Polymorphonuclear granulocytes induce myocardial dysfunction during ischemia and in later reperfusion of hearts exposed to low-flow ischemia.

Polymorphonuclear granulocytes (PMNs) are known to contribute to reperfusion injury of the heart. However, whether PMNs compromise myocardial function of hearts exposed to a low-flow ischemia has not been determined. Moreover, not much is known about deleterious effects of PMNs at different times during ischemia and reperfusion. Isolated, working guinea pig hearts were subjected to 30 min of low-flow ischemia and reperfusion. Homologous PMNs were applied as 1-min boluses in the presence of thrombin during either ischemia or the first or fifth minute of reperfusion, and postischemic recovery of external heart work (REHW) and intracoronary PMN retention (PMNR) were quantified. In further experiments, the radical scavenger superoxide dismutase (SOD) was added. Compared with controls without PMNs (REHW, 92.4%), application of PMNs led to a significant loss of myocardial function, which was detected at all three examination times. Moreover, intracoronary PMNR increased significantly in comparison with that of controls with hearts not exposed to ischemia or reperfusion. On the other hand, addition of SOD significantly increased REHW. Intracoronary PMNR was not significantly changed by coapplication of SOD. We conclude that thrombin-stimulated PMNs applied at different times during ischemia and reperfusion significantly impaired cardiac function in hearts exposed to a low-flow ischemia.

A thrombocyte-induced myocardial dysfunction in the ischemic and reperfused guinea pig heart is mediated by reactive oxygen species.

In recent investigations, we could demonstrate that thrombocytes are able to contribute to ischemia- and reperfusion-induced injury of the heart. The aim of the current study was to investigate whether reactive oxygen species are responsible for induction of myocardial dysfunction under these conditions. Isolated, perfused, and pressure-volume work-performing guinea pig hearts were exposed to a 30-min low-flow ischemia (1 ml/min) and were reperfused (5 ml/min). Washed, homologous blood platelets were administered as a 1-min bolus (20,000 per microliter of perfusion buffer), either during the 15th minute of ischemia or in the first or fifth minute of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer)). The radical scavengers superoxide dismutase (SOD; 10 U/ml perfusate) and catalase (30 U/ml perfusate) were added during ischemia or in the first or fifth minute of reperfusion, respectively. Intracoronary platelet retention (in percentage of platelets applied) and recovery of EHW (postischemic EHW in percentage of preischemic EHW) were quantified. Ischemic and reperfused hearts with time-matched application of platelets but without administration of SOD or catalase served as controls. Interestingly, both administration of SOD during ischemia and in reperfusion significantly improved recovery of EHW (88.4 +/- 2%, 82. 6 +/- 1%, and 90 +/- 3%, respectively) as compared with the case of controls (56.2 +/- 3%, 42 +/- 2%, and 75 +/- 2%, respectively). Platelet retention, however, was not significantly influenced by administration of SOD during ischemia or reperfusion (26 +/- 2%, 31 +/- 2%, and 26 +/- 2%) compared with controls (30.5 +/- 3%, 33 +/- 2%, and 22 +/- 3%, respectively). Coadministration of catalase, on the other hand, exhibited some cardioprotective potential only in the first minute of reperfusion (recovery, 61% +/- 4%) as compared with the case of control (42 +/- 2%). We conclude that thrombocytes under conditions of ischemia and reperfusion are able to induce a myocardial dysfunction mediated by reactive oxygen species. Superoxide seems to play a major role in this respect.