MODULATION OF MYOCARDIAL ECONOMY AND EFFICIENCY IN MAMMALIAN FAILING AND NONFAILING MYOCARDIUM BY CALCIUM-CHANNEL ACTIVATION AND BETA-ADRENERGIC STIMULATION

Objective: We investigated the energy-metabolic consequences of positi ve inotropic stimulation by the calcium channel activator, BAY K 8644, in comparison with isoprenaline, focussing both on the economy of for ce development and the efficiency of external work. Methods: In the fi rst instance, heat liberation was measured in isometrically contractin g right ventricular papillary muscles from guinea pigs by means of ant imony-bismuth thermopiles; in the second instance, external work and m yocardial oxygen consumption were analyzed in isolated failing and non -failing wet-king rat hearts. Results: In the guinea pig muscle strip preparations BAY K 8641 (10(-5) M) and isoprenaline (10(-8) M) increas ed peak developed force from 13.7+/-2.7 to 37.6+/-14.9 mN/mm(2) and fr om 13.6+/-5.2 to 38.8+/-3.3 mN/mm(2), respectively (P <0.01). Stress-t ime integral was increased from 10.3+/-3.0 to 34.7+/-19.2 mN . s/mm(2) by BAY K 8644 and from 9.5+/-2.4 to 23.0+/-1.6 mN . s/mm(2) by isopre naline. Whereas a significant decrease in the ratio between stress-tim e integral and initial heat (/Pdt/IH) (i.e., economy of isometric cont raction) was observed for isoprenaline (5.26+/-1.91 before and 3.11+/- 0.72 N . m . s . J(-1) after treatment (P <0.01)), BAY K 8644 did not significantly alter this index (5.26+/-2.39 before and 6.22+/-2.63 N . m . s . J(-1) after treatment). Similar results were obtained for the ratio between stress-time integral and tension-dependent heat. Signif icantly more calcium ions were required for equieffective activation o f the contractile proteins with isoprenaline as compared to BAY K 8644 . In working preparations of sham-operated and infarcted rat hearts, t he increase in myocardial oxygen consumption per minute (Delta MVO(2)) for a given increase in external work per minute (Delta P) was signif icantly higher with isoprenaline than with equipotent concentrations o f BAY K 8644 or high calcium. Conclusions: Inotropic myocardial stimul ation by BAY K 8644 is associated with higher economy and efficiency t han stimulation by isoprenaline when analyzed both by heat measurement s in isometric preparations and by myocardial oxygen consumption in wo rking heart preparations.