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 posti schemic heart function in conjunction with adenosine effects on intrac oronary platelet adhesion. Homologous platelets were infused into the coronaries of isolated guinea pig hearts, either during low-flow ische mia or during reperfusion, and external heart work (EHW) and intracoro nary 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 a denosine-receptor blocker theophylline, the A(1)-receptor blocker 8-cy clopentyl-1,3-dipropylxanthine (DPCPX), and the A(2)-reccptor blocker 3.7-dimethyl-1 -propargylxanthine (DMPX). The importance of nitric oxi de and prostaglandin I-2 (PGI(2)) was tested by using nitio-L-arginine (NOLAG) and indomethacin, respectively. When platelets were applied w ith thrombin during low-flow ischemia, EHW recovered to only 63 +/- 4% of the preischemic value, as compared with 89 +/- 3% without platelet s (p < 0.05). Despite thrombin platelets incurred no significant funct ional loss when applied in the first minute of reperfusion (but again in the fifth minute): however, when theophylline was also present, rec overy of EHW amounted to only 42 +/- 12%. Intracoronary adhesion of pl atelets was negligible without thrombin. and highest during low-flow i schemia with thrombin (35 +/- 3% of the applied number). No adhesion o ccurred during the first minute of reperfusion, whereas in the fifth m inute, adhesion was again 20.8 +/- 4%. Dipyridamole increased adenosin e release and attenuated adhesion at this time. Theophylline increased adhesion in the first minute of reperfusion (33 +/- 6.4%), whereas NO LAG and indomethacin proved to be ineffective. DPCPX and DMPX each Inc reased platelet retention during the first minute of reperfusion, thei r effects being additive. Intracoronary adhesion of platelets induced by thrombin in isolated hearts can reduce postischemic recovery of hea rt function. During reperfusion, but not during low-flow, endogenous a denosine can prevent platelet adhesion and loss of myocardial function , an action mediated both by A(1)- and A(2)-receptor-dependent mechani sms.