytes after infarction, large infarcts were produced in rats that were killed 2-3 days later. Measurements of global ventricular dynamics indicated that left ventricular failure and right ventricular dysfunction occurred in experimental animals. These alterations in ventricular pump function were associated with increases in ventricular weight-to-body weight ratio, indicative of developing cardiac hypertrophy. Such a response was coupled with a 6.6-fold increase in ANG II receptor mRNA in myocytes from the left ventricle. A 2.3-fold increase in the expression of ANG II receptor in myocytes from the right ventricle was also found. Radioligand binding assay documented a 44% increase in the density of ANG II receptors on left ventricular myocytes of infarcted hearts. To establish whether the induction of genes commonly associated with myocyte hypertrophy was present, the message for c-myc and c-jun was biventricularly assessed. Myocardial infarction was accompanied by overexpressions of c-myc and c-jun that were more prominent in left than in right ventricular myocytes. In conclusion, the enhanced expression of ANG II receptor and its receptor protein and c-myc and c-jun in myocytes may participate in the reactive growth processes of these cells after infarction.

Animals↗
PubMed1993

Propionyl-L-carnitine limits chronic ventricular dilation after myocardial infarction in rats.

To determine whether propionyl-L-carnitine (PLC) administration ameliorates ventricular remodeling after myocardial infarction, we performed coronary occlusion in rats and examined the long-term effects of the drug 19-24 wk after surgery. In view of the well-established role of angiotensin-converting enzyme (ACE) inhibitors in the reduction of ventricular dilation after infarction, the therapeutic impact of oral PLC (60 mg/kg) was compared with that of enalapril (1 mg/kg). Infarct size measured planimetrically was found to be comparable in untreated, PLC-treated, and enalapril-treated rats, averaging 40-46% of the left ventricular free wall. Heart weight was increased 14, 16, and 11% with no treatment, with PLC, and with enalapril, respectively. The relationship between left ventricular filling pressure and chamber volume demonstrated that PLC and enalapril significantly prevented the expansion in cavitary size after infarction. These protective influences were observed throughout the range of filling pressures measured, from 0 to 30 mmHg. At a uniform reference point of filling pressure of 4 mmHg, untreated infarcted hearts showed an expansion in ventricular volume of 2.17-fold (P < 0.0001). Corresponding increases in this parameter after PLC and enalapril were 36 and 43%, respectively, both not statistically significant. Moreover, PLC was capable of reducing the alterations in myocardial compliance associated with myocardial infarction. In conclusion, PLC reduces the magnitude of decompensated eccentric hypertrophy produced by myocardial infarction in a manner similar to that found with ACE inhibition.

Administration, Oral↗
PubMed1993

Segmental calculation of left ventricular wall stresses.

A procedure for calculating left ventricular wall stresses segmentally was devised. Rectangular coordinates of the wall surfaces as seen in longitudinal section were plotted with the long axis as the x-axis. For each cavity point, a third-order polynomial (cubic spline) was fitted to the point together with several adjacent points on either side of it; the cavity radius (normal to cavity surface) at the point was found algebraically from the spline's coefficients. Each cavity radius was matched with the most symmetrical one from the opposite cavity surface. The point of intersection of the cavity radius with the outer surface was found, and a midwall point was identified from logarithmic means of cavity and outer radial lengths. For each midwall point, a cubic spline was fitted to that point together with several adjacent points on either side of it, and the midwall radius at that point was determined algebraically from the spline's coefficients. Each midwall radius was matched to the most symmetrical one from the opposite midwall. The locus of points at equal radial distances from opposite midwalls forms the axis. The midwall radius of curvature (r theta) orthogonal to the meridian at each point was taken as the radial distance from the midwall to the axis. Midwall meridional radius of curvature (r phi) was calculated from the spline's coefficients. Thickness (h) was calculated from intersections between the midwall radius and the inner and outer surfaces. For each point, meridional tension (T phi) was calculated as T phi = Pr theta/2, and hoop tension (T theta) was calculated as T theta = (Pr theta/2)(2 - r theta/r phi) where P is transmural pressure. Stresses were calculated as tensions divided by thicknesses (sigma phi = T phi/h, sigma theta = T theta/h), or more directly as sigma phi = Pr theta/2h and sigma theta = (Pr theta/2h)(2 - r theta/r phi). This procedure was validated with simple chamber shapes, and it has been applied to left ventricles.

Animals↗
PubMed1993

Alterations in ANG II responsiveness in left and right myocardium after infarction-induced heart failure in rats.

To determine the effects of coronary arterial occlusion on the contractile response of the heart to angiotensin II (ANG II) administration, large infarcts were surgically induced in Sprague-Dawley rats at 2 mo of age. Forty-eight hours later, hearts from experimental animals presented a hemodynamic profile indicative of left ventricular failure and right ventricular dysfunction and revealed a loss of mass of 49.3 +/- 10.8% of the left ventricle inclusive of the interventricular septum. Plasma renin activity was found to be decreased by 48% in animals with occlusion of the left main coronary artery. Left and right posterior papillary muscles removed from these same hearts were evaluated mechanically in the presence and absence of ANG II. Contractile performance was impaired in left ventricular myocardium from infarcted rats as evidenced by the inability to attain developed tension similar to that seen in control rats. In addition, peak rates of tension rise and decay were significantly depressed. A reduction in contraction duration was also found in experimental animals, limiting the active state of the myocardium. ANG II resulted in a depression in the force-generating ability of left and right papillary muscles of control and experimental animals. Importantly, the negative inotropic effect of ANG II affected the left and right myocardium from infarcted rats by nearly twofold and threefold more than the corresponding muscles from controls. Morphometric evaluation revealed the absence of damage in both papillary muscles from control hearts and in the right muscles from experimental animals. However, necrotic tissue comprised 28.3 +/- 9.8% of left papillary muscles obtained from infarcted ventricles. It is concluded that ANG II administration resulted in reduced mechanical performance of rat myocardium. Coronary arterial ligation potentiated this phenomenon, and such a negative effect may have implication in infarction induced heart failure in vivo.

Angiotensin II↗
PubMed1993

Effects of hypertension and coronary constriction on cardiac function, morphology, and contractile proteins in rats.

In an attempt to elucidate the effects of two major risk factors of heart failure in humans, high blood pressure and coronary artery disease, renal hypertension and coronary artery constriction were induced singularly and in combination in rats, and the functional, structural, and biochemical alterations of the myocardium were examined 12-13 wk later. Renal hypertension (RH), coronary narrowing (CN), and their association (NH) resulted in left ventricular failure demonstrated by a significant increase in left ventricular end-diastolic pressure, a decrease in +dP/dt and -dP/dt, and a reduction in stroke volume and cardiac output. Measurements of ventricular loading documented that RH was characterized by elevations in systolic and diastolic wall stress of 42 and 160%, respectively. Corresponding changes with NH were 80 and 315%. CN was accompanied by an augmentation of diastolic wall stress only (280%). The abnormalities in mural stress were coupled with reductions in systolic and diastolic wall thickness-to-chamber radius ratios of 39 and 29% after CN. These anatomic parameters were preserved with RH, whereas the systolic wall thickness-to-chamber radius ratio was reduced 31% with NH. Structurally, multiple foci of replacement fibrosis were found with each intervention. The sites of tissue injury and their volume percent in the myocardium were comparable with CN and RH but were significantly more numerous and occupied a larger fraction of the ventricular wall in the presence of NH. Biochemically, the calcium dose-response curve of myofibrillar Mg2+ adenosinetriphosphatase (ATPase) activity did not vary with CN, RH, and NH. In contrast, a marked decrease in Ca2+ myosin ATPase activity was found in NH rats in association with a shift in myosin isoenzymes from V1 to V3. In conclusion, multiple physiological, morphological, and biochemical factors may participate in the generation of the abnormalities in ventricular loading with hypertension and/or coronary artery stenosis.

Animals↗
PubMed1993

Cytosolic calcium transients in myocytes isolated from rats with ischemic heart failure.

Mechanical performance and cytosolic Ca2+ dynamics were characterized in myocytes isolated from left and right ventricles of rats with ischemic heart failure. Seven days after coronary artery narrowing (CAN) in rats filling pressures were elevated, whereas systolic pressures and ejection of blood were depressed. Left ventricular myocytes increased 18% in length and 19% in width, whereas right myocytes expanded longitudinally by 23% and transversely by 24%. Contractile behavior of myocytes displayed reductions in myocyte shortening and velocity of shortening, despite prolongation of time to peak shortening. Diastolic Ca2+ increased by 32 and 39% in left and right myocytes of CAN animals, whereas peak systolic Ca2+ in left ventricular myocytes was depressed (22%). Time to peak Ca2+ was prolonged by 68% in left myocytes. Moreover, time required for peak Ca2+ to return to diastolic levels was prolonged in left myocytes. Regression analysis revealed correlations between end-diastolic pressure and diastolic Ca2+ and peak developed pressure and systolic Ca2+. Thus ischemic heart failure finds its cellular basis in a depression in myocyte contractility that may in turn be due to alterations in cytosolic Ca2+ handling.

Animals↗