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Polymorphonuclear leukocytes reduce cardiac function in vitro by release of H2O2
R Kraemer1, B Seligmann, K M Mullane
1Department of Pharmacology, New York Medical College, Valhalla 10595.
Abstract:
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.
Insights
Polymorphonuclear leukocytes (PMNs) impair cardiac function by releasing hydrogen peroxide (H2O2). This study shows PMNs significantly decrease contractile force in isolated heart muscles, with H2O2 identified as the primary mediator.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Inflammation Research
Background:
- Polymorphonuclear leukocytes (PMNs) are linked to myocardial injury after ischemia.
- Understanding PMN's direct impact on cardiac contractility is crucial.
Purpose of the Study:
- To investigate the direct effects of PMNs on cardiac contractile function.
- To identify the specific mechanisms by which PMNs induce cardiac dysfunction.
Main Methods:
- Isolated rabbit right ventricular papillary muscles were exposed to varying concentrations of purified PMNs.
- Contractile function was measured, and the role of reactive oxygen species was assessed using scavengers and direct hydrogen peroxide (H2O2) exposure.
Main Results:
- PMNs caused a concentration-dependent reduction in papillary muscle contractile force and its derivatives.
- PMN-induced dysfunction correlated with PMN activity.
- Catalase attenuated the contractile loss, while superoxide dismutase did not. Direct H2O2 exposure mimicked PMN effects.
Conclusions:
- PMNs likely reduce cardiac contractile function through the release of hydrogen peroxide (H2O2).
- H2O2 is a key mediator of PMN-induced cardiac dysfunction in this model.