Human thrombocytes are able to induce a myocardial dysfunction in the ischemic and reperfused guinea pig heart mediated by free radicals-role of the GPIIb/IIIa-blocker tirofiban.

Abstract

In recent studies, we could demonstrate a myocardial dysfunction induced by homologous platelets in ischemic and reperfused guinea pig hearts. Aim of the current study was to find out whether or not this is a phenomenon specific for platelets isolated from guinea pigs and to further examine the mechanisms of a possible cardiodepressive effect of human platelets. Isolated guinea pig hearts were exposed to a 30 min low-flow ischemia (1 ml/min) and reperfused. Human thrombocytes were administered as bolus (20.000 thrombocytes/microl perfusion buffer) in the 15(th) min of ischemia or in the 1(st) or 5(th) min of reperfusion in the presence of thrombin. Recovery of external heart work (REHW) and intracoronary platelet retention (RET) were quantified in percent. In additional experiments, the GPIIb/IIIa-blocker tirofiban (10 microg/ml perfusion buffer) or the radical scavenger superoxide dismutase (SOD-10 U/ml perfusion buffer) were added. Platelet application in the absence of tirofiban, either during ischemia (REHW 75.4 +/- 4%, RET 22.2 +/- 2%) or the 1st min (REHW 71.6 +/- 1%, RET 31.2 +/- 2%) or the 5th min of reperfusion (REHW 63.2 +/- 4%, RET 40.5 +/- 1%) led to a significant reduction of REHW and a significant increase of RET. The coapplication of tirofiban, on the other hand, prevented RET at all three times of platelet application (1.1 +/- 1.7%, 0% or 2.1 +/- 1.2%, respectively). An improvement of REHW, however, could only be noticed during ischemia (89 +/- 2%), whereas coapplication of tirofiban in early (72.9 +/- 3%) or in late reperfusion (74.6 +/- 2%) did not lead to a significant increase of REHW. Coapplication of SOD, on the other hand, significantly improved REHW in early (88.1 +/- 1) or late (95.9 +/- 1) reperfusion but not during ischemia (83.5 +/- 2). Corresponding to REHW, RET was changed significantly by coapplication of SOD during early (1 +/- 2%) or late (0%) reperfusion but not during ischemia (21.1 +/- 4%). We conclude that human thrombocytes are able to induce a myocardial dysfunction in ischemic and reperfused guinea pig hearts mediated by reactive oxygen species and independent of intracoronary platelet adhesion.

• Authors: Christian Seligmann, Yusuf Simsek, Mike Schimmer, Tobias Leitsch, Andreas Bock, Heinz-Peter Schultheiss
• Journal: Life sciences (Life Sci) Vol. 71 Issue 19 Pg. 2319-29 (Sep 27 2002) ISSN: 0024-3205 [Print] Netherlands
• PMID: 12215379 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Platelet Glycoprotein GPIIb-IIIa Complex
• Tyrosine
• Superoxide Dismutase
• Tirofiban

Topics

• Animals
• Blood Platelets (physiology)
• Cardiac Output (drug effects, physiology)
• Disease Models, Animal
• Fibrinolytic Agents (pharmacology)
• Guinea Pigs
• Humans
• In Vitro Techniques
• Male
• Myocardial Reperfusion Injury (etiology, pathology, physiopathology)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Platelet Transfusion
• Superoxide Dismutase (pharmacology)
• Tirofiban
• Tyrosine (analogs & derivatives, pharmacology)