Does tumor necrosis factor-alpha (TNF-alpha) contribute to myocardial reperfusion injury in anesthetized rats?
1. This study examined the potential role of tumor necrosis factor-alpha (TNF-alpha) in myocardial ischemia-reperfusion injury using an anesthetized rat model of myocardial infarction. 2. The key endpoints were infarct size and serum TNF-alpha levels (measured by a specific ELISA technique). 3. Three groups of rats were studied: vehicle controls (n=6); positive controls for infarct size reduction (ischemic preconditioning; n=6); and a group treated with the selective inhibitor of PDE-IV and TNF-alpha production, rolipram (1 mg/kg i.v. 10-min prereperfusion + 1 microg/kg per minute through 1-hr reperfusion, n=6). 4. Baseline preischemia levels of serum TNF-alpha were low (approximately 0.1 nM) and showed a trend for further reduction in all treatment groups at 1 min and 3 hr into the postischemia reperfusion period. 5. Infarct size (68+/-2% of the ischemic area in controls) was significantly reduced (41% decrease) by preconditioning, but was unchanged in rolipram-treated animals. 6. Collectively, these data argue against an important role for TNF-alpha in lethal reperfusion injury in this rat model of myocardial infarction.
McVey
M
M
Department of Cardiovascular Discovery (NW4), Rhône-Poulenc Rorer, Collegeville, PA 19426, USA.
Perrone
M H
MH
Clark
K L
KL
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure; D004797:Enzyme-Linked Immunosorbent Assay; D006339:Heart Rate; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000502:physiology*
D011760:Pyrrolidinones; D014409:Tumor Necrosis Factor-alpha; D020889:Rolipram