title: Decreased coronary microvascular reactivity after cardioplegic arrest in patients with uncontrolled diabetes mellitus.
abstract: BACKGROUND
  We investigated the effects of cardioplegic arrest and reperfusion on coronary arteriolar responses to endothelium-dependent and -independent vasodilators and associated signaling pathways in uncontrolled diabetic, well controlled diabetic, and case-matched nondiabetic patients undergoing coronary artery bypass graft surgery.
  
  
  METHODS
  Coronary arterioles from harvested right atrial tissues were dissected pre- and post-cardioplegic arrest and reperfusion from uncontrolled diabetic (n = 10; hemoglobin A1c = 9.3 ± 0.3), well controlled diabetic (n = 10; hemoglobin A1c = 6.2 ± 0.2), and nondiabetic patients (n = 10; hemoglobin A1c = 5.1 ± 0.1) undergoing coronary artery bypass graft surgery.
  
  
  RESULTS
  The baseline microvascular response to adenosine 5'-diphosphate, substance P, and sodium nitroprusside of arterioles from uncontrolled diabetic patients were decreased compared to the respective response from nondiabetic or well controlled diabetic patients (P < .05). The vasodilatory responses to adenosine 5'-diphosphate and substance P after cardioplegic arrest and reperfusion were significantly decreased in all 3 groups compared to pre-cardioplegic arrest and reperfusion responses (P < .05). However, these decreases were more pronounced in the uncontrolled diabetic group (P < .05). The expression of protein kinase C-α, protein kinase C-β, and protein oxidation in atrial tissues was significantly increased in the uncontrolled diabetic group compared to the nondiabetic or controlled diabetes groups.
  
  
  CONCLUSIONS
  Uncontrolled diabetes is associated with endothelium-dependent and -independent vascular dysfunction of coronary arterioles. In addition, uncontrolled diabetes worsens the recovery of coronary arteriolar function after cardioplegic arrest and reperfusion. These alterations are associated with an increased expression/activation of protein kinase C-α and protein kinase C-β and enhanced oxidative stress.
authors: Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors: Jun
authors: J
authors: Feng
authors: Louis M
authors: LM
authors: Chu
authors: Nikola
authors: N
authors: Dobrilovic
authors: Yuhong
authors: Y
authors: Liu
authors: Arun K
authors: AK
authors: Singh
authors: Frank W
authors: FW
authors: Sellke
mesh_terms: D000368:Aged; D001160:Arterioles / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism; D014664:Vasodilation
chemical_list: D015415:Biomarkers; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha