ACE-INHIBITION PREVENTS POSTISCHEMIC CORONARY LEUKOCYTE ADHESION AND LEUKOCYTE-DEPENDENT REPERFUSION INJURY

Objective: Polymorphonuclear leukocytes (PMN), retained in the microva scular bed, can contribute to postischemic myocardial reperfusion inju ry. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN d ependent reperfusion injury in isolated guinea pig hearts. Methods: He arts (n = 5 per group) were subjected to 15 min of ischemia. Immediate ly thereafter, a bolus of PMN was injected into the coronary system. E xternal heart work (EPW) and total cardiac nitric oxide release were m easured. For microscopic evaluation, hearts received rhodamine 6G labe lled PMN after ischemia, were arrested 5 min later and further perfuse d with FITC dextran (0.1%). Localization of retained PMN was assessed by fluorescence microscopy. Leukocyte activation was studied by FAGS a nalysis of the adhesion molecule CD11b before and after coronary passa ge of the PMN. The ACE-inhibitor cilazaprilat (Cila, 2 gamma M) and th e NO-synthase inhibitor nitro-L-arginine (NOLAG, 10 mu M) were used to modulate nitric oxide formation of the heart. Results: Postischemic E HW recovered to 67 +/- 5% (controls) and 64 +/- 6% (Cila) of the preis chemic value. Addition of PMN severely depressed recovery of EHW (39 /- 2%) and NO release (39 +/- 6% of the preischemic value). Simultaneo usly, ischemia led to a substantial increase in postcapillary PMN adhe sion (from 21 +/- 5 to 172 +/- 27 PMN/mm(2) surface) and CD11b-express ion of the recovered PMN (3-fold). Cila attenuated postischemic PMN ad hesion (83 +/- 52 PMN/mm(2)) and activation of PMN, whereas it improve d recovery of work performance (64 +/- 4%) and NO release (65 +/- 3%) in the presence of PMN. Conversely, NOLAG increased PMN adhesion (284 +/- 40 PMN/mm(2)) and myocardial injury. We conclude that ACE-inhibiti on prevents leukocyte dependent reperfusion injury mainly by inhibitio n of postcapillary leukocyte adhesion. The effect may be mediated by N O, given the proadhesive effect of NOLAG. (C) 1997 Elsevier Science B. V.