TIMING OF MAGNESIUM THERAPY AFFECTS EXPERIMENTAL INFARCT SIZE

Background Controversy exists regarding the use of magnesium in the tr eatment of acute myocardial infarction (AMI) because of apparent confl icting results from clinical trials. One hypothesis to explain the var ious clinical observations proposes that the timing of magnesium admin istration significantly influences its therapeutic effect; ie, supraph ysiological levels of Mg2+ must be present at the time of reperfusion for magnesium to produce clinical benefit. Methods and Results These e xperiments evaluated the effect of varying the timing of magnesium adm inistration during AMI. Female Yorkshire swine (34 to 42 kg) underwent thoracotomy and 50 minutes of left anterior descending coronary arter y (LAD) occlusion, followed by 3 hours of reperfusion. In the first gr oup, MgSO4 (250 mg of magnesium diluted in 60 cm(3) saline) was infuse d into the LAD over 12 minutes, beginning immediately with the onset o f reperfusion (n=6, Mg-early group). In the second group, MgSO4 was gi ven after I hour of reperfusion (n=6, Mg-late group). Six pigs receive d 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), 035 +/- 0.08 g/kg (Mg-late), and 0.42 +/- 0.0 4 g/kg for the control group. Compared with the control group, signifi cant (P=.029) reduction in infarct size occurred in the Mg-early group but not in the Mg-late group. Conclusions We conclude that intracoron ary MgSO4 delivered during reperfusion can significantly diminish infa rct size in swine, but the timing of administration is critical.