The effects of ischemic preconditioning on resting coronary flow and reactive hyperemia: involvement of A1 adenosine receptors.
During the myocardial protection induced by ischemic preconditioning a reduction in myocardial metabolism occurs due to activation of the A1 adenosine receptors. This study investigates whether preconditioning changes both resting coronary flow and the magnitude of coronary reactive hyperemia and whether A1 adenosine receptors are involved in the observed changes. Experiments were performed in 14 goats (30-50 kg body weight). After the animals were anesthetized with ketamine, an electromagnetic flow-probe was used to record blood flow in the left circumflex coronary artery. Distal to the probe, an occluder was placed to produce ischemic preconditioning and reactive hyperemia. Preconditioning was obtained with two periods of 2.5 min of coronary occlusion separated from each other by 5 min of reperfusion. Coronary reactive hyperemia was obtained with 15 s of occlusion of the artery before and after preconditioning. In a group of goats before preconditioning 0.2 mg kg(-1) of 8-cyclopentyl-dipropylxanthine (CPX), an A1 adenosine receptor blocker, were given intravenously. In all animals ischemic preconditioning did not alter resting coronary flow, but, in the absence of A1 adenosine receptor blockade, reduced the reactive hyperemic response. The total hyperemic flow and the excess/debt flow ratio were reduced by about 25% and 30% respectively. The A1 adenosine receptor blockade "per se" did not cause any change in the resting flow and in the parameters of the reactive hyperemia. Unlike what observed in the absence of blockade, after CPX ischemic preconditioning was unable to reduce total hyperemic flow and the excess/debt flow ratio. The results suggest that ischemic preconditioning reduces the coronary hyperemic response by decreasing the myocardial metabolism through the activation of the A1 adenosine receptors.
Pagliaro
P
P
Dipartimento di Scienze Cliniche e Biologiche dell'Università di Torino, Orbassano, Italy. pagliaro@pasteur.sluigi.unito.it
Penna
C
C
Gattullo
D
D
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation; D006041:Goats; D006940:Hyperemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D014970:Xanthines; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine