Adenosine A1 receptor activation reduces myocardial reperfusion effects on intrinsic cardiac nervous system.
The intrinsic cardiac nervous system is the final common integrator of regional cardiac function. The ischemic myocardium modifies this nervous system. We sought to determine the role that intrinsic cardiac neuronal P(1) purinergic receptors play in transducing myocardial ischemia and the subsequent reperfusion. The activity generated by ventricular neurons was recorded concomitant with cardiac hemodynamic variables in 44 anesthetized pigs. Regional ventricular ischemia was induced by briefly occluding (30 s) the ventral interventricular coronary artery distal to the arterial blood supply of identified ventricular neurons. Adenosine (100 microM) was administered to these neurons via their local arterial blood supply during or immediately after transient coronary artery occlusion. Occlusion was also performed following local administration of adenosine A(1) [8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] or A(2) [3,7-dimethyl-1-propargylxanthine (DMPX)] receptor blocking agents. The activity generated by ventricular neurons was modified by transient coronary artery occlusion and the subsequent reperfusion (||Delta|| 112 +/- 14 and 168 +/- 34 impulses/min, respectively; P < 0.01 vs. preischemic states). Locally administered adenosine attenuated neuronal responses to reperfusion (-75%; P < 0.01 compared with normal reperfusion) but not ischemia. The neuronal stabilizing effects that adenosine elicited during reperfusion persisted in the presence of DMPX but not DPCPX. It is concluded that activation of neuronal adenosine A(1) receptors stabilizes the intrinsic cardiac nervous system during reperfusion.
Arora
R C
RC
Department of Anatomy and Neurobiology and Department of Surgery, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Armour
J A
JA
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013552:Swine; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine