Postextrasystolic mechanical restitution in closed-chest dogs. Effect of heart failure.

Academic Article

Abstract

  • BACKGROUND: Postextrasystolic mechanical restitution (MRPES) 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 MRPES 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. MRPES curves were constructed by expressing normalized mechanical response as a function of the PESI. Control MRPES 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 MRPES kinetics at each antecedent ESI (P < .025), increased normalized maximal contractile response (CRmax, P < .01), and shortened PESI0 (P < .025). Increases in the TC and CRmax 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 CRmax 128.6 +/- 4.9%, ESI of 300 ms versus 104.9 +/- 1.0%, ESI of 450 ms; P < .005). CONCLUSIONS: MRPES 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 MRPES 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.
  • Authors

    Published In

  • Circulation  Journal
  • Keywords

  • Animals, Calcium, Cardiac Complexes, Premature, Dogs, Electrophysiology, Female, Heart Failure, Male, Myocardial Contraction
  • Author List

  • Prabhu SD; Freeman GL
  • Start Page

  • 2652
  • End Page

  • 2659
  • Volume

  • 92
  • Issue

  • 9