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Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation

Lundgren, Jakob LU ; Sandqvist, Anna ; Hedeland, Mikael ; Bondesson, Ulf ; Wikström, Gerhard and Rådegran, Göran LU (2018) In Scandinavian Cardiovascular Journal 52(4). p.196-204
Abstract

Objective. Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. Design. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the... (More)

Objective. Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. Design. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. Results. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Conclusions. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered “normal” after HT.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ADMA, heart failure, heart transplantation, L-Arginine, Nitric Oxide, right heart catheterization
in
Scandinavian Cardiovascular Journal
volume
52
issue
4
pages
196 - 204
publisher
Taylor & Francis
external identifiers
  • pmid:29648475
  • scopus:85045237387
ISSN
1401-7431
DOI
10.1080/14017431.2018.1459823
language
English
LU publication?
yes
id
52f22f10-d934-40bc-88da-fd9598c7adfb
date added to LUP
2018-04-26 16:04:55
date last changed
2020-01-13 00:40:12
@article{52f22f10-d934-40bc-88da-fd9598c7adfb,
  abstract     = {<p>Objective. Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. Design. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. Results. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Conclusions. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered “normal” after HT.</p>},
  author       = {Lundgren, Jakob and Sandqvist, Anna and Hedeland, Mikael and Bondesson, Ulf and Wikström, Gerhard and Rådegran, Göran},
  issn         = {1401-7431},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {196--204},
  publisher    = {Taylor & Francis},
  series       = {Scandinavian Cardiovascular Journal},
  title        = {Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation},
  url          = {http://dx.doi.org/10.1080/14017431.2018.1459823},
  doi          = {10.1080/14017431.2018.1459823},
  volume       = {52},
  year         = {2018},
}