Protective effects of vitamins A and E pretreatment in venous ischemia/reperfusion injury

It has been suggested that venous ischemia is more injurious to tissue viability than is arterial ischemia of equivalent duration. The precise mechanism of tissue damage due to venous ischemia is still not well-determined. Current research has shown that it is multifactorial, and that lipid peroxides, prostanoid metabolism, and a free radical mechanism are the major contributors. Vitamins A and E are lipid-soluble vitamins that have been suggested to be successful in the treatment of arterial ischemia/reperfusion injury due to their antioxidant properties. In the present study, the authors examined the protective effects of vitamins A and E pretreatment on reperfusion injury induced by venous occlusion of rat epigastric island flaps based on an epigastric artery and vein pedicle. In the first part of the study, to determine critical ischemia time, epigastric island skin flaps (3 x 6 cm) were elevated on their vascular pedicles in 40 male Sprague Dawley rats. Total venous occlusion of the skin flap was produced by ligating all draining veins and clamping the epigastric vein. Arterial inflow was left intact. Rats were randomly assigned to five groups (n=8) for 2, 5, 7, 9, and 10 hr of venous ischemia. Despite the occurrence of widespread reperfusion injury, reflow was established (p<0.005) at 9 hr. In the second part of the study, 20 rats were randomly divided into four groups (n=5). The effects of vitamins A and E following 9 hr ischemia/reperfusion injury were examined. Rats were pretreated with vitamin E, vitamin A and vitamins A+E for 5 days. At the end of the fifth day, each rat had undergone an epigastric island skin flap and venous occlusion, as described above. Mean surviving flap area (percent) and plasma lipid peroxides (TBARs), total thiol content (t-SH), glutathione peroxidase (Gpx), and superoxide dismutase (SOD) were determined for each rat. Results suggest that, in the prevention of venous ischemia/reperfusion injury, vitamin A and vitamin E are not effective when used as single agents; however, when used in combination, they significantly increase surviving flap area by a synergistic effect.