M. Mcvey et al., DOES TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) CONTRIBUTE TO MYOCARDIALREPERFUSION INJURY IN ANESTHETIZED RATS, General pharmacology, 32(1), 1999, pp. 41-45
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.