EFFECTS OF ISOPROTERENOL ON MYOCARDIAL RELAXATION RATE - INFLUENCE OFTHE LEVEL OF LOAD

The present work was undertaken to test the hypothesis that the level of the load faced by the myocardium influences the effects of isoprote renol on relaxation rate. Responses to cumulative doses of isoproteren ol (from 10(-10) to 10(-6) M) were studied in rat left ventricular pap illary muscle stimulated 12 beats/min at 29-degrees-C in 0.5 mM extrac ellular calcium and preloaded at initial muscle length corresponding t o apex of length-active tension curve (L(max); group 1, n = 20) or at 95% of L(max) (group 2, n = 9). A control group (group 3, n = 8) was s tudied every 15 min for 75 min. We measured maximum unloaded shortenin g velocity (V(max)), normalized positive and negative peak force deriv atives (+dF and -dF, respectively) of the fully isometric twitch, and peak lengthening velocity of the isotonic twitch with preload only (Vl (max)). In group 1, V(max) and +dF increased under 10(-10) and 10(-9) M isoproterenol, respectively, and -dF increased under 10(-9) M isopro terenol (115 +/- 13 vs. 96 +/- 12 mN.s-1.mm-2, P = 0.01). Conversely, Vl(max) increased under 10(-7) M isoproterenol only (2.34 +/- 0.19 vs. 1.45 +/- 0.18 L(max)/s, P < 0.001). In group 2, both -dF and Vl(max) increased under 10(-7) M isoproterenol only (P = 0.015 and 0.011, resp ectively). In group 3, -dF and Vl(max) did not vary in time. Our resul ts suggest a load-revealed (or length-revealed) difference in the dose dependence of the various biochemical processes involved in the effec ts of isoproterenol during myocardial relaxation.