Role of TNF-alpha in myocardial dysfunction after hemorrhagic shock and lower-torso ischemia.
Ruptured abdominal aortic aneurysm (RAAA) repair, a combination of hemorrhagic shock and lower-torso ischemia, is associated with a 50-70% mortality. Myocardial dysfunction may contribute to the high rate of mortality after aneurysm repair. We attempted to determine whether RAAA repair results in cardiac dysfunction mediated by tumor necrosis factor-alpha (TNF-alpha). We modeled aortic rupture and repair in the rat by inducing hemorrhagic shock to a mean blood pressure of 50 mmHg for 1 h, followed by supramesenteric clamping of the aorta for 45 min. After 90 min of reperfusion, cardiac contractile function was assessed with a Langendorff preparation. Myocardial TNF-alpha, ATP and creatine phosphate (CP) levels, and markers of oxidant stress (F(2)-isoprostanes) were measured. Cardiac function in the combined shock and clamp rats was significantly depressed compared with sham-operated control 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 in myocardial ATP, CP, or F(2)-isoprostanes. TNF-alpha neutralization improved 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 immunoneutralization of TNF-alpha indicates that TNF-alpha mediates a significant portion of the myocardial dysfunction in this model.
Shahani
R
R
Divisions of Vascular and Cardiac Surgery, Toronto General Hospital; and The Department of Surgery, University of Toronto, Ontario, Canada M5G 2C4.
Marshall
J G
JG
Rubin
B B
BB
Li
R K
RK
Walker
P M
PM
Lindsay
T F
TF
D000255:Adenosine Triphosphate / Q000032:analysis; D017542:Aneurysm, Ruptured / Q000150:complications / Q000601:surgery*; D000818:Animals; D000906:Antibodies; D001011:Aorta; D017544:Aortic Aneurysm, Abdominal / Q000150:complications / Q000601:surgery*; D009202:Cardiomyopathies / Q000209:etiology* / Q000503:physiopathology; D003250:Constriction; D007511:Ischemia / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D009195:Peroxidase / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*; D016277:Ventricular Function, Left
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D009195:Peroxidase