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 myocardial infarction-reperfusion, but only if given before reperfusion. The mechanisms underlying this effect have not been established, nor has the discrepancy between these results and the lack of efficacy in the Fourth International Study of Infarct Survival (ISIS-4) been explained.


OBJECTIVE
The study was undertaken to examine the hypothesis that Mg2+ protects 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 2-deoxyglucose or to profound hypoxia.


RESULTS
Nonpaced cells shortened at a mean of 8.8 min after onset of metabolic 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 [Mg2+](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 shortened 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 there 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).


CONCLUSIONS
We find no evidence to support the hypothesis that [Mg2+] protects myocardium threatened by ischemia. This is consistent with clinical data but contradicts data from animal experiments.
Gallagher
M M
MM
Department of Pharmacology and Therapeutics, University of College Cork, Ireland.
Allshire
A P
AP
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D002478:Cells, Cultured; D005947:Glucose / Q000633:toxicity; D008274:Magnesium / Q000378:metabolism*; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D011042:Poisons / Q000633:toxicity; D051381:Rats; D012966:Sodium Cyanide / Q000633:toxicity
C115456:2-deoxy-glucose tetraacetate; D002121:Calcium Channel Blockers; D011042:Poisons; D008278:Magnesium Sulfate; D008274:Magnesium; D005947:Glucose; D012966:Sodium Cyanide