Correlation of Myocyte Lengthening to Chamber Dilation in the Spontaneously Hypertensive Heart Failure (SHHF) Rat

Tamura, Tetsutaro; Onodera, Tatsuyuki; Said, Suleman; Gerdes, A. Martin

doi:10.1006/jmcc.1998.0775

Cited by 53 publications

(49 citation statements)

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“…Cellular responses to CHF and exercise training. In dilated cardiomyopathy, the elongation of cardiomyocytes resulting from the series addition of sarcomeres occurs in the absence of further increases in myocyte cross-sectional area (17,18,63). A morphological hallmark of dilated HF is, therefore, a marked increase in cardiomyocyte LWR (17,18,44,63).…”

Section: Discussionmentioning

confidence: 99%

“…In dilated cardiomyopathy, the elongation of cardiomyocytes resulting from the series addition of sarcomeres occurs in the absence of further increases in myocyte cross-sectional area (17,18,63). A morphological hallmark of dilated HF is, therefore, a marked increase in cardiomyocyte LWR (17,18,44,63). Such an increase in LWR was observed in the Ͻ22HF group and is consistent with the gross morphological alterations in LV chamber dimension that occur in dilated HF (17) where an increase in LV chamber radius and a decrease in wall thickness combine to pathologically increase ventricular wall stress.…”

Section: Discussionmentioning

confidence: 99%

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Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Emter

McCune²,

Sparagna³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 289: H2030 -H2038, 2005. First published July 1, 2005; doi:10.1152/ajpheart.00526.2005.-Data regarding the effectiveness of chronic exercise training in improving survival in patients with congestive heart failure (CHF) are inconclusive. Therefore, we conducted a study to determine the effect of exercise training on survival in a well-defined animal model of heart failure (HF), using the lean male spontaneously hypertensive HF (SHHF) rat. In this model, animals typically present with decompensated, dilated HF between ϳ18 and 23 mo of age. SHHF rats were assigned to sedentary or exercise-trained groups at 9 and 16 mo of age. Exercise training consisted of 6 mo of low-intensity treadmill running. Exercise training delayed the onset of overt HF and improved survival (P Ͻ 0.01), independent of any effects on the hypertensive status of the rats. Training delayed the myosin heavy chain (MyHC) isoform shift from ␣-to ␤-MyHC that was seen in sedentary animals that developed HF. Exercise was associated with a concurrent increase in cardiomyocyte length (Ϸ6%), width, and area and prevented the increase in the length-to-width ratio seen in sedentary animals in HF. The increases in proteinuria, plasma atrial natriuretic peptide, and serum leptin levels observed in rats with HF were suppressed by low-intensity exercise training. No significant alterations in sarco (endo)plasmic reticulum Ca 2ϩ ATPase, phospholamban, or Na ϩ / Ca 2ϩ exchanger protein expression were found in response to training. Our results indicate that 6 mo of low-intensity exercise training delays the onset of decompensated HF and improves survival in the male SHHF rat. Similarly, exercise intervention prevented or suppressed alterations in several key variables that normally occur with the development of overt CHF. These data support the idea that exercise may be a useful and inexpensive intervention in the treatment of HF. myosin heavy chain; proteinuria; cardiomyocyte morphology; atrial natriuretic peptide; leptin HEART DISEASE is a leading cause of death among men and women in Western industrialized societies. Cardiovascular disease (CVD) currently affects over 70 million Americans, 65 million of which are estimated to have high blood pressure and nearly 5 million are diagnosed with congestive heart failure (CHF) (2). With the diagnosis of CHF, life expectancy decreases dramatically and chances of survival decrease with 70 -80% of patients dying within 8 yr (2). Although chronic exercise training has clearly been shown to be beneficial in attenuating risk factors for CVD, including high blood pressure and cholesterol levels, insulin resistance, and obesity (9,14,53,58), the utility of exercise as a clinical intervention for patients with developing CHF is less clear. Currently, there is a lack of clarity regarding the efficacy of chronic exercise training as a treatment and in reducing mortali...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Emter

McCune²,

Sparagna³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…Echocardiographic studies in the SHHF rat demonstrate left ventricular dysfunction (left ventricular ejection fraction Ͻ40%) at 17-18 mo of age (31). There is also evidence of progressive cardiac hypertrophy in the SHHF rats, evidenced as an increase in heart weights (36).…”

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confidence: 94%

Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

Sridhar¹,

Dech²,

Lacombe³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats. Am J Physiol Heart Circ Physiol 291: H2192-H2198, 2006. First published June 9, 2006 doi:10.1152/ajpheart.01146.2005.-Hypertension is a common cause of heart failure, and ventricular arrhythmias are a major cause of death in heart failure. The spontaneous hypertension heart failure (SHHF) rat model was used to study altered ventricular electrophysiology in hypertension and heart failure. We hypothesized that a reduction in the inward rectifier K ϩ current (IK1) and expression of pacemaker current (If) would favor abnormal automaticity in the SHHF ventricle. SHHF ventricular myocytes were isolated at 2 and 8 mo of age and during end-stage heart failure (Ն17 mo); myocytes from age-matched rats served as controls. Inward IK1 was significantly reduced at both 8 and Ն17 mo in SHHF rats compared with controls. There was a reduction in inward IK1 due to aging in the controls only at Ն17 mo. We found a significant increase in If at all ages in the SHHF rats, compared with young controls. In controls, there was an age-dependent increase in If. Action potential recordings in the SHHF rats demonstrated abnormal automaticity, which was abolished by the addition of an If blocker (10 M zatebradine). Increased If during hypertension alone or combined increases in If with reduced IK1 during the progression to hypertensive heart failure contribute to a substrate for arrhythmogenesis. aging; pacemaker current; inward rectifier potassium current; abnormal automaticity HYPERTENSION CAN LEAD TO COMPENSATORY hypertrophy in cardiac muscle. Chronically, these compensatory mechanisms can become maladaptive, and cardiomyopathy and heart failure can result (22). Experimental animal studies in hypertrophy and heart failure have shown abnormalities in ion channel function, altered expression and function of proteins involved in excitation-contraction coupling, and an increased propensity for cardiac arrhythmias (16,30,32). Clinically, ventricular arrhythmias occur in 80% of heart failure patients (11). However, the mechanisms of arrhythmogenic electrophysiological remodeling during hypertension and hypertensive heart failure are not fully elucidated.Spontaneous hypertensive heart failure (SHHF) rats develop hypertension at an early age. In contrast to spontaneously hypertensive rats (SHRs), the SHHF rats consistently develop reproducible, hypertensive heart failure in an age-dependent manner (26). Echocardiographic studies in the SHHF rat demonstrate left ventricular dysfunction (left ventricular ejection fraction Ͻ40%) at 17-18 mo of age (31). There is also evidence of progressive cardiac hypertrophy in the SHHF rats, evidenced as an increase in heart weights (36).Hypertension and heart failure can increase the pacemaker current (I f ) in the ventricular myocardium (4 -7). This can pathologically alter the diastolic phase of the action potential and enhance abnormal automaticity. In addition, aging has been shown to increase I f density i...

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“…25 To measure myocyte and sarcomere lengths, the myocytes were isolated from formalinfixed tissue by means of the potassium hydroxide digestion method, according to Tamura et al 26 Briefly, small pieces of formalin-fixed tissue were rinsed in PBS and put into 12.5 mol/L KOH solution for 24 hours. Rod cells were then separated by filtration through nylon mesh (250 m).…”

Section: Myocardial Collagen Content and Myocyte Morphometrymentioning

confidence: 99%

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

et al. 2004

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Abstract-Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (nϭ15) and in sham-operated animals (nϭ15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, PϽ0.05), and significant increase of myocyte length (ϩ29% at 3 months, PϽ0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (ϩ117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.

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Correlation of Myocyte Lengthening to Chamber Dilation in the Spontaneously Hypertensive Heart Failure (SHHF) Rat

Cited by 53 publications

References 0 publications

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Low-intensity exercise training delays onset of decompensated heart failure in spontaneously hypertensive heart failure rats

Abnormal diastolic currents in ventricular myocytes from spontaneous hypertensive heart failure rats

Different Growth Factor Activation in the Right and Left Ventricles in Experimental Volume Overload

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