Adenosine endogenously released during early reperfusion mitigates postischemic myocardial dysfunction by inhibiting platelet adhesion.
The purpose of this study was to investigate platelet effects on postischemic heart function in conjunction with adenosine effects on intracoronary platelet adhesion. Homologous platelets were infused into the coronaries of isolated guinea pig hearts, either during low-flow ischemia or during reperfusion, and external heart work (EHW) and intracoronary platelet adhesion were determined. In most experiments, thrombin was added to the perfusate. The influence of endogenous adenosine was studied by use of the uptake blocker dipyridamole and the unspecific adenosine-receptor blocker theophylline, the A1-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and the A2-receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX). The importance of nitric oxide and prostaglandin I2 (PGI2) was tested by using nitro-L-arginine (NOLAG) and indomethacin, respectively. When platelets were applied with thrombin during low-flow ischemia, EHW recovered to only 63 +/- 4% of the preischemic value, as compared with 89 +/- 3% without platelets (p < 0.05). Despite thrombin, platelets incurred no significant functional loss when applied in the first minute of reperfusion (but again in the fifth minute); however, when theophylline was also present, recovery of EHW amounted to only 42 +/- 12%. Intracoronary adhesion of platelets was negligible without thrombin, and highest during low-flow ischemia with thrombin (35 +/- 3% of the applied number). No adhesion occurred during the first minute of reperfusion, whereas in the fifth minute, adhesion was again 20.8 +/- 4%. Dipyridamole increased adenosine release and attenuated adhesion at this time. Theophylline increased adhesion in the first minute of reperfusion (33 +/- 6.4%), whereas NOLAG and indomethacin proved to be ineffective. DPCPX and DMPX each increased platelet retention during the first minute of reperfusion, their effects being additive. Intracoronary adhesion of platelets induced by thrombin in isolated hearts can reduce postischemic recovery of heart function. During reperfusion, but not during low-flow, endogenous adenosine can prevent platelet adhesion and loss of myocardial function, an action mediated both by A1- and A2-receptor-dependent mechanisms.
Department of Physiology, University of Munich, Germany.
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Seligmann
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Kupatt
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Becker
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Zahler
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Beblo
D000241:Adenosine / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010973:Platelet Adhesiveness / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists
D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D058915:Purinergic P1 Receptor Antagonists; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D000241:Adenosine