AJP - Heart and Circulatory Physiology, Vol 258, Issue 6 1847-H1855, Copyright © 1990 by American Physiological Society
Polymorphonuclear leukocytes reduce cardiac function in vitro by release of H2O2
R. Kraemer, B. Seligmann and K. M. Mullane
Department of Pharmacology, New York Medical College, Valhalla 10595.
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.
