The mechanical and energetic effects of the adenosine triphosphate-sensitive potassium channel opener cromakalim at 50 microM and 100 microM were determined on guinea pig left ventricular papillary muscles and compared with those of low calcium concentration (n = 9 in each group). Both concentrations of cromakalim induced a negative inotropic effect (decrease in maximum shortening velocity at preload only and maximum extent of muscle shortening at preload only, P < .01 and P < .001 at 50 and 100 microM, respectively; maximum isometric active force normalized per cross-sectional area during the isometric twitch, P < .001; positive peak of the isometric force derivative normalized per cross-sectional area, P < .001) and a negative lusitropic effect (decrease in maximum lengthening velocity at preload only and negative peak of the isometric force derivative normalized per cross-sectional area, P < .01 and P < .001 at 50 and 100 microM, respectively). At 100 microM, the decrease in relaxation parameters was more marked than that in contraction parameters under isotonic conditions, as shown by the decrease in the slope of the relationship between peak lengthening velocity and maximum extent of muscle shortening (P < .01); this result reflects an intrinsic negative relaxant effect. No relaxant effect was found under isometric conditions at either concentration. The mechanical effects of low calcium were similar to those of cromakalim 100 microM, which suggests that the drug acted mainly by reducing the cellular calcium entry. Despite the negative mechanical effect of cromakalim, mechanical efficiency was preserved. This could partly explain the cardioprotective effect of cromakalim during ischemia.