Failure of magnesium to protect isolated cardiomyocytes from effects of hypoxia or metabolic poisoning

Background: MgSO4 appears to reduce infarct size in animal models of myocar dial infarction-reperfusion, but only if given before reperfusion. The mech anisms underlying this effect have not been established, nor has the discre pancy between these results and the lack of efficacy in the Fourth Internat ional Study of Infarct Survival (ISIS-4) been explained. Hypothesis: The study was undertaken to examine the hypothesis that Mg2+ pr otects myocardium threatened by ischemia. Methods: We studied the effects of extracellular magnesium [Mg2+](e) at 0.6 and 1.8 mmol/l on isolated myocytes exposed to 2.5 mmol/l NaCN + 5 mmol/l l-deoxyglucose or to profound hypoxia. Results: Nonpaced cells shortened at a mean of 8.8 min after onset of metab olic inhibition in [Mg2+](e) = 1.8 mmol/l, 9.6 min in [Mg2+](e) = 0.6 mmol/ l (not significant). Paced cells shortened after 9.5 min in [Mg2+](e) = 1.8 mmol/l, 10.2 min at [Mg2+](e) = 0.6 mmol/l. On washout of inhibitors, 93% of cells underwent hypercontracture at [Mg2+](e) = 1.8 mmol/l, 94.8% at [Me 2+](e) = 0.6 mmol/l. During hypoxia, nonpaced cells in [Mg2+](e) = 1.8 mmol /l shortened after 67 +/- 11 min compared with 62.5 + 28 min at [Mg2+](e) = 0.6 mmol/l. Paced cells shatened after 25.8 +/- 12.9 min at [Mg2+](e) = 1. 8 mmol/l and after 28.7 +/- 13.6 min at [Mg2+](e) = 0.6 mmol/l. Although th ere was a trend toward longer survival at higher [Mg2+](e), the difference was small and not significant (p > 0.05, Student's paired t-test). Conclusion: We find no evidence to support the hypothesis that [Me2+] prote cts myocardium threatened by ischemia. This is consistent with clinical dat a but contradicts data from animal experiments.