Influence of low-flow infusion and magnesium on tissue necrosis during regional ischemia in the canine myocardium

Abstract

Passive intracoronary perfusion of therapeutic agents has been used in the clinical setting to attenuate the effects of brief episodes of myocardial ischemia. The objective of this study was to assess the effects of low-flow coronary infusion with or without Mg2+ on tissue necrosis and cardiac hemodynamics after prolonged regional ischemia. In 33 anesthetized dogs (5 excluded during study), the left anterior descending coronary artery was occluded for 6 h. Dogs were assigned to three groups: the first group (n = 8) was subjected to 6 h coronary occlusion without low-flow perfusion (controls), the second group (n = 10) received a low-flow coronary infusion of Ringer's lactate (Mg2+-free), and the third group (n = 10) received a low-flow coronary infusion of Ringer's lactate plus Mg2+ sulfate (15 mM). Tissue necrosis was evaluated using tetrazolium staining and was normalized to the principal baseline predictors of infarct size including anatomic risk zone (microsphere autoradiography) and coronary collateral flow. In control hearts, infarct size comprised 51.1 ± 4.1% of the risk zone (40.8 ± 5.1% left ventricular cross-sectional area (LV)). In the Mg2+-free and Mg2+ groups, risk zone size was 17.3 ± 2.2 and 16.8 ± 1.8% LV (p < 0.05 vs. controls), while infarct size was 23.1 ± 3.1 and 24.9 ± 8.1% (p < 0.05 vs. controls), respectively. Coronary collateral flow in the endocardium was similar for all of the experimental groups; however, hearts subjected to ischemia with low-flow perfusion of Ringer's lactate demonstrated significantly higher epicardial coronary collateral flow levels compared with controls. Our findings demonstrate that low-flow infusion of Ringer's solution (with or without Mg2+) into the ischemic zone produced significantly smaller infarcts; however, after 6 h of ischemia we could not demonstrate an additional beneficial effect of Mg2+.Key words: myocardial ischemia, infarct size, low-flow passive perfusion, Mg2+.