EFFECTS OF RYANODINE ON CARDIAC CONTRACTION, EXCITATION-CONTRACTION COUPLING AND TREPPE IN THE CONSCIOUS DOG

The effects of ryanodine on left ventricular (LV) function and hemodyn amics were studied in 16 conscious dogs, chronically instrumented for measurements of LV pressures and dimensions. Systemic infusion of ryan odine (0.5-4 mu g/kg i.v.) resulted in a dose-dependent depression of cardiac contraction, For example, ryanodine, 4 mu g/kg i.v., decreased LV fractional shortening by 30.5 +/- 4.1%, LV dP/dt by 41.5 +/- 4.0% and Vcf(c) by 37.8 +/- 4.1%, while increasing the isovolumic relaxatio n time constant, tau, from 23.1 +/- 1.4 to 34.1 +/- 3.6 ms without a m ajor effect on preload or afterload. Ryanodine also depressed (P<0.05) the plateau phase of the mechanical restitution and post-extrasystoli c potentiation responses, indicating a direct effect on excitation-con traction coupling. The heart rate dependent positive staircase (''Trep pe'') was significantly enhanced (P<0.05) after ryanodine infusion, i. e. LV dP/dt rose by 43.1 +/- 4.7% with an increase in heart rate from 150 to 240 beats/min in the presence of ryanodine 4 mu g/kg, but by on ly 7.5 +/- 2.1% without ryanodine, The more pronounced ''Treppe'' in t he conscious dog under the condition of impaired SR calcium release ca used by ryanodine, supports the concept that the classical Bowditch '' Treppe'' reflects either a state of myocardial depression due to alter ation in SR calcium handling, or enhanced availability of trans-sarcol emmal Ca2+ influx. This finding may help to understand the discrepancy in the importance of the ''Treppe'' between conscious animals and mor e isolated preparations. (C) 1995 Academic Press Limited