SHHF/Mcc-cp Rat: Model of Obesity, Non-insulin-dependent Diabetes, and Congestive Heart Failure

McCune, Sylvia A.; Baker, Peter B.; Stills, Harold F.

doi:10.1093/ilar.32.3.23

Cited by 60 publications

(47 citation statements)

References 15 publications

(9 reference statements)

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“…In this regard, it should be noted that histological and ultrastructural studies of failing SHHF ventricles have noted marked interstitial and perivascular fibrosis, a reduction in myofibrils, myofibrillar disorganization, and streaking of Z bands. 10 These ultrastructural changes could well lead to a decrease in functional force-producing units and account for at least a part of the decline in maximal Ca 2ϩ -dependent force observed in the present study. Nevertheless, the fact that single skinned myocytes from a rat pressure-overload model of heart failure also exhibit a marked reduction of maximal Ca 2ϩ -activated force 22 hints that the predominant change resides within the myofilaments themselves, not in extracellular factors or myocyte loss.…”

Section: Comparison With Previous Studiessupporting

confidence: 51%

Origin of Contractile Dysfunction in Heart Failure

et al. 1999

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Background-Chronic congestive heart failure is a common, often lethal disorder of cardiac contractility. The fundamental pathophysiology of the contractile failure remains unclear, the focus being on abnormal Ca 2ϩ cycling despite emerging evidence for depressed myofilament function. to activate the myofilaments in failing muscle, partially compensating for the marked dysfunction of the contractile machinery. Conclusions-Our results indicate that myofilament activation is severely blunted in heart failure, but concomitant changes in [Ca 2ϩ ] i kinetics minimize the contractile depression. These results challenge prevailing concepts regarding the pathophysiology of heart failure: the myofilaments emerge as central players, whereas changes in Ca 2ϩ cycling are reinterpreted as compensatory rather than causative.

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Section: Comparison With Previous Studiessupporting

confidence: 51%

Origin of Contractile Dysfunction in Heart Failure

et al. 1999

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“…SHHF rats were obtained from the colony produced by S. McCune at the Ohio State University (25). Only phenotypically lean SHHF rats of either sex were used for this study.…”

Section: Methodsmentioning

confidence: 99%

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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“…31,33 In obese SHHF, the onset of CHF rats is much earlier, and, similar to their lean counterparts, obese SHHF males develop CHF before obese SHHF females. 34 …”

Section: Sex and Rodent Models Of Chfmentioning

confidence: 99%