Codère-Maruyama Takumi, Schricker Thomas, Shum-Tim Dominique, Wykes Linda, Nitschmann Evan, Guichon Céline, Kristof Arnold S, Hatzakorzian Roupen
Department of Anesthesia, McGill University, Montreal, Quebec, Canada;
Department of Anesthesia, McGill University, Montreal, Quebec, Canada.
Am J Physiol Regul Integr Comp Physiol. 2016 Dec 1;311(6):R1085-R1092. doi: 10.1152/ajpregu.00334.2016. Epub 2016 Oct 5.
Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-H]glucose and l-[1-C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: -13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 μmol·kg·h, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 μmol·kg·min, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.
心脏手术会引发炎症应激反应,导致蛋白质分解代谢,这一过程即使仅靠高剂量胰岛素治疗也无法逆转。为了确定高胰岛素-正常血糖钳夹术和围手术期补充氨基酸(AA)是否能改善全身蛋白质平衡,将20例计划进行择期冠状动脉搭桥手术的患者随机分为两组,分别在术中和术后接受高胰岛素-正常血糖钳夹术,一组补充静脉氨基酸,另一组不补充。术前和术后使用[6,6-H]葡萄糖和l-[1-C]亮氨酸的首剂持续输注来量化全身蛋白质和葡萄糖代谢。还分析了脂肪组织和血清细胞因子,以测量它们对补充氨基酸合成代谢作用的反应性。在高胰岛素-正常血糖钳夹期间,补充氨基酸成功刺激了全身蛋白质合成,并在术后产生了正的全身蛋白质平衡(胰岛素组:-13.6±4.5与胰岛素+氨基酸组:2.1±5.4μmol·kg·h,P<0.001)。两组内源性葡萄糖生成均受到同等程度的抑制(胰岛素组:0.0±3.8与胰岛素+氨基酸组:1.6±1.6μmol·kg·min,P = 0.230)。补充氨基酸导致血清和组织白细胞介素-6发生显著变化(胰岛素组:246.6±111.2与胰岛素+氨基酸组:124.5±79.3 pg/ml,P = 0.011)。总之,高胰岛素-正常血糖钳夹技术与补充氨基酸相结合,可在心脏直视手术后诱导合成代谢状态,这可通过正的全身蛋白质平衡来量化。