The efficiency of chemomechanical energy transduction (contractile efficiency) of the left ventricle (LV) has been calculated from the linear correlation of the systolic pressure-volume area (PVA) of the LV and its O2 consumption (VO2). Thus far, a wide range of acute interventions, including adrenergic agents, Ca(2+)-sensitizing drugs, and Ca2+ channel blockers have not altered contractile efficiency. In contrast, hyperthyroidism has been reported to decrease contractile efficiency, an effect attributed at the cross-bridge level to an increase in the V1/V3 myosin isoenzyme ratio. We hypothesized that an acute intervention which directly alters cross-bridge cycling would also change contractile efficiency. Accordingly, 2,3-butanedione monoxime (BDM), a negative inotropic agent that is thought to directly inhibit cross-bridge formation, was administered to seven excised, red blood cell-perfused, isovolumically beating rabbit LVs. At 3-4 mM perfusate concentration, BDM resulted in the following reversible mechanical and energetic effects compared with control. Contractility, assessed by the slope (Emax) of the end-systolic pressure-volume relation, decreased by 11% (196.6 +/- 25.9 vs. 222 +/- 28 mmHg/ml). Both the time to end systole (Tmax) and relaxation half time (T1/2) decreased. The slope of the VO2-PVA relation decreased by 20% (1.55 +/- 0.44 x 10(-5) vs. 1.95 +/- 0.52 x 10(-5) ml O2 x mmHg-1 x ml-1), equivalent to an increase in contractile efficiency from 36.5 +/- 10.4 to 46.4 +/- 14.4%, while the O2 costs of the mechanically unloaded LV decreased by 12% (0.0258 +/- 0.0060 vs. 0.0292 +/- 0.0064 ml O2 x beat-1 x 100 g-1). Finally, BDM also produced coronary vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)