Effects of isradipine on hemodynamic parameters and ventricular tachycardia in healed myocardial infarction

de Langen, C. D.; van den Toren, E. W.; Tio, R. A.; Lie, K. I.; Wesseling, H.

The calcium-entry blocker isradipine was tested in a closed-chest pig model for chronic myocardial infarction. Ischemia was evoked in anesthetized pigs (25-35 kg) by inflating a catheter ballon in the left anterior descending coronary artery for at least 45 min. Hemodynamic monitoring and signal averaging of X, Y, and Z electrocardiographic leads were performed (150 beat, filtered at 50 Hz). After reperfusion, all animals developed an accelerated idioventricular rhythm and high creatine kinase (CPK) plasma levels. Coronary venous purines and catecholamines increased transiently. Two hours after reperfusion, heart rate was elevated from the initial 87.5 .+-. 6.3 to 126 .+-. 6.4 beats/min (p < 0.01) and the pressure-rate product (PRP, an index of oxygen demand) from 9,530 .+-. 630 to 11,950 .+-. 790 mm Hg/min (p < 0.05). After 2 weeks, surviving pigs had a decreased stroke volume (98 .+-. 18 versus the initial 124 .+-. 14 .mu.l/kg, p < 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 .+-. 6.5 versus 65.7 .+-. 2.9 ms, initially; p < 0.05), and ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of isradipine (1 .mu.g/kg/min for 30 min), the cardiac index increased from 92 .+-. 14 to 133 .+-. 8.7 ml/min .cntdot. kg (p < 0.02). Even at a higher heart rate, the PRP dropped from 12,600 .+-. 1,900 to 10,560 .+-. 1,400 mm Hg/min (p < 0.05). Sustained monomorphic tachycardias were inductible in five pigs before and in three pigs after isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found. Therefore, isradipine is well-tolerated in chronic infarction and might be beneficial as an aferload-reducing agent in patients with tachyarrhythmias.