Effects of trapidil on diltiazem-induced changes of mechanical and electrical properties in isolated rabbit...

Effects of trapidil on diltiazem-induced changes of myocardial properties were investigated mechanically and electrophysiologically in tissues isolated from rabbit hearts. Application of diltiazem (10(-6) M) on right atria significantly decreased both force development and contraction rate. Additional administration of trapidil (10(-4) M) in the presence of diltiazem significantly restored the magnitude of force development without changes in contraction rate. Electrical stimulation to left atria and papillary muscles with varying frequencies produced a frequency-dependent increase in force developments (Bowditch's staircase). Diltiazem (10(-6) M) caused a depression of contractile force hence inhibited the staircase upon increasing frequency of stimulations. Additional application of trapidil (10(-4) M) partially but significantly restored the staircase. Intracellular recordings with microelectrodes clarified that trapidil increased the amplitude of slow responses which was being depressed by the treatment of diltiazem. Our findings suggest that trapidil, when applied successively to diltiazem, may diminish the inhibitory effects of diltiazem on hearts.