Tumor necrosis factor involvement in myocardial ischaemia-reperfusion injury.
The role of tumor necrosis factor-alpha was investigated in an anaesthetized rat model of coronary artery ligation (60 min) and reperfusion (MI/R). Sham-occluded rats (sham MI/R) were used as controls. Survival rate, myocardial necrosis, myocardial myeloperoxidase activity, serum creatinine kinase activity and serum and macrophage tumor necrosis factor-alpha were studied. Ischaemia-reperfusion injury significantly reduced survival rate (45%), produced marked myocardial injury, increased serum creatinine kinase activity and increased myocardial myeloperoxidase activity in the area-at-risk and in the necrotic area. Serum tumor necrosis factor-alpha was undetectable during the occlusion period, but increased significantly upon release of the coronary artery. At the end of reperfusion, macrophage tumor necrosis factor-alpha was also increased. Passive immunization with a hyperimmune serum containing antibodies against murine tumor necrosis factor-alpha significantly increased survival rate (80%), lowered myocardial necrosis, reduced the increase in serum creatinine kinase activity and decreased myeloperoxidase activity in the area-at-risk and in the necrotic area. These data are consistent with an involvement of tumor necrosis factor-alpha in myocardial ischaemia-reperfusion injury.
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
F
F
Squadrito
D
D
Altavilla
B
B
Zingarelli
M
M
Ioculano
G
G
Calapai
G M
GM
Campo
A
A
Miceli
A P
AP
Caputi
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D006339:Heart Rate / Q000502:physiology; D007116:Immunization, Passive; D008264:Macrophages / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology* / Q000401:mortality; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D003402:Creatine Kinase