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Results for “Hypertrophy”

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At least 217 records · Page 12Linked to original sources

PubMed2003

Angiotensin II-induced hypertrophy of proximal tubular cells requires p27Kip1.

BACKGROUND: Angiotensin II (Ang II), as a single factor, induces hypertrophy of cultured proximal tubular cells of various species. Cells undergoing hypertrophy are arrested in the G1 phase of the cell cycle. Ang II also stimulated the expression of p27Kip1, an inhibitor of cyclin-dependent kinases (CDK). Although previous studies inhibiting p27Kip1 expression with antisense oligonucleotides suggested that this CDK inhibitor is important for Ang II-induced hypertrophy of proximal tubular cells, nonspecific effects of antisense technology, and the inability to transfect 100% of cells raised concerns about the true role of p27Kip1 in tubular hypertrophy. METHODS: Proximal tubular cells were isolated and cultured from wild-type (p27Kip1+/+) and knockout (p27Kip1-/-) mice. p27Kip1 genomic and protein expression was evaluated. Proximal tubular cell origin was confirmed by expression of various markers [3M-1 antigen, gamma-glutamyltransferase, angiotensin-converting enzyme (ACE)]. Cell proliferation (cell number, 3[H]thymidine incorporation) and hypertrophy (de novo protein synthesis as measured by 3[H]leucine incorporation, hypertrophy index, cell size) were evaluated. CDK2 and CDK4 activities were determined by an in vitro kinase assay. In addition, cell cycle analysis was performed by flow cytometry. p27Kip1 expression was reconstituted in two different clones of p27Kip1-/- proximal tubular cells using an inducible vector system based on ecdysone response elements. RESULTS: In accordance with previous studies, 10-7 mol/L Ang II induces hypertrophy and cell cycle arrest of p27Kip1+/+ proximal tubular cells. In contrast, Ang II facilitated cell cycle progression of two p27Kip1-/- proximal tubular cell lines without inducing hypertrophy. Ang II activates CDK4/cyclin D kinase activity in p27Kip1+/+ and -/- tubular cells, but stimulates CDK2/cyclin E activity only in wild-type cells. However, in the presence of Ang II, reconstituting p27Kip1 expression in p27Kip1-/- tubular cells using an inducible expression system, restored G1 phase arrest and the hypertrophic phenotype. Ang II did not induce apoptosis of either p27Kip1+/+ or -/- tubular cells. CONCLUSION: Our findings are the first clear evidence that p27Kip1 is required for Ang II-induced hypertrophy of proximal tubular cells. However, although p27Kip1 expression is an absolute requirement for this hypertrophy, reconstitution experiments revealed that other factors induced by Ang II contribute to this hypertrophy.

Angiotensin II↗

PubMed2004

Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice.

Cardiac hypertrophy and heart failure remain leading causes of death in the United States. Many studies have suggested that, under stress, myocardium releases factors triggering protein synthesis and stimulating myocyte growth. We identified and cloned myotrophin, a 12-kDa protein from hypertrophied human and rat hearts. Myotrophin (whose gene is localized on human chromosome 7q33) stimulates myocyte growth and participates in cellular interaction that initiates cardiac hypertrophy in vitro. In this report, we present data on the pathophysiological significance of myotrophin in vivo, showing the effects of overexpression of cardio-specific myotrophin in transgenic mice in which cardiac hypertrophy occurred by 4 weeks of age and progressed to heart failure by 9-12 months. This hypertrophy was associated with increased expression of proto-oncogenes, hypertrophy marker genes, growth factors, and cytokines, with symptoms that mimicked those of human cardiomyopathy, functionally and morphologically. This model provided a unique opportunity to analyze gene clusters that are differentially up-regulated during initiation of hypertrophy versus transition of hypertrophy to heart failure. Importantly, changes in gene expression observed during initiation of hypertrophy were significantly different from those seen during its transition to heart failure. Our data show that overexpression of myotrophin results in initiation of cardiac hypertrophy that progresses to heart failure, similar to changes in human heart failure. Knowledge of the changes that take place as a result of overexpression of myotrophin at both the cellular and molecular levels will suggest novel strategies for treatment to prevent hypertrophy and its progression to heart failure.

Animals↗

PubMed1994

Hypertrophy causes delayed conduction in human and guinea pig myocardium: accentuation during ischaemic perfusion.

OBJECTIVE: The aim was to investigate why cardiac hypertrophy causes increased vulnerability to arrhythmias during myocardial ischaemia. METHODS: The electrophysiological basis for this increased vulnerability was studied in isolated perfused guinea pig hearts obtained 50 and 150 d after aortic constriction, and in sham operated controls. Cellular electrophysiology, conduction, and refractory periods were examined during control perfusion and during low flow (coronary flow reduced to 10% of control) and zero flow ischaemia. ECGs in patients with left ventricular hypertrophy and in controls matched for age and heart rate were also studied. RESULTS: Aortic constriction increased heart weight:body weight ratio by 33% at 50 d and by 69% at 150 d. Action potentials were unchanged in hypertrophied hearts. Significant conduction delay occurred in 150 d hypertrophied hearts [conduction time index 23(SEM 4) ms v 18(3) ms, p < 0.001; QRS width 40(1) ms v 35(1) ms, p < 0.01], but not in 50 d hypertrophied hearts. Conduction delay was also present in humans with left ventricular hypertrophy [QRS width 96(13) ms v 87(8) ms, p < 0.01]. Although the QTc interval was increased in humans, at 422(23) ms v 411(17) ms in controls, p < 0.05, this could be explained by the increased QRS duration. During ischaemia, ventricular arrhythmias tended to occur earlier in hypertrophied hearts. Hypertrophy was also associated with a greater increase in conduction delay. Ischaemia reduced action potential duration and refractory periods; the reduction in action potential duration was attenuated by hypertrophy (p < 0.01), although the reverse was apparent during low flow ischaemia at 50 d. CONCLUSIONS: Delayed conduction is an important feature of severe cardiac hypertrophy in guinea pigs and man. Hypertrophy is associated with accentuated conduction delay and altered repolarisation during ischaemia.

Animals↗

PubMed1994

Milrinone, a cyclic AMP-phosphodiesterase inhibitor, has differential effects on regional myocardial work and oxygen consumption in experimental left ventricular hypertrophy.

OBJECTIVE: The aim was to test the hypothesis that local myocardial work and O2 consumption would respond differentially to milrinone, a selective cyclic AMP-phosphodiesterase inhibitor, in left ventricular hypertrophy due to differences in myocardial cyclic AMP-phosphodiesterase activity. METHODS: The effect of milrinone on regional segment work and regional O2 consumption was measured in 12 open chest anaesthetised dogs with left ventricular hypertrophy induced by valvular aortic stenosis and in 10 age matched control dogs. Regional myocardial work was calculated as the integrated product of instantaneous force development (miniature transducer) and segment shortening (sonomicrometer). Regional O2 consumption was calculated from coronary blood flow (radiolabelled microspheres) and O2 saturations in small regional vessels (microspectrophotometry). Low Km phosphodiesterase activity was assayed by measuring the hydrolysis of radiolabelled cyclic AMP. RESULTS: Milrinone increased left ventricular dP/dtmax by approximately 60-70% in both control [2808(SEM 314) to 4584(660) mm Hg.s-1] and left ventricular hypertrophy [3279(258) to 5589(470) mm-Hg.s-1]. Regional work increased significantly in control [612(88) to 955(101) g.mm.min-1], while the increase was not significant in left ventricular hypertrophy [859(139) to 974(172) g.mm.min-1]. Regional O2 consumption increased significantly with milrinone in left ventricular hypertrophy [8.1(1.2) to 13.1(2.4) ml O2.min-1.100 g-1], but the increase was not significant in control [6.9(1.2) to 7.4(1.0) ml O2.min-1.100 g-1]. Myocardial stiffness during ejection was increased by milrinone to a significantly greater extent in animals with left ventricular hypertrophy. These effects were not related to differences in cyclic AMP-phosphodiesterase activity between control hearts and hearts with left ventricular hypertrophy [393(45) v 402(36) pmol.mg protein-1.1]. CONCLUSIONS: Differences between the hypertrophied and normal canine myocardium in response to milrinone are either due to altered levels of cyclic AMP production in left ventricular hypertrophy, to effects of milrinone that are unrelated to cyclic AMP-phosphodiesterase inhibition, or to other differences in hypertrophied hearts. The greater stiffness of the myocardium in left ventricular hypertrophy may require a greater energy expenditure to increase the amount of work it performs.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1993

Relationship between cardiovascular hypertrophy and cardiac baroreflex function in spontaneously hypertensive and stroke-prone rats.

OBJECTIVE: To determine whether the reduced baroreceptor-heart rate reflex sensitivity in genetically hypertensive rats is related to the level of cardiac or vascular hypertrophy. DESIGN: Young spontaneously hypertensive rats (SHR), stroke-prone hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats were treated chronically with the angiotensin converting enzyme (ACE) inhibitor perindopril in different regimens in order to produce a wide-ranging combination of cardiac and vascular hypertrophy. METHODS: All strains were treated with perindopril (0.1, 0.3, 1 or 3 mg/kg per day) in their drinking water from 4 until 9 weeks of age. Additional groups of SHR were treated with perindopril (3 mg/kg per day) from 4 until 12 weeks and from 4 until 14 weeks of age. At 13 weeks of age all animals were chronically instrumented with arterial and venous catheters. One week later, steady-state sigmoidal mean arterial pressure-heart rate reflex curves were obtained in the conscious rats by the injection of pressor and depressor agents before and after the administration of atenolol (1 mg/kg, intravenously) to determine the vagal component. The minimum and the maximum blood pressure produced by nitroprusside and methoxamine, respectively, after simultaneous ganglion and beta-adrenoceptor blockade were used as an index of whole body vascular hypertrophy. The left ventricular to body weight ratio was measured at the end of the experiment. RESULTS: At 14 weeks of age, mean arterial pressure, the maximum and minimum autonomically blocked blood pressure and the left ventricular to body weight ratio were 34, 20, 9 and 17% higher, respectively, in SHR, and 56, 35, 27 and 39% higher, respectively, in SHRSP than in WKY rats. Perindopril treatment dose-dependently reduced both cardiac and vascular hypertrophy but to different extents. The highest doses reduced mean arterial pressure and the autonomically blocked maximum and minimum blood pressure in both hypertensive strains to the levels of untreated WKY rats but approximately 50% of the cardiac hypertrophy was still present. The left ventricular to body weight ratio was normalized in SHR only with the longer term perindopril treatments. A comparison of the baroreflex function curves in untreated SHR and SHRSP showed that the vagal component of the heart rate range was markedly reduced compared to that in WKY rats. Treated SHRSP had a normal mean arterial pressure and a normal autonomically blocked maximum and minimum blood pressure, but their vagal heart rate range was only 63% of that in WKY rats. The heart rate range in SHR treated from 4 to 9 weeks of age was only marginally greater than that of untreated SHR, despite prevention of hypertension and vascular hypertrophy. In SHR treated from 4 until 12 weeks of age, which prevented cardiac hypertrophy, the vagal heart rate range was markedly greater. With perindopril from the age of 4 to 14 weeks, the vagal baroreflex heart rate range was similar to that of WKY rats. Thus the improvement in the vagal heart rate range was more closely related to the prevention of cardiac hypertrophy (r = 0.73, P < 0.001) than vascular hypertrophy or a blood pressure elevation. Since there were no further changes in the indices of hypertrophy, the presence of the ACE inhibitor was likely to have been responsible for restoring the remaining 35% of the vagal baroreflex not affected by structural factors. CONCLUSIONS: These results suggest that prevention of cardiac rather than vascular hypertrophy is the major requirement for normalizing the vagal component of the baroreceptor-heart rate reflex in hypertensive rats. However, structural changes accounted for only about two-thirds of the vagal deficit. The remainder was restored by the presence of an ACE inhibitor, suggesting that the vagal component of the baroreceptor-heart rate reflex is normally suppressed by the renin-angiotensin system.

Animals↗

PubMed1999

Modulation of adrenergic receptors during left ventricular hypertrophy development and after regression by captopril.

The objective of this study was to analyze adrenergic receptors during cardiac hypertrophy development, after establishment of cardiac hypertrophy and after regression of cardiac hypertrophy by an angiotensin-converting enzyme inhibitor. Left ventricular hypertrophy (LVH) was induced by abdominal aortic stenosis. After surgery, plasma norepinephrine concentrations (PNE) and left ventricular adrenergic receptors from rat hearts subjected to aortic stenosis were assessed during cardiac hypertrophy development (at 3, 7, 15, and 30 days of aortic stenosis), once cardiac hypertrophy had been established (7 and 14 weeks after the stenosis) and after regression of cardiac hypertrophy by an antihypertensive dose (200 mg/kg/day) of captopril. The presence of LVH was observed from day 7 after stenosis. PNE had significantly increased after 15 days but returned to control values 30 days after surgery. The density of alpha1-adrenoceptors was found to decrease with development of hypertrophy. Once hypertrophy had been established, 7 weeks from stenosis, PNE was not different from control; however, the density of alpha1-adrenoceptors continued to diminish, whereas PNE and the density of beta-adrenoceptors were no different from control values. Fourteen weeks after stenosis, a significant decrease in PNE was recorded, and no change in alpha1- but an increase in beta-adrenoceptors was observed. LVH was reversed by treatment with captopril; PNE was similar in control and stenosed treated animals. The density of alpha1-adrenoceptors was decreased when compared with control animals, and no change in the density of beta-adrenoceptors was observed with treatment. In conclusion, a decrease of alpha1-adrenoceptors was associated with LVH development and earlier stages of established cardiac hypertrophy. Later stages of established cardiac hypertrophy were characterized by no change in alpha1- and an increase in beta-adrenoceptors. Treatment with captopril induced LVH regression and decreased the number of alpha1-adrenoceptors without any change in beta-adrenoceptors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

The health burden of breast hypertrophy.

Women seeking consultation for the surgical relief of symptoms associated with breast hypertrophy have been the focus of many studies. In contrast, little is known about those women with breast hypertrophy who do not seek symptomatic relief. The purpose of this study was to describe the health burden of breast hypertrophy by using a set of validated questionnaires and to compare women with breast hypertrophy who seek surgical treatment with those who do not. In addition, this latter group was compared with a group of control women without breast hypertrophy. Women seeking consultation for surgery were recruited from 14 plastic-surgery practices. Control subjects were recruited by advertisements in primary-care offices and newspapers. Women were asked to complete a self-report questionnaire that included the European Quality of Life (EuroQol) questionnaire, McGill Pain Questionnaire, Multidimensional Body Self Relations Questionnaire (MBSRQ), the Short Form-36 (SF-36) questionnaire, and questions regarding breast-related symptoms, comorbidities, and bra size. Descriptive statistics were compiled for three groups of women: (1) hypertrophy patients seeking surgical care, (2) hypertrophy control subjects (those whose reported bra-cup size was a D or larger), and (3) normal control subjects (those whose reported bra-cup size was an A, B, or C). The multiple linear regression method was used to compare the health burdens across groups while adjusting for other variables. Two hundred ninety-one women seeking surgical care and 195 control subjects were enrolled in the study. The 184 control subjects with bra-cup information available were further separated into 88 hypertrophy control subjects and 96 normal control subjects. In the control group, bra-cup size was correlated with health-burden measures, whereas in the surgical candidates, it was not. When scores were compared across the three groups, significant differences were found in all health-burden measures. The surgical candidates scored more poorly on the EuroQol utility, McGill pain rating index, MBSRQ appearance evaluation, physical component scale of the SF-36, and on breast symptoms than did the two control groups. In addition, the hypertrophy control subjects scored more poorly than the normal control subjects. With multiple linear regression analysis incorporating important potential confounders, the poorer scores in the surgical candidates remained statistically significant. It was concluded that breast hypertrophy in those seeking surgical care and those not seeking surgery has a significant impact on women's quality of life as measured by validated and widely used self-report instruments including the EuroQol, MBSRQ, McGill Pain Questionnaire, and the SF-36. Likewise, a new assessment instrument for breast-related symptoms also demonstrated greater symptomatology in women with breast hypertrophy.

Adult↗

PubMed1998

Dispersion of ventricular repolarization in left ventricular hypertrophy: influence of afterload and dofetilide.

INTRODUCTION: Increased dispersion of ventricular repolarization is observed in cardiac hypertrophy and is associated with sudden cardiac death. At present, there is little information about the effects of cardiac hemodynamics and antiarrhythmic drugs on dispersion of repolarization in disease states. We compared the effects of increasing afterload and the Class III antiarrhythmic drug, dofetilide, on dispersion of ventricular repolarization in hypertrophied rabbit hearts to normal rabbit hearts. METHODS AND RESULTS: Cardiac hypertrophy was induced in rabbits by abdominal aortic banding. Isolated hearts were studied 49+/-4 days postsurgery in the working heart mode using a blood-buffer perfusate. The action potential duration (APD) was measured from eight sites on the epicardium of the heart at low (50+/-7 mmHg) afterload and high afterload (97+/-12 mmHg) at baseline and during dofetilide perfusion. APD dispersion, determined as the difference between the maximal and minimal APD, was greater in hypertrophied hearts (42+/-8 msec) compared with control hearts (26+/-8 msec, P < 0.05) at baseline and low afterload. Increasing afterload caused a decrease in APD dispersion in hypertrophied hearts (P < 0.05) but not in control hearts, and APD dispersion was similar in hypertrophied hearts (31+/-9 msec) compared with control hearts (30+/-9 msec, P = NS). During dofetilide perfusion, APD dispersion remained greater in hypertrophied hearts (60+/-39 msec) compared with control hearts (30+/-13 msec, P < 0.05) at low afterload but not high afterload. Increasing afterload caused shortening of the APD in most regions of the control hearts, whereas APD did not shorten significantly in hypertrophied hearts at baseline and tended to increase during dofetilide perfusion. During dofetilide perfusion, the maximal change in APD recorded from the posterior wall of the left ventricle following an increase in afterload was -18+/-21 msec in control hearts and 7+/-21 ms in hypertrophied hearts (P < 0.05). CONCLUSION: Epicardial APD dispersion decreases in hypertrophied hearts following an increase in afterload, and this response is mediated in part by the absence of afterload-induced shortening of the APD. This effect may be due in part to altered responses of the delayed rectifying current to cardiac loading conditions in the setting of cardiac hypertrophy.

Action Potentials↗

PubMed1995

Preservation of peristaltic reflex in hypertrophied ileum of guinea pig.

Chronic obstruction of the guinea pig ileum leads to distension and muscular hypertrophy, but how this affects passive biomechanical and nerve-mediated contractions and clearance known as peristaltic reflex is unclear. Ileum of controls had a diameter of 3.0 +/- 1.1 mm and a circular muscle thickness of 37.2 +/- 11.2 microns; 4 wk after placement of a nonconstricting Gore-Tex band, the ileum was distended to 10.0 +/- 0.19 mm, and its muscle had hypertrophied to 195.0 +/- 61.2 microns. Hypertrophied segments exceeded controls in capacity (e.g., 5.1 +/- 1.1 vs. 1.1 +/0 0.2 ml at 6 cm), compliance, and hysteresis. Threshold volumes and pressures that triggered the reflex were 3.3 +/- 1.3 ml and 3.1 +/- 0.01 mmHg in hypertrophied vs. 0.7 +/- 0.2 ml and 1.5 +/- 0.2 mmHg in controls. The diameter increase that triggered the reflex was 1.4 +/- 0.1 mm in hypertrophied segments and 0.6 +/- 0.1 mm in controls. Hypertrophied segments generated fewer contractions of virtually double the amplitude and failed to generate a pressure differential between up- and downstream sites as controls did. Hypertrophied segments generated larger stroke volumes and cumulative clearance than controls. The ratio of antegrade to retrograde clearance was similar in hypertrophied and control segments. The length of the occluding segment in hypertrophied preparations exceeded that of controls. Control contractions indented the antimesenteric border and propagated antegrade from their site of origin; bizarre writhing movements of hypertrophied segments made their contractions difficult to monitor. Thus distension and muscular hypertrophy do not interfere with the ability of the chronically obstructed guinea pig ileum to generate a peristaltic reflex at least as readily and as powerful and as effective in clearing the lumen as controls.

Animals↗

PubMed2000

Impact of different partition values on prevalences of left ventricular hypertrophy and concentric geometry in a large hypertensive population : the LIFE study.

Left ventricular (LV) hypertrophy and concentric remodeling have been defined by using a variety of indexation methods and partition values (PVs) for LV mass and relative wall thickness (RWT). The effects of these methods on the distribution of LV geometric patterns in hypertensive subjects remain unclear. Echocardiograms were obtained in 941 patients with stage I to III hypertension and LV hypertrophy by ECG. LV mass was calculated by using different methods of indexation for body size and different PVs to identify hypertrophy: LV mass/body surface area (g/m(2)) PV for men/women 116/104, 125/110, or 125/125; LV mass/height (g/m) PV 143/102 or 126/105; and LV mass/height(2.7) (g/m(2.7)) PV 51/51 or 49.2/46.7. RWT was calculated by either 2xend-diastolic posterior wall thickness (PWT)/end-diastolic LV internal dimension (LVID) or end-diastolic interventricular septum dimension+end-diastolic PWT/end-diastolic LVID. LV hypertrophy or remodeling was present in 63% to 86% of subjects, and LV hypertrophy was present in 42% to 77%. By any index, eccentric hypertrophy was the common LV geometric pattern. Use of interventricular septum dimension+PWT/LVID to calculate RWT slightly increased the prevalence of normal geometry and eccentric hypertrophy compared with the use of 2xPWT/LVID. Subjects with LV hypertrophy identified by only LV mass/height(2.7) PV 49.2/46.7 were more obese, whereas those identified by only LV mass/body surface area PV 116/104 were taller and thinner than those in the 2 concordant groups with or without LV hypertrophy by both criteria. By either criterion, there were no significant differences between different LV geometric patterns in clinical cardiovascular disease. Hypertensive patients with LV hypertrophy by ECG have a high prevalence of geometric abnormalities, especially eccentric hypertrophy, irrespective of method of indexation or PV. LV mass indexation by body surface area or height(2.7) identifies lean and obese subjects, respectively. We found no difference in prevalent cardiovascular disease in subjects identified by either criterion, suggesting a similar high risk.

Aged↗

PubMed1996

Action potential and plateau ionic currents in moderately and severely DOCA-salt hypertrophied rat hearts.

Ventricular hypertrophy is associated with an increase in action potential (AP) plateau amplitude and duration. In a model of cardiac hypertrophy by DOCA-pellet implantation in uninephrectomized saline-drinking rats, we have previously demonstrated that the influence of hypertrophy was to reduce Ito1 density, the process being fully reversible after elimination of DOCA pellets. In that study the decrease of Ito1 density appeared to vary from moderate reduction to complete suppression which could explain, at least in part, the AP lengthening. In the present study the effect of the degree of hypertrophy (moderate and severe hypertrophy) was investigated on rat ventricular action potential plateau amplitude and duration, high threshold calcium current, Ica-L, Na-Ca exchange current, INa-Ca, transient outward potassium current, Ito1, and sustained outward potassium current Isus. Ventricular action potentials of isolated perfused hearts were recorded by means of standard floating microelectrodes and ionic currents of single ventricular myocytes were measured using the whole-cell recording patch-clamp technique. We show that: (1) AP plateau amplitude and duration increase more markedly in severe than in moderate hypertrophy; (2) the decrease in Ito1 density is much larger in severe than in moderate hypertrophy whereas ICa-L, INa-Ca and i(sus) densities remain unaltered in either state of hypertrophy. After suppression of Ito1 by 3 mM 4-aminopyridine, action potential plateau amplitude and duration remain increased in severely hypertrophied rat hearts compared to sham rats. Therefore, although these results designate Ito1 reduction as the main cause of hypertrophy-induced AP changes, those occurring in severe hypertrophy cannot be uniquely explained by a quasi-complete extinction of Ito1.

Action Potentials↗

PubMed1997

Energy metabolism in normal and hypertrophied right ventricle of the ferret heart.

Using an isolated ferret heart preparation (Langendorff perfusion, perfusion pressure 90 mmHg), energy metabolism has been characterized in right and left ventricles from control and hypertrophied hearts. Hypertrophy was induced by pulmonary artery clipping for 30-45 days (right ventricle wall weight/body weight ratio increased by 70%). Myocardial contents of high energy phosphate compounds, glycogen and lactate, and the activities of some enzymes were biochemically measured in perfused hearts and also after ischemic arrest (30 min global ischemia). In hypertrophied right ventricles, PCr (-46%), Cr (-34%) levels, creatine kinase activity (-18%) were significantly decreased compared with control. ATP and Pi levels were not affected by hypertrophy. The adenylate energy charges were similar (0.85-0.86) in both types of heart. The activities of hexokinase (+26%), aldolase (+212%), pyruvate kinase (+14%) and glucose 6-phosphate dehydrogenase (+107%) were increased by hypertrophy. The LDH isozyme pattern was significantly changed such that LDH3 was decreased by 11%, and LDH4 and LDH5 were increased by a factor 1.4 and 2.9 respectively in hypertrophy. After 30 min of global ischemia, PCr level was decreased by 89 and 79% in control and hypertrophied ventricles respectively. ATP level was depressed by 41 in control and only by 21% in hypertrophied muscles. Altogether, the present data suggested that, in the adult ferret heart, the capacity for the ATP synthesis could be maintained during hypertrophy by the enhancement of the glycolytic pathway. The smaller decline of ATP after ischemia in hypertrophied tissue could be explained by a lower consumption of ATP in the hypertrophied compared to the control heart during the earliest period of ischemia.

Adenosine Triphosphate↗

PubMed1984

Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension.

The relations between some pressure and humoral factors, and some echocardiographic indexes of left ventricular (LV) hypertrophy were studied in 64 patients with essential hypertension. Fifty-seven percent of these patients showed echocardiographic evidence of LV hypertrophy (LV mass greater than 215 g). Multivariate stepwise regression analysis showed that only mean blood pressure (BP) and circulating norepinephrine (NE) levels were significantly related to LV mass index in the group of patients with LV hypertrophy. However, mean BP was the only factor related to LV mass index in the subgroup of patients with LV hypertrophy and plasma NE within the normal laboratory range, whereas NE was the sole factor related to LV mass index in the subgroup with LV hypertrophy and abnormally elevated NE levels (greater than mean + 2 standard deviations of the normal laboratory range). Correlation of LV mass index vs NE was -0.35 (not significant) in the former group of patients and 0.89 (p less than 0.01) in the latter group. NE showed no relation with the echocardiographic variables in the hypertensive patients without LV hypertrophy; in this group, diastolic BP was the only factor related to LV mass index. Circulating NE levels were slightly higher in patients with LV hypertrophy (213 +/- 68 ng/liter) than in those without LV hypertrophy (187 +/- 46 ng/liter), but differences were not significant when adjusting NE for age. Plasma renin activity was not dissimilar in the absence or presence of hypertrophy. In conclusion, our findings suggest that NE might be associated with pressure factors in regulating LV hypertrophy development only in a subgroup of hypertensive patients characterized by echocardiographic LV hypertrophy and abnormally elevated circulating NE levels.

Adult↗

PubMed1988

Clinical significance and prognostic importance of left ventricular hypertrophy in non-Q-wave acute myocardial infarction.

Left ventricular (LV) hypertrophy is known to be an independent risk factor for cardiac death, but its significance in non-Q-wave acute myocardial infarction (AMI) has not been assessed previously. In a randomized diltiazem-placebo-controlled therapeutic trial of non-Q-wave AMI confirmed by creatine kinase-MB (CK-MB), 126 of 544 patients (23%) exhibited LV hypertrophy using standard voltage criteria. Compared to patients without LV hypertrophy, patients with LV hypertrophy were significantly older (65 vs 60 years, p less than 0.0001) and had smaller peak adjusted CK levels (490 +/- 376 vs 666 +/- 726 IU/liter, p less than 0.001) than patients without LV hypertrophy. Patients with and without LV hypertrophy did not differ significantly in acute mortality during hospitalization, progression to Q waves, reinfarction by CK-MB criteria or angina associated with transient electrocardiographic changes. Compared with patients without LV hypertrophy, those patients with non-Q-wave AMI and LV hypertrophy had a 2-fold higher incidence of reinfarction (24 vs 12%, p less than 0.005) and death (19 vs 9%, p = 0.044) during the first year of follow-up. Multivariate regression analysis revealed that the relative risk of death and reinfarction during the initial year after AMI was increased by a factor of 1.7 and 2.1 among patients with LV hypertrophy, respectively. It was therefore concluded that, although patients with LV hypertrophy and non-Q-wave AMI have smaller enzymatic infarcts and the same short-term prognosis as do patients without LV hypertrophy, their reinfarction and mortality rates are significantly increased during the first year of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1995

Propionyl L-carnitine improvement of hypertrophied rat heart function is associated with an increase in cardiac efficiency.

Although propionyl L-carnitine improves contractile function of hypertrophied rat hearts, the mechanism(s) by which it does this are not known. One postulated mechanism is that propionyl L-carnitine reverses the alterations in energy metabolism that occur secondary to the carnitine deficiency seen in hypertrophied myocardium. This study determined the effects of chronic propionyl L-carnitine administration on myocardial carnitine content and energy metabolism in hypertrophic hearts from male Wistar Kyoto rats. Pressure-overload hypertrophy was produced by constriction of the abdominal aorta in juvenile rats. Propionyl L-carnitine was administered to the rats via the drinking water for an 8 week period (60 mg.kg(-1).day-1). Myocardial function and metabolic analysis was determined in isolated working hearts obtained from aortic-banded and sham-operated (control) animals at the end of the 8 week study period. Carnitine content was significantly decreased in hypertrophied hearts compared to control hearts, but was normalized by propionyl L-carnitine treatment. Propionyl L-carnitine treatment also prevented the decrease in cardiac work that occurred in hypertrophied hearts compared to control hearts. The primary change in energy substrate use in hypertrophied hearts was a decrease in fatty acid oxidation rates. Glucose and lactate oxidation were similar in control and hypertrophied hearts. While glycolytic rates were slightly higher at moderate workloads, this was not seen at high workloads. Surprisingly, propionyl L-carnitine treatment did not reverse the depression of fatty acid oxidation seen in hypertrophied rat hearts. In fact, a further significant decrease in fatty acid oxidation occurred, such that the contribution of fatty acid oxidation to ATP production decreased from 35 to 26%. Since propionyl L-carnitine treatment increased cardiac work in hypertrophied hearts despite an overall decrease in ATP production rates, an increase in cardiac efficiency was seen. In treated vs. untreated hypertrophied hearts efficiency (cardiac work/ATP produced) increased from 0.23 to 0.40 ml.mm Hg.mumol ATP-1.g dry weight at high workloads. These data suggest that the beneficial effect of propionyl L-carnitine on mechanical function in the hypertrophied heart does not result from a normalization of fatty acid oxidation, but rather from an increase in the efficiency of translating ATP production into cardiac work.

Acetyl Coenzyme A↗

PubMed1992

Segmental systolic responses to brief ischemia and reperfusion in the hypertrophied canine left ventricle.

OBJECTIVES AND BACKGROUND: Left ventricular hypertrophy is associated with increased mortality, increased myocardial infarct size and an increased incidence of sudden death. Although reperfusion after ischemia has been shown to result in decreased infarct size and recovery of systolic thickening, it is unknown how left ventricular hypertrophy might influence recovery of regional systolic thickening after ischemia and reperfusion. We hypothesized that left ventricular hypertrophy might attenuate or abolish the functional response to reperfusion. METHODS: Three groups of chronically instrumented, conscious dogs (dogs with left ventricular hypertrophy and hypertension; dogs with left ventricular hypertrophy and reduced blood pressure and a control group without hypertrophy and with normal blood pressure) underwent 15 min of ischemia and 24 h of reperfusion. Segmental systolic thickening was measured by sonomicrometers and myocardial segments were grouped by percent of control segmental systolic thickening retained at 15 min of ischemia (class 1 greater than or equal to 67%, class 2 from 0% to 66%, class 3 less than 0% control systolic thickening). The recovery of each class of segment was measured serially during reperfusion. Hemodynamic variables and regional myocardial blood flow were also measured. RESULTS: There were no differences among groups in recovery of segmental systolic thickening for class 1 segments. Systolic thickening in class 2 (hypokinetic) segments was significantly depressed (p less than 0.05 compared with control value) in the group with left ventricular hypertrophy and reduced blood pressure (but not in the group with hypertrophy and hypertension) during early reperfusion; systolic thickening in class 3 (dyskinetic) segments showed a similar trend in the group with hypertrophy and reduced pressure. CONCLUSIONS: Although left ventricular hypertrophy with hypertension did not attenuate the contractile response to reperfusion, hypertrophy with reduced blood pressure was associated with significantly greater depression of segmental systolic thickening early during reperfusion.

Animals↗

PubMed1983

Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a two-dimensional echocardiographic study.

The distribution of left ventricular hypertrophy was assessed by M-mode and two-dimensional echocardiography in 89 patients with hypertrophic cardiomyopathy. Myocardial thickness was measured in the septum and the free and posterior wall in both the proximal and distal left ventricle. All patients had at least one myocardial region that was hypertrophied. The predominant pattern of hypertrophy was defined as symmetric (31%), asymmetric septal (55%) and distal ventricular (14%). The spectrum of wall thickness measurements between patients with symmetric hypertrophy was wide (1.5 to 4.5 cm) and was not related to age. In patients with asymmetric septal hypertrophy, the distribution of hypertrophy conformed to previously described patterns; hypertrophy was localized to the anterior septum (14%) or the anterior and posterior septum (35%) or involved both the septum and the left ventricular free wall (51%). The patients with distal ventricular hypertrophy had marked papillary muscle thickening, and only 1 of 12 patients could be correctly diagnosed using M-mode echocardiography. The proportion of patients with symmetric and distal ventricular hypertrophy was greater than that reported when patients are selected on the basis of M-mode diagnostic criteria. This reflects the limitations of the M-mode technique in the assessment of left ventricular hypertrophy and suggests that the recognition and understanding of hypertrophic cardiomyopathy have been biased by patients with asymmetric septal hypertrophy who previously were most readily identified.

Adolescent↗

PubMed1986

An echocardiographic study of localized subaortic hypertrophy.

A prospective echocardiographic investigation was undertaken to determine the prevalence and significance of localized subaortic hypertrophy in 1000 consecutive patients presenting for a routine echocardiographic examination. Localized septal hypertrophy was diagnosed when the subaortic septum was hypertrophied (greater than 1.4 cm) and was 50% thicker than the mid-point of the septum. Patients with hypertrophic cardiomyopathy and fixed subvalvular aortic stenosis were excluded. Eight cases of localized subaortic hypertrophy were identified. In 7 the appearances of the left side of the interventricular septum were similar with an apparently sigmoid shape (reversed S on its side) and in 1 with associated mitral stenosis the septum was a tapered wedge. All patients with localized subaortic hypertrophy had left ventricular hypertrophy (left ventricular mass or posterior wall thickness greater than 2 SD from normal) with a normal size cavity due to aortic valve disease (2 patients were also hypertensive). Of the 180 patients with aortic valve disease, localized subaortic hypertrophy was found in 10% of those with left ventricular hypertrophy and 33% of those with asymmetrical septal hypertrophy (septum to posterior wall ratio of greater than 1.5:1). There was no evidence of subaortic stenosis by pulsed and continuous wave doppler echocardiography (8 cases) and cardiac catheterization (6 cases). The aetiology of this discrete localized muscular bulge is unclear but is presumably due to change in shape of the septum with left ventricular hypertrophy. However, this finding has important implications as a cause of asymmetrical septal hypertrophy and because of the possible false diagnosis of subvalvular stenosis and its effect on ultrasound measurements.

Adolescent↗