title: Preoperative unstable angina causes venous adaptation to surgical graft injury.
abstract: Ischemic preconditioning may provide a systemic organ protection, evident as the phenomenon known as remote preconditioning. Unstable angina may be a clinical analogue to ischemic preconditioning. Vein graft harvesting induces inflammation of the graft wall. We hypothesized that preoperative unstable angina preconditions vein grafts and reduces the inflammatory response to graft harvesting. Consecutive patients with stable or unstable angina undergoing open heart surgery (n = 12 in each group) were studied. Saphenous vein biopsies were collected at the start of graft harvesting, and when the last proximal anastomosis to the aorta was finished (average 112 minutes later). Gene expression of inflammatory mediators (tumor necrosis factor alpha, interleukin-1beta (IL-1beta), E-selectin (CD62E), intercellular leukocyte adhesion molecule 1, inducible nitric oxide synthase, endothelin-1) increased after surgical handling (semiquantitative RT-PCR). In vein grafts from unstable patients the increase was attenuated for Il-1beta (p < 0.004) and CD62E (p < 0.001). In stable patients the protein expression of IkappaBalpha and heat shock protein72 was reduced by surgical handling (p < 0.04), but was not influenced in unstable patients (immunoblotting). In vitro relaxation to acetylcholine was enhanced, and contractions to phenylephrine and endothelin-1 were attenuated in veins rings from unstable patients (p < 0.003). In conclusion, surgical handling of vein grafts induces inflammation of the vessel wall. This response was reduced in grafts from patients with unstable angina, indicating a possible systemic preconditioning-like effect of acute coronary syndromes.
authors.affiliation: Institute of Basic Medical Science, Dept. of Physiology University of Oslo, 1103 Blindern, 0317, Oslo, Norway. guro.valen@medisin.uio.no
authors.forename: Guro
authors.initials: G
authors.lastname: Valen
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hinokiyama
authors.forename: Jenny
authors.initials: J
authors.lastname: Vedin
authors.forename: Jarle
authors.initials: J
authors.lastname: Vaage
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000503:physiopathology*; D000789:Angina, Unstable / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D019040:E-Selectin / Q000096:biosynthesis; D019332:Endothelin-1 / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D053583:Interleukin-1beta / Q000096:biosynthesis; D019194:Ischemic Preconditioning; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012501:Saphenous Vein / Q000473:pathology* / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019332:Endothelin-1; D050884:HSP72 Heat-Shock Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase