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 (Mg(2+)-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 Mg(2+)-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.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of cardioprotection by single-dose magnesium prophylaxis on isoprenaline-induced myocardial infarction in adult Wistar rats

“…The ISO-induced MI disease model mimics cardiovascular stress disorders that not only produce infarction, but in which intracellular Mg 2+ deficiency may play a role. 31 , 32 Nevertheless, in our study, Mg 2+ pre-treatment did not alter infarct size, suggesting a lack of Mg 2+ cardioprotection, as also reported in other studies, 13 , 14 and at the same time, contradicting the results of some previous studies. 7 - 11 …”

“…In animal studies, Mg 2+ reduced infarct size 7 - 11 and inhibited myocardial apoptosis 12 under certain conditions, but not others. 13 , 14 There is therefore a need for further experimental and clinical studies on Mg 2+ therapy.…”

Effect of Platelet GPIIb/IIIa Receptor Blockade With MK383 on Infarct Size and Myocardial Blood Flow in a Canine Reocclusion Model

“…Collateral blood flow (ie, subendocardial layer blood flow) during 120-minute occlusion period was not affected by treatment with MK383. Collateral blood flow is a baseline predictor of infarct size 31,32 ; an inverse relationship exists between collateral blood flow and infarct size (ie, larger infarcts with low flow and vice versa). 33,34 This relationship was found in dogs subjected to the reocclusion protocol; the relation shifted downward ( P = 0.014; mean likelihood ratio) in MK383 dogs suggesting a cardioprotective effect but protection was not caused by improved perfusion within the ischemic myocardium.…”

Influencing Mortality in Cardiac Disorders by Controlling Arrhythmias or by Cardioprotection: Whither Magnesium?

“…Magnesium had no benefit on infarct size or remodeling. Kingma et al (37), using a dog permanent occlusion model, demonstrated a similar result in that no difference was demonstrated in the infarct size in dogs in whom the coronary bed distal to the occlusion was perfused with a Ringer's lactate solution with added magnesium, compared to perfusion with Ringer's lactate alone. The results of these studies suggest that the benefits of magnesium on pump function are probably related to myocardial protection involving the ischemic region rather than a global improvement in cardiac function.…”