Kortekaas Kirsten A, Lindeman Jan H N, Reinders Marlies E J, Palmen Meindert, Klautz Robert J M, de Groot Philip G, Roest Mark
Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, Netherlands.
Interact Cardiovasc Thorac Surg. 2013 Sep;17(3):523-30. doi: 10.1093/icvts/ivt243. Epub 2013 Jun 4.
Post-cardiac surgery vasoplegia is a common complication of cardiac surgery, characterized by profound loss of systemic vascular resistance. This results in severe hypotension, high cardiac output and metabolic acidosis reflecting inadequate tissue perfusion. The pathophysiological mechanisms underlying this syndrome remain unknown. We hypothesized that this vasoplegia reflects endothelial dysfunction, either as pre-existing condition or as a consequence of the surgical procedure.
To examine these mechanisms, six established and distinct markers of endothelial cell activation were measured pre- and perioperatively in patients undergoing mitral valve surgery. Arterial (radial artery) and myocardial venous blood samples (coronary sinus) were collected simultaneously over the reperfused heart at various time points during the first hour after reperfusion. Additional samples were collected at baseline (brachial vein) and 1 day post-reperfusion (radial artery). Post-cardiac surgery vasoplegia was defined as a mean arterial blood pressure of <60 mmHg, with a cardiac index of ≥2.2 l/min/m(2) treated with continuous intravenous administration of norepinephrine.
No myocardial release of endothelial cell activation markers was observed upon reperfusion in patients with vasoplegia (n = 15; mean age 71 years, 73% male). In contrast, in patients without vasoplegia (n = 24; mean age 64 years, 54% male), reperfusion was characterized by a myocardial release of three endothelial cell activation markers. Myocardial von Willebrand Factor propeptide, osteoprotegerin and interleukin-8 were increased 107% (P < 0.001), 106% (P = 0.02) and 116% (P = 0.009), respectively, compared with arterial levels upon reperfusion. Similar systemic levels of all markers were found upon reperfusion in both groups, except for 120% increased soluble P-selectin (sP-selectin) levels in vasoplegia patients (P = 0.03). Remarkably, postoperative vasoplegia was identified with baseline von Willebrand Factor propeptide levels with a cut-off value of 11.9 nM as well as with baseline sP-selectin levels with a cut-off value of 64.4 ng/ml.
Pre-existing endothelial cell activation, reflected by higher baseline von Willebrand Factor propeptide and sP-selectin levels, is a predisposing factor for post-cardiac surgery vasoplegia. The pre-existing endothelial cell activation may have resulted in desensibilization of endothelium in patients who develop vasoplegic syndrome, resulting in no myocardial release of endothelial cell activation markers upon reperfusion.
心脏手术后血管麻痹是心脏手术常见的并发症，其特征为全身血管阻力显著降低。这会导致严重低血压、高心输出量和代谢性酸中毒，反映出组织灌注不足。该综合征的病理生理机制尚不清楚。我们推测这种血管麻痹反映了内皮功能障碍，可能是术前就存在的状况，也可能是手术操作的结果。
为研究这些机制，对接受二尖瓣手术的患者在术前及围手术期测量了六种已确定且不同的内皮细胞活化标志物。在再灌注后第一小时的不同时间点，同时采集动脉（桡动脉）和心肌静脉血样本（冠状窦）。在基线（肱静脉）和再灌注后1天（桡动脉）采集额外样本。心脏手术后血管麻痹定义为平均动脉血压<60 mmHg，心脏指数≥2.2 l/min/m²，且需持续静脉输注去甲肾上腺素进行治疗。
血管麻痹患者（n = 15；平均年龄71岁，73%为男性）再灌注时未观察到心肌释放内皮细胞活化标志物。相比之下，无血管麻痹的患者（n = 24；平均年龄64岁，54%为男性），再灌注的特征是心肌释放三种内皮细胞活化标志物。与再灌注时的动脉水平相比，心肌血管性血友病因子前体、骨保护素和白细胞介素-8分别增加了107%（P < 0.001）、106%（P = 0.02）和116%（P = 0.009）。两组再灌注时所有标志物的全身水平相似，但血管麻痹患者可溶性P-选择素（sP-选择素）水平增加了120%（P = 0.03）。值得注意的是，术后血管麻痹可通过基线血管性血友病因子前体水平（临界值为11.9 nM）以及基线sP-选择素水平（临界值为64.4 ng/ml）来识别。
较高的基线血管性血友病因子前体和sP-选择素水平所反映的术前存在的内皮细胞活化，是心脏手术后血管麻痹的一个易感因素。术前存在的内皮细胞活化可能导致发生血管麻痹综合征患者的内皮脱敏，从而在再灌注时心肌未释放内皮细胞活化标志物。
