Magnesium In Acute Myocardial Infarction Research Articles

Acute myocardial infarction, reperfusion injury, and intravenous magnesium therapy: Basic concepts and clinical implications

The concept of reperfusion-induced injury has aroused special interest during the past decade as thrombolysis and direct angioplasty were introduced for early restoration of coronary blood flow in patients with acute myocardial infarction. There is experimental and clinical evidence that oxygen-derived free radicals (oxyradical hypothesis), activation of the complement system (complement hypothesis), and disturbance in calcium homeostasis (calcium hypothesis) may account for the development of reperfusion injury. Data from numerous animal experiments and clinical trials suggest that magnesium, a physiologic calcium blocker, may be efficacious for reduction of reperfusion injury. Despite encouraging results from previous clinical trials that revealed beneficial effects of intravenous magnesium therapy with respect to mortality, left ventricular function, and infarct size, a recently published large-scale trial (ISIS-4) provided conflicting data and caused major controversy. Further clinical trials, well-designed and carefully conducted, should elucidate the beneficial effects of magnesium in acute myocardial infarction, especially in conjunction with new and aggressive reperfusion techniques.

Magnesium in acute myocardial infarction: Overview of available evidence

Despite improvements in the outcome of patients with acute myocardial infarction (MI) during the past three decades, room for improvement exists in elderly patients and in patients who are not candidates for thrombolysis. Animal models suggest that magnesium supplementation before reperfusion reduces infarct size. Statistical analysis of the randomized trials of magnesium in MI reveals a gradient of response. When higher risk patients were enrolled, a greater benefit of magnesium was observed; progressively smaller benefits of magnesium occurred as the control group mortality approached 7%, at which point no benefit was detected. Although the ISIS-4 study enrolled more than 58,000 patients, no reduction in mortality was seen, probably as a result of a low control group mortality and relatively late administration of the magnesium. Because the potential benefit of magnesium in MI remains an open question, additional trials are needed before this inexpensive and easily administered therapy is prematurely cast aside.

Review of clinical evidence--is there a role for supplemental magnesium in acute myocardial infarction in high-risk populations (patients ineligible for thrombolysis and the elderly)?

Review of clinical evidence--is there a role for supplemental magnesium in acute myocardial infarction in high-risk populations (patients ineligible for thrombolysis and the elderly)?

Mega-trials and management of acute myocardial infarction

Clinical management of acute myocardial infarction has been strongly influenced by large, simple trials (mega-trials) with unrestrictive protocols and limited data collection. The design has been adopted to increase statistical power to a maximum. Its validity rests on an effective randomisation procedure and intention-to-treat analysis of deaths. Experience has shown that mega-trials tend to generate effect-estimates nearer the null than those from conventional trials or meta-analyses. When a small or absent observed treatment effect (or subgroup effect) in a mega-trial contrasts with the results of conventionally designed trials, it is necessary to assess both null bias and failure to increase the true treatment effect to a maximum in the mega-trial. Null bias will arise when the contrast between treatment and no-treatment, or between subgroups, is blunted either by non-protocol therapy or by inaccuracy of data, including misclassification between subgroups. Each is more likely with an unrestrictive design. To increase the true treatment effect to a maximum, trial conditions must be specified with insight into mechanism, dose-dependence, and time-dependence. The mega-trial design is therefore unsuited to an exploratory role. These issues are illustrated by the examples of nitrates, angiotensin-converting-enzyme inhibitors, and magnesium in acute myocardial infarction but have general relevance to the validity and generalisability of simple trials.

Magnesium in acute myocardial infarction

EDITOR,—Salim Yusuf and Marcus Flather1 offer no satisfactory explanation for the statistical incompatibility (P>0.0001 for heterogeneity) between the inefficacy of magnesium in the fourth international study of infarct survival (ISIS-4)2 and the clearly positive pooled results of the 10 other trials of intravenous magnesium in acute myocardial infarction. Magnesium has been reported to protect contractile function in a dozen experimental models of myocardial ischaemia and reperfusion and is now known to act during the first few minutes of reperfusion.3 4 ISIS-4 was unique in that most …

Magnesium therapy in acute myocardial infarction.

The trials reviewed in this study investigated the effect of intravenous magnesium on arrhythmias and mortality in acute myocardial infarction. Nine trials were carried out in the pre-thrombolytic era. They varied in set-up, number of patients, dose of magnesium, follow-up and the type of arrhythmias analyzed. Magnesium reduced mortality in most studies, but the reduction was significant in only three of them. Two meta-analyses of the smaller studies revealed a 55% reduction in mortality. In the LIMIT-2, in which 2300 patients were enrolled, magnesium reduced mortality significantly by 24%. The effect of magnesium on arrhythmias was less clear. Preliminary results of ISIS-4, in which magnesium among others was administered together with thrombolytic agents, did not provide evidence of benefit in patients with suspected myocardial infarction. At present there are no arguments for the use of magnesium in acute myocardial infarction.

Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction : Horner SM: Circulation 86:774–779, 1992

BACKGROUNDTo ascertain the effect of the intravenous administration of magnesium in acute myocardial infarction on the frequency of arrhythmias and mortality, a meta-analysis of randomized controlled trials was performed.METHODS AND RESULTSThe study included 930 patients with acute myocardial infarction admitted to primary referral hospitals. Administration of magnesium in acute myocardial infarction was associated with a 49% reduction in ventricular tachycardia and fibrillation. The incidence of cardiac arrest was reduced by 58%. The frequency of supraventricular tachycardias was also lower. Overall, there was a 54% reduction in mortality.CONCLUSIONSIntravenous magnesium is a safe and effective method of reducing the frequency of arrhythmias and mortality in acute myocardial infarction.

The Rationale of Magnesium Supplementation in Acute Myocardial Infarction

Magnesium is the second most abundant intracellular cation in the human body, next to potassium, and is involved in more than 300 different enzymatic reactions, including glucose use; the synthesis of fat, protein, and nucleic acids; the metabolism of adenosine triphosphate; muscle contraction; and some membrane transport systems. 1,2 Over recent years, evidence has accumulated that patients with acute myocardial infarction (AMI) are magnesium deficient 3,4 and develop an increased hypomagnesemia during the acute phase of the infarct. 5-8 Hypomagnesemia might be due to migration from extracellular to intracellular space, 9 which is caused by catecholamine-induced lipolysis forming in soluble magnesium soaps, as demonstrated in animal experiments. 6,10,11 Furthermore, experiments in animals and humans have shown that the acute as well as the chronic reduction in extracellular magnesium levels are harmful to the myocardium in the setting of acute ischemia. 12-14 While the metabolism of magnesium in AMI and the incidence

Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction.

To ascertain the effect of the intravenous administration of magnesium in acute myocardial infarction on the frequency of arrhythmias and mortality, a meta-analysis of randomized controlled trials was performed. The study included 930 patients with acute myocardial infarction admitted to primary referral hospitals. Administration of magnesium in acute myocardial infarction was associated with a 49% reduction in ventricular tachycardia and fibrillation. The incidence of cardiac arrest was reduced by 58%. The frequency of supraventricular tachycardias was also lower. Overall, there was a 54% reduction in mortality. Intravenous magnesium is a safe and effective method of reducing the frequency of arrhythmias and mortality in acute myocardial infarction.

Possible pharmacological actions of magnesium in acute myocardial infarction.

This paper reviews the pharmacological effects on the cardiovascular system which occur when serum magnesium concentration is raised above the physiological range (0.7-0.95 mM), and considers how the clinical course of acute myocardial infarction might be modified in consequence