Polymorphonuclear leukocytes reduce cardiac function in vitro by release of H2O2.
Polymorphonuclear leukocytes (PMNs) have been implicated in postischemic myocardial injury and associated derangements in contractile function. To examine the direct effects of PMNs on cardiac function, isolated right ventricular papillary muscles of the rabbit were exposed to increasing concentrations of purified rabbit PMNs in the presence of cimetidine. PMNs induced a significant concentration-dependent decrease in contractile function, where 5 x 10(5) PMNs/ml reduced contractile force to 75 +/- 2.1% of control (vs. 95 +/- 5% for time control; P less than 0.005). Similar decreases were also observed for peak positive and negative first derivatives of contractile force. The degree of PMN-induced contractile dysfunction correlated with the activity of the PMNs in an aggregation assay (r = 0.82, P less than 0.01). The loss of contractile function in response to PMNs was attenuated by catalase, which metabolizes H2O2, but not by superoxide dismutase, a scavenger of the superoxide anion. PMNs can convert H2O2 to either the hypochlorite anion or the hydroxyl radical, which are removed by methionine or mannitol, respectively. However, these scavengers did not ameliorate the PMN-induced loss of cardiac function. Exposure of papillary muscles to H2O2 resulted in a concentration-dependent decrease in contractile function where 100 microM reduced contractile force to 78 +/- 4%, an effect prevented by catalase. Thus PMNs reduce the contractile function of isolated papillary muscles probably by the release of H2O2.
Kraemer
R
R
Department of Pharmacology, New York Medical College, Valhalla 10595.
Seligmann
B
B
Mullane
K M
KM
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002449:Cell Aggregation; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006632:Histamine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D006997:Hypochlorous Acid / Q000494:pharmacology; D008353:Mannitol / Q000494:pharmacology; D008715:Methionine / Q000494:pharmacology; D009200:Myocardial Contraction; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010210:Papillary Muscles / Q000502:physiology; D013482:Superoxide Dismutase / Q000494:pharmacology
D000838:Anions; D008353:Mannitol; D006997:Hypochlorous Acid; D006632:Histamine; D008715:Methionine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase