An increase in heart rate produces positive inotropic and lusitropic effects, with an increase in peak tension, and abbreviation of relaxation time in normal cardiac muscle from most mammalian species, including man. However, the effect of an increase in heart rate on the inotropic and lusitropic properties of cardiac muscle from patients with heart failure is not clear. Accordingly, we examined the force-frequency relationship in isolated myocardium from six patients with end-stage heart failure, and compared the findings to those obtained in myocardium from six patients without heart failure who died from non-cardiac causes. The force-frequency relationship was also assessed in the presence of inotropic drugs. In cardiac muscle isolated from normal hearts, active tension increased as the frequency of stimulation was increased. However, this relationship was attenuated or reversed in cardiac muscle from failing human hearts, particularly at rapid rates of stimulation (i.e., 1 Hz) where a fall in isometric force development typically occurred. This fall in active tension was exacerbated by inotropic agents known to increase [Ca++](i) (calcium, acetylstrophanthidin) but was abolished by inotropic agents which increase cyclic adenosine monophosphate (forskolin, caffeine). Moreover, the increase in force at rapid stimulation rates in cardiac muscle from control hearts was abolished by inotropic agents known to increase [Ca++](i) (acetylstrophanthidin, DPI). In terms of diastolic function, increases in end-diastolic tension that occurred at faster pacing rates were greater in cardiac muscle from patients with end-stage heart failure compared to controls, and could be exacerbated by agents that increase [Ca++](i) (acetylstrophanthidin) and diminished by agents which increase cyclic adenosine monophosphate (forskolin). These data suggest that intracellular calcium handling is abnormal and that a calcium overload state may develop at high frequencies of stimulation in myocardium from patients with end-stage heart failure, and may be due in part to a decrease in basal cyclic adenosine monophosphate concentrations.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Applied Cardiology|
|State||Published - Jan 1 1988|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine