ROLE OF POLYMORPHONUCLEAR LEUKOCYTES IN REPERFUSION INJURY OF GLOBALLY ISCHEMIC RAT-HEART

OBJECTIVE: Polymorphonuclear leukocytes (PMNs) have recently been obse rved to generate oxygen free radical (OFR) species during regional myo cardial ischemia-reperfusion. This study evaluated the role of PMN-der ived OFR in reperfusion injury of globally ischemic rat heart. METHODS : Isolated rat hearts were perfused with recirculating medium as follo ws: hydrogen peroxide; PMNs; PMNs plus phorbol myristate acetate (PMA) ; PMNs plus PMA plus OFR scavengers (superoxide dismutase [SOD] plus c atalase, preprotection and reperfusion); ischemia-reperfusion (34 degr ees C); ischemia-reperfusion (34 degrees C) plus OFR scavengers; ische mia-reperfusion (34 degrees C) plus PMNs; and ischemia-reperfusion (34 degrees C) plus PMNs plus ORF scavengers. Left ventricular (LV) systo lic (developed pressure [P-max], +dP/dt) and diastolic (left ventricul ar end-diastolic pressure [LVEDP], -dP/dt, LV compliance, LV wall stif fness) functions were evaluated. LV contracture development was studie d by applying the quick stretch test. RESULTS: In vitro hydrogen perox ide perfusion significantly reduced LV contractility and caused a mark ed increase in LVEDP. PMN-derived OFR (mainly hydrogen peroxide) cause d serious derangements in LV systolic and diastolic and diastolic func tions and produced a significant calcium-dependent LV contracture. Isc hemia-reperfusion (34 degrees C) in the absence of PMNs produced predi ctable abnormalities in LV function and caused severe ATP-dependent LV contracture. Ischemia-reperfusion (34 degrees C) in the presence of P MNs significantly enhanced reperfusion injury. LVEDP increased conside rably and a condition of irreversible contracture (stone heart) develo ped. OFR scavengers (SOD and catalase) were effective in preserving LV diastolic function and in neutralizing the additional component of in jury caused by in vitro or in situ activation of PMNs. However, OFR sc avengers failed to offer any significant improvement in LV systolic fu nctions. CONCLUSIONS: Results of these studies indicate that: first, a ctivated PMNs produce significant amounts of hydrogen peroxide; second , OFR released by activated PMNs during perfusion caused a significant depression of LV systolic and diastolic function; third, PMNs enhance d reperfusion injury of the globally ischemic rat heart; and fourth, t he OFR scavengers SOD and catalase minimized changes in LV diastolic f unction, whereas LV systolic function showed little improvement.