Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.
Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI.
Surgery. 2020 Feb;167(2):493-498. doi: 10.1016/j.surg.2019.07.018. Epub 2019 Sep 4.
Cardiac surgery and cardiopulmonary bypass are associated with alterations in blood pressure in the perioperative period, which, if uncontrolled, can result in end organ damage or dysfunction. Microvessels, significant contributors to blood pressure, both in the myocardium and peripheral skeletal muscle, have diminished responsiveness to major mediators of vascular tone, including thromboxane and serotonin after cardiopulmonary bypass. Responsiveness of these vessels to β-adrenergic stimulation, a major mediator of vascular tone, has not yet been studied. In this report, we investigated the role of β-adrenergic receptors in vascular tone regulation in human skeletal muscle microvessels before and after β-adrenergic stimulation.
Skeletal muscle microvessels were isolated from patients undergoing cardiac surgery before and after cardiopulmonary bypass. Vessels were exposed in an ex vivo model to the β-adrenergic agonist isoproterenol, or the direct adenylyl cyclase activator, forskolin, and the selective β-receptor antagonist ICI18.551 hydrochloride plus isoproterenol. Immunofluorescence of β receptors and Western blotting were also performed.
Microvessels showed diminished responsiveness to isoproterenol (10 to 10M) after cardiopulmonary bypass (n = 8/group, P = .01). Pretreatment with the selective β-2 blocker ICI18.551 (10M) prevented isoproterenol-induced microvascular relaxation (P = .001). Forskolin-induced relaxation response was also significantly diminished after cardiopulmonary bypass (n = 4/group, P < .05 versus before cardiopulmonary bypass). No significant changes in the total protein expression of β-1, β-2, and β-3 receptors were detected by western blotting or immunofluorescence.
Microvessels isolated from human skeletal muscle show diminished responsiveness to isoproterenol and its downstream activator forskolin after cardiopulmonary bypass, suggesting there is an alteration in β-adrenergic receptor responsive in adenylate cyclase. The relaxation response to isoproterenol was via activation β-2 receptors without changes in β-adrenergic receptor abundance.
心脏手术和心肺旁路术会导致围手术期血压发生变化，如果血压得不到控制，可能会导致终末器官损伤或功能障碍。微血管是心肌和外周骨骼肌血压的重要贡献者，在心肺旁路术后，对血管紧张素的主要介质，包括血栓素和 5-羟色胺的反应性降低。这些血管对β-肾上腺素能刺激的反应性，作为血管紧张素的主要介质，尚未得到研究。在本报告中，我们研究了β-肾上腺素能受体在心肺旁路术前和术后调节人骨骼肌微血管紧张度中的作用。
在心肺旁路术前和术后，从接受心脏手术的患者中分离出骨骼肌微血管。在体外模型中，将血管暴露于β-肾上腺素能激动剂异丙肾上腺素或直接激活腺苷酸环化酶的 forskolin，以及选择性β-受体拮抗剂 ICI18.551 盐酸盐加异丙肾上腺素。还进行了β受体免疫荧光和 Western 印迹。
心肺旁路术后，微血管对异丙肾上腺素（10 至 10M）的反应性降低（每组 n=8，P=0.01）。用选择性β-2 阻断剂 ICI18.551（10M）预处理可防止异丙肾上腺素诱导的微血管松弛（P=0.001）。心肺旁路术后，福斯柯林诱导的松弛反应也显著降低（每组 n=4，P<0.05 与心肺旁路术前）。Western 印迹或免疫荧光检测未发现β-1、β-2 和β-3 受体的总蛋白表达有显著变化。
从人骨骼肌中分离出来的微血管在心肺旁路术后对异丙肾上腺素及其下游激活剂福斯柯林的反应性降低，提示β-肾上腺素能受体在腺苷酸环化酶中的反应性发生改变。异丙肾上腺素的松弛反应是通过激活β-2 受体而不是通过β-肾上腺素能受体丰度的变化来实现的。
