Effect Of Inhalaton Of Nebulized NTG On Acute Hypoxic Pulmonary Arterial Hypertension And Myocardial Impairment In Newborn Infants

Hypoxaemia induced by perinatal asphyxia is one of the major causes of neonatal death,and the myocardial impairment,lung injury and encephalopathy occur commonly.The high incidence of neonatal myocardial impairment induced by asphyxia is also associated with the sustaining increase of pulmonary arterial pressure and pulmonary vascular resistance.As a serious complication of perinatal asphyxia, persistent pulmonary hypertension of newborn(PPHN) can lead to substantial hypoxaemia and heart disfunction,even to death.Nowadays,successful application of some new treatments especially the technology of inhaled nitric oxide(iNO) has greatly decreased the mortality and morbidity of PPHN from 50%to 20%.NO as a selective vasodilator can effectively decrease pulmonary hypertension.Recent studies suggest that inhaled nitric oxide(NO) may play an important role in the pathophysiology of pulmonary hypertension,and exert novel cardioprotection. Unfortunately,the technology can not be universally generalized for needing mechanical ventilation and strict monitor system,plus,its potent toxicity and the cost are also worrisome.Nitroglycerin(NTG),as one of NO donors,can release nitric oxide(NO) and thereby provide a means of delivering NO to its site of action,which is a potent vascular smooth muscle relaxant.Recent reports show that nebulization of nitroglycerin(NTG) can selectively reduce pulmonary hypertension and meliorate the myocardial impairment in model experiment research.However,there is no clinical data about the effect of nebulization of NTG on PPHN induced by perinatal asphyxia and no report the effect on hypoxic myocardial impairment.In this study,we investigated the effect of nebulization of NTG(neb-NTG) on pulmonary hypertension and myocardial impairment induced by hypoxia in newborn infants.PartⅠThe Efficacy of Inhalation of Nebulized Nitroglycerin in Neonatal Pulmonary Hypertension Induced by AsphyxiaObjective(1) To evaluate the efficacy and safety of inhalation of neb-NTG as NO donor in neonatal pulmonary hypertension induced by asphyxia。(2) Establish a strategy of inhalation of neb-NTG for the treatment of PPHN.Methods A total of 33 neonates with acute hypoxic pulmonary hypertension were treated with inhaled neb-NTG.All the neonates underwent serial Doppler echocardiography through detecting tricuspid regurgitation jet(TR) or PDA shunting to estimate systolic pulmonary artery pressure(SPAP) prior to,during and after application of inhalation of neb-NTG.The relief of pulmonary hypertension was combined together with the improvement of hypoxemia to evaluate the efficacy of inhalation of neb-NTG,which was categorized as follows:①complete remission: Hypoxemia was corrected,and SPAP was continually lower than 40mmHg,which wouldn't rebound even if NTG inhalation had been stopped more than 12h;②improved:Hypoxemia was also corrected,and SPAP was decreased more than 10mmHg,but still beyond 40mmHg;③invalid:SPAP was decreased less than 10mmHg,and/or hypoxemia couldn't be corrected.Results(1) Among 33 cases,complete remission was observed in 24,improved in 7,and invalid in 2.(2) The times of inhalation neb-NTG were ranged from 1 to 9.More than 96%cases achieved remission and improvement just need 6 times of inhalation neb-NTG.(3) Among 33 cases,SPAP decreased from(62.15±15.36) mmHg to(43.46±10.32) mmHg,(39.82±16.03) mmHg,(49.16±16.60) mmHg,(35.46±8.01) mmHg, (32.66±5.07) mmHg prior to initiation of inhalation and 30-60 min,3-4 hour,5-6 hour after initiation of treatment,the end and 6-12 hour after the end of the treatment, respectively(P＜0.01).Systolic blood pressure remained from(55.91±16.07) mmHg to(60.61±14.24) mmHg with no significant changes during the period.Conclusions(1) Inhalation nebulized nitroglycerin is a highly selective pulmonary vasodilator, and is effective in reducing pulmonary hypertension induced by asphyxia.It wouldn't rebound when NTG inhalation is stopped.(2) The suggested strategy in clinical application:neb-NTG is inhaled 1 time per 6 hour,lasting 30 minutes every time,and repeated 6 times.The dose administered is different according to the way of ventilation,as 40ug/kg in patient with mechanical ventilation,50ug/kg in patient with CPAP,80ug/kg in patient with normal nebulization. (3) Nebulization of NTG doesn't cause methemoglobinemia and other toxicity in newborn at the dosage used in this studyPartⅡThe Protective Effect of Inhalation of Nebulized Nitroglycerin in Neonatal Heart Impairment Induced by HypoxiaObjective Exposure to hypoxia is considered to be a cause of myocardial impairment in newborn associated with increase of pulmonary artery pressure and pulmonary vascular resistance.The aim of the present study was to observe and evaluate the efficacy and security of inhalation of nebulized nitroglycerin on neonatal heart impairment induced by hypoxia.Method A total of 53 neonates with hypoxia were divided into two groups according to pulmonary arterial pressure.One group(33 cases) with pulmonary hypertension treated with nebulized nitroglycerin.The control group(23 cases) had no pulmonary hypertension.All the neonates underwent serial echocardiography evaluation before and during therapy to estimate the heart function,including left ventricular ejection fraction(LVEF),right ventricular ejection fraction(RVEF),ratio of peak E velocity and peak A velocity of mitral flow and tricuspid flow(MVE / A and TVE / A),isovalumic relaxation time of left ventricle(LVIRT),ratio of acceleration time and ejection time of pulmonary arterial flow(RVACT/ET).The levels of CK-MB and cTnI in serum before and 4 days after therapy were detected.Result(1) In the NTG group,serum CK-MB and cTnI were(94.25±26.11) IU/1 and (0.74±0.0.19) ng/ml at baseline,,respectively,and decreased significantly at 4 days after nebulization(P＜0.05);Echocardiography showed the LVEF,FS,RVEF,ME/A, TE/A and RACT/RVET were significantly higher at 12h and 48h after initiation of inhalation than those at baseline,and IVRTc was decreased at the same time(P＜0.05). Both of the diastolic function and systolic function of RV and LV ameliorated obviously,and the improvement of RV function was faster and more obvious as compared with LV function.(2) In the control group,serum CK-MB decrease from(98.79±19.03) IU/1 to (44.29±14.39) IU/1 at baseline and 4 days later,serum cTnI was(0.30±0.06) ng/ml at baseline and no significantly defference with that at 4 days later.There were no significant difference in each of LVEF,FS RVEF,ME/A,TE/A,ⅣRTc and RACT/RVET at baseline,12-24 and 48-72h after treatment,respectively.(3) Compared the two groups,we found the heart function in the NTG groups was lower than that in control group at baseline(P＜0.05);With inhalated,the heart function in the NTG groups was significantly higher than that in control group at 48-72h after treatment(P＜0.05),Conclusions(1) Pulmonary hypertension of newborn induced by asphyxia can worsen myocardial impairment and cardiac function。(2) Inhalation of nebulized nitroglycerin can reduce myocardial impairment induced by hypoxia and improve heart function in newborn,especially the right ventricular function.No toxicity or systemic effects has been observed at the dosage given in this study.Neb-NTG is a highly selective pulmonary vasodilator,and is effective in reducing pulmonary hypertension.It can alleviate myocardial impairment and protect the myocardial function after hypoxia.This offers a new and practical therapeutic approach in neonatal pulmonary hypertension.