Accentuated negative inotropism of verapamil after ischaemic intervention in isolated working rat heart

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Abstract
We examined the effects of a clinically relevant concentration (2×10−7 mol·litre−1) of verapamil on the cardiac functions of isolated working rat hearts during global ischaemia (15 min) and reperfusion (30 min). The aorta and the left atrium of each heart of male Sprague-Dawley rats were cannulated for perfusion with Krebs-Henseleit solution, and a soft elastic catheter was introduced into the left ventricle through the left atrial cannula. Verapamil slightly increased the left ventricular end-diastolic pressure, and slightly decreased the left ventricular dP/dt, but did not reduce the left ventricular peak systolic pressure before ischaemia. During the early phase of ischaemia and reperfusion, verapamil (n=6) lowered the left ventricular peak systolic pressure and the left ventricular dP/dt in comparison with the controls (n=6) (left ventricular peak systolic pressure 45.4± 16.9 versus 60.9±15.2 mmHg: p−1: p<0.05, after 30 min of reperfusion). Fifteen min of ischaemia resulted in no increase in the creatine kinase release during reperfusion. The creatine kinase release was not different in the two groups during the experiment. Thus, the negative inotropic effect of verapamil was accentuated by the ischaemic intervention. Myocardial protection may be achieved by reducing the left ventricular peak systolic pressure and thereby the oxygen consumption. On the other hand, in clinical application to patients with extensive myocardial ischaemia, verapamil may cause untoward deterioration in cardiac functions.