(Circulation. 1995;91:176-185.)
© 1995 American Heart Association, Inc.
Effect of Tachycardia Heart Failure on the Restitution of Left Ventricular Function in Closed-Chest Dogs
From the Department of Medicine, University of Texas Health Science Center at San Antonio, and Audie Murphy Memorial Veterans Hospital, San Antonio, Tex.
Correspondence to Sumanth D. Prabhu, MD, Department of Medicine/Cardiology, University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78284-7872.
Background Cardiac mechanical restitution and relaxation restitution are thought to be physiological correlates of the recovery kinetics of Ca2+ release mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ handling, we sought to delineate changes in mechanical and relaxation restitution produced by heart failure.
Methods and Results Six dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions and after tachycardia heart failure (THF) produced by rapid LV pacing for 3 to 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at graded extrasystolic intervals (ESIs). Mechanical response was assessed from single-beat elastance. Relaxation was assessed from the time constant of isovolumic relaxation (tau), the average rate of pressure fall during isovolumic relaxation (Ravg), and peak negative dP/dt, the first derivative of LV pressure. Normalized mechanical and relaxation responses plotted against ESI produced monoexponential curves of mechanical and relaxation restitution. THF depressed baseline contractile and relaxation parameters compared with control (end-systolic elastance, 4.7±0.4 versus 7.1±0.5 mm Hg/mL, P<.005; tau, 34.8±2.2 versus 26.7±1.2 ms, P<.05; all values mean±SEM). THF slowed mechanical restitution and delayed development of peak contractile response, with the time constant of mechanical restitution increasing from 61.8±6.9 to 100.2±9.6 ms, P<.01. THF abolished the biphasic behavior of relaxation restitution, and this relation was approximated by a single monoexponential function. There was no difference in the time constants of the first phase of relaxation restitution at control and after THF (TCR1, normalized 1/Ravg, 44.3±5.6 versus 42.0±8.5 ms, P=NS; TCR1, normalized (dP/dtmin)-1, 42.2±6.3 versus 36.7±4.3 ms, P=NS).
Conclusions These results indicate that THF alters the recovery kinetics of SR Ca2+ release to a significantly greater extent than those of SR Ca2+ sequestration and that the abnormal time course of Ca2+ availability to the myofilaments is the rate-limiting step in the recovery of cardiac function after a depolarization.
Key Words: mechanics • calcium • myocardial contraction • heart failure
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