EFFECT OF MIVAZEROL ON MYOCARDIAL LACTATE PRODUCTION BLOOD-FLOW AND ELECTROCARDIOGRAPHIC SIGNS OF ISCHEMIA-INDUCED BY CORONARY-ARTERY LIGATION IN THE ANESTHETIZED DOG

Ischaemic injury In a number of animal models is reduced by mivazerol 2-hydroxy-3-[(1-H-imidazoI-4-yl)methyl]-benzamide, CAS 125472-02-8). T his effect aias accompanied by a reduction in heart rate. The effect o f mivazerol on myocardial blood flow and lactate production in the isc haemic myocardium was examined at constant heart rate by right atrial pacing in an anaesthetised open-chest dog model, Three periods of isch aemia were induced by coronary occlusion for 5 min. The first is-ham) and the second in the absence of the drug and the third 15 min after 1 0 nmol/kg i.V. Arteriovenous differences in plasma lactate using a loc al vein and coronary sinus draining the ischaemic and non-ischaemic my ocardium, respectively, were measured before and 4 min after coronary occlusion. Blood flow (microspheres) was determined at 3 min of ischae mia. Mivazerol reduced lactate production by the ischaemic area from 2 .6 +/- 1.2 to 1.5 +/- 0.9 mmol/l (paired t-test, p<0.01), but blood Ro w to the ischaemic sub-endocardium was not changed: 0.19 +/- 0.1 vs 0. 21 +/- 0.12 ml . g(-1). min(-1). Mean ST segment elevation tended to b e reduced 1.6 +/- 1.0 vs 3.8 +/- 3.0 mV (one-sided paired t-test, p = 0.05). Mivazerol exerts its anti-ischaemic effect at least in part by a reduction in ischaemic lactate production but not by increasing isch aemic blood flow.