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Polymorphonuclear granulocytes induce myocardial dysfunction during ischemia and in later reperfusion of hearts
C Seligmann1, A Bock, T Leitsch
1Department of Cardiology, University Hospital Benjamin Franklin, Free University of Berlin, D-12200 Berlin, Germany. cseligmann@talknet.de
Abstract:
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.
Insights
Polymorphonuclear granulocytes (PMNs) significantly impair heart function during low-flow ischemia and reperfusion. These white blood cells caused cardiac damage when introduced during ischemia or reperfusion, highlighting their role in myocardial injury.
Area of Science:
- Cardiovascular Research
- Hematology
- Ischemia-Reperfusion Injury
Background:
- Polymorphonuclear granulocytes (PMNs) are implicated in cardiac reperfusion injury.
- The specific impact of PMNs on myocardial function during low-flow ischemia and their temporal effects during ischemia/reperfusion remain unclear.
Purpose of the Study:
- To determine if PMNs compromise myocardial function in hearts subjected to low-flow ischemia.
- To investigate the deleterious effects of PMNs at different time points during ischemia and reperfusion.
Main Methods:
- Isolated, working guinea pig hearts underwent 30 minutes of low-flow ischemia and reperfusion.
- Homologous PMNs were administered during ischemia or early reperfusion with thrombin.
- External heart work recovery (REHW) and PMN retention (PMNR) were measured.
- The effect of superoxide dismutase (SOD) was evaluated.
Main Results:
- PMN application significantly reduced myocardial function (REHW) regardless of administration timing.
- Intracoronary PMN retention (PMNR) was elevated compared to controls.
- Superoxide dismutase (SOD) significantly improved REHW but did not alter PMNR.
Conclusions:
- Thrombin-stimulated PMNs significantly impair cardiac function in low-flow ischemic conditions.
- PMNs contribute to myocardial dysfunction during both ischemic and reperfusion phases.
- Antioxidant therapy with SOD shows potential in mitigating PMN-induced cardiac damage.