Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and.

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Presentation transcript:

Pharmacologic relaxation of vein grafts is beneficial compared with pressure distention caused by upregulation of endothelial nitric oxide synthase and nitric oxide production Ada W.Y. Chung, PhD, Pooja Rauniyar, BSc, Honglin Luo, MD, PhD, York N. Hsiang, MD, Cornelis van Breemen, DVM, PhD, Elena B. Okon, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 132, Issue 4, Pages 925-932 (October 2006) DOI: 10.1016/j.jtcvs.2006.04.033 Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 A, An illustration showing the beneficial effects of nitric oxide (NO). In the vasculature NO is generated from L-arginine by both constitutive and inducible NO synthase (endothelial NO synthase (eNOS) in endothelium and inducible NO synthase (iNOS) in smooth muscle cells (SMCs)). NO exerts its protective effects by inducing smooth muscle relaxation; inhibiting SMC proliferation, migration, and synthesis of extracellular matrix (ECM); inhibiting platelet and leukocyte activation and adhesion; and stimulating endothelial cells proliferation. B, We hypothesize that the replacement of pressure distention with pharmacologic vasodilatators in vein grafting preserves endothelium and NO formation in the vein graft. The augmented bioavailability of NO would be beneficial to suppress vascular remodeling and vein graft occlusion. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Vasomotor properties. A, Contraction of porcine undistended and distended veins in response to α-adrenergic stimulation (50 μmol/L phenylephrine [PE]) and acetylcholine (Ach)–induced relaxation (10 nmol/L to 3 μmol/L) and contraction induced by depolarization (80 mmol/L K+). B, Length-tension curves of an undistended (dotted line) and a distended (solid line) porcine vein. Results are representative of 6 similar experiments. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 von Willebrand factor–stained cross-sections from undistended (control, A) and distended (B and C) veins indicating the presence of endothelial cells. Movat-stained sections showing the elastin fibril structure (black) in the undistended (D) and distended (E) veins. Scale bars = 0.05 mm. Representative images from 7 to 8 independent experiments are shown. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Regulation of gene transcription of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in vein grafts prepared by pressure distention and pharmacologic vasodilatators. A, Representative polymerase chain reaction results showing the mRNA transcription of eNOS, iNOS, and β-actin (loading control). B, Bar chart is the densitometric measurement of iNOS transcription. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 Regulation of nitric oxide synthase expression in vein grafts prepared by pressure distention and pharmacologic vasodilatators. Densitometric measurement of protein expressions of endothelial nitric oxide synthase (eNOS; A), inducible nitric oxide synthase (iNOS; B), and phospho-eNOS Ser1177 (C) is shown. Insets, representative immunoblots showing eNOS, iNOS phospho-eNOS Ser1177, and β-actin immunoreactivity. *P < .05. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 Enzymatic activities of nitric oxide synthase (NOS) and concentrations of nitrate and nitrite determined by using a colorimetric assay. Bar charts are the averaged NOS activities (upper panel) and the sum of concentrations of nitrate and nitrite (lower panel). *P < .05. The Journal of Thoracic and Cardiovascular Surgery 2006 132, 925-932DOI: (10.1016/j.jtcvs.2006.04.033) Copyright © 2006 The American Association for Thoracic Surgery Terms and Conditions