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(Circulation. 1995;92:2652-2659.)
© 1995 American Heart Association, Inc.

Articles

Postextrasystolic Mechanical Restitution in Closed-Chest Dogs

Effect of Heart Failure

Sumanth D. Prabhu, MD; Gregory L. Freeman, MD

From the Department of Medicine, University of Texas Health Science Center at San Antonio, and the 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 Postextrasystolic mechanical restitution (MR_PES) is thought to be an expression of intracellular Ca²⁺ handling by cardiac sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca²⁺ homeostasis, we sought to delineate MR_PES behavior before and after the production of heart failure to obtain insights into the relation between altered mechanical performance and Ca²⁺ handling.

Methods and Results Ten dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions; 6 dogs also were studied after tachycardia heart failure (THF) produced by rapid LV pacing for 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at fixed extrasystolic intervals (ESIs; 300, 375, or 450 ms) and graded postextrasystolic intervals (PESIs). Postextrasystolic mechanical response was assessed using single-beat elastance. MR_PES curves were constructed by expressing normalized mechanical response as a function of the PESI. Control MR_PES was a monoexponential function whose time constant (TC) and PESI–axis intercept (PESI₀) increased significantly (P<.01) with increases in the antecedent ESI. THF significantly slowed MR_PES kinetics at each antecedent ESI (P<.025), increased normalized maximal contractile response (CR_max, P<.01), and shortened PESI₀ (P<.025). Increases in the TC and CR_max were most pronounced with the smallest antecedent ESI (percent control postextrasystolic TC 363.7±60.5%, ESI of 300 ms versus 139.0±15.1%, ESI of 450 ms, P<.005; percent control CR_max 128.6±4.9%, ESI of 300 ms versus 104.9±1.0%, ESI of 450 ms; P<.005).

Conclusions MR_PES is much less dynamic in THF: The failing heart operates at lower levels of contractile performance after higher stimulation frequencies and cannot increase its speed of contractile recovery to compensate for higher heart rate. Prolongation of MR_PES kinetics is consistent with depression of SR Ca²⁺ release mechanisms in THF and implicates this site in the loss of the capacity of the failing heart to maintain mechanical performance with tachycardia.

Key Words: tachycardia • heart failure • mechanics • contractility • systole

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