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21 June 2011

Human internal thoracic artery grafts exhibit severe morphological and functional damage and spasmic vasomotion due to oxidative stress

Levente KissABCDEFG, Rita BenkoBCD, Endre KovacsB, Tamas SzerafinB, Katalin ModisBCD, Csaba SzaboAG, Zsombor LaczaACDEG

DOI: 10.12659/MSM.881853

Med Sci Monit 2011; 17(7): CR411-416

Abstract

Background: The internal thoracic artery (ITA) is the first choice for myocardial revascularization, but atherosclerotic lesions and perioperative vasospasm may still limit its functionality. Oxidative stress via the peroxynitrite – poly-(ADP-ribose) polymerase (PARP) cascade plays an important role in the pathogenesis of impaired vascular tone via endothelial injury. We aimed to investigate and describe the histology, PARP activation and functionality of ITA grafts and to assess the possible beneficial effect of PARP-inhibition.
Material/Methods: ITA specimens from 47 patients (26 men, mean age 66.2±1.7 years) who underwent coronary bypass surgery were processed for histological and immunohistochemical studies for oxidative stress and PARP activation, and were functionally tested with acetylcholine (ACh) and sodium nitroprusside (SNP) with or without PARP inhibition.
Results: The sections showed atherosclerotic alterations and oxidative and nitrosative stress were evidenced by positive 3-nitrotyrosine, 4-hydroxynonenal and PAR stainings. Functionally, 88.1% reacted to K-Krebs, 68.7% exhibited contraction after 1 µM phenylephrine, 29.9% exhibited relaxation to 30 µM Ach, and all precontracted segments relaxed to 30 µM SNP. High amplitude vasomotion was observed in 47.8% of the segments, which could be abolished by the application of 10 µM SNP.Incubation of the preparations with PJ34 did not improve endothelium-dependent vasodilation.
Conclusions: ITA grafts are severely damaged both morphologically and functionally in patients undergoing coronary artery bypass surgery, but PARP inhibition cannot improve their functional characteristics. The topical use of SNP to the ITA during the operation may improve vascular functions by dilating the vessels and eliminating the eventual spasmic vasomotion.

Keywords: Poly(ADP-ribose) Polymerases - metabolism, Peroxynitrous Acid - metabolism, Oxidative Stress - physiology, Mammary Arteries - surgery, Histological Techniques, Analysis of Variance, Aldehydes, Spasm - physiopathology, Tyrosine - analogs & derivatives, Vascular Grafting - adverse effects, Vasomotor System - physiopathology

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