DOES TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) CONTRIBUTE TO MYOCARDIALREPERFUSION INJURY IN ANESTHETIZED RATS

1. This study examined the potential role of tumor necrosis factor-alp ha (TNF-alpha) in myocardial ischemia-reperfusion injury using an anes thetized 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 precondi tioning; n = 6); and a group treated with the selective inhibitor of P DE-IV and TNF-alpha production, rolipram (1 mg/kg IV 10-min prereperfu sion + 1 mu g/kg per minute through 1-hr reperfusion, n = 6). 4. Basel ine preischemia levels of serum TNF-alpha were low (similar to 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 siz e (68 +/- 2% of the ischemic area in controls) was significantly reduc ed (41% decrease) by preconditioning, but was unchanged in rolipram-tr eated animals. 6. Collectively, these data argue against an important role for TNF-alpha in lethal reperfusion injury in this rat model of m yocardial infarction. (C) 1998 Elsevier Science Inc.