Role of TNF-alpha in myocardial dysfunction after hemorrhagic shock and lower-torso ischemia

Ruptured abdominal aortic aneurysm (RAAA) repair, a combination of hemorrha gic shock and lower-torso ischemia, is associated with a 50-70% mortality. Myocardial dysfunction may contribute to the high rate of mortality after a neurysm repair. We attempted to determine whether RAAA repair results in ca rdiac dysfunction mediated by tumor necrosis factor-alpha (TNF-alpha). We m odeled aortic rupture and repair in the rat by inducing hemorrhagic shock t o a mean blood pressure of 50 mmHg for 1 h, followed by supramesenteric cla mping of the aorta for 45 min. After 90 min of reperfusion, cardiac contrac tile function was assessed with a Langendorff preparation. Myocardial TNF-a lpha, ATP and creatine phosphate (CP) levels, and markers of oxidant stress (F-2-isoprostanes) were measured. Cardiac function in the combined shock a nd clamp rats was significantly depressed compared with sham-operated contr ol rats but was similar to that noted in animals subjected to shock alone. Myocardial TNF-alpha concentrations increased 10-fold in the combined shock and clamp rats compared with sham rats, although there was no difference i n myocardial ATP, CP, or F-2-isoprostanes. TNF-alpha neutralization improve d cardiac function by 50% in the combined shock and clamp rats. Hemorrhagic shock is the primary insult inducing cardiac dysfunction in this model of RAAA repair. An improvement in cardiac contractile function after immunoneu tralization of TNF-alpha indicates that TNF-alpha mediates a significant po rtion of the myocardial dysfunction in this model.