RELAXANT EFFECTS OF ISOPROTERENOL IN ISOLATED CARDIAC-MUSCLE - INFLUENCE OF LOADING PATTERNS

The purpose of this study was to test the hypothesis that loading patt erns (i.e., loading sequence, total load, and preload) modulate the re laxant effects of isoproterenol. The effects of isoproterenol (10(-6) M) on peak rate of force decline (-dF/dt) were studied in rat left ven tricular papillary muscle (n = 24) with respect to two sequences of re laxation: the classical, isotonic-isometric sequence, in which tension fall occurs at initial muscle length, and the physiological, isometri c-isotonic sequence, in which tension fall occurs at end-systolic musc le length. The influences of muscle load and initial length were accou nted for in the evaluation of relaxation rate by plotting -dF/dt again st the entire range of loads both at preload = maximum length (L(max)) and 90% L(max). The main results are the following: 1) in the classic al, isotonic-isometric sequence of relaxation, and whatever the preloa d, the magnitude of the relaxant effect of isoproterenol increased wit h load; 2) after reversal into the physiological, isometric-isotonic s equence of relaxation, the relaxant effect of isoproterenol behaved in dependently of load level in muscle preloaded at L(max); 3) conversely , in muscle preloaded at 90% L(max) and relaxing according to the phys iological sequence, the relaxant effect of isoproterenol increased wit h load; and 4) the peak relaxant effect of isoproterenol was proportio nally higher in the physiological sequence of relaxation than in the c lassical one and occurred at a similar level of load, whatever the loa ding sequence and whatever the preload level. Our results indicate tha t loading patterns finely modulated the relaxant effects of isoprotere nol and that muscle length, both before the contraction phase and at t he onset of relaxation phase, influenced the effects of isoproterenol on myocardial relaxation rate.