Pulmonary vasoreactivity and vasoactive mediators in children with pulmonary hypertension

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.

Combined effect of aerosolized iloprost and oxygen on assessment of pulmonary vasoreactivity in children with pulmonary hypertension

“…Their mean age was 5.06±3.88; the median age was 4.5 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) years. The demographical and clinical properties of the patients are presented in Table 1.…”

“…As far as patients with primary pulmonary hypertension are concerned, response to the pulmonary vasoreactivity test is a significant marker for survival and can identify patients who will benefit from chronic medical treatment. Therefore, the identification of pulmonary vascular reactivity is of critical importance in the management of patients with PAH (3)(4)(5).…”

Pulmonary vasoreactivity testing with inhaled iloprost in children with pulmonary hypertension related to congenital heart disease

“…prostacyclin can be used for this purpose, [4,11] but oxygen and iNO are most commonly used in children. [2,12] In patients with CHD, pure oxygen is initially used for pulmonary vasoreactivity testing because it is readily available and easy to administer. Although oxygen has been widely used to assess pulmonary vasoreactivity in children with CHD, dissolved oxygen must be taken into account in order to avoid false positive results.…”

“…However, there are only a limited number of relevant studies that have focused on the use of this agent in pediatric patients. [4,7,12,17] Iloprost is a selective, short-acting vasodilator and a prostacyclin analogue with a stable structure. It has a half-life of 20-30 minutes and is readily available in many countries.…”

“…[12,27] In a study that featured both pediatric and adult patients, i.v. adenosine and inhaled iloprost were used for vasoreactivity testing in patients with idiopathic pulmonary hypertension.…”