EFFECT OF CHRONIC ORAL SUPPLEMENTATION WITH ALPHA-TOCOPHEROL ON MYOCARDIAL STUNNING IN THE DOG

Recent clinical and experimental studies have suggested that antioxida nt supplements might actually have harmful as well as beneficial effec ts in the setting of cardiovascular disease. The mechanisms underlying the beneficial effects of the various antioxidants are poorly underst ood in humans. Reperfusion-associated myocardial injury, and particula rly the phenomenon of stunning, is important because it occurs in clin ical settings and may condition the prognosis after short ischemic ins ult. We studied the effects of chronic (3 months) alpha-tocopherol sup plementation with a large oral dose (500 mg daily) on myocardial contr actility (stunning) and ventricular arrhythmias in a dog model of shor t ischemia followed by reperfusion. Twenty dogs were randomized to eit her an a-tocopherol supplemented or a control group. After 3 months, d ogs were anesthetized and underwent a 20-min coronary artery occlusion followed by reperfusion. Myocardial regional blood flow was measured by the radioactive microsphere technique and myocardial contractility by sonomicrometry. Plasma alpha-tocopherol was measured by high-perfor mance liquid chromatography in all dogs. Twelve dogs (seven supplement ed and five controls) developed ventricular fibrillation at reperfusio n, showing no difference between groups. Hemodynamic parameters, blood flow in the ischemic area (collateral flow), and area at risk were si milar in the two groups. Regional systolic segment shortening in the i schemic area was similar during ischemia and reperfusion in both group s, representing 41 +/- 15% (mean +/- SEM) of baseline contractility in controls and 51 +/- 8% in supplemented dogs after 150 min of reperfus ion. Plasma alpha-tocopherol level was higher in supplemented than in controls (19.1 +/- 1.6 and 6.9 +/- 0.6 mg/L; p < 0.001). Thus a long-t erm large dose of alpha-tocopherol had no significant effect on postis chaemic ventricular arrhythmias and dysfunction (myocardial stunning) in this canine model. These data suggest that if alpha-tocopherol supp lementation might be useful to improve the prognosis of coronary patie nts, it is likely not by interfering with the stunning phenomenon.