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 balloon 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 beats, 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 less than 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 less than 0.05). After 2 weeks, six surviving pigs had a decreased stroke volume (98 +/- 18 versus the initial 124 +/- 14 microliters/kg, p less than 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 +/- 6.5 versus 65.7 +/- 2.9 ms, initially; p less than 0.05), and
ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of
isradipine (1 microgram/kg/min for 30 min), the cardiac index increased from 92 +/- 14 to 133 +/- 8.7 ml/min.kg (p less than 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 less than 0.05). Sustained monomorphic
tachycardias were inducible in five pigs before and in three pigs after
isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found.(ABSTRACT TRUNCATED AT 250 WORDS)