title: Changes in microvascular reactivity after cardiopulmonary bypass in patients with poorly controlled versus controlled diabetes.
abstract: BACKGROUND
  We investigated the effects of cardiopulmonary bypass (CPB) on peripheral arteriolar reactivity and associated signaling pathways in poorly controlled (UDM), controlled (CDM), and case-matched nondiabetic (ND) patients undergoing coronary artery bypass grafting (CABG).
  
  
  RESULTS
  Skeletal muscle arterioles were harvested before and after CPB from the UDM patients (hemoglobin A1c [HbA1c]=9.0 ± 0.3), the CDM patients (HbA1c=6.3 ± 0.15), and the ND patients (HbA1c=5.2 ± 0.1) undergoing CABG surgery (n=10/group). In vitro relaxation responses of precontracted arterioles to endothelium-dependent vasodilators adenosine 5'-diphosphate (ADP) and substance P and the endothelium-independent vasodilator sodium nitroprusside (SNP) were examined. The baseline responses to ADP, substance P, and SNP of arterioles from the UDM patients were decreased as compared with microvessels from the ND or CDM patients (P<0.05). The post-CPB relaxation responses to ADP and substance P were significantly decreased in all 3 groups compared with pre-CPB responses (P<0.05). However, these decreases were more pronounced in the UDM group (P<0.05). The post-CPB response to SNP was significantly decreased only in the UDM group, not in the other 2 groups compared with pre-CPB. The expression of protein kinase C (PKC)-α, PKC-β, protein oxidation, and nitrotyrosine in the skeletal muscle were significantly increased in the UDM group as compared with those of ND or CDM groups (P<0.05).
  
  
  CONCLUSIONS
  Poorly controlled diabetes results in impaired arteriolar function before and after CPB. These alterations are associated with the increased expression/activation of PKC-α and PKC-β and enhanced oxidative and nitrosative stress.
authors.affiliation: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.forename: Louis M
authors.initials: LM
authors.lastname: Chu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Singh
authors.forename: Nikola
authors.initials: N
authors.lastname: Dobrilovic
authors.forename: James G
authors.initials: JG
authors.lastname: Fingleton
authors.forename: Richard T
authors.initials: RT
authors.lastname: Clements
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001160:Arterioles / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D001026:Coronary Artery Bypass; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D004198:Disease Susceptibility; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009599:Nitroprusside / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics; D013373:Substance P / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D009599:Nitroprusside; D051057:Proto-Oncogene Proteins c-akt; D013373:Substance P; D014443:Tyrosine; D014665:Vasodilator Agents; C002744:3-nitrotyrosine