Infarct size and magnesium: insights into LIMIT-2 and ISIS-4 from experimental studies

Abstract

The role of magnesium in the regulation of various processes in cellular metabolism suggests that it may have a beneficial effect in patients with myocardial infarction (MI). Between 1981 and 1991 several small randomised clinical trials reported the results of various magnesium protocols in suspected acute MI. 1 Morton BC Smith FM McKibbon TJ Mair RC Poznanski WJ Magnesium therapy in acute myocardial infarction.. Magnesium Bull. 1981; 1: 192-194 Google Scholar , 2 Morton BC Smith FM Nair RC McKibbo TG Poznanski WJ The clinical effects of magnesium sulphate treatment in acute myocardial infarction.. Magnesium Bull. 1984; 4: 133-136 Google Scholar , 3 Morton BC Nair RC Smith FM McKibbon TG Poznanski WJ Magnesium therapy in acute myocardial infarction: a double blind study.. Magnesium. 1984; 3: 346-352 PubMed Google Scholar , 4 Rasmussen HS McNair P Norregard P Backer V Lindeneg O Balslev S Intravenous magnesium in acute myocardial infarction.. Lancet. 1986; 1: 234-236 Summary PubMed Scopus (201) Google Scholar , 5 Rasmussen HS Gronbaek M Cintin C Balslev S Norregard P McNair P One-year death rate in 270 patients with suspected acute myocardial infarction, initially treated with intravenous magnesium or placebo.. Clin Cardiol. 1988; 11: 377-381 Crossref PubMed Scopus (46) Google Scholar , 6 Smith LF Heagerty AM Bing RF Barnett DB Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality.. Int J Cardiol. 1986; 12: 175-180 Summary Full Text PDF PubMed Scopus (116) Google Scholar , 7 Abraham AS Rosenmann D Kramer M et al. Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction.. Arch Intern Med. 1987; 147: 753-755 Crossref PubMed Scopus (156) Google Scholar , 8 Feldstedt M Bouchelouche P Svenningsen A et al. Failing effect of magnesium substitution in acute myocardial infarction.. Eur Heart J. 1988; 9: 226 Google Scholar , 9 Feldstedt M Boesgaard S Bouchelouche P et al. Magnesium substitution in acute ischaemic heart syndromes.. Eur Heart J. 1991; 12: 1215-1218 Crossref PubMed Scopus (51) Google Scholar , 10 Shechter M Hod H Marks N Kaplinsky E Behar S Rabinowitz B Beneficial effect of magnesium sulfate in acute myocardial infarction.. Am J Cardiol. 1990; 66: 271-274 Summary Full Text PDF PubMed Scopus (103) Google Scholar , 11 Ceremuzynski L Jurgiel R Kulakowski P Gebalska J Threatening arrhythmias in acute myocardial infarction are prevented by intravenous magnesium sulphate.. Am Heart J. 1989; 118: 1333-1334 Summary Full Text PDF PubMed Scopus (72) Google Scholar Most found reduced mortality, a lower incidence of ventricular arrhythmias, or both, when magnesium salts were given intravenously to patients with suspected MI. In total, 1301 patients were studied and although the treatment regimens varied substantially, a meta-analysis of these trials 12 Teo KK Yusuf S Collins R Held PH Peto R Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.. BMJ. 1991; 303: 1499-1503 Crossref PubMed Scopus (285) Google Scholar showed an overall beneficial effect of magnesium administration. However, two subsequent large clinical trials have provided conflicting results. The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2), 13 Woods KL Fletcher S Roffe C Haider Y Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2).. Lancet. 1992; 339: 1553-1558 Summary PubMed Scopus (479) Google Scholar found a 24% reduction in 28-day mortality whereas the fourth International Study of Infarct Survival (ISIS-4) showed no benefit. 14 ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58 050 patients with suspected acute myocardial infarction.. Lancet. 1995; 345: 669-685 Summary PubMed Scopus (1493) Google Scholar As a result, there is no consensus among clinicians that magnesium is beneficial in suspected MI. Laboratory studies in which magnesium was given to animals with acute MI have implied a beneficial effect and have provided a plausible explanation for the discrepancy between LIMIT-2 and ISIS-4. These studies offer interesting messages to experimentalists and clinicians and may point the way to a more satisfactory interpretation of the large clinical trials of magnesium therapy.