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Pulmonary vasoreactivity and vasoactive mediators in children with pulmonary hypertension
M Gorenflo1, M Bettendorf, K Brockmeier
1Dept. Ped. Cardiology, University Children's Hospital, INF 153, 69120 Heidelberg, Germany. Matthias_Gorenflo@med.uni-heidelberg.de
Insights
Oxygen and nitric oxide (NO) help identify reactive pulmonary vasculature in children with pulmonary hypertension. However, cyclic guanosine monophosphate (cGMP) levels increase with NO regardless of hemodynamic response.
Area of Science:
- Pediatric Cardiology
- Pulmonary Hypertension Research
- Vasoactive Mediator Studies
Background:
- Pulmonary hypertension (PH) in children requires understanding vasodilator responses.
- The correlation between hemodynamic changes and vasoactive mediator levels during acute testing is unclear.
Purpose of the Study:
- To assess the effects of oxygen, nitric oxide (NO), and prostanoids on pulmonary hemodynamics in pediatric PH.
- To investigate the relationship between hemodynamic responses and plasma levels of endothelin-1 (ET-1), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP).
Main Methods:
- Retrospective analysis of 14 children with PH (median age 4 years).
- Hemodynamic parameters (pulmonary/systemic pressure and resistance ratios) measured at baseline, during oxygen, and NO inhalation.
- Plasma levels of ET-1, cGMP, and cAMP analyzed in conjunction with vasodilator challenges and prostanoid administration (prostacyclin, iloprost).
Main Results:
- Pulmonary vasodilation observed in 2/14 patients with oxygen and 4/14 with NO.
- NO inhalation increased cGMP levels significantly (10.9 to 21.3 nM/L) irrespective of hemodynamic response.
- No association found between increased FiO2 and changes in ET-1, cGMP, or cAMP levels.
Conclusions:
- Oxygen and NO are valuable in identifying reactive pulmonary vasculature in pediatric PH.
- Elevated cGMP levels during NO inhalation do not correlate with individual hemodynamic responses.
- Further research is needed to fully elucidate the role of vasoactive mediators in PH management.
Abstract:
We assessed the effect of oxygen, nitric oxide (NO) and prostanoids (prostacyclin and iloprost) on pulmonary hemodynamics and plasma levels of vasoactive mediators in children with pulmonary hypertension (PH). It is not known whether the hemodynamic response during acute vasodilator testing correlates with changes in plasma levels of endothelin-1 (ET-1), cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP). In this retrospective analysis 14 children at a median age of 4 years and 3 months [1.8 months-13 years] with a median pulmonary resistance to perfusion of 10.1 [2.1-37.7]. Wood-Units x m2 were studied. Diagnoses included PH due to congenital heart disease (AVSD n = 5; VSD n = 2; PDA n = 1) or unknown causes (n = 6). The ratios of pulmonary/systemic pressure (Pp/Ps) and of pulmonary/systemic resistance (Rp/Rs) were recorded a) at baseline, b) during oxygen (FiO2 = 1.0) and c) while on NO (80 ppm max., at FiO2 = 0.23). In 13 out of 14 children prostanoids were given additionally: 7 received prostacyclin (i.v.) and 6 were given iloprost which was nebulized. ET-1, cGMP and cAMP were measured in blood samples taken from the pulmonary vein or left ventricle at baseline, during increased FiO2, during NO inhalation and while on prostanoids. Pulmonary vasodilation in response to oxygen was found in 2/14 patients. 4/14 patients responded to NO and 2/7 to prostacyclin i.v. Increased FiO2 was not associated with changes in plasma concentrations of ET-1, cGMP or cAMP. NO inhalation was followed by an increase in cGMP levels from 10.9 [5.5-55.4] nM/L to 21.3 [6.4-76.3] nM/L independent from the individual hemodynamic response. Oxygen and NO identify most children with reactive pulmonary vasculature. cGMP plasma levels do not correlate with individual hemodynamic responses to NO.