Biomedical subjects

J M Capasso

Publications and source records attributed to J M Capasso.

At least 37 records · Page 2Linked to original sources

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↗

PubMed1993

Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats.

To determine the effects of acute myocardial infarction on the regulation of angiotensin II (Ang II) receptors and contractile performance of left and right ventricular myocytes, coronary artery ligation was surgically induced in rats, and Ang II receptor density and affinity and the mechanical properties of surviving muscle cells were examined 1 week later. Physiological determinations of cardiac pump function revealed the presence of ventricular failure, which was associated at the cellular level with a depression in the velocity of myocyte shortening and relengthening, a prolongation of time to peak shortening, and a reduction in the extent of cell shortening. These abnormalities in single-cell function were more prominent in left than in right ventricular myocytes. Cellular hypertrophy was documented by increases in cell length and width, which were also greater in the spared myocytes of the infarcted left ventricle. Reactive hypertrophy was accompanied by a 1.84- and 1.85-fold increase in the density of Ang II receptors on left and right myocytes, respectively. On the other hand, the affinity of Ang II receptors for the radiolabeled antagonist was not altered. However, Ang II-stimulated phosphoinositol turnover was enhanced by 3.7- and 2.5-fold in left and right myocytes, respectively, after infarction. Ventricular myocytes were found to possess the AT1 receptor subtype exclusively. In conclusion, myocardial infarction leads to impairment in the contractile behavior of the remaining cells and to the activation of Ang II receptors and effector pathway associated with these receptors, which may be involved in the reactive growth adaptation of the viable myocytes.

Angiotensin Receptor Antagonists↗

PubMed1993

Myocardial infarction, cardiac anatomy and ventricular loading.

To see whether the hypertrophic response of the surviving myocardium after infarction leads to a complete reconstitution of ventricular mass, the left coronary artery was ligated in rats and the animals killed one month later. In infarcts affecting an average of 38% of the free wall of the left ventricle, the ratio of wall thickness to chamber radius remained essentially constant. On the other hand, the ratio decreased significantly in the presence of infarcts involving an average of 60% of the ventricular wall. In addition, inadequate growth adaptations were detected in both groups of infarcts with respect to myocyte volume and length and to capillary volume and length. These defects in the regeneration of myocardial structures were associated with elevations in diastolic wall stress which were more prominent in the larger infarct group. The limited growth reaction of the myocyte and vascular compartments may be implicated in the persistence of cardiac dysfunction and failure late after infarction.

Animals↗

PubMed1992

Extensive digestion of Na+,K(+)-ATPase by specific and nonspecific proteases with preservation of cation occlusion sites.

This paper extends our recent report that renal Na+,K(+)-ATPase is digested by trypsin in the absence of Ca2+ and presence of Rb+ ions to a stable 19-kDa fragment and smaller membrane-embedded fragments of the alpha chain and essentially intact beta chain. These are referred to as "19-kDa membranes." Occlusion of both Rb+ (K+) or Na+ ions is preserved, but ATP-dependent functions are lost (Karlish, S. J. D., Goldshleger, R., and Stein, W. D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4566-4570). We now show that extensive digestion with nonselective fungal proteases (Pronase and proteinase K) alone, in combination, or after tryptic digestion can remove up to 70% of membrane protein without destroying Rb+ occlusion. In the most heavily digested membranes, the 19-kDa fragment or a slightly shorter 18.5-kDa fragment and smaller fragments of the alpha chain remain, whereas the beta chain is largely digested, leaving smaller membrane-embedded fragments (13-15 kDa). For either trypsin or Pronase digestion, preservation of Rb+ occlusion and the specific fragmentation pattern is observed only in the absence of divalent metal ions (Mg2+ or Ca2+) and presence of either Rb+ or Na+ or congener ions. Tryptic digestion at pH 7.0 can split the beta chain into two fragments of approximately 50 and 16 kDa joined by an S-S bridge. The 16-kDa fragment is protected against further digestion by the presence of Rb+ ions, but probably is not directly involved in occluding cations. Tryptic 19-kDa membranes show a clear and reproducible fragmentation pattern in which all predicted membrane segments are identifiable. Families of fragments from 19-kDa membranes, including seven peptides of 7.6-11.7 kDa, have been separated by size-exclusion high performance liquid chromatography, concentrated, and resolved on 16.5% Tricine gels. N-terminal sequences of the different fragments have been determined after transfer to polyvinylidene difluoride paper. The most interesting findings are as follows. (a) Whereas the 19-kDa tryptic fragment begins at Asn831 as reported previously, the 18.5-kDa Pronase fragment begins at Thr834. (b) Fragments in tryptic 19-kDa membranes of 7.6-11.7 kDa begin at Asp68, Ile263, and Gln737, respectively. These include all putative transmembrane segments other than those in the 19-kDa fragment. (c) A Pronase fragment of 7.8 kDa begins at Thr834, i.e. apparently the 19-kDa fragment has been partially cut, without loss of Rb+ occlusion. (d) Tryptic 16- and approximately 50-kDa fragments of the beta chain begin at Ala5 and Gly143, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1992

Cellular basis of ventricular remodeling in hypertensive cardiomyopathy.

This review summarizes the effects of long-term pressure overload hypertrophy on the right and left ventricular myocardium. In particular, the role that the fundamental processes of myocyte growth plays in the remodeling of the wall is analyzed quantitatively. Moreover, emphasis is placed on the observation that the duration of the overload is an important component of the onset, development, and progression of time-dependent myocardial dysfunction associated with hypertensive cardiomyopathy. The deterioration in ventricular pump function is postulated to be accompanied by myocyte cellular hyperplasia and capillary proliferation in an attempt to increase the thickness of the ventricular wall and, consequently, to decrease the magnitude of systolic and diastolic stress generated by the elevation in ventricular systolic and end-diastolic pressures. Myocyte cellular hyperplasia constitutes an essential growth reserve mechanism of the heart. Regeneration of damaged and lost myocardium may be accomplished by hyperplasia of myocytes, a phenomenon considered not feasible for several decades.

Cardiomyopathies↗

PubMed1992

Re-expression of alpha skeletal actin and regulation of alpha 1 adrenoceptor signalling in DOCA-salt hypertension in rats.

OBJECTIVE: To determine the effects of increased sympathetic nervous system activity in humoral hypertension on the regulation of surface alpha 1 adrenoceptors and signal transduction, deoxycorticosterone acetate (DOCA) salt hypertension was induced in rats and the animals killed three weeks following the initiation of hypertension. METHODS: Experiments were performed on male Sprague-Dawley rats, weighing 250-300 g, divided into two groups: DOCA-salt (n = 75), and control (n = 60). Radioligand binding studies of the alpha 1 adrenoceptors, noradrenaline stimulated phosphoinositol turnover, ADP ribosylation of 41 kD substrate by pertussis toxin, and myocardial noradrenaline content were measured in the ventricular myocardium. The expression of sarcomeric actin isoforms was examined by northern blot and hybridisation with specific oligonucleotide probes. RESULTS: The density of alpha 1 adrenoceptors was decreased by 51% in DOCA-salt treated rats. However, noradrenaline stimulated phosphoinositol turnover in myocytes from DOCA-salt hearts was not diminished. The relative quantities of pertussis toxin labelled substrates did not differ in experimental and control hearts. Myocardial noradrenaline content was reduced by 60% in DOCA-salt hearts. Northern blots on RNA extracted from hypertrophic hearts of DOCA-salt treated rats showed an upregulation of alpha skeletal actin. CONCLUSIONS: The adrenergic state present in short term DOCA-salt hypertensive hypertrophy is characterised by enhanced signal transduction via the alpha 1 adrenoceptors and the re-expression of alpha skeletal actin in enlarging myocytes.

Actins↗

PubMed1992

Heterogeneity of ventricular remodeling after acute myocardial infarction in rats.

To determine the effects of acute myocardial infarction on the extent and distribution of systolic and diastolic wall stress on the surviving myocardium, coronary artery occlusion was produced in rats, and the animals were killed 1 wk later. After hemodynamic measurements in vivo, the characteristics of cardiac anatomy at end diastole and peak systole were mimicked in vitro by fixing hearts under diastolic conditions or barium-induced contracture. In the presence of infarcts inducing a 48% loss of myocytes, left ventricular failure was documented by increases in left ventricular minimal and end-diastolic pressures and decreases in peak systolic pressure and positive and negative rates of pressure change with time. End-diastolic and end-systolic volumes increased, whereas stroke volume and cardiac output diminished. Ventricular remodeling in diastole consisted of an increase in the longitudinal axis while both longitudinal and transverse mid-chamber diameters were augmented after systolic contraction. Left ventricular chamber volume enlarged by 44% through a 20% augmentation in the longitudinal diameter and increases in the transverse luminal diameter of 13, 21, 32, and 37% in four consecutive sites from the equatorial region to the apex. As a consequence of infarction, systolic thickening of the spared myocardium of the free wall was reduced progressively from the base to the apex. In the interventricular septum of the infarcted heart, systole thickening occurred mostly in the equatorial region and was reduced at the basal and apical portions. The interaction of hemodynamic impairment with the architectural rearrangements of the wall and chamber provoked a 1.9-fold increase in overall stress on the spared myocardium. However, diastolic stress was augmented by 6.8-fold, markedly exceeding the 1.1-fold increase in systolic stress. Thus large infarcts of the rat left ventricle due to left main coronary occlusion lead to a change in shape of the heart from ellipsoidal to cylindrical. The elevation in overall stress may condition the unfavorable long-term outcome of the infarcted heart.

Animals↗

PubMed1992

Amelioration of effects of hypertension and diabetes on myocardium by cardiac glycoside.

To determine whether digoxin protects the myocardium during the initial phases of hypertension and diabetes combined, adult male Wistar rats with two-kidney, one-clip renal hypertension and streptozotocin-induced diabetes mellitus were treated with digoxin (500 micrograms.kg-1.day-1) by gavage for 10 wk immediately after the onset of hypertension and diabetes. Systemic arterial blood pressures, ventricular pressures, the first time derivative of left ventricular pressure, diastolic wall stress, and the quantitative analysis of the number and distribution of myocardial lesions and capillary density of the myocardium were measured. In comparison to untreated hypertensive-diabetic animals, digoxin-treated rats showed a lesser elevation in left ventricular end-diastolic pressure and diastolic and systolic wall stress despite comparable degrees of hypertension and blood glucose levels. In addition, chamber diameter was smaller and the diffusion distance for oxygen was within normal values in animals treated with this glycoside. However, the numerical density of the foci of replacement fibrosis was similar to that found in untreated hypertensive-diabetic animals. In conclusion, digoxin reduces the magnitude of ventricular remodeling and diastolic wall stress in this model of hypertension and diabetes.

Animals↗

PubMed1992

Cellular mechanisms of ventricular failure: myocyte kinetics and geometry with age.

To determine whether heart failure is a consequence of alterations in cardiac cellular performance, myocytes were isolated from Fischer 344 rats at 4, 12, 20, and 29 mo of age and studied mechanically and morphometrically. Left ventricular myocyte length increased by 14.5, 14.4, and 24.0% at 12, 20, and 29 mo when compared with 4-mo-old animals. An 11.4 and 14.2% increase in length was seen for right ventricular myocytes from 4 to 12 mo and from 20 to 29 mo, respectively. Although no change in cell width was seen in either ventricle as a function of age, myocardial cells were more irregular in shape and consistently longer in the left ventricle at 20 and 29 mo. Left myocytes at 29 mo revealed diminished velocities of shortening (31.7%) and relengthening (59.5%). Contraction duration increased due to a 28.9% prolongation of time to peak shortening and a 26.5% increase in time to relengthening, resulting in a 25.8% decrease in myocyte shortening at 29 mo. Similar changes were observed in right ventricular myocytes, but they occurred later in life. Thus the alterations in myocyte geometry and depression in contractile performance seen here are major contributors to the eccentric dilated ventricular chamber and diminished pump function previously documented in the age-related transition from normal cardiac dynamics to left ventricular dysfunction and failure.

Aging↗

PubMed1992

Long-term coronary stenosis in rats: cardiac performance, myocardial morphology, and contractile protein enzyme activity.

To determine the effects of chronic nonocclusive coronary constriction on cardiac hemodynamics, myocardial structure, and contractile protein enzyme activity, the left coronary artery was narrowed in rats, and measurements of ventricular pump function, extent and localization of tissue damage, and myofibrillar Mg2+ and Ca2+ myosin adenosinetriphosphatase (ATPase) activities were measured 3 mo later. In the presence of coronary artery stenosis averaging 56%, two different degrees of depression in global cardiac performance were identified, and the animals were divided in two groups. In the first group, left ventricular end-diastolic pressure (LVEDP) was increased and LV+ and/or--the first derivative of LV pressure (dP/dt) were decreased, whereas in the second group end-diastolic and peak systolic LV pressures, LV+ and -dP/dt and right ventricular dynamics were all impaired. Thus left ventricular dysfunction and failure occurred with coronary narrowing. Structurally, multiple foci of replacement fibrosis were found across the left ventricular wall, but the number of these lesion profiles was 2.6-fold larger in failing animals than in rats with cardiac dysfunction. Biochemically, Mg(2+)-ATPase activity in myofibrils and Ca2+ myosin ATPase were not altered biventricularly. On the other hand, a shift from V1 to V3 myosin isoenzymic content occurred in the failing left ventricle. In conclusion, the late impairment in ventricular pump function associated with prolonged coronary artery stenosis appears to be sustained more by the magnitude of myocardial damage than by defects in contractile protein enzyme activity.

Animals↗

PubMed1992

Mechanical performance of spared myocytes after myocardial infarction in rats: effects of captopril treatment.

To determine the effects of myocardial infarction-induced left ventricular failure on the mechanical characteristics of the remaining viable myocytes, coronary arterial occlusion was performed in rats, and cell function was examined 1 wk later. Moreover, to establish the mechanisms by which treatment with angiotensin-converting enzyme inhibitors ameliorates cardiac dynamics, captopril was administered immediately after surgery, and the contractile behavior of the unaffected cells was similarly analyzed 7 days later. The severe impairment in left-side pump function was found to be associated with a decrease in the velocities of myocyte shortening and relengthening and peak shortening despite a prolongation of contraction duration. In addition, a uniform property was recognized in myocytes from infarcted and noninfarcted hearts. Longer cells manifested greater velocity of shortening, whereas wider cells of identical length exhibited depressed shortening velocity. After infarction, the depression in cell contractility coupled with lateral expansion of myocytes exceeded the influence on cell mechanical behavior linked to myocyte lengthening leading to an overall decrease in contractility of the hypertrophied cells. Captopril therapy preserved, in part, the ability of myocytes to shorten and relengthen, which was accompanied by a decrease in the lateral and longitudinal expansions of these cells.

Animals↗

PubMed1992

Chronic coronary arterial stenosis impairs alpha 1-adrenoreceptor signaling and cardiac performance in rats.

Coronary stenosis was induced in rats to determine whether chronic coronary artery constriction resulted in impairment of cardiac pump performance, alterations in alpha 1-adrenoreceptor signal transduction, and inadequate myocardial hypertrophy, and these parameters were examined 6 mo later. A 50% reduction in coronary diameter was associated with an elevation in left ventricular end-diastolic pressure, whereas left ventricular peak systolic pressure, rate of pressure rise and decay were reduced. The hypertrophic response was modest, since statistically significant increases of 11% and 23% in left and right ventricular weights were measured. Radioligand binding documented an 18% and a 38% statistically significant reduction in alpha 1-adrenoreceptor density of the left and right myocardium, respectively. ADP ribosylation of the 41-kDa substrate by pertussis toxin showed a 16% significant decrease of this parameter in the left myocardium. Moreover, a 29% decrease in norepinephrine stimulated phosphoinositol turnover was seen in myocytes, and this change was statistically significant. The depressed generation of intracellular second messengers linked to the alpha 1-adrenoreceptors was found in conjunction with a 19% significant reduction in myocardial norepinephrine content. In conclusion, the long-term effects of coronary stenosis involve impaired transduction of adrenergic signals, which, in combination with constraints on myocardial growth, may participate in the onset of ventricular dysfunction in this model.

Actins↗