Khan Tanveer A, Bianchi Cesario, Ruel Marc, Feng Jun, Sellke Frank W
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
J Thorac Cardiovasc Surg. 2007 Mar;133(3):682-8. doi: 10.1016/j.jtcvs.2006.09.025.
Mesenteric ischemia is a rare but potentially devastating complication of cardiac surgery with cardiopulmonary bypass. We hypothesized that alterations in mitogen-activated protein kinase pathways contribute to mesenteric microcirculatory dysfunction resulting from cardiopulmonary bypass.
Pigs underwent cardiopulmonary bypass (n = 6) for 90 minutes and postbypass reperfusion for 180 minutes. Sham operations (n = 6) were performed on controls. Mesenteric tissue was harvested before bypass and after postbypass reperfusion. Microvascular contraction to phenylephrine and vasopressin was examined by videomicroscopy. Contractile responses with inhibition of the extracellular regulated kinase 1/2 (ERK1/2) pathway by PD98059 (30 micromol/L) and p38 kinase inhibition by SB203580 (1 micromol/L) also were determined. Activated forms of ERK1/2 and p38 kinase were measured by Western blot. ERK1/2 and p38 activity were localized in mesenteric tissue by immunohistochemistry.
Contractile responses to phenylephrine were increased at 180 minutes after cardiopulmonary bypass (+49.7% +/- 5.5%, P < .01), whereas contraction to vasopressin was unchanged. ERK1/2 pathway inhibition reduced contractile responses to phenylephrine at baseline and 180 minutes after bypass (both P < .01) but had no effect on contraction to vasopressin. p38 Kinase inhibition decreased the contractile responses to vasopressin at baseline and 180 minutes after bypass (both P < .01) but did not alter the contractile response to phenylephrine. Activated ERK1/2 levels were increased by more than 40% at 180 minutes after bypass (P < .01). Protein levels of activated p38 kinase were not changed. The increased ERK1/2 activity was associated with mesenteric arterioles by immunohistochemistry.
A differential pattern of mesenteric vasomotor regulation exists after cardiopulmonary bypass that may contribute to the risk of mesenteric ischemia after cardiac surgery.
肠系膜缺血是心脏体外循环手术中一种罕见但可能具有毁灭性的并发症。我们推测丝裂原活化蛋白激酶途径的改变会导致体外循环引起的肠系膜微循环功能障碍。
猪接受90分钟的体外循环（n = 6）及体外循环后180分钟的再灌注。对照组进行假手术（n = 6）。在体外循环前及体外循环后再灌注后采集肠系膜组织。通过视频显微镜检查肠系膜组织对去氧肾上腺素和血管加压素的微血管收缩情况。还测定了用PD98059（30 μmol/L）抑制细胞外调节激酶1/2（ERK1/2）途径和用SB203580（1 μmol/L）抑制p38激酶后对血管收缩反应的影响。通过蛋白质印迹法检测ERK1/2和p38激酶的活化形式。通过免疫组织化学法确定ERK1/2和p38活性在肠系膜组织中的定位。
体外循环后180分钟时，肠系膜组织对去氧肾上腺素的收缩反应增强（+49.7%±5.5%，P <.01），而对血管加压素的收缩反应未改变。抑制ERK1/2途径可降低基线时及体外循环后180分钟时对去氧肾上腺素的收缩反应（均P <.01），但对血管加压素的收缩反应无影响。抑制p38激酶可降低基线时及体外循环后180分钟时对血管加压素的收缩反应（均P <.01），但不改变对去氧肾上腺素的收缩反应。体外循环后180分钟时，活化的ERK1/2水平升高超过40%（P <.01）。活化的p38激酶蛋白水平未改变。免疫组织化学显示，ERK1/2活性增加与肠系膜小动脉有关。
体外循环后存在肠系膜血管舒缩调节的差异模式，这可能导致心脏手术后发生肠系膜缺血的风险增加。
