Timing of magnesium therapy affects experimental infarct size

Background: Controversy exists regarding the use of magnesium in the treatment of acute myocardial infarction (AMI) because of apparent conflicting results from clinical trials. One hypothesis to explain the various clinical observations proposes that tile timing of magnesium administration significantly influences its therapeutic effect; ie, supraphysiological levels of Mg²⁺ must be present at the time of reperfusion for magnesium to produce clinical benefit. Methods and Results: These experiments evaluated the effect of varying the timing of magnesium administration during AMI. Female Yorkshire swine (34 to 42 kg) underwent thoracotomy and 50 minutes of left anterior descending coronary artery (LAD) occlusion, followed by 3 hours of reperfusion. In the first group, MgSO₄ (250 mg of magnesium diluted in 60 cm³ saline) was infused into the LAD over 12 minutes, beginning immediately with the onset of reperfusion (n = 6, Mg- early group). In the second group, MgSO₄ was given after 1 hour of reperfusion (n=6, Mg-late group). Six pigs received saline instead of magnesium and served as the control group. Lethal arrhythmias were significantly reduced in the Mg-early group. Infarct size was determined by vital staining. Infarct size was 0.16±0.05 g/kg body wt (Mg-early), 0.35±0.08 g/kg (Mg-late), and 0.42±0.04 g/kg for the control group. Compared with the control group, significant (P=.029) reduction in infarct size occurred in the Mg-early group but not in the Mg-late group. Conclusions: We conclude that intracoronary MgSO₄ delivered during reperfusion can significantly diminish infarct size in swine, but the timing of administration is critical.