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Differing Effects of Inotropic Agents on Length Change Deactivation of Isolated Rat Myocardium
  1. John K. Leach,
  2. Lincoln E. Ford,
  3. John M. Perea,
  4. Laura A. Grimes,
  5. Betty J. Skipper
  1. From the Department of Neurosciences (J.K.L., J.M.P., L.A.G.), University of New Mexico School of Medicine, Albuquerque, NM
  2. Department of Medicine (J.K.L., J.M.P., L.A.G.), University of New Mexico School of Medicine, Albuquerque, NM
  3. Department of Family and Community Medicine (B.J.S.), University of New Mexico School of Medicine, Albuquerque, NM
  4. Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine (L.E.F.), Indianapolis, Ind.
  1. Address correspondence to: John K. Leach, MD, Department of Neurosciences, BMSB 145, University of New Mexico School of Medicine, 915 Camino de Salud, Albuquerque, NM 87131-5223. E-mail jleach{at}salud.unm.edu
  2. Supported in part by the Dedicated Health Research Funds of the University of New Mexico School of Medicine and the Fraternal Order of Eagles Max Baer Heart Fund.

Abstract

Background A rapid change in length of cardiac muscle during isometric contraction is followed by developed force that is less than appropriate for the new length because of deactivation of the contractile system. Length change deactivation may have favorable or unfavorable effects on cardiac function, depending on the circumstances under which it is produced.

Methods Left ventricular papillary muscles from male Sprague-Dawley rats were arranged for recording of isometric force. After each control or reference isometric contraction, a quick release-quick stretch V-step was applied to the following contraction. For each repetition of control and experimental contractions, the time of application of V-steps was increased by 20 ms until peak force was reached. Effects of these V-steps were assessed from ratios of peak redeveloped force to peak force in an isometric reference contraction. Slopes of plots of these ratios versus time after the onset of the contraction were used to quantify the effects of inotropic agents on deactivation.

Results Increasing calcium from 2.5 to 5.0 or 7.5 mM increased force by 12±4% (mean±SEM), did not change time to peak, and did not significantly alter the deactivation slope. Adding 5 mM epinephrine increased force by 16±5%, decreased time to peak by 34±3%, and increased the deactivation slope by 106±9% (P<0.001). Caffeine had variable effects on peak force, increased time to peak by 47±4%, and decreased the deactivation slope by 71±5% (P<0.001).

Conclusions The quantitatively different effects of the three agents on length change deactivation slopes and time to peak force suggest a common mechanism, probably involving thin-filament cooperativity.

Key Words
  • papillary muscle
  • length change deactivation
  • inotropy
  • calcium
  • caffeine
  • epinephrine

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