Kinetics of tumor necrosis factor alpha in plasma and the cardioprotective effect of a monoclonal antibody to tumor necrosis factor alpha in acute myocardial infarction.
BACKGROUND
Inflammation plays a critical role in acute myocardial infarction (AMI) and tumor necrosis factor alpha (TNF-alpha) is a potent inflammatory trigger. This study was designed to examine the kinetics of TNF-alpha in plasma in patients with AMI and the potential benefit of inhibition of TNF-alpha monoclonal antibody in AMI.


RESULTS
TNF-alpha levels in plasma were measured in 42 patients with AMI. TNF-alpha levels were elevated at 4 hours after onset of chest pain and declined to control values at 48 hours. TNF-alpha levels were higher in patients with Killip III and IV than in those with Killip I and II (P <.01). To examine the pathogenic role of TNF-alpha, New Zealand White rabbits were treated with buffer or a TNF-alpha monoclonal antibody before left anterior descending artery (LAD) ligation. Treatment with the TNF-alpha monoclonal antibody decreased area of necrosis, number of circulating endothelial cells, and lipid peroxidation product malonaldehyde bis(dimethyl acetal). There was a significant correlation of TNF-alpha levels with peak CK-MB in AMI patients, and area of necrosis, MDA, and circulating endothelial cells in rabbits (all P <.05).


CONCLUSIONS
TNF-alpha release early in the course of AMI contributes to myocardial injury and dysfunction. Treatment with the monoclonal antibody against TNF-alpha can be cardioprotective, particularly in the setting of heart failure in patients with AMI.
Li
D
D
Department of Medicine, University of Florida and VA Medical Center, Gainesville, FL, USA.
Zhao
L
L
Liu
M
M
Du
X
X
Ding
W
W
Zhang
J
J
Mehta
J L
JL
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde