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PubMed1995

Comparison of twitch force and calcium handling in papillary muscles from right ventricular pressure overload hypertrophy in weanling and juvenile ferrets.

OBJECTIVE: The aim was to compare differences in peak twitch force occurring despite similar degrees of right ventricular hypertrophy in ferrets with pulmonary artery banding at either weanling or juvenile age. METHODS: After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical function (that is, isometric twitch force and passive stiffness), intracellular [Ca2+] using the calcium indicator aequorin, markers of myocardial energy supply, and quantified connective tissue content were studied. RESULTS: It was previously found that there was a reduced peak isometric twitch force despite normal [Ca2+]i in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling ferrets (POHw) age 7 weeks. POHw animals showed a similar degree of hypertrophy to that found in the POHj. However, there was a greater peak twitch force in hypertrophied muscles at higher [Ca2+]o. There was no difference in peak [Ca2+]i: -3.1(SEM 0.1) v -3.1(0.3) (log fractional luminescence) at 16 mM [Ca2+]o for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2)% in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+]i in POHw, passive stiffness in papillary muscles was increased. Retrospective analysis of tissue from POHj revealed a connective tissue content of 24(6.8)% (P << 0.001). Thus the decreased peak twitch force reported in POHj might in part be due to an increase in fibrous connective tissue. In this study, lactate dehydrogenase was significantly higher (38%) in POHw animals. In contradistinction, total creatine kinase activity and total creatine content were significantly less (22%) in hearts from POHj animals, indicating differences in myocyte remodelling despite similar degrees and durations of hypertrophy. CONCLUSIONS: Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increased fibrosis, there is also molecular remodelling in the myocyte, as demonstrated by a decrease in the creatine kinase system.

Animals↗
PubMed1994

Different effects of an angiotensin converting enzyme inhibitor and a calcium antagonist on protein metabolism in rats with right ventricular hypertrophy.

OBJECTIVE: We examined the effects of a calcium antagonist and an angiotensin converting enzyme (ACE) inhibitor on contractile and non-contractile protein metabolism and cardiac function in a monocrotaline-induced right ventricular hypertrophy model, in order to define the effects of these drugs on cardiac hypertrophy. METHODS: One week after monocrotaline injection, male Sprague-Dawley rats were given either a calcium antagonist (nilvadipine; 3 mg/kg per day) or an ACE inhibitor (delapril-HCl; 30 mg/kg per day) for 2 weeks. Right ventricular pressure, the right ventricle: (left ventricle + interventricular septum) ratio, myosin isoenzymes, collagen concentration, collagen types and contractility of right ventricular free wall were examined. RESULTS: In untreated rats significant monocrotaline-induced right ventricular hypertrophy with an increase in the proportion of collagen types III and V was observed. There were no significant changes in collagen concentration. Both drugs reduced right ventricular pressure to the same degree and decreased right ventricular hypertrophy. However, the inhibitory effect of delapril on right ventricular hypertrophy was stronger than that of nilvadipine. Nilvadipine reduced the collagen concentration and reversed changes in collagen types, whereas delapril did not have any significant effect on collagen concentration or collagen types. Cardiac contractility was improved by delapril, but not by nilvadipine. CONCLUSIONS: The results show that a calcium antagonist disproportionately inhibited contractile and non-contractile protein metabolism, whereas an ACE inhibitor proportionally inhibited them and improved cardiac function in a model of right ventricular hypertrophy. The improvement in cardiac function may be due partly to the proportional inhibition of contractile and non-contractile proteins elicited by an ACE inhibitor.

Absorptiometry, Photon↗
PubMed1996

[Left-ventricular hypertrophy as a cardiac risk factor: role of the renin-angiotensin-aldosterone system].

Left-ventricular hypertrophy is the result of cardiac adaptation to global or regional overstress and represents an important cardiovascular risk factor, increasing the risk for development of congestive heart failure and incidence of sudden death. This review describes the pathophysiological and biochemical mechanisms involved in the development of left-ventricular hypertrophy and cardiac fibrosis with particular emphasis on the role of angiotensin II and aldosterone. Central to the cascade of cardiac fibrosis is the increased production or reduced degradation of collagen proteins in fibroblasts. Collagen proteins are proteins needed for the alignment of cellular compartments and the development of forces, contraction and relaxation of the heart. If overexpressed, an important rise of wall stiffness is observed in addition to a reduced capacity to provide oxygen to the cardiac tissue. This latter explains why in areas of histologically hypertrophied heart muscle atrophied muscle cells are observed. The characterization of the second-messenger systems involved in the regulation of cardiac cells as well as the identification of angiotensin-II receptor subtype and angiotensin IV is described. Both of these receptors are present on cardiac fibroblasts and stimulate these to collagen production, which can be inhibited by antagonists or the generation of angiotensin II by ACE inhibitors. In some forms of left-ventricular hypertrophy and in patients with congestive heart failure in addition to elevated angiotensin-II levels, increased aldosterone levels are observed. Aldosterone raises upon stimulation by angiotensin II and upon reduction of angiotensin-II generation subsequent to ACE inhibition through an escape mechanism. The contribution of aldosterone to left-ventricular hypertrophy and cardiac fibrosis can be prevented and reduced by the administration of its antagonist, spironolactone. Further and larger clinical trials are needed and in progress to evaluate if the combination of an ACE inhibitor with spironolactone potentiates the reduction of left-ventricular hypertrophy and if this translates in a reduction of the cardiovascular risk.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

The significance of glomerular hypertrophy in focal segmental glomerulosclerosis.

It is not clear whether glomerular hypertrophy is linked to the pathogenesis of human focal segmental glomerulosclerosis (FSGS). To probe the significance of glomerular hypertrophy in relation to development of FSGS, we studied 16 adults with primary FSGS by morphometry, and the findings were compared to age- and sex-matched subjects with minimal lesion. Mean glomerular volume (MGV), mesangial volume density, mesangial volume per glomerulus, and cortical interstitial volume density [Vv(int/cortex)] were significantly increased in the FSGS patients when compared to the minimal lesion patients. The increase in mesangial volume in FSGS was mainly due to expansion of mesangial matrix. In FSGS, MGV was related directly to % of glomeruli with glomerulosclerosis (r = 0.47, p < 0.05), to mesangial volume per glomerulus (r = 0.57, p < 0.01), and to Vv(int/cortex) (r = 0.47, p < 0.05). The percentage of glomerulosclerosis correlated directly with Vv(int/cortex) (r = 0.83, p < 0.0005), and with mesangial volume per glomerulus (r = 0.47; p < 0.05) in FSGS. Also, there was a direct relationship between Vv(int/cortex) and mesangial volume per glomerulus (r = 0.49; p < 0.05) in FSGS. Glomerular hypertrophy observed in our patients with primary FSGS was intercorrelated with the extent of glomerulosclerosis, mesangial expansion and interstitial fibrosis. Glomerular hypertrophy seems to be one of the morphological facets present in FSGS. Glomerular hypertrophy tends to coexist with FSGS rather than precede its development. Thus, in biopsies diagnosed with minimal lesion the presence of glomerular hypertrophy appears to be an indication that the coexistent FSGS lesions are undetected as a result of sampling problems.

Adult↗
PubMed1996

Hypertension and left ventricular hypertrophy.

In response to high blood pressure, left ventricular hypertrophy develops. But in hypertension, the myocardial hypertrophied structure is abnormal. The prevalence of this hypertrophy is influenced by age, gender, weight, race, genetics and the severity of high blood pressure. By echocardiography, it has been possible to detect non invasively and more precisely this hypertrophy and its anatomical pattern which is not uniform. This cardiac response is influenced by hemodynamic but also by non hemodynamic factors, but the exact mechanisms are not yet well understood. The humoral and tropic factors particularly affect the cardiac remodeling. Left ventricular hypertrophy has been noted by itself to be an independent risk factor for sudden death, ventricular arrhythmias, myocardial ischemia, and heart failure. Very early hypertension, diastolic dysfunction is noted. The progression to systolic failure in moderate hypertension usually occurs over several decades. According to the worse prognosis of left ventricular hypertrophy, it has been suggested that the reversibility of this anatomical modification by antihypertensive treatment is beneficial. Preliminary data support this idea.

Echocardiography↗
PubMed1996

Cytoskeletal role in the contractile dysfunction of cardiocytes from hypertrophied and failing right ventricular myocardium.

We have shown on the levels of the sarcomere and the cardiocyte that increased microtubule density accounts, to a remarkable degree, for the contractile dysfunction characteristic of pressure-overload right ventricular hypertrophy. In this study, we have asked whether these linked phenotypic and contractile abnormalities persist during the transition to right heart failure in this model and whether, following this transition, microtubule depolymerization remains effective in restoring normal cellular contractile function when characterized in terms of sarcomere mechanics. The feline right ventricle was pressure overloaded by pulmonary artery banding. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. These measurements were made in control cats and in operated cats having right ventricular hypertrophy alone or hypertrophy with associated right heart failure; the left ventricle from each heart served as a normally loaded same-animal control. We show here both that alterations in microtubule density and sarcomere mechanics are a persistent and progressive feature of the hypertrophied and then failing cat right ventricle and that the ratio of polymerized to free tubulin is selectively increased in the failing right ventricle. The mechanical defect, though more severe in failing than in hypertrophied right ventricles, was normalized by microtubule depolymerization. Because we find persistent and progressive increases both in microtubules and in the functional consequence of aberrant sarcomere mechanics during the transition from hypertrophy to failure when right ventricular pressure overloading is severe, this cytoskeletal abnormality may well contribute to the contractile dysfunction characteristic of right heart failure in this model.

Animals↗
PubMed1996

Arterial blood pressure and left ventricular hypertrophy in haemodialysis patients.

OBJECTIVE: To test the hypothesis that there is an association between arterial blood pressure and left ventricular hypertrophy and patterns of ventricular geometry, defined echocardiographically, in a group of stable haemodialysis patients with a low prevalence of extrarenal diseases. DESIGN AND METHODS: Patients with end-stage renal failure treated by regular haemodialysis (aged 44.3 +/- 12.9 years, n = 103, among whom 52 men and 23 blacks, dialysis duration 49.8 +/- 35.3 months) were subjected to echocardiographic evaluation (M-mode, bidimensional and Doppler) on the day preceding dialysis. The average of all predialysis blood pressure determinations during the 3 months preceding the tests (34-38 determinations in each patient) were used as baseline data. Univariate and multivariate tests were used to assess the main variables associated with echocardiographically defined cardiac alterations and with patterns of ventricular geometry. RESULTS: The systolic blood pressure was significantly associated with the left ventricular mass index and was significantly and independently correlated with left ventricular hypertrophy, posterior wall hypertrophy, left ventricle dilation and increased relative wall thickness. Other significant correlations were between the haematocrit level and left ventricular hypertrophy and between age and altered systolic and diastolic functions. Concentric ventricular hypertrophy was observed only in patients with a history of hypertension, whereas the prevalence of normal geometry was higher in patients without a history of hypertension. CONCLUSION: The systolic blood pressure is an important factor influencing the occurrence of left ventricular hypertrophy in haemodialysis patients and also affects the left ventricle geometry in this population.

Adult↗
PubMed1997

Silent myocardial ischaemia and left ventricle hypertrophy in diabetic patients.

The purpose of this study was to evaluate the ability of three noninvasive techniques to detect silent myocardial ischaemia and analyse the factors associated with this condition, particularly left ventricular hypertrophy, in diabetic patients. An ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole intravenous infusion, ambulatory 48 h ECG monitoring and an echocardiographic study were performed in 92 diabetic patients without cardiac symptoms but with > or = 2 additional cardiovascular risk factors. At least one of these tests was positive in 28 patients (30.4%), suggesting silent myocardial ischaemia. Twenty-four of these patients had a coronary angiography which showed significant coronary stenosis in only 9 cases. An accurate echocardiographic tracing was obtained in 79 patients, particularly in 7 of the 9 with coronary stenosis. Left ventricular hypertrophy was detected in 34 patients, 6 of whom had coronary stenosis. In patients with left ventricular hypertrophy, the positive predictive values of myocardial scintigraphy and the ECG stress test were respectively 50% and 100%, as compared to only 33% and 11% in those without hypertrophy. In summary, coronary stenoses were found in < 10% of asymptomatic diabetic patients with > or = 2 cardiovascular risk factors, but more frequently in individuals with left ventricular hypertrophy. Thus, silent myocardial ischaemia should be searched for first in diabetic patients with hypertrophy, for which the stress test was the most accurate detection method in this study.

Adult↗
PubMed1976

[Cytologic analysis of the secretory epithelium of submaxillary salivary glands hypertrophied by repeated amputation of the lower incisors in rats].

Repeated amputation of the lower incisor in August line rats induced hypertrophy of the submandibular and sublingual salivary glands. This was true hypertrophy accompanied by hypertrophy of the structural units (acini, cells, nuclei). Cell hypertrophy depended on the hypertrophy of the organellae and the accumulation of secretory materials in the cells. Hypertrophy of the nuclei of acinar cells was conditioned by polyploidisation. Polyploidisation and the changes in the cell ulctrastructure in the submandibular salivary glands pointed to the increase in the functional activity of the organ.

Animals↗
PubMed1996

[Effects of m-Nif and Nif on left ventricle hypertrophy in rats induced by partial ligation of abdominal aorta].

Partial ligation of the abdominal aorta of rats was adopted to induce left ventricle hypertrophy (LVH). The effects of m-nifedipine (m-Nif) and nifedipine (Nif) on prevention of hypertrophy and the possible mechanism were investigated. The wet weights of the left ventricle (WWLV) of the LVH group were increased compared with those of the sham operated group. After treatment with m-Nif and Nif for 4 wks, the WWLV decreased by 25% +/- 9% and 16% +/- 9%, respectively. The pressure-volume (P-V) curve of the hypertrophied group was markedly elevated, which means that the myocardial compliance was decreased, and the stiffness coefficient of the hypertrophied group was significantly elevated than that of the sham operated group, but the groups treated with m-Nif or Nif were significantly improved. The characteristics of the left ventricular myocardial DHP binding sites were studied. The results showed that the Kd and the Bmax were similar in the m-Nif, Nif and hypertrophied groups, but the total number of the DHP receptors (TNR) of the LVH group was markly increased than that of the sham operated group, but the TNR of the m-Nif and Nif groups were the same as that of the sham operated group. These results suggest that the effects of m-Nif and Nif on preventing cardiac hypertrophy and improving myocardial compliance may be related to their depressing the TNR of DHP.

Animals↗
PubMed1990

Disproportionate septal hypertrophy associated with erythroblastosis fetalis.

We retrospectively reviewed clinical and echocardiographic data on 10 newborns with erythroblastosis fetalis who were admitted to our nurseries between 1984 and 1988 and who required a double-volume exchange transfusion and neonatal intensive care. Echocardiograms were performed in the first 48 hours of life. In 5 patients, disproportionate septal hypertrophy was demonstrated; 1 additional patient had biventricular hypertrophy with a thickened septum but not disproportionate septal hypertrophy. The mean septal: left ventricular free-wall ratio for the group (n = 10) was 1.37. No correlation was apparent between the occurrence of disproportionate septal hypertrophy and newborn glucose, bilirubin, or hematocrit values. When analyzed separately, the 4 patients who did not receive intrauterine blood transfusions had a ratio of 1.73 +/- 0.21 (mean +/- SEM); this was significantly greater than the ratio in the 6 patients who were transfused in utero (1.13 +/- 0.24). In patients who underwent transfusions, there was no correlation between the number of transfusions and the septal:left ventricular ratio. This study reports a significant but previously unrecognized cardiac hypertrophy with disproportionate septal hypertrophy in patients with erythroblastosis fetalis. Our data suggest a sparing effect of intrauterine fetal transfusions. The mechanism by which these transfusions may affect the hypertrophic development of the myocardium remains to be determined.

Cardiomyopathy, Hypertrophic↗
PubMed1991

Angiotensin-converting enzyme inhibition, cell growth, and left ventricular hypertrophy in hypertension.

Left ventricular hypertrophy is now recognized as an important risk marker in cardiovascular morbidity and mortality. Left ventricular hypertrophy is an integral component of the complex pathophysiology of primary hypertension and results from mechanical, neurohumoral, and genetic factors. The renin-angiotensin system is involved with the production of left ventricular hypertrophy, not only through the effects on systemic arterial blood pressure but also by both direct and indirect effects on myocardial cell growth. The angiotensin-converting enzyme (ACE) inhibitors are effective drugs for reducing blood pressure in primary hypertension. ACE inhibitor therapy is also associated with regression of left ventricular hypertrophy and restoration of normal diastolic and systolic left ventricular function. Regression of left ventricular hypertrophy is associated with improved prognosis. Thus, when left ventricular hypertrophy regression is a goal of antihypertensive treatment, the ACE inhibitors are effective drugs.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2004

Inhibition of phenylephrine-induced cardiac hypertrophy by docosahexaenoic acid.

Many of the cardiovascular benefits of fish oil result from the antiarrhythmic actions of the n-3 polyunsaturated lipids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The beneficial effects of DHA/EPA in patients with coronary artery disease and myocardial infarction may also result from modulation of the myocardial hypertrophic response. Hypertrophy was assessed in neonatal cardiomyocytes exposed to phenylephrine (PE) by measuring cell surface area, total protein synthesis ((14)C leucine incorporation), and the organization of sarcomeric alpha-actinin and by monitoring expression of atrial natriuretic factor (ANF). We report that PE induced a twofold increase in cell surface area and protein synthesis in cardiomyocytes. The hypertrophied cardiomyocytes also exhibited increased expression of ANF in perinuclear regions and organization of sarcomeric alpha-actinin into classical z-bands. Treatment of cardiomyocytes with 5 microM DHA effectively prevented PE-induced hypertrophy as shown by inhibition of surface area expansion and protein synthesis, inhibition of ANF expression, and prevention of alpha-actinin organization into z-bands. DHA treatment prevented PE-induced activation of Ras and Raf-1 kinase. The upstream inhibition of Ras --> Raf-1 effectively prevented translocation and nuclear localization of phosphorylated extracellularly regulated kinase 1 and 2 (Erk1/2). These effects consequently led to inhibition of nuclear translocation, and hence, activation of the downstream signaling enzyme p90 ribosomal S6 kinase (p90(rsk)). These results indicate that PE-induced cardiac hypertrophy can be minimized by DHA. Our results suggest that inhibition of Ras --> Raf-1 --> Erk1/2 --> p90(rsk) --> hypertrophy is one possible pathway by which DHA can inhibit cardiac hypertrophy. In vivo studies are needed to confirm these in vitro effects of DHA.

Animals↗
PubMed2007

TGFbeta inducible early gene-1 (TIEG1) and cardiac hypertrophy: Discovery and characterization of a novel signaling pathway.

Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGFbeta inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to the control (1.13 +/- 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and myofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81-fold increase in pituitary tumor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG(-/-) mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse.

Animals↗
PubMed1994

Effect of angiotensin II on calcium release phenomena in normal and hypertrophied single cardiac myocytes.

The effects of angiotensin II (Ang II) (10(-9) M to 10(-7) M) on calcium releases were established in ventricular myocytes from normal and renal hypertensive adult rats. From each peak systolic indo-1 ratio (405 nm/480 nm), amplitude variation, duration (rise time and fall time), and frequency of spontaneous calcium releases were investigated on freshly isolated cardiomyocytes at rest or under electrical stimulation. The following changes were observed: (1) in spontaneous contracting myocytes, an increase in frequency of calcium transients at 10(-7) M in normal cells (+157%, P < 0.05) and at whatever angiotensin II concentration in hypertrophied cells (10(-9) M: +79% P < 0.05; 10(-8) M +82%, P < 0.01; 10(-7) M: +285%, P < 0.01) with a greater sensitivity of hypertrophied cells to Ang II (P < 0.05 at 10(-9) M, P < 0.01 at 10(-8) M). (2) In stimulated myocytes, a prolongation of the duration of calcium transients at 10(-7) M in normal cells (+68%, P < 0.01) and at 10(-9) M, 10(-8) M, 10(-7) M in hypertrophied cells: (+36%, P < 0.05; +39%, P < 0.01; +77%, P < 0.01) with a greater sensitivity of hypertrophied myocytes (P < 0.05 at 10(-9) M and 10(-8) M). An increase in duration may be explained by the occurrence of calcium releases during the fall time of calcium transients. Thus, both in normal and hypertrophied myocytes, Ang II induced the occurrence of calcium releases with increased sensitivity of hypertrophied cells to Ang II. Such calcium releases are known to be a possible cause of arrhythmias termed "triggered activity".

Angiotensin II↗
PubMed1996

Mild hypoxia induces hypertrophy of cultured neonatal rat cardiomyocytes: a possible endogenous endothelin-1-mediated mechanism.

Hypoxic or ischemic stresses on cardiomyocytes may cause a variety of compensatory responses including cell hypertrophy. In this study, we examined whether hypoxia induces hypertrophy of cardiomyocytes in vitro and whether hypoxia-induced hypertrophy is inhibited by an endothelin A receptor antagonist (BQ123). Neonatal rat cardiomyocytes were cultured in 10% O2/85% N2/5% CO2 or 95% N2/5% CO2 to produce a mild or severe hypoxic condition, respectively. Cardiomyocytes exposed to severe hypoxia revealed degenerative morphological changes and a decrease of cell number, suggesting the toxicity of severe hypoxia on cardiomyocytes. In contrast, cardiomyocytes with mild hypoxia developed hypertrophy; cell surface area of cardiomyocytes as evaluated by an image analyser system increased by 1.6-fold over control after 48 h. [3H]leucine incorporation into the cells was significantly increased by mild hypoxia but decreased by severe hypoxia, mRNA level of skeletal alpha-actin, a genetic marker of cardiac hypertrophy, up-regulated after 6-24 h by mild hypoxia. A transient increase of preproET-1 mRNA and a time-dependent increase of ET-1 protein in the culture medium were also observed in cardiomyocytes exposed to mild hypoxia. BQ123 partially inhibited either hypoxia-induced [3H]leucine incorporation or skeletal alpha-actin mRNA in a dose-dependent manner. These data suggest that mild hypoxia induces hypertrophy of cardiomyocytes and that activation of endogenous ET-1 may, at least in part, mediate this hypertrophic responses as an autocrine/ paracrine factor.

Actins↗
PubMed1997

Altered cardiac mechanism and sarcoplasmic reticulum function in pressure overload-induced cardiac hypertrophy in rats.

Cardiac sarcoplasmic reticulum (SR) sequesters Ca2+ and plays a crucial role in the regulation of intracellular Ca2+. Its functional properties are central to the excitation-contraction (E-C) cycle of cardiac muscle. In this study, we examined the hypothesis that alterations in SR function occur during the development of hypertrophy of the left ventricle (LV) induced in rats by pressure overload secondary to abdominal aortic coarctation. Ten days, 4 and 8 weeks after the operation, hemodynamic parameters were measured using a catheter-tip manometer. The SR vesicles of hypertrophic LV (group A) and sham-operated LV (group S) at each stage were used to study Ca2+ release and uptake, and to characterize the ryanodine receptor. Moderate hypertrophy was observed in group A even at the earliest stage. Systolic LV pressure and peak +dP/dt were significantly increased in group A. There were no significant change in diastolic LV pressure in either group at any stage. Hemodynamic data indicated that LV function in group A was enhanced during the development of the hypertrophy. The amount of Ca2+ release and uptake, and the number of ryanodine binding sites on the SR were higher in group A than in group S at both early and middle stages. However, 8 weeks after the operation, SR activity was normal, even though cardiac function was still augmented. Our results indicated that LV hypertrophy induced by pressure overload is associated with altered intracellular Ca2+ regulation, as reflected by the increased Ca2+ release and uptake functions of the SR and the quantitative change in the number of ryanodine receptors during the early stages of the development of hypertrophy. Therefore, alterations in the SR Ca2+ transport capacity could account, at least in part, for the alterations in E-C coupling seen in hypertrophy.

Adaptation, Physiological↗
PubMed1999

Glucose utilization and glycogen turnover are accelerated in hypertrophied rat hearts during severe low-flow ischemia.

We undertook this study to determine if the metabolism of exogenous glucose and glycogen in hypertrophied hearts differed from that in normal hearts during severe ischemia. Thus, rates of glycolysis (3H2O production) and oxidation (14CO2 production) from exogenous glucose and glycogen were measured in isolated working control (n = 13) and hypertrophied (n = 12) hearts from sham-operated and aortic-banded rats during 40 min of severe low-flow ischemia. Hearts, in which glycogen was prelabelled with [5-3H]- or [14C]-glucose, were paced and perfused with Krebs-Henseleit solution containing 1.2 mM palmitate, 5.5 mM [5-3H]- or [14C]-glucose (different from the isotope used to label glycogen), 0.5 mM lactate and 100 microU/ml insulin during ischemia. Rates of glycolysis from exogenous glucose (3301 +/- 122 v 2467 +/- 167 nmol/min/g dry wt, mean +/- S.E.M., P < 0.05) and glucose from glycogen (808 +/- 27 v 725 +/- 21 nmol/min/g dry wt, P < 0.05) were accelerated in hypertrophied hearts compared to control hearts. However, rates of oxidation of exogenous glucose and glucose from glycogen were not significantly different between the two groups. As observed in normoxic non-ischemic hearts, glucose from glycogen was preferentially oxidized compared to exogenous glucose. Additionally, rates of glycogen synthesis (167 +/- 7 v 140 +/- 9 nmol/min/g dry wt, P < 0.05) were increased in hypertrophied hearts compared to control hearts during severe low-flow ischemia indicating that glycogen turnover (i.e. simultaneous synthesis and degradation) was accelerated in the hypertrophied heart. Thus, we demonstrate that glucose utilization and glycogen turnover are accelerated in the hypertrophied heart during severe low-flow ischemia as compared to the normal heart.

Animals↗