Mazer C David, Briet Francoise, Blight Katherine R, Stewart Duncan J, Robb Malcolm, Wang Zhilan, Harrington Alana M, Mak William, Li Xiaomao, Hare Gregory M T
Department of Anesthesia, University of Toronto, St. Michael's Hospital, Seneca College, Toronto, Ontario, Canada.
J Thorac Cardiovasc Surg. 2007 Jan;133(1):13-20. doi: 10.1016/j.jtcvs.2006.06.047.
Hemodilution and endothelial nitric oxide synthase genetic polymorphism may contribute to cerebral and renal injury after cardiopulmonary bypass. This study tested the hypothesis that cardiopulmonary bypass and anemia stimulate an increase in cerebral and renal endothelial nitric oxide synthase gene expression in an experimental model of cardiopulmonary bypass.
Anesthetized rats underwent a sham procedure without cardiopulmonary bypass (sham, n = 5), normothermic bypass for 1 hour (CPB, n = 7), or bypass plus hemodilutional anemia (CPB anemia, n = 9). After 24 hours of recovery, RNA was extracted from the cerebral cortex, renal cortex, and renal medulla. Quantitative reverse transcriptase polymerase chain reaction was used to assess endothelial nitric oxide synthase messenger RNA levels in brain and kidney tissues.
The hemoglobin concentration of anemic CPB rats was significantly lower than that of nonanemic rats on bypass (64 +/- 5 vs 99 +/- 8 g x L(-1), P < .001). Cerebral cortical endothelial nitric oxide synthase messenger RNA levels were increased after cardiopulmonary bypass relative to those of the sham group (11.2 +/- 4.2 vs 6.3 +/- 1.5 fg, P = .031), without a further increase in anemic rats. Renal medullary endothelial nitric oxide synthase messenger RNA levels were significantly higher in the CPB anemia group than in the sham and CPB groups (7.1 +/- 4.4 fg vs 1.8 +/- 0.4 fg vs 3.0 +/- 0.6 fg, P < .001). Renal cortical endothelial nitric oxide synthase messenger RNA levels did not change significantly.
Normothermic cardiopulmonary bypass was associated with higher endothelial nitric oxide synthase messenger RNA levels in kidney and brain than was the sham procedure 24 hours after cardiopulmonary bypass. Anemia accentuated the increase in renal medullary, but not cerebral cortical, endothelial nitric oxide synthase expression. These data provide an approach for exploring potential mechanisms by which endothelial nitric oxide synthase may contribute to renal and cerebral dysfunction after cardiopulmonary bypass and anemia.
血液稀释和内皮型一氧化氮合酶基因多态性可能与体外循环后的脑和肾损伤有关。本研究检验了以下假设：在体外循环实验模型中，体外循环和贫血会刺激脑和肾内皮型一氧化氮合酶基因表达增加。
对麻醉大鼠进行假手术（未进行体外循环，假手术组，n = 5）、常温体外循环1小时（体外循环组，n = 7）或体外循环加血液稀释性贫血（体外循环贫血组，n = 9）。恢复24小时后，从大脑皮质、肾皮质和肾髓质提取RNA。采用定量逆转录聚合酶链反应评估脑和肾组织中内皮型一氧化氮合酶信使核糖核酸水平。
体外循环贫血组大鼠的血红蛋白浓度显著低于非贫血体外循环大鼠（64±5 vs 99±8 g·L⁻¹，P <.001）。与假手术组相比，体外循环后大脑皮质内皮型一氧化氮合酶信使核糖核酸水平升高（11.2±4.2 vs 6.3±1.5 fg，P =.031），贫血大鼠未进一步升高。体外循环贫血组肾髓质内皮型一氧化氮合酶信使核糖核酸水平显著高于假手术组和体外循环组（7.1±4.4 fg vs 1.8±0.4 fg vs 3.0±0.6 fg，P <.001）。肾皮质内皮型一氧化氮合酶信使核糖核酸水平无显著变化。
常温体外循环后24小时，与假手术相比，肾和脑中内皮型一氧化氮合酶信使核糖核酸水平较高。贫血加剧了肾髓质而非大脑皮质内皮型一氧化氮合酶表达的增加。这些数据为探索内皮型一氧化氮合酶可能导致体外循环和贫血后脑和肾功能障碍的潜在机制提供了一种方法。
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