TY - JOUR
T1 - Impaired endothelium-dependent relaxation after coronary reperfusion injury
T2 - Evidence for G-protein dysfunction
AU - Evora, Paulo R.B.
AU - Pearson, Paul J.
AU - Schaff, Hartzell V.
N1 - Funding Information:
This study was supported in part by CNPq Conselho Nacional de Desenvolvimento Cientifico e Technologico, Brazil, and the Mayo Foundation.
PY - 1994/6
Y1 - 1994/6
N2 - This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G-protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetylcholine was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-l-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, waa unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium-dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury lead to G-protein dysfunction in the endothelium.
AB - This study was done to determine whether abnormal receptor-dependent release of endothelium-derived relaxing factor (EDRF) might be caused by G-protein dysfunction. Dogs were exposed to global myocardial ischemia (45 minutes, induced by aortic cross-clamping) followed by reperfusion (60 minutes) while on cardiopulmonary bypass, and coronary arteries were then studied in vitro in organ chamber experiments. After reperfusion, endothelium-dependent relaxation to the receptor-dependent agonists adenosine diphosphate and acetylcholine was significantly impaired as well as to sodium fluoride, which acts on a pertussis toxin-sensitive G-protein. In contrast, endothelium-dependent relaxations to the receptor-independent agonists A23187 and phospholipase C were normal. Furthermore, endothelium-dependent relaxation to poly-l-arginine (molecular weight, 139,200), which appears to induce endothelium-dependent relaxation of the canine coronary artery by a nonnitric oxide pathway, waa unaffected by ischemia and reperfusion. These experiments suggest that global myocardial ischemia and reperfusion selectively impair receptor-mediated release of EDRF (nitric oxide) but that the ability of the endothelial cell to produce EDRF or generate endothelium-dependent relaxation to nonnitric oxide-dependent agonists remains intact. We hypothesize that coronary reperfusion injury lead to G-protein dysfunction in the endothelium.
UR - http://www.scopus.com/inward/record.url?scp=0028241372&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028241372&partnerID=8YFLogxK
U2 - 10.1016/0003-4975(94)90121-X
DO - 10.1016/0003-4975(94)90121-X
M3 - Article
C2 - 8010801
AN - SCOPUS:0028241372
SN - 0003-4975
VL - 57
SP - 1550
EP - 1556
JO - The Annals of thoracic surgery
JF - The Annals of thoracic surgery
IS - 6
ER -