CARDIAC INJURY BY ACTIVATED LEUKOCYTES - EFFECT OF CYCLOOXYGENASE ANDLIPOXYGENASE INHIBITION EVALUATED BY ELECTRON-MICROSCOPIC MORPHOMETRY

Leukocytes can take part in an inflammatory response in the heart afte r myocardial infarction or cardio-thoracic surgery, To investigate the injurious mechanism of activated polymorphonuclear leukocytes (PMN), isolated rat hearts were perfused with phorbol 12-myristate 13-acetate (PMA) activated PMN (3 x 10(6)/ml) alone for 10 min, in combination w ith a mixture of oxygen free radical scavengers (superoxide dismutase + catalase + thiourea) or in combination with ibuprofen (IBU), a cyclo oxygenase inhibitor or diethylcarbamazine (DCM), a lipoxygenase inhibi tor or BW 755C, a dual inhibitor of cyclooxygenase and lipoxygenase an d an oxygen free radical scavenger. After 30 min of recovery, the hear ts were perfusion-fixed with glutaraldehyde for electron microscopical examination, Based on examination of 25 micrographs per heart obtaine d by a random sampling procedure and on morphometric methods, volume f ractions (Vv) of mitochondria (mite), altered mitochondria (alt mite), myofilament, and cellular edema were measured as fractions of myocyte volume. The most important finding was that Vv(alt mito/myocyte) was 0.09 +/- 0.16 and 0.02 +/- 0.04 in the hearts receiving PMN + PMA alon e and when scavengers were added, respectively, whilst no changes in m itochondrial ultrastructure was observed after addition of IBU, BW 755 C or DCM, Vv(mito/myocyte) was for PMN + PMA alone: 0.33 +/- 0.04, + s cavengers: 0.29 +/- 0.02, + IBU:0.29 +/- 0.02, + BW 755C: 0.23 +/- 0.0 3, + DCM: 0.28 +/- 0.02 (mean +/- S.D., *P<0.05 compared to PMN + PMA ). Capillary wall volume (cap wall) as a fraction of the whole capilla ry was also quantified, Vv(cap wall/cap) was for PMN + PMA alone: 0.26 +/- 0.06, + scavengers: 0.22 +/- 0.03, + IBU: 0.19 +/- 0.04, + BW755 C:0.21 +/- 0.03, + DCM: 0.15 +/- 0.04 (*P<0.05). These results furthe r strengthen the notion that activated PMN are intravascularly active. In addition to exerting a cardiodepressive effect the present study s hows that activated PMN can induce structural changes in the heart thr ough the combined action of oxygen free radicals and arachidonic acid metabolites. (C) 1996 Academic Press Limited