BACKGROUND: Activation of protein kinase C plays an important role in ischemic preconditioning. Given that protein kinase C is activated by an increase in the intracellular Ca2+ concentration ([Ca2+]i) and that myocardial ischemia and reperfusion increase [Ca2+]i, the effect of transient exposures to Ca2+ on infarct size and the effect of administration of EGTA during ischemic and alpha1-adrenoceptor-mediated preconditioning on the limitation of infarct size were investigated in the canine heart. METHODS AND RESULTS: In open-chest dogs, 5 minutes after the completion of either three 5-minute infusions of CaCl2 or four 5-minute infusions of the alpha1-adrenoceptor agonist methoxamine into the coronary artery, the coronary arteries were occluded for 90 minutes; this occlusion was followed by a 6-hour reperfusion in both the Ca2+ preconditioning and methoxamine groups. Infarct sizes in the Ca2+ preconditioning (15.8+/-2.3%) and methoxamine (10.1+/-2.2%) groups were significantly (P<.01) smaller than in the control group (42.5+/-2.9%), and administration of either an inhibitor of protein kinase C (GF109203X) or an inhibitor of ecto-5'-nucleotidase (alpha,beta-methyleneadenosine 5'-diphosphate) reduced the infarct size-limiting effect of Ca2+ preconditioning. Administration of EGTA during ischemic or alpha1-adrenoceptor-mediated preconditioning inhibited both the infarct size-limiting effect and the activation of protein kinase C and ecto-5'-nucleotidase induced by these procedures. CONCLUSIONS: [Ca2+]i during ischemic and alpha1-adrenoceptor-mediated preconditioning plays an important role in the infarct size-limiting effect of these procedures by activating protein kinase C and ecto-5'-nucleotidase in the canine heart.
BACKGROUND: Activation of protein kinase C plays an important role in ischemic preconditioning. Given that protein kinase C is activated by an increase in the intracellular Ca2+ concentration ([Ca2+]i) and that myocardial ischemia and reperfusion increase [Ca2+]i, the effect of transient exposures to Ca2+ on infarct size and the effect of administration of EGTA during ischemic and alpha1-adrenoceptor-mediated preconditioning on the limitation of infarct size were investigated in the canine heart. METHODS AND RESULTS: In open-chest dogs, 5 minutes after the completion of either three 5-minute infusions of CaCl2 or four 5-minute infusions of the alpha1-adrenoceptor agonist methoxamine into the coronary artery, the coronary arteries were occluded for 90 minutes; this occlusion was followed by a 6-hour reperfusion in both the Ca2+ preconditioning and methoxamine groups. Infarct sizes in the Ca2+ preconditioning (15.8+/-2.3%) and methoxamine (10.1+/-2.2%) groups were significantly (P<.01) smaller than in the control group (42.5+/-2.9%), and administration of either an inhibitor of protein kinase C (GF109203X) or an inhibitor of ecto-5'-nucleotidase (alpha,beta-methyleneadenosine 5'-diphosphate) reduced the infarct size-limiting effect of Ca2+ preconditioning. Administration of EGTA during ischemic or alpha1-adrenoceptor-mediated preconditioning inhibited both the infarct size-limiting effect and the activation of protein kinase C and ecto-5'-nucleotidase induced by these procedures. CONCLUSIONS: [Ca2+]i during ischemic and alpha1-adrenoceptor-mediated preconditioning plays an important role in the infarct size-limiting effect of these procedures by activating protein kinase C and ecto-5'-nucleotidase in the canine heart.
Authors: Joel P French; Karyn L Hamilton; John C Quindry; Youngil Lee; Patrick A Upchurch; Scott K Powers Journal: FASEB J Date: 2008-04-16 Impact factor: 5.191