Elevated ventricular filling pressures ultimately result in systemic and pulmonary venous congestion and edema, and are thus in large part responsible for the manifestations of congestive heart failure. Although inadequate myocardial contractile performance can cause such elevations in filling pressures, the contribution of diastolic factors such as incomplete relaxation, variable diastolic tone (tonus), and ventricular viscoelastic properties is uncertain. The proposed studies will develop methodology related to the detection and quantitation of segmental myocardial compliance in both normal and ischemic myocardial segments in humans. Using this and previously developed methodology, we plan to study five questions: (a) Does transient myocardial ischemia in the human heart result in impaired relaxation and/or sustained partial contraction of ischemic myocardial segments in diastole? (b) What is the relationship (if any) between the altered left ventricular diastolic pressure-volume relationship characteristic of angina pectoris and increased diastolic tone? (c) Is increased diastolic tone (if present) related to increased intracelular Ca ions levels (relative to the ability of sarcoplasmic reticulum to sequester Ca ions and therefore subject to attenuation by agents which prevent increased intracellular ions (blockade of slow channel ions influx by nifedipine) and potentiation by agents that favor increased intracellular ions (increased Na ion -Ca ions exchange by digitalis glycosides)? (d) Are myocardial relaxation and diastolic tone altered in patients with congestive heart failure? and (e) Are viscoelastic properties such as hysteresis and creep important in the human heart?
NIH ExPorter
NIH ExPorter