Copyright © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited. <zdoi;10.1097/ALN.0000000000001642> Anesthesiology, V 127 • No 1 70 July 2017 L EFT ventricular hypertrophy is an adaptational response to an increased load that involves increased protein syn- thesis and cardiomyocyte size. However, with pathologic con- ditions such as hypertension or after myocardial infarction, maladaptive cardiac hypertrophy can result in tissue fbrosis and is associated with a greater mortality due to heart failure and arrhythmia. 1,2 Moreover, left ventricular hypertrophy is associated with changes in the density, structure, and coronary vasodilator capacity so that the cross-sectional diameter of endomyocardial capillaries and coronary reserve are decreased even in the absence of detectable coronary atherosclerosis. 3,4 Interestingly, activated mutants of the G-protein α-subunit Gq promote myocardial hypertrophy. 5 In line with these studies, knockout of Gq or the functionally similar G protein G11 in cardiomyocytes abolished pressure overload–induced myocardial hypertrophy. 6 Activation of the Gq pathway via angiotensin II and the angiotensin II receptor type 1 7 results in activation of phospholipase c beta, which hydrolyses the plasma membrane phosphatidylinositol What We Already Know about This Topic • Previous studies have demonstrated angiotensin II receptor type 1–mediated activation of the α-subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and may promote hypertrophy-induced myocardial damage • This study determined whether a TT(-695/-694)GC polymorphism in the human Gq promoter is associated with differences in (1) myocardial Gq protein expression, (2) vascular reactivity, and (3) myocardial damage after coronary artery bypass grafting What This Article Tells Us That Is New • The GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased Gq protein expression, augmented angiotensin II receptor type 1–related vasoconstriction, and increased myocardial injury after coronary artery bypass grafting Copyright © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved. Anesthesiology 2017; 127:70-7 ABSTRACT Background: Angiotensin II receptor type 1–mediated activation of the α-subunit of the heterotrimeric Gq protein evokes increased vasoconstriction and may promote hypertrophy-induced myocardial damage. Te authors recently identifed a TT(-695/-694)GC polymorphism in the human Gq promoter, the GC allele being associated with an increased prevalence of cardiac hypertrophy. In this article, the authors tested whether the TT(-695/-694)GC polymorphism is associated with diferences in (1) myocardial Gq protein expression, (2) vascular reactivity, and (3) myocardial damage after coronary artery bypass grafting. Methods: Gq protein expression was measured in right atrial muscle from 55 patients undergoing coronary artery bypass grafting as were skin perfusion changes (n = 18; laser Doppler imaging), saphenous vein ring vascular reactivity (n = 50, organ bath) in response to angiotensin II, and myocardial damage (227 patients undergoing coronary artery bypass grafting), as assessed by postoperative cardiac troponin I concentration. Results: Myocardial Gq expression was greater in GC/GC genotypes (GC/GC vs. TT/TT: 1.27-fold change; P = 0.006). Skin perfusion after intradermal angiotensin II injection decreased only in GC/GC genotypes (P = 0.0002). Saphenous vein rings exposed to increasing angiotensin II concentrations showed an almost doubled maximum contraction in GC/GC compared with individuals with the TT/TT genotype (P = 0.022). In patients undergoing coronary artery bypass grafting, baseline cardiac ejection fraction was diferent (GC/GC: 55 ± 13%; GC/TT: 54 ± 14%; TT/TT: 48 ± 15%; P = 0.037) and postopera- tive peak cardiac troponin I was greater in patients with the GC/GC (11.5 ± 13.8 ng/ml) than in patients with the GC/TT (9.2 ± 9.2 ng/ml) or patients with the TT/TT genotype (6.6 ± 4.8 ng/ml, P = 0.015). Conclusions: Te GC/GC genotype of the TT(-695/-694)GC polymorphism is associated with increased Gq protein expres- sion, augmented angiotensin II receptor type 1–related vasoconstriction, and increased myocardial injury after coronary artery bypass grafting, highlighting the impact of Gq genotype variation. (ANESTHESIOLOGY 2017; 127:70-7) Submitted for publication November 8, 2016. Accepted for publication March 13, 2017. From Klinik für Anästhesiologie und Intensivmedizin (U.H.F., S.K., T.K., J.P.), Die Blutdruck Praxis, Dorsten (A.M.), Klinik für Thorax- und kardiovaskuläre Chirurgie (H.J., M.T.), and Institut für Pharmakogenetik (W.S.), Universität Duisburg-Essen, Essen; and Universitätsklinikum Essen (U.H.F., S.K., T.K., J.P., H.J., M.T.), Essen, Germany. GNAQ TT(-695/-694)GC Polymorphism Is Associated with Increased Gq Expression, Vascular Reactivity, and Myocardial Injury after Coronary Artery Bypass Surgery Ulrich H. Frey, Prof. Dr. med., Stefanie Klenke, Dr. med., Anna Mitchell, Privatdozentin Dr. med., Tim Knüfermann, Cand. med., Heinz Jakob, Prof. Dr. med., Matthias Thielmann, Prof. Dr. med., Winfried Siffert, Prof. Dr. med., Jürgen Peters, Prof. Dr. med.