Transpulmonary vascular gradients of nitric oxide pathway metabolites and asymmetrical dimethyl-<smcaps>L</smcaps>-arginine in the flow – or pressure-overloaded pulmonary vasculature

cc2154 CCJ Meeting abstract Transpulmonary vascular gradients of nitric oxide pathway metabolites and asymmetrical dimethyl-<smcaps>L</smcaps>-arginine in the flow – or pressure-overloaded pulmonary vasculature Kreuder J Zimmermann R Tsikas D Michel-Behnke I Schranz D

Department of Paediatric Cardiology, Justus-Liebig-University, Medical School, Hannover, Germany

Department of Clinical Pharmacology, Medical School, Hannover, Germany

Critical Care 4th International Symposium on the Pathophysiology of Cardiopulmonary Bypass: Endothelial Damage. Abstracts Meeting abstracts 4th International Symposium on the Pathophysiology of Cardiopulmonary Bypass: Endothelial Damage. Abstracts Munich, Germany

29 November 2002

1364-8535 2003 7 Suppl 1 8 10.1186/cc2154 18 2 2003

Objectives

Alterations in pulmonary vascular nitric oxide (NO) production have been implicated in the regulation of pulmonary vascular tone and the development of pulmonary hypertension (PH). Asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of NO synthesis, has been suggested to counteract endothelial NO production.

Methods

Transpulmonary gradients of nitrite (NO₂), nitrate (NO₃) and ADMA were determined in patients with increased pulmonary flow (Qp) before (1) and after (2) interventional closure of atrial septal defect (ASD), and in patients with increased pulmonary vascular resistance (Rp) (3). Twenty patients with ASD: median age 6.1 years (range 3.5–17.1 years), median Qp/Qs 2.1, Rp/Rs < 0.12. Twenty patients with PH: median age 8.1 years (range 1.2–13.5 years), median Rp/Rs 1.1 (range 0.36–1.79). NO₂, NO₃(chromatography mass spectrometry) and ADMA (high-performance liquid chromatography) were measured in plasma samples from the main pulmonary artery (PA) and femoral artery (SA).

Results

(1) In ASD patients, NO₂showed a significant gradient with a median SA : PA ratio of 1.34 (P < 0.01), but this was not so for ADMA (1.05) or NO₃(1.01). (2) After closure, SA : PA ratio of NO₂decreased to 0.89 (P < 0.05), indicating a switch from NO₂production to NO₂consumption, whereas ADMA (1.00) and NO₃(0.99) remained unchanged. (3) In PH, significant transpulmonary gradients were observed for ADMA (1.11; P < 0.05) and NO₃(1.03), but not for NO₂(0.84). Median levels of ADMA in SA (4.08 μmol/l) were higher than those in ASD before (3.67 μmol/l) and after (3.55 μmol/l) closure (P < 0.05).

Conclusions

Analysis of transpulmonary metabolite gradients may provide significant insights into the vascular NO pathway in the overloaded pulmonary circulation. Reversible augmentation of intra-pulmonary vascular NO synthesis in ASD patients contrasts with the inappropriate NO synthesis in patients with increased Rp, to which intrapulmonary ADMA formation may significantly contribute.