Ryanodine and left ventricular function in intact dogs: Dissociation of force-based and velocity-based indexes

Sumanth D. Prabhu, M. Marius Rozek, David R. Murray, Gregory L. Freeman

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After anesthesia and autonomic blockade, nine dogs chronically instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied before and after the intravenous administration of 4 μg/kg ryanodine, a specific inhibitor of the sarcoplasmic reticulum Ca2+ release channel. Ryanodine prolonged LV contraction and relaxation (P < 0.001) without changing heart rate, end- diastolic volume (EDV), or end-systolic pressure. Velocity-dependent mechanical parameters were significantly depressed, including the maximal rate of LV pressure rise (dP/dt(max); P < 0.002), the mean velocity of circumferential fiber shortening (P < 0.002), the slope of the dP/dt(max)- EDV relation (P < 0.05), and the time constant of LV relaxation (P < 0.01). In contrast, the slopes of the end-systolic pressure-volume (P(ES)-V(ES)) and stroke work (SW)-EDV relations, both force-based parameters, were increased (P < 0.05) or maintained, respectively. Ryanodine reduced overall LV contractile performance, evidenced by significant rightward shifts of the P(ES)-V(ES), dP/dt(max)-EDV, and SW-EDV relations and reduced SW at constant preload (P < 0.02). Thus, in the closed-chest dog, low-dose ryanodine resulted in 1) generalized slowing of LV mechanical events without changes in heart rate or lead, 2) dissociation of velocity-based and force-based measures of LV function, with depression of the former but enhancement or maintenance of the latter, and 3) reduced overall LV inotropic performance. These effects are consistent with ryanodine-induced alterations of the Ca2+ transient and altered sarcoplasmic reticulum Ca2+ availability.

Original languageEnglish
Pages (from-to)H1561-H1568
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number3 42-3
StatePublished - 1997


  • Calcium handling
  • Cardiac mechanics
  • Ventricular contraction
  • Ventricular relaxation


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