Role of polymorphonuclear leukocytes in reperfusion injury of globally ischemic rat heart.

OBJECTIVE: Polymorphonuclear leukocytes (PMNs) have recently been observed to generate oxygen free radical (OFR) species during regional myocardial ischemia-reperfusion. This study evaluated the role of PMN-derived OFR in reperfusion injury of globally ischemic rat heart. METHODS: Isolated rat hearts were perfused with recirculating medium as follows: hydrogen peroxide; PMNs; PMNs plus phorbol myristate acetate (PMA); PMNs plus PMA plus OFR scavengers (superoxide dismutase [SOD] plus catalase, preprotection and reperfusion); ischemia-reperfusion (34 degrees C); ischemia-reperfusion (34 degrees C) plus OFR scavengers; ischemia-reperfusion (34 degrees C) plus PMNs; and ischemia-reperfusion (34 degrees C) plus PMNs plus OFR scavengers. Left ventricular (LV) systolic (developed pressure [Pmax], +dP/dt) and diastolic (left ventricular end-diastolic pressure [LVEDP], -dP/dt, LV compliance, LV wall stiffness) functions were evaluated. LV contracture development was studied by applying the quick stretch test. RESULTS: In vitro hydrogen peroxide perfusion significantly reduced LV contractility and caused a marked increase in LVEDP. PMN-derived OFR (mainly hydrogen peroxide) caused serious derangements in LV systolic and diastolic functions and produced a significant calcium-dependent LV contracture. Ischemia-reperfusion (34 degrees C) in the absence of PMNs produced predictable abnormalities in LV function and caused severe ATP-dependent LV contracture. Ischemia-reperfusion (34 degrees C) in the presence of PMNs significantly enhanced reperfusion injury. LVEDP increased considerably and a condition of irreversible contracture (stone heart) developed. OFR scavengers (SOD and catalase) were effective in preserving LV diastolic function and in neutralizing the additional component of injury caused by in vitro or in situ activation of PMNs. However, OFR scavengers failed to offer any significant improvement in LV systolic functions. CONCLUSIONS: Results of these studies indicate that: first, activated 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 enhanced reperfusion injury of the globally ischemic rat heart; and fourth, the OFR scavengers SOD and catalase minimized changes in LV diastolic function, whereas LV systolic function showed little improvement.