Planned Second look laparotomy in neonatal volvulus - A safe approach for bowel salvage.

Midgut volvulus can result in gangrene and loss of large segments of intestine. After correction of volvulus the viability of intestine may improve and if given sufficient time a large portion of intestine may be saved. A planned second look laparotomy in babies with volvulus and doubtful gut viability can be helpful in saving large bowel segment. We present a case of a newborn baby admitted with bilious vomiting, abdominal distension and melena. An urgent exploratory laparotomy showed midgut volvulus with near gangrene of about 35 cm of proximal jejunum and bluish discoloration of the rest of the small bowel. After de-rotation and warm packs, the vascularity of ileum & distal jejunum returned to normal, however the proximal jejunum remained dusky and bruised. Ladd's procedure was done and a decision was made to close the abdomen with a plan for a 2nd look laparotomy after 24 hours. A relook laparotomy performed after 24 hours showed, a well vascularized small bowel. No bowel resection was required and abdomen was closed. The baby improved and was discharged in stable condition with no long-term ischemic complications. This case indicates that a second look laparotomy may provide time for revascularization of the intestine with doubtful vascularity and avoid unnecessary bowel resection.

Creating a Framework for Medical Professionalism: An Initial Consensus Statement From an Arab Nation.

Background Medical professionalism has received increased worldwide attention, yet there is limited information on the applicability and utility of established Western professionalism frameworks in non-Western nations. Objective We developed a locally derived consensus definition of medical professionalism for the United Arab Emirates (UAE), which reflects the cultural and social constructs of the UAE and the Middle East. Methods We used a purposive sample of 14 physicians working in the UAE as clinical and education leaders. This expert panel used qualitative methods, including the world café, nominal group technique, the Delphi method, and an interpretive thematic analysis to develop the consensus statement. Results The expert panel defined 9 attributes of medical professionalism. There was considerable overlap with accepted Western definitions, along with important differences in 3 aspects: (1) the primacy of social justice and societal rights; (2) the role of the physician's personal faith and spirituality in guiding professional practices; and (3) societal expectations for professional attributes of physicians that extend beyond the practice of medicine. Conclusions Professionalism is a social construct influenced by cultural and religious contexts. It is imperative that definitions of professionalism used in the education of physicians in training and in the assessment of practicing physicians be formulated locally and encompass specific competencies relevant to the local, social, and cultural context for medical practice. Our goal was to develop a secular consensus statement that encompasses culture and values relevant to professionalism for the UAE and the Arab region.

Biochemical, radiological, and genetic characterization of congenital hypothyroidism in Abu Dhabi, United Arab Emirates.

BACKGROUND: Congenital hypothyroidism (CH) is caused by thyroid gland (TG) dysgenesis or inadequate thyroid hormone biosynthesis in a structurally normal gland. Different etiologies are known to be associated with various clinical, biochemical and imaging markers and a subset of cases have an underlying genetic basis. Despite the presence of neonatal screening programs in the UAE, there is a lack of data on the disease etiology in the area. We aim to study the etiology of CH in our center and examine its relationship with the clinical, biochemical, genetic and radiological features. METHODS: Patients with CH who were followed in our center between 2011 and 2014 are enrolled in the study. Data collected included gender, gestational age, history of CH in a first-degree relative, initial thyroid stimulating hormone (TSH) and thyroxine (T4) levels, imaging findings, associated disease/malformation and treatment details. Selected patients with associated systemic disease or familial CH underwent genetic testing. RESULTS: Sixty-five patients were enrolled. Ten patients underwent genetic study: seven patients with associated congenital disease/malformation, one with a sibling and two with cousins with CH. Forty-nine subjects had technetium99 and/or ultrasound scans. Dyshormonogenesis was diagnosed in two-thirds of the patients. Three patients of 10 tested had likely causative genetic mutations; two homozygous thyroid peroxidase (TPO) and one heterozygous thyroid stimulating hormone receptor (TSHR) missense mutations. CONCLUSIONS: Dyshormonogenesis is the commonest etiology in CH in the studied group. It is expected that genetic mutations are more prevalent in our region due to the nature of the CH etiology and the rate of high consanguinity rate.

Angiostatins decrease in the kidney of newborn piglets after hypoxia-reoxygenation.

Little is known about the expression of kidney angiostatin in the hypoxia and reoxygenation of neonates. In this study, we compared the effect of 21% and 100% reoxygenation on kidney levels of angiostatin and its related factors in newborn piglets subjected to hypoxia-reoxygenation. Newborn piglets were subjected to 2h hypoxia followed by 1h of reoxygenation with either 21% or 100% oxygen and observed for 4days. There were 3 isoforms (38, 43 and 50kDa) of angiostatins identified in the kidney tissue of newborn piglets with the 38kDa being the major isoform (~60%). The 38kDa, but not 43 and 50kDa, angiostatin isoform correlated significantly with the levels of total angiostatin and plasminogen (r=0.95 and r=0.58, respectively). On day 4 of recovery in 100% hypoxic-reoxygenated group, there were decreases in kidney tissue levels of plasminogen, total angiostatin, angiostatin (38 and 43kDa, but not 50kDa), whereas no significant changes were found in the 21% hypoxic-reoxygenated group when compared to the sham-operated piglets with no hypoxia-reoxygenation. Both 21% and 100% hypoxic-reoxygenated groups did not show significant changes in kidney tissue levels of 50kDa angiostatin, MMP-2, MMP-9 and HIF-1alpha. In comparison to 21% oxygen, neonatal resuscitation with 100% oxygen decreased the kidney tissue levels of plasminogen and angiostatin that may play a role in neonatal kidney injury and altered renal development in adulthood.

Effects of N-acetylcysteine on intestinal reoxygenation injury in hypoxic newborn piglets resuscitated with 100% oxygen.

BACKGROUND: Neonatal asphyxia may lead to the development of ischemia-reperfusion induced intestinal injury, which is related to oxygen-derived free radical production. N-Acetylcysteine (NAC) is a thiol-containing antioxidant which increases intracellular stores of glutathione. OBJECTIVES: Using a swine model of neonatal hypoxia-reoxygenation, we examined whether administration of NAC after resuscitation improved intestinal perfusion and reduced intestinal damage. METHODS: Twenty-four piglets (1-4 days old, 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of superior mesenteric arterial flow and oxygen delivery. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control and NAC treatment (150 mg/kg i.v. at 0 or 10 min of reoxygenation followed by infusion 100 mg/kg/h) groups. During hypoxia-reoxygenation, intestinal tissue glutathione content, caspase-3 activity and reoxygenation injury were examined. RESULTS: After 2 h of hypoxia, piglets were acidotic and hypotensive, with significantly depressed blood flow and oxygen delivery to the small intestine. Upon reoxygenation, hemodynamics recovered as did oxygen supply to the small intestine. After 4 h of reoxygenation, the NAC treatment improved mesenteric flow and oxygen delivery. Despite reducing the increase in caspase-3 activities after hypoxia-reoxygenation by NAC treatment, no significant differences in the glutathione content and histological grading of ileal injury were found among the experimental groups. CONCLUSIONS: In newborn piglets with hypoxia-reoxygenation, NAC may improve mesenteric blood flow and oxygen delivery without significant effect on tissue glutathione content. The protective role of NAC in the reoxygenated intestine after severe hypoxia warrants further investigation.

Epinephrine versus dopamine to treat shock in hypoxic newborn pigs resuscitated with 100% oxygen.

Shock and tissue hypoperfusion are common after asphyxia. We compared systemic and regional hemodynamic effects of epinephrine and dopamine in the treatment of shock and hypotension in asphyxiated newborn piglets resuscitated with 100% oxygen. Twenty-four piglets (1-3 days old; weight, 1.4-2.6 kg) were acutely instrumented to measure cardiac index (CI), carotid, mesenteric and renal arterial blood flows, and mean systemic (SAPs) and pulmonary arterial pressures (PAPs). Piglets had normocapnic alveolar hypoxia (F(IO2)=0.08-0.10) for 50 min and reoxygenated with F(IO2)=1.0 for 1 h then F(IO2)=0.21 for 3.5 h. After 2 h reoxygenation, either dopamine (2 microg kg(-1) min(-1)) or epinephrine (0.2 microg kg(-1) min(-1)) was given for 30 min in a blinded randomized manner, which was then increased to maintain SAP (within 10% of baseline, pressure-driven dose) for 2 h. Hypoxia caused hypotension (SAP, 44%+/-3% of baseline), cardiogenic shock (CI, 41%+/-4%), and metabolic acidosis (mean pH, 7.04-7.09). Upon reoxygenation, hemodynamic parameters immediately recovered but gradually deteriorated during 2 h with SAP at 45+/-1 mmHg, CI at 74+/-9% of baseline, and pH 7.32+/-0.03. Low doses of either drug had no significant systemic and renal hemodynamic response. Epinephrine (0.3-1.5 microg kg(-1) min(-1)) for 2 h increased SAP and CI (with higher stroke volume) and decreased pulmonary vascular resistance (with reduced PAP-SAP ratio), whereas the responses with dopamine (10-25 microg kg(-1) min(-1)) were modest. Low-dose epinephrine improved mesenteric and carotid arterial flows, whereas the pressure-driven doses of epinephrine and dopamine increased carotid and mesenteric arterial flows, respectively. To treat shock in asphyxiated newborn piglets resuscitated with 100% oxygen, epinephrine exhibits an inotropic action compared with dopamine, whereas both catecholamines can increase carotid and mesenteric perfusion.

Cardio-renal recovery of hypoxic newborn pigs after 18%, 21% and 100% reoxygenation.

OBJECTIVES: We examined the effects of 18%, 21% or 100% oxygen on the recovery of the heart and kidneys in a short-term survival model of neonatal hypoxia-reoxygenation (HR). DESIGN: Controlled, block-randomized animal study. SETTING: University animal research laboratory. SUBJECT: Large White piglets (1-3 days, 1.7-2.5 kg). INTERVENTIONS: Piglets received normocapnic hypoxia (15% oxygen) (2 h) and were reoxygenated with 18%, 21% or 100% oxygen (1 h) (n=7 per group) then 21% oxygen (2 h). Sham-operated pigs (n=7) had no HR. MEASUREMENTS AND RESULTS: Seventeen of 21 HR piglets recovered from moderate hypoxemia (mean PaO(2) 27-33 mmHg and pH 7.20-7.22, associated with tachycardia and hypotension). Systemic arterial pressure, heart rate, left renal arterial flow, oxygen transport, plasma troponin-I and creatinine levels were monitored and recovered with no differences among HR groups over 4 days after resuscitation. The 100% group had increased myocardial oxidative stress (oxidized glutathione levels) and the most cardiac HR-induced injury. There were no differences in renal oxidative stress and HR-induced injury among groups. Early oxygenation at 1 h after resuscitation correlated with the plasma troponin-I level at 6 h (r = -0.51 and 0.64 for SaO(2) and systemic oxygen extraction ratio, p<0.05, respectively) and renal HR-induced injury at 4 days (r =0.61 for renal oxygen delivery, p<0.05). CONCLUSIONS: In hypoxic piglets, 18%, 21% and 100% reoxygenation caused similar systemic and renal hemodynamic and functional recovery. The indicators of oxidative stress and HR injury in myocardial and renal tissues suggest that the reoxygenation with 100% oxygen appears sub-optimal and the use of 18% oxygen offers no further benefit, when compared with 21% oxygen.

Persistent neurochemical changes in neonatal piglets after hypoxia-ischemia and resuscitation with 100%, 21% or 18% oxygen.

BACKGROUND: Neonatal hypoxia-ischemia (HI) is a common complication of pregnancy and delivery. Conventional clinical practice is to resuscitate neonates with 100% O2, and evidence is building to suggest resuscitation with lower O2 concentrations is safer. Significant neurochemical changes are associated with HI injury and persistent changes in amino acids are related to cell death, therefore we used a swine survival model of neonatal HI-reoxygenation (HI/R) to investigate the effects of resuscitation with 100%, 21% or 18% O2 on amino acid neurotransmitters. METHODS: In a blinded randomized fashion, following permanent ligation of the left common carotid artery, newborn pigs (1-4 d, 1.7-2.5 kg) received alveolar normocapnic hypoxia (FiO2=0.15, 2h) and were reoxygenated with 18%, 21% or 100% O2. After a 4-day survival period, brain regions were processed for amino acid levels using high-performance liquid chromatography (HPLC). RESULTS: Results showed that resuscitation with different O2 concentrations caused hemispheric and regional changes in all amino acids investigated including glutamate, alanine, gamma-amino butyric acid, glycine and aspartate, 4 days post-HI. Resuscitation with 100% O2 significantly increased glutamate and glycine in the dorsal cortex contralateral to the ligated common carotid artery, compared to piglets resuscitated with 21% O2. Additionally, piglets resuscitated with 21% O2 had significantly lower alanine levels than those resuscitated with 18% O2. CONCLUSION: Significant resuscitation-dependent changes in amino acid neurotransmitters are still evident 4 days post-HI in the newborn piglet. These data suggest that persistent changes in neurochemistry occur 4 days after HI/R and further studies are warranted to elucidate the consequences of this on neonatal brain development.

The systemic, pulmonary and regional hemodynamic recovery of asphyxiated newborn piglets resuscitated with 18%, 21% and 100% oxygen.

OBJECTIVES: The increase in oxidative stress following neonatal hypoxia-reoxygenation can be related to subsequent cardiovascular deficits. We compared the acute systemic, pulmonary and regional hemodynamic recovery in hypoxic newborn pigs reoxygenated by low (18%) or high (100%) concentration of oxygen with that by 21% oxygen. STUDY DESIGN: Pigs (1-3 days, 1.5-2.5 kg) were acutely instrumented to continuously measure pulmonary artery flow (surrogate for cardiac index), mean and pulmonary artery pressures, common carotid, superior mesenteric and renal artery flow indices. After 1h of normocapnic alveolar hypoxia (8-10% oxygen), animals were randomized to receive 18%, 21% or 100% oxygen for 1h then 21% oxygen for 3 h (n=7 per group). Sham-operated pigs (n=6) had no hypoxia-reoxygenation. RESULTS: Severe hypoxia caused significant compromises in systemic and regional hemodynamics and oxygen delivery (vs. shams). Despite reoxygenation, mean arterial pressure remained significantly lower than that of shams with no difference among hypoxic-reoxygenated groups. There was an oxygen-dependent recovery of pulmonary artery pressure. Cardiac index improved with reoxygenation but deteriorated over time in the 100% group. Both 18% and 100% groups had lower systemic oxygen delivery. Regional flows and oxygen delivery in all hypoxic-reoxygenated piglets were similarly reduced in all groups. CONCLUSIONS: In this swine model of neonatal hypoxia-reoxygenation, resuscitation with 18% and 100% oxygen results in differential compromises in systemic and pulmonary circulations when compared with 21% oxygen.

Expression of angiostatin and its related factors in the plasma of newborn pigs with hypoxia and reoxygenation.

Little is known about angiostatin and its related factors in the hypoxia-reoxygenation of neonates. In this study we compared the effect of 21% and 100% reoxygenation on temporal changes in the plasma level of these factors in newborn piglets subjected to hypoxia. Newborn piglets were subjected to 2 h hypoxia followed by 1 h of reoxygenation with either 21% or 100% oxygen and observed for 4 days. On day 4 of recovery in 100% hypoxic-reoxygenated group, there were increases in total angiostatin, plasminogen/plasmin and MMP-2 levels, and decreases in VEGF levels (vs. respective baseline levels, all P <0.001), whereas no significant temporal changes were found in the 21% hypoxic-reoxygenated and sham-operated groups. Angiostatin levels correlated positively with the levels of MMP-2 and HIF-1alpha and negatively with VEGF levels in 100% hypoxic-reoxygenated group (all P <0.05). In comparison to 21% oxygen, neonatal resuscitation with 100% oxygen was found to increase the levels anti-angiogenic factors.

N-acetylcysteine improves the hemodynamics and oxidative stress in hypoxic newborn pigs reoxygenated with 100% oxygen.

Neonatal asphyxia may lead to cardiac and renal complications perhaps mediated by oxygen free radicals. Using a model of neonatal hypoxia-reoxygenation, we tested the hypothesis that N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of pulmonary and renal artery flow (cardiac index [CI] and renal artery flow index [RAFI], respectively) and mean blood pressure. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control, and NAC treatment (i.v. bolus of 150 mg/kg given at 10 min of reoxygenation followed by 100 mg/kg per h infusion) groups. Myocardial and renal tissue glutathione content and lipid hydroperoxide levels were assayed, and histology was examined. After 2 h of hypoxia, all animals were acidotic (pH 6.96 +/- 0.04) and in cardiogenic shock with depressed renal blood flow. Upon reoxygenation, CI and RAFI increased but gradually deteriorated later. The NAC treatment prevented the decreased CI, stroke volume, mean blood pressure, systemic oxygen delivery, RAFI, and renal oxygen delivery at 2 to 4 h of reoxygenation observed in hypoxic controls (versus shams, all P < 0.05). The myocardial and renal tissue glutathione content was significantly higher in the NAC treatment group (versus controls). The CI and RAFI at 4 h of reoxygenation correlated with the tissue glutathione redox ratio (r = 0.5 and 0.6, respectively, P < 0.05). There were no significant differences in heart rate, pulmonary artery pressure, systemic oxygen uptake, and tissue lipid hydroperoxide levels between groups. No histologic injury was found in the heart or kidney. In this porcine model of neonatal hypoxia and 100% reoxygenation, NAC improved cardiac function and renal perfusion, with improved tissue glutathione content.

Temporal platelet aggregatory function in hypoxic newborn piglets reoxygenated with 18%, 21%, and 100% oxygen.

Thromboembolic and bleeding complications are common after asphyxia. We studied the temporal effects of different oxygen concentrations used in resuscitating hypoxic newborn piglets on platelet aggregatory function. Alveolar normocapnic hypoxia (fractional inspired oxygen concentration = 0.15) was induced in piglets (1-4 d, 1.7-2.5 kg) for 2 h, followed by reoxygenation with 18%, 21%, or 100% oxygen for 1 h and then 21% for 2 h (n = 8-9 per group). Control piglets underwent surgery with no hypoxia-reoxygenation (n = 5). Platelet counts and collagen-stimulated (2-10 microg/mL) whole blood aggregation were studied at normoxic baseline and at 3 h, 2 d, and 4 d of recovery. Platelet activation markers including plasma thromboxane B2 and matrix metalloproteinase 2 and 9 levels were measured. At 2 h hypoxia (mean PaO2 30-35 mmHg), all piglets were hypotensive and acidotic (mean pH 7.19-7.24). In 100% reoxygenation piglets, the concentration-response curves of collagen-stimulated platelet aggregation were significantly shifted upward at 3 h and 2 d of recovery with no differences in the collagen concentration required to induce 50% of maximum aggregation, and this normalized to baseline on 4 d. In the 18% and 21% reoxygenated groups, there were no changes in platelet aggregation during the experiment. Platelet counts were not different between groups and over time. Hypoxic-reoxygenated piglets had increased plasma thromboxane B2 (100% group) and matrix metalloproteinase-2 levels (21% and 100% groups) (versus respective baseline, P < 0.05), with no difference between experimental groups. These findings suggest transient platelet activation in hypoxic newborn piglets resuscitated with 100% but not with 18% and 21% oxygen, of which the clinical significance requires further investigation.

The effect of hypoxia on plasma angiostatin and related factors in newborn pigs.

Hypoxia is a potent stimulus of angiogenic factors and angiostatin can inhibit angiogenesis. Little is known about the expression of angiostatin and its related factors in hypoxic newborns. Using a swine model of neonatal hypoxia, we hypothesized that hypoxia would decrease plasma levels of angiostatin in a time-dependent fashion. In this study newborn piglets underwent hypoxia (15-18% oxygen) for 3 hr, were allowed to recover in 21% oxygen and were then observed for 96 hr. Sham-operated piglets did not experience hypoxia. Plasma levels of angiostatin, plasminogen/plasmin, MMP-2 and -9, and VEGF were determined at normoxic baseline; at the end of hypoxia; at 5 hr; and at 96 hr post-hypoxia. Plasma levels of angiostatin, but not plasminogen/plasmin, decreased significantly at the end of hypoxia and 5 hr after hypoxia compared with the sham-operated group (P < 0.05). Plasma MMP-2 levels at the end of hypoxia were lower in the hypoxic group than in sham animals (P < 0.005). In the hypoxic but not sham-operated group, plasma levels of angiostatin and MMP-2 were positively correlated (r = 0.69; P < 0.001). Plasma MMP-9 and VEGF levels were not different between sham-operated and hypoxic groups and did not correlate with plasma angiostatin levels. In conclusion, hypoxia showed a transient suppressive effect on the expression of plasma angiostatin in newborn piglets. This may imply an inhibitory role of hypoxia on MMP-2 and the proteolytic cleavage of plasminogen to angiostatin.

N-acetylcysteine administration improves platelet aggregation in hypoxia-reoxygenation injury.

Platelet activation and dysfunction occurs upon hypoxia and reoxygenation and is associated with oxygen free radical generation and matrix metalloproteinase (MMP) -2 and -9 activation. The effect of NAC on platelet function in newborn piglets after asphyxia was studied along with plasma MMP-2 and MMP-9 activities. Piglets (1-4 day, 1.4-2.2 kg) were acutely instrumented for the induction of normocapnic hypoxia (10-15% O2) for 2hr followed by reoxygenation for 1hr with 100% O2 and then 3hr with 21% O2. Animals were randomized to 3 groups (n = 6 each); sham, control and treatment with NAC upon reoxygenation (150 mg/kg i.v. bolus and 100 mg/kg/hr i.v. infusion). Platelet count and collagen (2, 5 and 10 microg/mL)-stimulated whole blood aggregation were studied at baseline and after 4hr reoxygenation. Plasma MMP -2 and -9 activities were analyzed by gelatin zymography. Piglets had severe hypoxia (PaO2 32 +/- 2 vs. 65 +/- 2 mmHg sham; p < 0.05) and metabolic acidosis (pH 6.96 +/- 0.04 vs. 7.33 +/- 0.01 sham; p < 0.05). At 4hr of reoxygenation, platelet counts decreased similarly in all experimental groups, and no animal had a platelet count < 100 x 10(9)/L. Platelet aggregation was significantly reduced with a rightward shift of concentration-response curve. NAC treatment improved platelet aggregatory function at 4hr of reoxygenation (p < 0.05). Plasma MMP-9, but not MMP-2, activities were increased with NAC treatment (147 +/- 19 vs. 51 +/- 20 and 42 +/- 11 AU of control and sham, respectively, p < 0.001). In a newborn piglet model of asphyxia and reoxygenation, NAC treatment effectively improves platelet aggregation when given upon resuscitation.

Intratracheal administration of sildenafil and surfactant alleviates the pulmonary hypertension in newborn piglets.

OBJECTIVE: To study systemic and pulmonary effects of low-dose sildenafil with surfactant in newborn piglets with pulmonary hypertension (PHT) induced by thromboxane A(2) analog (U46619). DESIGN/METHODS: Piglets (1-3 days, 1.7-2.5 kg) were mechanically ventilated and prepared for the continuous measurement of mean systemic and pulmonary arterial pressures (MAP and PAP, respectively), heart rate and pulmonary artery flow (as cardiac output). Following stabilization, PHT was induced by intravenous U46619 infusion (0.2-0.8 microg/kg/min) for 120 min. Piglets were randomized for intratracheal administration of surfactant (BLES, 4 ml/kg) with saline (n=6) or sildenafil (0.05 mg/kg, n=6) given after 60 min of U46619 treatment. Temporal changes of hemodynamic measurements were analyzed by two-way ANOVA. RESULTS: There was progressive PHT induced by U46619 (161% of baseline), with increased PAP and pulmonary vascular resistance and decreased cardiac output. Surfactant and sildenafil combined improved PAP along with reduced pulmonary vascular resistance. Cardiac output was higher with surfactant and sildenafil combined than surfactant alone. No significant changes in heart rate, stroke volume, MAP and systemic vascular resistance were observed. Ratio of PAP:MAP was lowered with surfactant and sildenafil combined. Systemic oxygen consumption was not different between groups but the oxygen extraction ratio was higher than baseline in surfactant alone (P<0.05). CONCLUSIONS: Adding low-dose sildenafil to surfactant is effective in alleviating the progressive PHT developed in newborn piglets induced by thromboxane A(2). Intratracheal sildenafil may be a useful therapeutic adjunct to critically ill neonates with PHT.