Effect of cardiotropic agents on the myocardial dysfunction of hyperdynamic sepsis

We have previously shown that in vitro myocardial performance is impaired in rats during the hyperdynamic, hypermetabolic phase of sepsis. Although the heart in the resting animal generated an elevated cardiac output, the isolated, perfused heart showed a depressed ventricular function curve. In the present studies, interventions to improve contractile function (increased perfusate calcium concentration or perfusion with ouabain) or to decrease calcium availability to the myofibrils (verapamil and tetracaine) were investigated using the isolated perfused working heart. These studies showed that increasing or decreasing calcium concentration in the perfusion medium had little effect on ventricular performance in the septic group, whereas ouabain enhanced performance by approximately 25%. Addition of verapamil at a dose that caused a minimal decrease in myocardial work (cardiac output x peak systolic pressure) in control hearts showed a 20-25% increase in work in the experimental hearts. Increased levels of verapamil caused a greater depression in myocardial performance in the control hearts than in the hearts from septic rats. Thus, it appears that a multifaceted defect may be present in these hearts with a derangement that can be slightly improved with either ouabain or verapamil. Since neither intervention could completely reverse the myocardial dysfunction in hyperdynamic sepsis, it appears that the defect may be due to other factors in addition to calcium availability for contraction.