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The interactions of the inotropic effects of verapamil (0.05-2.0 mumol l-1), calcium (0.33-5.2 mmol l-1) and post extra systolic potentiation (PESP) as induced by paired stimulation were studied in isolated rabbit and rat hearts under isovolumic and isotonic conditions. At low doses of verapamil, contractions were depressed, but those elicited by paired stimulation showed less depression than contractions of the same rate during single stimulation and even exceeded the unpotentiated contractions without verapamil. At high doses of verapamil contractility could not be restored by paired stimulation. Although contractions were restored to control level by an increase in extra-cellular calcium they were still abnormal in the sense that PESP could not be elicited. The excitation-contraction (e-c) uncoupling due to low calcium perfusion could be counteracted by paired stimulation but e-c uncoupling due to high dose verapamil could not be reversed by paired stimulation. Our results support the view that PESP does not only depend on augmented slow channel calcium influx but also on an enhanced calcium shift within the sarcoplasmic reticulum. We are doubtful about the idea that PESP can be used clinically to counteract the negative inotropic effect of high doses of verapamil.

Post-extra systolic potentiation: Influence of calcium and verapamil in rat and rabbit hearts