|Changes in microvascular reactivity after cardiopulmonary bypass in patients with poorly controlled versus controlled diabetes.|
|PMID: 22965996 Owner: NLM Status: MEDLINE|
|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).
METHODS AND 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.
|Jun Feng; Yuhong Liu; Louis M Chu; Arun K Singh; Nikola Dobrilovic; James G Fingleton; Richard T Clements; Cesario Bianchi; Frank W Sellke|
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|Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't|
|Title: Circulation Volume: 126 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2012 Sep|
|Created Date: 2012-09-11 Completed Date: 2012-11-27 Revised Date: 2013-09-16|
Medline Journal Info:
|Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States|
|Languages: eng Pagination: S73-80 Citation Subset: AIM; IM|
|Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.|
|APA/MLA Format Download EndNote Download BibTex|
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Adenosine Diphosphate / pharmacology
Arterioles / drug effects
Cardiopulmonary Bypass / adverse effects*
Coronary Artery Bypass*
Cyclic AMP-Dependent Protein Kinases / biosynthesis, genetics
Diabetes Mellitus, Type 2 / blood, complications*, drug therapy, physiopathology
Endothelium, Vascular / drug effects, metabolism
Enzyme Induction / drug effects
Gene Expression Regulation / drug effects
Hemoglobin A, Glycosylated / analysis
Hypoglycemic Agents / pharmacology, therapeutic use*
Inflammation / etiology, physiopathology
Microcirculation / physiology*
Muscle, Skeletal / blood supply*
Nitroprusside / pharmacology
Phosphorylation / drug effects
Protein Processing, Post-Translational / drug effects
Proto-Oncogene Proteins c-akt / biosynthesis, genetics
Substance P / pharmacology
Tyrosine / analogs & derivatives, analysis
Vasoconstriction / drug effects
Vasodilator Agents / pharmacology
|HL-46716/HL/NHLBI NIH HHS; HL-69024/HL/NHLBI NIH HHS; R00 HL093352/HL/NHLBI NIH HHS; R01 HL046716/HL/NHLBI NIH HHS; R01 HL069024/HL/NHLBI NIH HHS; R01 HL085647/HL/NHLBI NIH HHS; T32 HL094300/HL/NHLBI NIH HHS; T32-HL094300/HL/NHLBI NIH HHS|
|0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 33507-63-0/Substance P; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 58-64-0/Adenosine Diphosphate; 76898-47-0/15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; EC 188.8.131.52/Proto-Oncogene Proteins c-akt; EC 184.108.40.206/Cyclic AMP-Dependent Protein Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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