Stamler A, Wang H, Weintraub R M, Hariawala M D, Fink M P, Johnson R G
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
J Surg Res. 1998 Feb 1;74(2):165-72. doi: 10.1006/jsre.1997.5238.
The lung injury regularly associated with cardiopulmonary bypass (CPB) may be linked to gut mucosal dysfunction occurring as the result of mucosal ischemia associated with nonpulsatile CPB. To examine this possibility we postulated that the weak-beta 2 agonist dopexamine would improve gut mucosal blood flow, thereby decreasing gut and lung dysfunction seen after CPB in sheep.
Anesthetized sheep had 2 h of hypothermic (24 degrees C), nonpulsatile CPB, and 60 min of cold, blood cardioplegic arrest. After warming they were separated from CPB for 2 h of reperfusion. Before and during CPB, dopexamine at 2 micrograms/kg/min (n = 7) or saline (n = 7) were infused in a blinded fashion. Hemodynamic parameters were measured. Biatrial thromboxane B2 levels were obtained. Mesenteric arterial flow (QSMA), mucosal flow (Qmuc), FD-4 clearance (ClFD-4), and tonometric pHi were measured at baseline and 30-min intervals on, and after, CPB.
After CPB, similar reductions in MAP were seen (P < 0.05 vs. baseline), but heart rate and the mean pulmonary vascular resistance were significantly increased in the dopexamine animals (P < 0.05 vs. placebo). Plasma thromboxane was similarly increased in both groups after CPB (P < 0.05 vs. baseline), returning to baseline 1 h after CPB. The Qsma was not altered, but a statistically significant decrease in Qmuc and pHi occurred in both groups (P < 0.05 vs. baseline). In both groups FD-4 clearance reached a peak 30 min after CPB (P < 0.05; dopexamine vs. baseline). After 2 h neither of these changes returned to control levels.
In this ovine model, gut mucosal ischemia and increased permeability occur with hypothermic CPB, but dopexamine administration during CPB, compared to placebo, neither ameliorates these intestinal derangements nor reduces post-CPB lung pathophysiology.
与体外循环（CPB）经常相关的肺损伤可能与因非搏动性CPB相关的黏膜缺血导致的肠黏膜功能障碍有关。为了检验这种可能性，我们推测弱β2激动剂多培沙明会改善肠黏膜血流，从而减少绵羊CPB后出现的肠和肺功能障碍。
麻醉的绵羊进行2小时低温（24摄氏度）、非搏动性CPB以及60分钟冷血心脏停搏。复温后，将它们与CPB分离进行2小时再灌注。在CPB前和CPB期间，以盲法输注2微克/千克/分钟的多培沙明（n = 7）或生理盐水（n = 7）。测量血流动力学参数。获取双心房血栓素B2水平。在基线以及CPB期间和CPB后每隔30分钟测量肠系膜动脉血流（QSMA）、黏膜血流（Qmuc）、FD-4清除率（ClFD-4）和张力测定法测量的pHi。
CPB后，两组平均动脉压（MAP）均有类似程度的降低（与基线相比，P < 0.05），但多培沙明组动物的心率和平均肺血管阻力显著增加（与安慰剂组相比，P < 0.05）。CPB后两组血浆血栓素均有类似程度的升高（与基线相比，P < 0.05），在CPB后1小时恢复至基线水平。QSMA未改变，但两组的Qmuc和pHi均出现统计学上显著的降低（与基线相比，P < 0.05）。两组的FD-4清除率在CPB后30分钟均达到峰值（P < 0.05；多培沙明组与基线相比）。2小时后，这些变化均未恢复至对照水平。
在这个绵羊模型中，低温CPB会导致肠黏膜缺血和通透性增加，但与安慰剂相比，CPB期间给予多培沙明既不能改善这些肠道紊乱，也不能减轻CPB后肺部的病理生理变化。
