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

Seligmann, C. G.; Schimmer, M; Leitsch, Tobias; Böck, Andreas; Simsek, Yusuf; Tschöpe, Carsten; Schultheiß, Heinz Peter

doi:10.1016/s0891-5849(00)00414-7

Cited by 12 publications

(12 citation statements)

References 21 publications

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“…The blocking effect of the antibody on endothelial cell-platelet adhesion has been proposed as the main explanation for these results, although no data on platelet accumulation were reported. On the other hand, administration of superoxide dismutase significantly improved the contractile recovery of platelet-perfused hearts without influencing platelet retention (38). Antagonization of isoprostane-thromboxane receptors also reversed the cardiodepressive effect associated with the presence of platelets in the perfusate without reducing platelet adhesion (20).…”

Section: Discussionmentioning

confidence: 95%

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

Mirabet

Garcı́a-Dorado

Inserte

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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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.

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Section: Discussionmentioning

confidence: 95%

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

Mirabet

Garcı́a-Dorado

Inserte

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Khandoga et al (29) showed that this contributes to microvascular injury and cell damage in the liver. This may be coupled with cardiac dysfunction as cardiac reoxygenation injury is also known to be partly mediated by platelets exposed to superoxide (30). The lung and pancreas may also be affected (31,32).…”

Section: Discussionmentioning

confidence: 99%

Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

et al. 2006

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Hemostatic disturbances are common in asphyxiated newborns after resuscitation. We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or 100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia was induced with an inspired oxygen concentration of 10 -15% for 2 h. Piglets were then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21% oxygen. Platelet counts and collagen (2, 5, and 10 g/mL)-stimulated whole blood aggregation were studied before hypoxia and at 4 h of post-hypoxia/ reoxygenation. Platelet function was studied using transmission electron microscopy and by measuring plasma thromboxane B 2 (TxB 2 ) and matrix metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated without hypoxia/reoxygenation. The hypoxemic (PaO 2 33 mm Hg) piglets developed hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet aggregation ex vivo was impaired as evidenced by a rightwarddownward shifting of the concentration-response curves. Electron microscopy showed features of platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased. Resuscitation with 100% but not 21% oxygen increased plasma TxB 2 levels. Platelet counts decreased after hypoxia/reoxygenation but were not different between groups during the experiment. Resuscitation of hypoxic newborn piglets caused platelet activation with significant deterioration of platelet aggregation ex vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate the activation of prostaglandin-thromboxane mechanistic pathway. MMP-2 (constitutive isoform, 72 kD) and MMP-9 (inducible isoform, 92 kD) are zinc-dependent endopeptidases that play an important role in the regulation of platelet aggregation (6 -9). MMPs are activated by proteolysis and oxidants including the peroxynitrite anion (6,10). Increased plasma MMP-2 and -9 activity with platelet dysfunction was observed in an animal model of extracorporeal circulation with a high oxygen environment (11). Lemke et al. (12) recently reported a surge in plasma MMP-9 activity in the first day of postnatal life, which is consistent with a change from a low to a high oxygen environment. Interestingly, in neonatal models of asphyxia, resuscitation with 100% oxygen is associated with higher oxidative stress and MMP-2 activities in the heart and brain than those with 21% oxygen (13,14). However, there is little information on the activity of MMPs in plasma and its relationship to platelet aggregatory function in the reoxygenation of asphyxiated newborns.Asphyxiated infants are often resuscitated with 100% oxygen, and this is associated with increased oxidative stress up to 28 d after birth (15). In the midst of the debate between the use of 21% or 100% oxygen in the resuscitation of asphyxiated newborns, we designed this study to examin...

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“…Both, PMN and thrombocytes, have been identified as the source of potentially detrimental mediators including cytokines and reactive oxygen species [5, 6, 13, 14]. Under conditions of ischemia and reperfusion of the heart, they are thereby able to mediate a cardiac contractile dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…From several studies we learned that reperfusion of ischemic myocardium has not only beneficial actions but that reperfusion itself can induce deleterious effects, eventually leading to a compromised myocardial function [1, 2, 3, 4]. Polymorphonuclear granulocytes (PMN) and thrombocytes play an important role via release or mediation of reactive oxygen species, in this context [5, 6]. The interaction of these cell species has been investigated under conditions of ischemia and reperfusion of isolated animal hearts [7, 8, 9].…”

Section: Introductionmentioning

confidence: 99%

PMN/Platelets Coinfused in Guinea Pig Hearts Exposed to Low-Flow Ischemia Have no Additive Cardiodepressive Effect

Seligmann

Leitsch²,

Kusus³

et al. 2003

J Vasc Res

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Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/µl or 20,000/µl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI₂ or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.

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

Cited by 12 publications

References 21 publications

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

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

Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

PMN/Platelets Coinfused in Guinea Pig Hearts Exposed to Low-Flow Ischemia Have no Additive Cardiodepressive Effect

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