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PubMed1996

Left ventricular hypertrophy and geometry in a population sample of elderly males.

BACKGROUND: Recent studies have shown that left ventricular geometric adaptation to hypertension is complex. The spectrum of geometric adaptations in a general population and its relationship to systolic and diastolic function has, however, not been investigated. OBJECTIVES AND METHODS: This echocardiographic and Doppler study investigated the relationships between left ventricular geometric shape (normal, concentric remodelling, concentric hypertrophy and eccentric hypertrophy) and left ventricular systolic and diastolic function in a population sample of 584 males aged 70 in Uppsala, Sweden. The influences of hypertension, coronary heart disease and diabetes mellitus were also evaluated. RESULTS: Sixteen percent of the healthy population (n = 167) demonstrated the presence of left ventricular hypertrophy (mainly eccentric). Subjects with hypertension (n = 115) showed an increased left ventricular mass (eccentric left ventricular hypertrophy 31%, concentric left ventricular hypertrophy 15%), when compared with healthy subjects (P < 0.001). Subjects with coronary heart disease (n = 32) without hypertension also showed an increased left ventricular mass (most often eccentric) (P < 0.05). Using Doppler determinations of cardiac index, no differences were found in cardiac index between the geometric groups. Raised total peripheral resistance, increased blood pressure and enlarged left atrium were found in both concentric and eccentric left ventricular hypertrophy (P < 0.01-0.05). Disturbed diastolic function was seen with a prolongation of the isovolumic relaxation time in eccentric (P < 0.01) and increased atrial-dependent left ventricular filling in concentric left ventricular hypertrophy (P < 0.05). CONCLUSION: Alterations in left ventricular geometry were common in this population-based study of elderly males, both in healthy subjects and in subjects with hypertension or coronary heart disease. Raised total peripheral resistance and left ventricular diastolic dysfunction were common findings in both concentric and eccentric left ventricular hypertrophy.

Aged↗
PubMed2004

Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3beta.

In vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by 3H leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation-induced hypertrophy. In addition, a beta2-adrenergic receptor (beta2-AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation-induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF-kappaB, and GATA DNA binding activities. However, only CREB DNA-binding was sustained during reoxygenation. Inhibition of PI3-kinase, ERK, and PKA abrogated reoxygenation-induced CREB DNA-binding without affecting CREB serine-133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation-induced GSK3beta kinase activity and CREB serine-129 de-phosphorylation. GSK3beta mutants resistant to phosphorylation blocked the stimulation of CRE-dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant-negative mutant of CREB abrogated hypoxia/reoxygenation-induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3beta by hypoxia/reoxygenation, possibly integrating PI3-kinase and ERK pathways downstream of beta2-AR and ROS, is a prerequisite for CRE-dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.

Adrenergic beta-Antagonists↗
PubMed2001

How well does contralateral testis hypertrophy predict the absence of the nonpalpable testis?

PURPOSE: We assessed the accuracy of contralateral testis hypertrophy for predicting monorchia in patients with a nonpalpable testis. MATERIALS AND METHODS: From May 1993 to September 1998 we evaluated 60 patients 7 months to 11 years old for a unilateral nonpalpable testis. Four patients were excluded from study who had received human chorionic gonadotropin or had signs of puberty. We correlated contralateral testis hypertrophy, defined as testis volume greater than 2 cc or testis length greater than 2 cm., with presence or absence of the nonpalpable testis. We also recorded the degree to which contralateral testis length less than 2.1 cm. correlated with the presence or absence of the nonpalpable testis. Laparoscopy and open exploration were performed in 52 and 4 cases, respectively. RESULTS: Contralateral testis hypertrophy greater than 2 cm. was noted in 16 patients, including 14 (87.5%) with monorchia and 2 (12.5%) with an intra-abdominal testis. Of the 15 patients with a contralateral measurement of 1.8 to 2.0 cm. 14 had monorchia (93%) and 1 had a tiny ovotestis. Of the 25 patients with a contralateral measurement of less than 1.8 cm. 13 (52%) had testes that were intra-abdominal in 11 and canalicular in 2. The optimal cutoff value for contralateral enlargement was 1.8 cm. (p = 0.00061). The most common laparoscopic finding in patients with contralateral testis hypertrophy greater than 2 cm. was blind ending vessels proximal to the internal ring in 56%. CONCLUSIONS: Contralateral testis hypertrophy is common in patients with a nonpalpable testis. Hypertrophy 1.8 cm. or greater predicts monorchia with an accuracy of about 90%. The finding of contralateral testis hypertrophy provides useful information for preoperative counseling, allowing us to inform parents that the nonpalpable testis is most likely absent. Exploration is still required. Laparoscopy is particularly advantageous in contralateral testis hypertrophy since it was the only procedure required in about half of our cases.

Child↗
PubMed2002

Unilateral calf hypertrophy seen in lumbosacral stenosis: case report and review of the literature.

STUDY DESIGN: A case report of a patient with neurogenic unilateral calf hypertrophy and review of the literature are reported. OBJECTIVES: To provide further evidence that S1 radiculopathy is predisposed to develop neurogenic muscle hypertrophy. SUMMARY OF BACKGROUND DATA: Calf hypertrophy, specifically hypertrophy of the gastrocnemius muscle, is a rare but recognized presentation of S1 and less commonly L5 radiculopathies. The pathophysiology of this is incompletely understood. METHODS: We present a 59-year-old patient with painless progressive distal right leg weakness and calf enlargement. Electrodiagnostic studies and MAGNETIC RESONANCE IMAGING scanning were performed to evaluate the extent and cause of radicular damage as the etiology for unilateral calf hypertrophy. RESULTS: Examination and electrodiagnostic studies revealed right L5, right S1, and left L5 radiculopathies. Imaging studies demonstrated lumbar stenosis at L3-L4, L4-L5, and L5-S1 vertebral levels as well as L4-L5 and L5-S1 foraminal stenosis. After decompressive surgery the progressive nature of the patient's symptomatology halted, and he had partial resolution of his deficits. CONCLUSION: Although the patient had bilateral L5 radiculopathies, he only had hypertrophy in the distribution of his right S1 radiculopathy. This supports the hypothesis that dysfunction of the S1 nerve root or its distribution is a predisposing factor to develop neurogenic muscle hypertrophy. Furthermore, patients presenting with unilateral calf hypertrophy need a careful diagnostic evaluation for S1 radiculopathy as well as to exclude asymmetric presentation of systemic neuromuscular conditions.

Electrodiagnosis↗
PubMed2003

Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction (BOO) leads to compensatory bladder hypertrophy. However, the hypertrophy mechanism remains elusive. We report that calcineurin (Cn) is involved in bladder hypertrophy. MATERIALS AND METHODS: Partial BOO was surgically induced in 10-week-old female Wistar rats. The bladder was excised 2, 4 and 6 weeks following surgery in 9 rats each. Histological study was performed at each time point. Cn expression was examined by Western blot analysis. Myosin heavy chain expression was evaluated on gels stained with Coomassie blue. Primary cultured bladder smooth muscle cells were infected with recombinant adenoviruses encoding a constitutive active form of CnA (DeltaCnA), CnB and lacZ, and cell size was measured. RESULTS: In histological findings bladder smooth muscle hypertrophy was observed 2 and 4 weeks after surgery. However, the thickened muscles became thinner 6 weeks after BOO. CnA expression 2 weeks after BOO increased 3.2-fold compared with that of controls. Expression significantly decreased 4 and 6 weeks after surgery. In contrast, CnB expression was unchanged throughout hypertrophy development. Changes in myosin heavy chain expression correlated with changes in CnA. We observed significant hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. Moreover, FK506, which is a potent inhibitor of Cn, blocked hypertrophy in DeltaCnA and CnB over expressing smooth muscle cells. CONCLUSIONS: These data suggest that Cn has an important role in the induction of bladder smooth muscle hypertrophy.

Animals↗
PubMed1993

The effect of cromakalim on the electrical properties of and [86Rb+] efflux from normal and hypertrophied rat bladder.

1. The activity of smooth muscle strips from normal and hypertrophied rat bladders was compared. The hypertrophied bladders were produced by partially obstructing the urethra 8-13 weeks previously. 2. Spontaneous mechanical activity was more frequent and smaller in amplitude in strips from normal than hypertrophied bladders and was less sensitive to cromakalim, being reversibly abolished by cromakalim at 10(-6) mol/L compared with 10(-7) mol/lL for hypertrophied bladder. 3. The mean resting membrane potentials of smooth muscle cells from normal and hypertrophied rat bladders were -47.2 and -47.6 mV, respectively. Bursts of spontaneous action potentials, corresponding to the mechanical activity, were seen in some cells. 4. Nifedipine at 10(-6) mol/L had no significant effect on the resting membrane potential. Occasional single spikes occurred with increased duration and the after hyperpolarization was abolished. Cromakalim at 10(-5) mol/L produced hyperpolarization of 3-9 mV and, in the continued presence of the drug, occasional singe spikes could be recorded from both normal and hypertrophied bladders. 5. Nifedipine at 10(-6) mol/L abolished movement but did not significantly alter [86Rb+] efflux from strips from either normal or hypertrophied bladders. Addition of cromakalim at 5 x 10(-6) or 5 x 10(-5) mol/L in the presence or absence of nifedipine increased efflux from the normal bladder by 30-40%. In the hypertrophied bladder the efflux increased by about 14% and 28% in the presence of 5 x 10(-6) and 5 x 10(-5) mol/L cromakalim, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed2001

Volume overload left ventricular hypertrophy: effects on coronary microvascular reactivity in rabbits.

The mechanisms controlling the coronary vascular responses of vessels perfusing the left ventricular (LV) myocardium that is hypertrophied from chronic volume overload are unclear. We hypothesised that endothelial function is compromised, and receptor-mediated contraction is exacerbated, in coronary resistance vessels from rabbits with LV hypertrophy compared to controls. The mitral valve of 10 rabbits was damaged surgically to cause mitral regurgitation and chronic volume overload, resulting in LV hypertrophy (LV hypertrophy rabbits). Echocardiographic assessment at 12 weeks verified that mitral regurgitation was present in LV hypertrophy but not sham-operated, weight- and age-matched animals (control rabbits; n = 17). Percentage increases from weeks 0 to 12 in LV cross-sectional area (47 +/- 7 % vs. 2 +/- 8 %), LV volume (47 +/- 14 % vs. 7 +/- 10 %) and LV mass (27 +/- 4 % vs. 3 +/- 6 %), were greater (all P < 0.05) in LV hypertrophy vs. control rabbits, respectively. At 12 weeks, coronary resistance vessel (approximately 130 microm, internal diameter) reactivity was evaluated using wire myography. Endothelium-dependent (i.e. acetylcholine, 10(-8)-10(-5) M) and -independent (i.e. sodium nitroprusside, 10(-9)-10(-4) M) relaxation, and receptor-mediated vasocontraction (i.e. endothelin-1, 10(-11)-10(-7) M) were similar between groups. However, tension development in response to nitric oxide synthase inhibition (10(-6) M N (G)-monomethyl-L-arginine) was greater (P < 0.05) in LV hypertrophy compared to control rabbits. These results indicate that while coronary resistance vessel function is similar between groups, our estimate of basal nitric oxide production is greater in vessels from LV hypertrophy than control rabbits.

Acetylcholine↗
PubMed2005

The effects of left ventricular hypertrophy on the respiratory changes in transmitral Doppler flow patterns of hypertension patients.

BACKGROUND: Left ventricular early diastolic fillings can be reduced by inspiration. However, the effects of left ventricular hypertrophy on such changes have not been studied before. This study was undertaken to investigate whether respiratory changes in transmitral Doppler flow were affected by left ventricular hypertrophy in hypertension patients. METHODS: Eighty-three patients (mean age 46 +/- 8 years, 49 males) with untreated essential hypertension were included in this study. Transmitral Doppler flow velocity was measured both at end-expiration and end-inspiration. Left ventricular mass was measured by M-mode echocardiography. We divided patients into two groups based on the presence of left ventricular hypertrophy or not. RESULTS: Twenty-one patients were diagnosed to have left ventricular hypertrophy. In patients without left ventricular hypertrophy, the peak early filling velocity decreased significantly (from 74 +/- 15 to 71 +/- 18 cm s(-1), P = 0.003), the peak atrial velocity increased significantly (from 65 +/- 17 to 74 +/- 15 cm s(-1), P < 0.001) and the early filling to atrial velocity ratio decreased significantly (from 1.2 +/- 0.3 to 1.1 +/- 0.3, P < 0.001) from end-expiration to end-inspiration. In patients with left ventricular hypertrophy, the parameters of transmitral Doppler flow pattern did not change during respiration. CONCLUSION: Respiratory changes in the transmitral Doppler flow velocity are blunted by left ventricular hypertrophy in hypertension patients. This phenomenon is probably contributed by the increased left ventricular wall stiffness in the left ventricular hypertrophy.

Adaptation, Physiological↗
PubMed1985

Myocardial perfusion in compensated and failing hypertrophied left ventricle.

This study examined blood flow in the hypertrophied left ventricle with and without failure. Left ventricular hypertrophy was produced in 20 dogs by banding the ascending aorta at 6-7 wk of age; studies were performed after animals reached adulthood. Sixteen dogs had compensated hypertrophy, while four dogs had cardiac failure manifested by left ventricular dilatation and end-diastolic pressures greater than 18 mmHg. The degree of hypertrophy, assessed by left ventricular-to-body weight ratio, was similar in animals with compensated hypertrophy (7.29 +/- 0.26 g/kg) and failure (8.45 +/- 0.15); both were greater than control (4.50 +/- 0.15, P less than 0.01). Left ventricular systolic pressure was similar in compensated hypertrophy (184 +/- 9 mmHg) and failure (226 +/- 29), as compared with control (130 +/- 4; P less than 0.01). Left ventricular blood flow measured with microspheres was 0.89 +/- 0.07 ml X min-1 X g-1 in control animals, was increased to 1.34 +/- 0.05 with compensated hypertrophy (P less than 0.001), and was further increased with failure to 1.86 +/- 0.40 (P less than 0.05). The left ventricular wall thickness-to-cavity diameter ratio was increased to 0.63 +/- 0.04 with compensated hypertrophy but was only 0.40 +/- 0.05 in dogs with failure (P less than 0.01), suggesting that wall stress was greater in hearts with failure. These data suggest that increased blood flow rates in dogs with failure resulted from increased myocardial O2 requirements due to increased systolic wall stress. Need for increased blood flow during resting conditions in dogs with failure would impair the ability for further coronary vasodilation during periods of cardiac stress.

Animals↗
PubMed1997

Alterations in sarcoplasmic reticulum calcium-storing proteins in pressure-overload cardiac hypertrophy.

The alterations of intracellular calcium (Ca2+) homeostasis may be responsible for the contractile defects in pressure-overload cardiac hypertrophy. The Ca(2+)-adenosinetriphosphatase (ATPase) protein level of the sarcoplasmic reticulum (SR) is reduced in the hypertrophied or failing heart. However, it is not known whether Ca(2+)-storing proteins, including calsequestrin and calreticulin, are also altered during cardiac hypertrophy. We quantified SR Ca(2+)-regulatory proteins using Western blot analysis in left ventricular (LV) muscle isolated from sham-operated control rats (n = 6) and rats with pressure overload 4 wk after abdominal aortic constriction (n = 7). The contractile function of isolated LV myocytes, assessed by the sarcomere motion measured with laser diffraction, was depressed in aortic-constricted rats. The SR Ca(2+)-ATPase protein level was decreased to 56 +/- 9% (SE) of the control value in hypertrophied myocardium (P < 0.01). The calsequestrin protein level was not altered, whereas calreticulin was increased by 120 +/- 3% of the control value in aortic-constricted rats (P < 0.05). The alterations in SR Ca(2+)-regulatory proteins were equally observed in hypertrophied hearts even when the results were normalized using the amounts of myosin heavy chain proteins in each sample. Immunohistochemical staining of calsequestrin in the control heart showed cross striations at the Z lines, whereas calreticulin was hardly observed within myocytes but was intense within interstitial fibroblasts. In the hypertrophied heart, calreticulin was observed at the perinuclear region within the myocyte cytoplasm. These data indicate that pressure-overload cardiac hypertrophy causes the alterations in SR Ca(2+)-storing proteins as well as in Ca(2+)-ATPase, which may contribute to the contractile dysfunction of the hypertrophied myocytes.

Animals↗
PubMedDate not supplied

Diastolic spectrum of left-ventricular hypertrophy: the impact of etiology and coronary artery disease on Doppler transmitral velocity.

UNLABELLED: Diastolic filling of hypertrophied left ventricles has frequently been observed by Doppler methods. We hypothesized that filling characteristics in hypertrophy vary with etiology and concurrent ischemia. For patients with hypertrophy, the left-ventricular ejection fraction was > 0.47 +/- 0.16, end-diastolic pressure was > 15 +/- 2 mm Hg, end-diastolic volume index was < 96 +/- 12 ml/m2 and left-ventricular mass index was 127 +/- 7 g/m2. Peak E (early) and peak A (late) diastolic velocities and E-wave deceleration time, respectively, were as follows (significant unless otherwise indicated): normal subjects (NS), 79 +/- 9 and 82 +/- 19 cm/s, and 151 +/- 7 ms; cardiomyopathic hypertrophy, 63 +/- 16, 83 +/- 15 (NS) and 193 +/- 63, aortic stenosis without coronary disease, 110 +/- 10, 128 +/- 12 and 158 +/- 22 (NS); aortic stenosis with coronary disease, 57 +/- 12, 86 +/- 26 (NS) and 187 +/- 39; hypertension without coronary disease, 107 +/- 9, 128 +/- 9 and 143 +/- 22 (NS); hypertension with coronary disease, 58 +/- 12, 84 +/- 26 (NS) and 189 +/- 29. CONCLUSIONS: Hypertrophied left ventricles filled with two diastolic Doppler patterns: a relaxation abnormality with low peak E and delayed deceleration in hypertrophic cardiomyopathy, and a compliance abnormality with tall peak E and normal deceleration in pressure overload hypertrophy. When coronary artery disease occurred with pressure overload hypertrophy, impaired relaxation was the dominant pattern. Therefore, in addition to the known physiologic influences on diastolic filling, the etiology and presence of coronary artery disease modulate the configuration of transmitral velocities into hypertrophied ventricles.

Aortic Valve Stenosis↗
PubMed1993

T-type Ca2+ current is expressed in hypertrophied adult feline left ventricular myocytes.

Macroscopic T-type Ca2+ currents, which are often observed in fetal and neonatal cardiac muscle cells, were not found in normal (0 of 17) adult feline ventricular myocytes. However, they were present in most (15 of 21) myocytes isolated from adult feline left ventricles with long-standing pressure-overload-induced hypertrophy. This is the first study to provide evidence in a large mammal, such as the cat, that T-type Ca2+ channels may be reexpressed in adults in association with hypertrophy resulting from slow progressive pressure overload. Importantly, this expression was stable for the duration of the hypertrophy process and was not associated with abrupt pressure overload. T-type Ca2+ currents were separated from L-type Ca2+ currents by exploiting the differences in their voltage dependence of steady-state inactivation. Depolarizations from -80 mV revealed a rapidly activating inward current that peaked in magnitude at -30 mV (-1.8 +/- 0.9 [mean +/- SD] pA/pF) and fully inactivated within 100 milliseconds in 15 of 21 hypertrophied myocytes studied. Further depolarizations activated progressively less T-type Ca2+ current, so that at +10 mV the L-type Ca2+ current predominated. In the hypertrophied myocytes that demonstrated both T-type and L-type Ca2+ currents, two distinct peaks occurred in their current-voltage relations. T-type Ca2+ currents were not evident in any of the 17 normal adult feline left ventricular myocytes studied. The purpose of T-type Ca2+ currents in hypertrophy is unclear. However, their presence may make hypertrophied myocardium more prone to spontaneous action potentials and increase the likelihood for arrhythmias in partially depolarized hypertrophied myocardium.

Animals↗
PubMed2006

Vascular endothelial growth factor prevents apoptosis and preserves contractile function in hypertrophied infant heart.

BACKGROUND: Cardiac hypertrophy is an adaptive response to increased workload that, if unrelieved, leads to heart failure. It has been reported that cardiomyocyte apoptosis contributes to failure, and that vascular endothelial growth factor (VEGF) treatment of hypertrophied myocardium increases capillary density and improves myocardial perfusion. In this study we hypothesized that VEGF treatment reduces cardiomyocyte apoptosis and thereby preserves myocardial contractile function. METHODS AND RESULTS: Newborn rabbits underwent aortic banding. At 4 and 6 weeks of age, hypertrophied animals were treated with intrapericardial administration of recombinant VEGF protein. Three groups of animals were investigated: age-matched controls (C), untreated hypertrophied (H), and VEGF-treated hypertrophied hearts (T). Cardiomyocyte apoptosis was determined by TUNEL staining and PARP cleavage (immunoblotting of nuclear extracts) and cardiac function by transthoracic echocardiography. Death attributable to severe heart failure occurred in 14 of 43 untreated and 2 of 29 VEGF-treated animals (P<0.01). TUNEL-positive cardiomyocyte nuclei (n/1000 nuclei) were significantly increased in untreated hearts at 5 weeks (H: 10+/-1.8 versus T: 3+/-0.7) and at 7 weeks (H: 13+/-3.6 versus T: 5+/-1.5; P<0.05). Increased apoptosis in untreated hypertrophy was also confirmed by the presence of PARP cleavage (H: 74+/-7 versus T: 41+/-4 arbitrary densitometry units; P<0.05). VEGF treatment preserved left ventricular mass, prevented dilation (T: 1.01+/-0.06 versus H: 0.77+/-0.07; P<0.05), and preserved contractility indices compared with untreated hearts. CONCLUSIONS: Lack of adaptive capillary growth impairs myocardial perfusion and substrate delivery in hypertrophying myocardium. VEGF treatment reduces myocardial apoptosis and prolongs survival in a model of severe progressive left ventricular hypertrophy. Promoting capillary growth with VEGF reduces apoptosis, preserves myocardial contractile function, and delays the onset of failure in pressure-loaded infant myocardium.

Animals↗
PubMed1995

Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

We tested the hypothesis that glycolytic inhibition by 2-deoxyglucose causes greater impairment of diastolic relaxation and intracellular calcium handling in well-oxygenated hypertrophied adult rat myocytes compared with control myocytes. We simultaneously measured cell motion and intracellular free calcium concentration ([Ca2+]i) with indo-1 in isolated paced myocytes from aortic-banded rats and sham-operated rats. There was no difference in either the end-diastolic or peak-systolic [Ca2+]i between control and hypertrophied myocytes (97 +/- 18 vs. 105 +/- 15 nM, 467 +/- 92 vs. 556 +/- 67 nM, respectively). Myocytes were first superfused with oxygenated Hepes-buffered solution containing 1.2 mM CaCl2, 5.6 mM glucose, and 5 mM acetate, and paced at 3 Hz at 36 degrees C. Exposure to 20 mM 2-deoxyglucose as substitution of glucose for 15 min caused an upward shift of end-diastolic cell position in both control (n = 5) and hypertrophied myocytes (n = 10) (P < 0.001 vs. baseline), indicating an impaired extent of relaxation. Hypertrophied myocytes, however, showed a greater upward shift in end-diastolic cell position and slowing of relaxation compared with control myocytes (delta 144 +/- 28 vs. 55 +/- 15% of baseline diastolic position, P < 0.02). Exposure to 2-deoxyglucose increased end-diastolic [Ca2+]i in both groups (P < 0.001 vs. baseline), but there was no difference between hypertrophied and control myocytes (218 +/- 38 vs. 183 +/- 29 nM, respectively). The effects of 2-deoxyglucose were corroborated in isolated oxygenated perfused hearts in which glycolytic inhibition which caused severe elevation of isovolumic diastolic pressure and prolongation of relaxation in the hypertrophied hearts compared with controls. In summary, the inhibition of the glycolytic pathway impairs diastolic relaxation to a greater extent in hypertrophied myocytes than in control myocytes even in well-oxygenated conditions. The severe impairment of diastolic relaxation induced by 2-deoxyglucose in hypertrophied myocytes compared with control myocytes cannot be explained by greater diastolic Ca2+ overload, which implicates an increase in myofilament Ca(2+)-responsiveness as a possible mechanism.

Adenosine Triphosphate↗
PubMed2004

Effect of potassium-channel opener therapy on reperfused infarction in hypertrophied hearts: demonstration of preconditioning by using functional and contrast-enhanced magnetic resonance imaging.

Effects of therapy with the potassium-channel opener and vasodilator nicorandil were studied in reperfused infarction of hypertrophied hearts by using magnetic resonance imaging (MRI), hemodynamic measurements, and histochemical staining. Aortic banding was performed on 22 Sprague-Dawley rats to induce left ventricular (LV) hypertrophy; 11 were the controls. Eight weeks later, the left coronary artery was occluded for 25 minutes in all 33 animals, followed by 3 hours of reperfusion. During occlusion, 11 rats with LV hypertrophy received nicorandil (0.1 mg/kg bolus and 1.5 mg/kg/h for 3 hours). The new necrosis-specific contrast agent Gadophrin-3 was administered to all animals to delineate infarction on multislice T1-weighted spin-echo MRI. Nicorandil increased ischemic tolerance of LV hypertrophy as shown by the reduction of infarction size from 19.3% +/- 1.3% to 10.0% +/- 2.5% LV (P = .005). Infarction size in treated animals was identical to control (9.3% +/- 1.6%). Close correlation was found between MRI and postmortem findings. Functional MRI revealed an improvement in ejection fraction in nicorandil-treated hearts (48.5% +/- 3.4% vs 38.1% +/- 3.2%, P = .04). LV end-diastolic volume and pressure, aortic pressure, and peripheral vascular resistance were highest in untreated hypertrophied hearts. Brief ischemia caused severe injury in hypertrophied hearts. Infusing nicorandil increased the tolerance of hypertrophied hearts to ischemia. MRI is a suitable technique for the evaluation of new therapies in LV hypertrophy.

Animals↗
PubMed1981

A histopathological study on the hypertrophy of the atrioventricular conduction system.

A microscopical study of the AV conduction system using a serial sectioning method, was performed on 81 autopsied hearts with blocks anywhere in the hearts without arrhythmia. Pre-blockade hypertrophy in the AV conduction system was seen in 38%, 38%, 50-58% corresponded respectively to 3 degrees AV block, 1-2 degrees AV block and bundle branch block (including left hemiblock). Post-blockade hypertrophy was also observed in 58%, 38% and 42-25% of the above mentioned types of blocks respectively. Hypertrophy anywhere in the AV conduction system was seen in 77%, 42%, 78%, 39%, 30% and 74% of the cases with blocks, sick sinus syndrome, pre-excitation syndrome, other arrhythmias, normal hearts and hypertrophied hearts without arrhythmia, respectively. Hypertrophy of the proximal AV conduction system to the bundle of His was specific for arrhythmia group, whereas hypertrophy of the bundle branches occurred in either hypertrophy without arrhythmia or in bundle branch block. Hypertrophy of the Purkinje cells was remarkable in sudden cardiac death by clinically-proved ventricular fibrillation. Incidence of sclerosis of the AV node artery was high in the arrhythmia group, especially the highest (90%) in the sudden death group.

Heart Arrest↗
PubMed2004

Cyclin-dependent kinase inhibitor, p21Waf1, regulates vascular smooth muscle cell hypertrophy.

In the process of vascular diseases, smooth muscle cells (SMC) undergo not only hyperplasia but also hypertrophy, resulting in vascular remodeling. A cyclin-dependent kinase inhibitor (CDKI), p21Waf1, has been shown to play an important role in SMC hyperplasia. Here we investigated a potential role of p21Waf1 in SMC hypertrophy. An exposure of cultured rat SMC to serum drove the cell cycle progression with up-regulation of various cell cycle markers and increased activities of cyclin-dependent kinases, but did not cause SMC hypertrophy. In contrast, incubation of SMC for 48 h with angiotensin II (AII, 100 nmol/l) resulted in a significant increase in the cell size measured by flowcytometric forward-angle light scatter assay, in association with an increase in the ratio of [3H]leucine/[3H]thymidine uptake, indicating SMC hypertrophy. At 48 h, p21Waf1 expression was up-regulated in SMC exposed to AII but not in those exposed to serum. These results suggest that p21Waf1 may be involved in hypertrophy. To further investigate this issue, two manipulations of the p21Waf1 gene were performed. Adenovirus-mediated over-expression of p21Waf1 not only reduced S-phasic cells but also caused hypertrophy, despite the exposure to serum. Antisense oligodeoxynucleotide for p21Waf1 inhibited the hypertrophy of SMC exposed to AII. Our data suggest that p21Waf1 may play a role in SMC hypertrophy as well.

Adenoviridae↗
PubMed1999

Angiotensin-converting enzyme gene polymorphism and geometric patterns of hypertensive left ventricular hypertrophy.

Polymorphism in the angiotensin-converting enzyme (ACE) gene has been found to be associated with left ventricular hypertrophy (LVH) in patients with essential hypertension (EHT) in certain populations. We sought to evaluate, in a Japanese population, whether ACE genotype is related to left ventricular mass, or to the geometry of LVH in EHT. Eighty-seven patients with EHT were examined. Their relative wall thickness (RWT) and left ventricular mass index (LVMI), determined by echocardiogram, were used to divide them into 4 groups: normal (normal RWT and LVMI, n = 35); concentric remodeling (increased RWT but normal LVMI, n= 10); eccentric hypertrophy (increased LVMI but normal RWT, n = 20); and concentric hypertrophy (increased LVMI and RWT, n = 22). Genetic analysis for ACE genotypes was performed on peripheral leukocytes using PCR techniques. Interventricular septal thickness and RWT were significantly greater in the patients with the DD genotype than in those with the II genotype, but LVMI did not differ among the three ACE genotypes. The frequency of the DD genotype was higher in the concentric hypertrophy group than in each of the other groups, and the frequency of the II genotype was lower in the concentric hypertrophy group than in either the normal or eccentric hypertrophy group. The geometric pattern of hypertensive LVH was associated with ACE genotype in a Japanese population. The DD genotype may contribute to concentric hypertrophy, but not to eccentric hypertrophy.

Adult↗