Endothelial dysfunction in the early postoperative period after major colon cancer surgery.

Sara Ekeløf; Mikkel Hjordt Larsen; Anne Marie Voigt Schou-Pedersen; Jens Lykkesfeldt; Jacob Rosenberg; Ismail Gögenur

doi:10.1093/bja/aew410

Endothelial dysfunction in the early postoperative period after major colon cancer surgery.

Sara Ekeløf, Mikkel Hjordt Larsen, Anne Marie Voigt Schou-Pedersen, Jens Lykkesfeldt, Jacob Rosenberg, Ismail Gögenur

19 Citationer (Scopus)

Abstract

Background. Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. Methods. Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. Results. Preoperative RHI was 1.86 (1.64-2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. Conclusions. RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine-nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registration. NCT02344771.

Originalsprog	Engelsk
Tidsskrift	British Journal of Anaesthesia
Vol/bind	118
Udgave nummer	2
Sider (fra-til)	200-206
ISSN	0007-0912
DOI	https://doi.org/10.1093/bja/aew410
Status	Udgivet - 1 feb. 2017

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10.1093/bja/aew410

http://bjanaesthesia.org/article/S0007091217300806/pdf

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@article{dc458c608320444db6b7019bcdb52cfc,

title = "Endothelial dysfunction in the early postoperative period after major colon cancer surgery.",

abstract = "Background. Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. Methods. Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. Results. Preoperative RHI was 1.86 (1.64-2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. Conclusions. RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine-nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registration. NCT02344771.",

author = "Sara Ekel{\o}f and Larsen, {Mikkel Hjordt} and Schou-Pedersen, {Anne Marie Voigt} and Jens Lykkesfeldt and Jacob Rosenberg and Ismail G{\"o}genur",

year = "2017",

month = feb,

day = "1",

doi = "10.1093/bja/aew410",

language = "English",

volume = "118",

pages = "200--206",

journal = "British Journal of Anaesthesia",

issn = "0007-0912",

publisher = "Oxford University Press",

number = "2",

}

TY - JOUR

T1 - Endothelial dysfunction in the early postoperative period after major colon cancer surgery.

AU - Ekeløf, Sara

AU - Larsen, Mikkel Hjordt

AU - Schou-Pedersen, Anne Marie Voigt

AU - Lykkesfeldt, Jens

AU - Rosenberg, Jacob

AU - Gögenur, Ismail

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background. Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. Methods. Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. Results. Preoperative RHI was 1.86 (1.64-2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. Conclusions. RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine-nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registration. NCT02344771.

AB - Background. Evidence suggests that endothelial dysfunction in the early postoperative period promotes myocardial injury after non-cardiac surgery. The aim of this study was to investigate the impact of colon cancer surgery on endothelial function and the association with the l-arginine-nitric oxide pathway postoperatively. Methods. Patients undergoing elective colon cancer surgery (n = 31) were included in this prospective observational cohort study. Endothelial function, as measured using the reactive hyperaemia index (RHI), was assessed non-invasively using digital pulse tonometry. RHI and plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), dihydrobiopterin and biopterin metabolites, tetrahydrobiopterin (BH4) and total biopterin were measured before surgery, at four h after surgery and at postoperative day one and two. Cardiac troponin I was measured before surgery and once daily on postoperative days one to four. Results. Preoperative RHI was 1.86 (1.64-2.11) and decreased significantly during the observation period (linear mixed effects model of serial measurements, P = 0.015). Both L-arginine (P < 0.001) and ADMA (P = 0.024) decreased during the postoperative period. All biopterin metabolites were significantly decreased after surgery. A significant positive correlation was found between logAUC(l-arginine/ADMA) and logAUC(RHI) (P = 0.015) and between logAUC(L-arginine/ADMA) and logAUC(BH4) (P = 0.015). None of the patients had cardiac troponin I elevations. Conclusions. RHI was attenuated in the first days after colon cancer surgery indicating acute endothelial dysfunction. Endothelial dysfunction correlated with disturbances in the L-arginine-nitric oxide pathway. Our findings provide a rationale for investigating the hypothesized association between acute endothelial dysfunction and cardiovascular complications after non-cardiac surgery. Clinical trial registration. NCT02344771.

U2 - 10.1093/bja/aew410

DO - 10.1093/bja/aew410

M3 - Journal article

C2 - 28100523

SN - 0007-0912

VL - 118

SP - 200

EP - 206

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

IS - 2

ER -

Endothelial dysfunction in the early postoperative period after major colon cancer surgery.

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