Jun Feng1, Kelsey Anderson1, Yuhong Liu1, Arun K Singh1, Afshin Ehsan1, Frank W Sellke2. 1. Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. 2. Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address: fsellke@lifespan.org.
Abstract
BACKGROUND: Diabetic patients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabetic patients undergoing CPB and cardiac surgery. METHODS: Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 μm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10-10 to 10-6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10-5M). RESULTS: The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabetic patients (P < 0.05). CONCLUSIONS: Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabetic patients undergoing cardiac surgery.
BACKGROUND:Diabeticpatients are associated with impaired peripheral microvascular function after cardiopulmonary bypass (CPB) and cardiac surgery. We hypothesized that upregulation of the inducible cyclooxygenase 2 (COX-2) contributes to altered microvascular reactivity of peripheral arterioles in diabeticpatients undergoing CPB and cardiac surgery. METHODS: Skeletal muscle samples of nondiabetic (ND) patients and patients with diabetes mellitus (DM; n = 8 per group) undergoing cardiac surgery were harvested before and after CPB. The protein expression/localization of COX-2 was assayed by Western blotting and immunohistochemistry. Peripheral arterioles were dissected from the harvested skeletal muscle tissue samples, the isolated arterioles (80-180 μm) were cannulated and pressurized, and changes in diameter were measured with video microscopy. In-vitro relaxation responses of precontracted arterioles were examined in the presence of the endothelium-dependent vasodilator bradykinin (10-10 to 10-6M) and in the presence or absence of the selective COX-2 inhibitor NS398 (10-5M). RESULTS: The post-CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CPB values in both the ND and DM groups (P < 0.05), whereas, this increase was higher in DM than that of ND (P < 0.05). In the DM arterioles, not the ND vessels, bradykinin-induced relaxation response was inhibited in the presence of the specific COX-2 inhibitor NS398 at baseline (P < 0.05). After CPB, bradykinin-induced relaxation response of the ND and DM arterioles was inhibited in the presence of the specific COX-2 inhibitor NS398, but this effect was more pronounced in the diabeticpatients (P < 0.05). CONCLUSIONS:Diabetes and CPB are associated with upregulation in COX-2 expression/activation in human peripheral microvasculature. This alteration may lead to altered peripheral microvascular reactivity in diabeticpatients undergoing cardiac surgery.
Authors: Jun Feng; Yuhong Liu; Kamal R Khabbaz; Robert Hagberg; Michael P Robich; Richard T Clements; Cesario Bianchi; Frank W Sellke Journal: Surgery Date: 2010-08-21 Impact factor: 3.982
Authors: Tamás Szerafin; Nóra Erdei; Tibor Fülöp; Eniko T Pasztor; István Edes; Akos Koller; Zsolt Bagi Journal: Circ Res Date: 2006-08-17 Impact factor: 17.367
Authors: Jun Feng; Yuhong Liu; Arun K Singh; Afshin Ehsan; Nicholas Sellke; Justin Liang; Frank W Sellke Journal: Surgery Date: 2016-11-09 Impact factor: 3.982
Authors: Jeffrey L Carson; Peter M Scholz; Anita Y Chen; Eric D Peterson; Jeffrey Gold; Stephen H Schneider Journal: J Am Coll Cardiol Date: 2002-08-07 Impact factor: 24.094
Authors: Yuhong Liu; An Xie; Arun K Singh; Afshin Ehsan; Gaurav Choudhary; Samuel Dudley; Frank W Sellke; Jun Feng Journal: J Am Heart Assoc Date: 2015-08-24 Impact factor: 5.501