GRADUAL REPERFUSION REDUCES INFARCT SIZE AND ENDOTHELIAL INJURY BUT AUGMENTS NEUTROPHIL ACCUMULATION

Background. Reperfusion causes injury to the coronary artery endotheli um primarily by neutrophil-mediated mechanisms. However, factors other than neutrophils may govern the extent of myocardial necrosis. This s tudy tests the hypothesis that gradual initiation of renew will reduce reperfusion injury and preserve postischemic endothelial function. Me thods. In 16 anesthetized dogs, the left anterior descending artery wa s ligated for 60 minutes. In one group, reperfusion was initiated abru ptly (abrupt, n = 8), whereas in the gradual reperfusion group (ramp, n = 8), flow was slowly initiated during the first 30 minutes of reper fusion. After reperfusion, coronary artery segments were isolated to a ssess postischemic endothelial function. Results. Infarct size (area o f necrosis/area at risk) was significantly reduced in the ramp group ( 28.2% +/- 2.0%) compared with abrupt (41.6% +/- 1.4%). Neutrophil accu mulation (myeloperoxidase) in the area at risk was significantly great er in the ramp group compared with abrupt (8.0 +/- 1.3 versus 3.5 +/- 0.8 U/g tissue). In isolated postischemic left anterior descending art erial rings, the concentration of acetylcholine that elicited a respon se 50% of the maximum possible response was significantly greater in a brupt (-6.88 +/- 0.04 log [mol/L]) than ramp (-7.62 +/- 0.04 log [mol/ L]) and control (-7.68 +/- 0.003 log [mol/L]), suggesting endothelial dysfunction. The concentration of A23187 that elicited a response 50% of the maximum possible response was similarly greater in abrupt (-7.2 4 +/- 0.03 log [mol/L]) versus ramp (-7.62 +/- 0.03 log [mol/L]) and c ontrol (-7.8 +/- 0.04 log [mol/L]). Smooth muscle dysfunction (respons e to sodium nitrite) also occurred in the abrupt rings. Conclusions. G radual reperfusion of an ischemic area reduces infarct size and preser ves endothelial function but paradoxically increases neutrophil accumu lation within the area at risk. (C) 1997 by The Society of Thoracic Su rgeons.