Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts

Abstract

Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.

Early expression of adhesion molecules after lung transplantation: Evidence for a role of aggregated P-selectin-positive platelets in human primary graft failure

“…15 These results coincide with the deleterious effect of platelets during organ reperfusion injury, 13 which is related to platelet activation represented by P-selectin expression. 16 P-selectin is a glycoprotein stored in Weibel-Palade bodies of endothelial cells and ␣-granules of platelets. 17,18 When the cell is activated, P-selectin can rapidly be brought to the cell surface.…”

Coronary microvascular reperfusion injury and no-reflow in acute myocardial infarction

“…8 However, GP IIb/IIIa blockade can stabilize the culprit lesion but it neither reduces microvascular platelet accumulation or infarct size after transient coronary occlusion in swine 60 nor protects against platelet-mediated injury isolated reperfused rat hearts. 61 The discrepancy in the reports needs further investigation.…”

Antagonism of selectin function attenuates microvascular platelet deposition and platelet-mediated myocardial injury after transient ischemia

“…Experiments in isolated rat hearts. Porcine platelets were isolated and resuspended in modified Tyrode buffer as described earlier (11). After activation with 0.1-U/ml hu- man thrombin, platelets were treated or not treated with 30-g/ml fucoidan-a concentration that has preserved ventricular function in blood-reperfused isolated hearts (22)-for 5 min at 37°C (final concentration, 4 ϫ 10 10 platelets/l).…”

“…After activation with 0.1-U/ml hu- man thrombin, platelets were treated or not treated with 30-g/ml fucoidan-a concentration that has preserved ventricular function in blood-reperfused isolated hearts (22)-for 5 min at 37°C (final concentration, 4 ϫ 10 10 platelets/l). We previously assessed that platelet incubation with this concentration of thrombin induces a marked increase in P-selectin expression but not aggregation (11), which is unaffected by subsequent incubation with fucoidan. Hearts from pentobarbital-anesthetized male SpragueDawley rats (n ϭ 16) were placed in a Langerdoff apparatus, perfused at 10 ml/min with modified Krebs-Henseleit bicarbonate buffer (11,25).…”

“…We previously assessed that platelet incubation with this concentration of thrombin induces a marked increase in P-selectin expression but not aggregation (11), which is unaffected by subsequent incubation with fucoidan. Hearts from pentobarbital-anesthetized male SpragueDawley rats (n ϭ 16) were placed in a Langerdoff apparatus, perfused at 10 ml/min with modified Krebs-Henseleit bicarbonate buffer (11,25). After equilibration, hearts were subjected to 40 min of no-flow ischemia followed by 60 min of reperfusion.…”