Human Heart Failure: Dilated Versus Familial Hypertrophic Cardiomyopathy

Abstract

Heart failure is an increasing public health problem with high morbidity and mortality (Cowie, 1997). The survival rates closely correlate with the severity of the heart disease with 50% of the patients classified as NYHA IV surviving only one year (Calif et al 1997; SOLVD Investigators, 1991). The survivability of heart failure patients correlates with the ejection fraction (Cohn et al 1997). The deficit in ventricular performance in failing hearts is directly related to a power deficit of the contractile apparatus. Power is the rate of doing work and at the cellular level is a mechanical expression of the myocyte’s force velocity relationship (power = force X velocity). The ability of the myocyte to develop force and velocity depends on the characteristics of the molecular motor myosin interacting with actin with the obligatory hydrolysis of ATP and the resulting power stroke. In this review we will describe and compare the mechanical and kinetic characteristics of the mechano-enzyme myosin from heart failure patients with dilated cardiomypathy and familial hypertrophie cardiomyopathy (Alpert et al 2002 Palmiter et al 2000, Hasenfuss et al 1992). The studies on heart tissue from patients with dilated cardiomyopathy take advantage of myothermal techniques for assessing the cross-bridge characteristics. In experiments involving tissues from patients with familial hypertrophie cardiomyopathy we use laser trap techniques for evaluating single molecule mechanics.

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Supported in part by USPHS Grants HL66157, HL55641, HL59408.