Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension

Jaegere, A. P. M. C. De; Anker, J. N. van den

doi:10.1183/09031936.98.12040932

Cited by 39 publications

(35 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous reports of neonates treated with iPGI 2 have shown significant improvement in oxygenation without demonstrating an improvement in RVSP. [1][2][3][4][5] Hence, it is likely that increased surfactant production resulting from stimulation of ATII by iPGI 2 was in part responsible for improvement in oxygenation in this ELBW infant with significant lung disease. We acknowledge that several of our interventions are known to improve hypoxemia.…”

Section: Discussionmentioning

confidence: 96%

“…12 iPGI 2 acts locally, avoiding the systemic effects of hypotension and rebound hypertension seen with intravenous use, and has been successfully used in infants to treat PPHN. [1][2][3][4][5] Inhaled PGI 2 has been shown in rat alveolar type II cells (ATII) to enhance surfactant formation when lungs are stretched. Under normal conditions, surfactant production increases when ATII undergo stretch.…”

Section: Discussionmentioning

confidence: 99%

“…Inhaled nitric oxide (iNO) is effective for treatment of PPHN in full-term infants by decreasing pulmonary vascular resistance, thereby decreasing right-to-left shunting and alleviating hypoxemia. Several case reports have similarly shown that inhaled prostacyclin (iPGI 2 ) is effective through pulmonary vasodilation in full-term and preterm infants with PPHN. [1][2][3][4][5] Hypoxemia in our patient was refractory to iNO but improved with iPGI 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Several case reports have similarly shown that inhaled prostacyclin (iPGI 2 ) is effective through pulmonary vasodilation in full-term and preterm infants with PPHN. [1][2][3][4][5] Hypoxemia in our patient was refractory to iNO but improved with iPGI 2 . We propose that this response may be due to a physiological mechanism different from pulmonary vasodilatation.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Can inhaled prostacyclin stimulate surfactant in ELBW infants?

et al. 2007

View full text Add to dashboard Cite

Respiratory distress syndrome (RDS) causes significant hypoxia in extremely low birth weight (ELBW) infants. We report an ELBW infant with RDS and pulmonary hypertension whose hypoxia did not respond to inhaled nitric oxide but improved with inhaled prostacyclin. We propose that inhaled prostacyclin alleviated the hypoxia by stimulating surfactant secretion. (2007) 27, 724-726; doi:10.1038/sj.jp.7211811 Journal of PerinatologyKeywords: persistent pulmonary hypertension; hypoxia; respiratory distress syndrome; prostacyclin; surfactant; extremely-low-birth-weight infant Background Hypoxemia is a feature of respiratory distress syndrome. Patent ductus arteriosus (PDA) and persistent pulmonary hypertension of the newborn (PPHN) can exacerbate hypoxemia. Inhaled nitric oxide (iNO) is effective for treatment of PPHN in full-term infants by decreasing pulmonary vascular resistance, thereby decreasing right-to-left shunting and alleviating hypoxemia. Several case reports have similarly shown that inhaled prostacyclin (iPGI 2 ) is effective through pulmonary vasodilation in full-term and preterm infants with PPHN. 1-5 Hypoxemia in our patient was refractory to iNO but improved with iPGI 2 . We propose that this response may be due to a physiological mechanism different from pulmonary vasodilatation.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Can inhaled prostacyclin stimulate surfactant in ELBW infants?

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Aerosolized PGI 2 reduced pulmonary pressures and improved right ventricular stroke volume in patients with PH undergoing cardiac surgery (22). The data on the effects in the neonate are anecdotal (5,23,24). IT instillation of PGI 2 at 50 ng/kg when injected as a bolus dose in four preterm infants with documented PH resulted in a significantly improved oxygenation index without systemic hypotension (23).…”

Section: Discussionmentioning

confidence: 99%

Effects of Prostacyclin and Milrinone on Pulmonary Hemodynamics in Newborn Lambs With Persistent Pulmonary Hypertension Induced by Ductal Ligation

et al. 2006

View full text Add to dashboard Cite

Prostacyclin (PGI 2 ) stimulates adenyl cyclase to synthesize cAMP within the vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP clearance by phosphodiesterase type III. We studied the dose response of pulmonary and systemic hemodynamics to intratracheal (IT) PGI 2 in newborn lambs with pulmonary hypertension (PH) and whether intravenous milrinone potentiate these effects. IT-PGI 2 at varying doses was administered to lambs with PH induced by prenatal ductal ligation. IT-PGI 2 doses were repeated in the presence of intravenous milrinone (bolus-100 g/kg followed by infusion at 1 g/kg/min). Increasing doses of IT-PGI 2 significantly decreased mean pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a significant reduction in PVR and a significant increase in PBF. Intravenous milrinone significantly shortened the onset, prolonged the duration and degree of pulmonary vasodilation produced by PGI 2 . We conclude that intravenous milrinone potentiates the pulmonary vasodilator effects of PGI 2 at lower doses. (Pediatr Res 60: 624-629, 2006) P PHN is a disorder of term and near term infants with significant morbidity and mortality. PPHN results from disruption of the normal decrease in PVR at birth. PGI 2 , the main cyclo-oxygenase product of arachidonic acid in the vascular tissue, is a potent vasodilator and its actions are mediated by cAMP (1,2). It is one of the important mediators of the decrease in PVR at birth (3,4). PGI 2 has been used widely in the treatment of adults with PH. Although there are reports of PGI 2 being used anecdotally in human infants (5,6), systematic studies on the dose response effects of PGI 2 in PPHN are lacking. Milrinone selectively inhibits PDE3, resulting in accumulation of cAMP in myocardium and vascular smooth muscle, improving myocardial performance and producing vasodilation. Milrinone has been used in patients to improve pulmonary hemodynamics in association with systemic hemodynamic dysfunction (7,8). Studies on the use of milrinone in neonates are lacking. Figure 1 shows the PGI 2 -cAMP signal transduction pathway in the vascular smooth muscle. PGI 2 and milrinone in combination can act synergistically in increasing cAMP levels and hence enhance the relaxation of the vascular smooth muscle.The newborn pulmonary circulation is different from the adult pulmonary circulation in its anatomy and physiology (9,10). The response of the infant with PPHN to NO is closer to that of newborn lambs with persistent pulmonary hypertension induced by ligation of the ductus arteriosus (11) than it is to the response of adult humans with PH. Examination of the responses to manipulating cAMP with PGI 2 and milrinone in such lambs seemed warranted in advance of clinical trials. Thus we studied the dose response to IT PGI 2 , the response to intravenous milrinone and enhancement of the effect of PGI 2 by milrinone in newborn lambs with PH induced by ligation o...

show abstract

Pulmonary Hypertension

Olschewski¹

2005

Evidence‐based Respiratory Medicine

View full text Add to dashboard Cite

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with chronic inflammation but the pathological mechanisms are largely unknown. Our study aimed to simultaneously profile a broad range of cytokines in the supernatant of pulmonary endarterectomy (PEA) surgical material, as well as prospectively in patients with CTEPH to investigate whether circulating cytokines are associated with haemodynamic and physical characteristics of CTEPH patients.Herein, we show that PEA specimens revealed a significant upregulation of interleukin (IL)-6, monocyte chemoattractant protein-1, interferon-c-induced protein-10 (IP)-10, macrophage inflammatory protein (MIP)1a and RANTES compared to lung tissue from healthy controls.In prospectively collected serum, levels of IL-6, IL-8, IP-10, monokine induced by interferon-c (MIG) and MIP1a were significantly elevated in CTEPH patients compared to age-and sex-matched healthy controls. In serum of idiopathic pulmonary arterial hypertension (IPAH) patients, only IP-10 and MIG were significantly increased. In CTEPH but not in IPAH, IP-10 was negatively correlated with cardiac index, 6-min walking distance and carbon monoxide diffusion capacity. In vitro, IP-10 significantly increased migration of freshly isolated adventitial fibroblasts.Our study is the first to show that IP-10 secretion is associated with poor pulmonary haemodynamics and physical capacity in CTEPH and might be involved in the pathological mechanism of PEA tissue formation. @ERSpublicationsIncreased circulating IP-10 associated with poor pulmonary haemodynamics and physical capacity in CTEPH patients http://ow.ly/yDX7U

show abstract

Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension

Cited by 39 publications

References 14 publications

Can inhaled prostacyclin stimulate surfactant in ELBW infants?

Can inhaled prostacyclin stimulate surfactant in ELBW infants?

Effects of Prostacyclin and Milrinone on Pulmonary Hemodynamics in Newborn Lambs With Persistent Pulmonary Hypertension Induced by Ductal Ligation

Pulmonary Hypertension

Contact Info

Product

Resources

About