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

Abstract

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.

Platelet Contributions to Myocardial Ischemia/Reperfusion Injury

“…However, there are opposing studies as well. Seligmann et al did not observe an additional effect of simultaneous applications of platelets and neutrophils over sole application of either of both in a study using isolated guinea pig hearts (76). In contrast, indications for a role of platelet neutrophil interactions in IRI were also found by different inhibition approaches of the P-selectin-P-selectin glycoprotein ligand 1(PSGL1) axis that led to alleviation of myocardial IRI.…”

Elevated platelet–leukocyte complexes are associated with, but dispensable for myocardial ischemia–reperfusion injury

“…For instance, simultaneous infusion of neutrophils and platelets during reperfusion of ischemic isolated guinea pig and rat hearts impaired cardiac function [ 20 , 29 , 49 ]. In line, blocking PNC-formation attenuated these adverse cardiac effects [ 21 ].…”

Platelets in Myocardial Ischemia/Reperfusion Injury

“…A study on isolated guinea pig hearts by Seligmann et al did not find an additional effect in the combined presence of platelets and neutrophils over the presence of only one cell type alone, questioning a causative role of PLC in IRI. 129 Furthermore, in a conference abstract, Starz et al reported that mice carrying a selective deletion of platelet P-selectin (P-selectin −/− bone marrow chimeras) display a blunted surge in circulating PLC after induction of experimental myocardial IRI. However, this did not result in any differences in infarct size, tissue inflammation, or long-term ejection fraction in comparison to P-selectin WT.…”