Effect of mivazerol on myocardial lactate production, blood flow and electrocardiographic signs of ischaemia induced by coronary artery ligation in the anaesthetised dog.
Ischaemic injury in a number of animal models is reduced by mivazerol (2-hydroxy-3-[(1-H-imidazol-4-yl) methyl]-benzamide, CAS 125472-02-8). This effect was accompanied by a reduction in heart rate. The effect of mivazerol on myocardial blood flow and lactate production in the ischaemic myocardium was examined at constant heart rate by right atrial pacing in an anaesthetised open-chest dog model. Three periods of ischaemic were induced by coronary occlusion for 5 min. The first (sham) and the second in the absence of the drug and the third 15 min after 10 nmol/kg i.v. Arteriovenous differences in plasma lactate using a local vein and coronary sinus draining the ischaemic and non-ischaemic myocardium, respectively, were measured before and after 4 min after coronary occlusion. Blood flow (microspheres) was determined at 3 min of ischaemia. 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 flow to the ischaemic sub-endocardium was not changed: 0.19 +/- 0.1 vs 0.21 +/- 0.12 ml.g-1.min-2. Mean ST segment elevation tended to be 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 ischaemic blood flow.
Riemersma
R A
RA
Cardiovascular Research Unit, University of Edinburgh, United Kingdom.
Debeer
L J
LJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D019344:Lactic Acid; C087969:mivazerol