Abstract: . . .  nitroglycerin has also been shown to decrease infarct Page 8 72 Section I / Pharmacologic Intervention expansion and improve regional and global left ventricular func- tion. 73,78 Large Trials The promising data from the small nitrate trials have prompted two large trials: the third Gruppo Italiano per lo Studio della Sopravvi- venza nellInfarto Miocardico-3 (GISSI-3) trial 70 and the fourth In- ternational Study of Infarct Survival (ISIS-4) 71 trial. A third is the European Study of Prevention of Infarct with Molsidomine (ESP- RIM) trial, which used molsidomine, not a true organic nitrate. Its active metabolite, linsidomine, however, is a nitric oxide donor and has vasodilating properties similar to those of nitroglycerin. 72 GISSI-3 In the GISSI-3 trial, 19,394 patients with acute MI were randomized to glyceryl trinitrate or open control and the ACE inhibitor lisinopril or open control in a 2 2 factorial design. 70 The patient received glyceryl trinitrate alone, lisinopril alone, combined glyceryl trinitrate and lisinopril, or neither. Patients were included if they presented within 24 hours of symptoms and were excluded if the study medica- tions were clearly indicated. Patients randomized to glyceryl trinitrate received a 24-hour . . .
. . .  -acetylcysteine or methionine has not produced consistent results. Other data suggest that neurohormonal activation during nitrate therapy may be important for the develop- ment of nitrate tolerance, and that ACE inhibitors and diuretics may counteract these effects and reduce tolerance. 93,94 MAGNESIUM The relevance of magnesium to the causation and management of ischemic heart disease is not well understood. Geographic compari- sons of entire regions have indicated that death rates from ischemic heart disease tend to be higher in areas where magnesium concentra- tions in soil and water are low. Several actions of the magnesium ion could provide some cardioprotective effects. 95 Low concentrations of magnesium in laboratory animals seem to potentiate catecholamine- induced myocardial necrosis. 96 Early after the onset of myocardial ischemia, magnesium infusion might limit the progression of is- chemic to infarcted myocardium and reduce the risk of arrhythmias induced by in . . .
--3000,2,750,2783,64636