Pretorius Mias, McFarlane Julie A, Vaughan Douglas E, Brown Nancy J, Murphey Laine J
Veterans Affairs Medical Center and Department of Anesthesiology, and Division of Cardiovascular Medicine.
Clin Pharmacol Ther. 2004 Oct;76(4):379-87. doi: 10.1016/j.clpt.2004.06.004.
This study tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitors potentiate activation of the kallikrein-kinin system during cardiopulmonary bypass (CPB).
The effects of CPB on concentrations of bradykinin and its metabolite bradykinin 1-5 (BK1-5) were determined in 31 patients taking an ACE inhibitor who were randomized to continue ACE inhibitors until coronary artery bypass surgery (ACE inhibitor group, N = 19) or to discontinue them 48 hours before surgery (no ACE inhibitor group, N = 12). Arterial and venous blood was sampled before CPB, at 30 minutes of CPB, at 60 minutes of CPB, after separation from CPB, and on postoperative day 1.
Arterial bradykinin ( P < .001 [from 22.4 +/- 24.1 fmol/mL to 86.2 +/- 98.7 fmol/mL in the no ACE inhibitor group]) and arterial ( P < .001) and venous ( P = .016) BK1-5 concentrations increased significantly during CPB. Arterial bradykinin concentrations were significantly higher ( P = .017), whereas BK1-5 concentrations ( P = .024) and the molar ratio of BK1-5/bradykinin ( P = .008) were significantly lower in the ACE inhibitor group compared with the no ACE inhibitor group. In addition, arterial bradykinin concentrations were significantly increased in smokers compared with nonsmokers ( P = .015), when we controlled for the ACE inhibitor group. There was no effect of smoking on ACE activity ( P = .597 overall). There was a significant inverse correlation between arterial bradykinin and mean arterial pressure ( r 2 = 0.2137, P = .010) and a significant correlation between arterial bradykinin and tissue-type plasminogen activator antigen concentrations ( r 2 = 0.174, P = .022) during CPB. Tissue-type plasminogen activator antigen was significantly higher in the ACE inhibitor group than in the no ACE inhibitor group (18.0 +/- 7.8 ng/mL versus 12.4 +/- 4.5 ng/mL, P = .016) but not in smokers compared with nonsmokers ( P = .451).
Preoperative ACE inhibitors and smoking potentiate the kinin response to CPB and may contribute to the hemodynamic and fibrinolytic response observed during CPB.
本研究检验了血管紧张素转换酶（ACE）抑制剂在体外循环（CPB）期间增强激肽释放酶-激肽系统激活的假说。
在31例服用ACE抑制剂的患者中，测定CPB对缓激肽及其代谢产物缓激肽1-5（BK1-5）浓度的影响。这些患者被随机分为两组，一组在冠状动脉搭桥手术前继续服用ACE抑制剂（ACE抑制剂组，N = 19），另一组在手术前48小时停用ACE抑制剂（无ACE抑制剂组，N = 12）。在CPB前、CPB 30分钟、CPB 60分钟、脱离CPB后及术后第1天采集动脉血和静脉血样本。
CPB期间，无ACE抑制剂组的动脉缓激肽浓度显著升高（P <.001，从22.4±24.1 fmol/mL升至86.2±98.7 fmol/mL），动脉（P <.001）和静脉（P =.016）BK1-5浓度也显著升高。与无ACE抑制剂组相比，ACE抑制剂组的动脉缓激肽浓度显著更高（P =.017），而BK1-5浓度（P =.024）和BK1-5/缓激肽的摩尔比（P =.008）显著更低。此外，在控制了ACE抑制剂组的情况下，吸烟者的动脉缓激肽浓度与非吸烟者相比显著升高（P =.015）。吸烟对ACE活性无影响（总体P =.597）。CPB期间，动脉缓激肽与平均动脉压之间存在显著负相关（r² = 0.2137，P =.010），动脉缓激肽与组织型纤溶酶原激活物抗原浓度之间存在显著正相关（r² = 0.174，P =.022）。ACE抑制剂组的组织型纤溶酶原激活物抗原显著高于无ACE抑制剂组（18.0±7.8 ng/mL对12.4±4.5 ng/mL，P =.016），但吸烟者与非吸烟者相比无显著差异（P =.451）。
术前ACE抑制剂和吸烟增强了CPB时的激肽反应，并可能导致CPB期间观察到的血流动力学和纤溶反应。
