The negative inotropic potency of compound D 600 in rat, guinea pig, and rabbit cardiac preparations.

The negative inotropic effect of compound D was examined in isolated cardiac preparations from several species. Based upon calculated pD2 values, D 600 was most potent in rabbit papillary muscles (pD2 = 7.54), similar or less potent in guinea pig left atria (pD2 = 6.92) and papillary muscles (pD2 = 6.84), and least potent in rat left atria (pD2 = 6.06) and papillary muscles (pD2 = 5.62). Force-frequency curves for rat cardiac tissues were displaced downward in a parallel manner by D 600 whereas for guinea pig and rabbit cardiac tissues D 600 produced greater negative inotropic effects at higher stimulation frequencies. These results suggest that the rat heart is the least dependent of the three species on extracellular calcium for contraction and that guinea pig and rabbit hearts are more dependent on extracellular calcium. The data further suggest that there is an increased dependence on extracellular calcium as heart rate increases in both the rabbit and guinea pig.