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Objective: The objective of the study was to determine perioperative B-type natriuretic peptide levels in infants and children undergoing bidirectional cavopulmonary anastomosis or total cavopulmonary connection, and the predictive value of B-type natriuretic peptide levels for outcome., Methods: Plasma B-type natriuretic peptide levels were measured before and 2, 12, and 24 hours after surgery in 36 consecutive patients undergoing bidirectional cavopulmonary anastomosis (n = 25) or total cavopulmonary connection (n = 11). B-type natriuretic peptide levels were evaluated as predictors of outcome., Results: B-type natriuretic peptide levels increased after surgery, peaking at 12 hours in most patients. In the bidirectional cavopulmonary anastomosis group, patients with 12-hour B-type natriuretic peptide > or = 500 pg/mL had a longer duration of mechanical ventilation (165 +/- 149 hours vs 20 +/- 9 hours, P = .004), longer intensive care unit stay (11 +/- 7 days vs 4 +/- 2 days, P = .001), and longer hospital stay (20 days +/- 12 vs 9 days +/- 5, P = .003). A 12-hour B-type natriuretic peptide > or = 500 pg/mL had a sensitivity of 80% and a specificity of 80% for predicting an unplanned surgical or transcatheter cardiac intervention, including transplantation (P = .03). In the total cavopulmonary connection group, preoperative B-type natriuretic peptide levels were highest in patients with total cavopulmonary connection failure compared with patients with a good outcome (88 +/- 46 pg/mL vs 15 +/- 6 pg/mL, P = .03)., Conclusion: Postoperative B-type natriuretic peptide levels predict outcome after bidirectional cavopulmonary anastomosis, and preoperative levels are greater in patients with both early and late total cavopulmonary connection failure compared with patients with a good outcome.

Objective: Extracorporeal life support is used in 3% to 8% of infants and children after cardiac surgery. B-type natriuretic peptide may have utility as a biomarker in these patients. The objective of this study was to investigate potential associations between changes in B-type natriuretic peptide during trials off extracorporeal life support and clinical outcome., Methods: Ten infants and children requiring extracorporeal life support after cardiac surgery were studied prospectively. Before separation from extracorporeal life support, a shunt was placed in the circuit, allowing for temporary trials off life support. Serum lactate, arterial-venous oxyhemoglobin saturation difference, and B-type natriuretic peptide levels were determined before each trial off life support and at the end of each trial off life support, and the ability to predict postoperative outcome from these data was evaluated., Results: During trials off extracorporeal life support, lactate, the arterial-venous oxyhemoglobin saturation difference, and B-type natriuretic peptide levels increased above pre-trial values (P < .05). Only the arterial-venous oxyhemoglobin saturation difference predicted successful separation from extracorporeal life support after a trial (P < .05). There were no associations between long-term outcome and alterations in lactate and the arterial-venous oxyhemoglobin saturation difference during the final trials off life support. However, an increase in B-type natruiretic peptide levels during the final trial off life support (trial/pre-trial ratio of >1) had a sensitivity of 80% and a specificity of 100% for predicting the need for an unplanned operation or death within 3 months (P < .05)., Conclusion: B-type natriuretic peptide determinations may be a useful tool for clinicians caring for infants and children requiring extracorporeal life support after cardiac surgery.

Objectives: Neonates undergoing cardiac surgery are at high risk for adverse outcomes. B-type natriuretic peptide is used as a biomarker in patients with cardiac disease, but the predictive value of B-type natriuretic peptide after cardiac surgery in neonates has not been evaluated. Therefore, the objective of this study was to determine the predictive value of perioperative B-type natriuretic peptide levels for postoperative outcomes in neonates undergoing cardiac surgery., Methods: Plasma B-type natriuretic peptide determinations were made before and 2, 12, and 24 hours after surgery in 36 consecutive neonates. B-type natriuretic peptide levels and changes in perioperative B-type natriuretic peptide were evaluated as predictors of postoperative outcome., Results: B-type natriuretic peptide levels at 24 hours were lower than preoperative levels (24-h/pre B-type natriuretic peptide ratio < 1) in 29 patients (81%) and higher (24-h/pre B-type natriuretic peptide ratio > or = 1) in 7 patients (19%). A 24-hour/pre B-type natriuretic peptide level of 1 or greater was associated with an increased incidence of low cardiac output syndrome (100% vs 34%, P = .002) and fewer ventilator-free days (17 +/- 13 days vs 26 +/- 3 days, P = .002), and predicted the 6-month composite end point of death, an unplanned cardiac operation, or cardiac transplant (57% vs 3%, P = .003). A 24-hour/pre B-type natriuretic peptide level of 1 or greater had a sensitivity of 80% and a specificity of 90% for predicting a poor postoperative outcome (P = .003)., Conclusion: In neonates undergoing cardiac surgery, an increase in B-type natriuretic peptide 24 hours after surgery predicts poor postoperative outcome.

The co-occurrence of congenital diaphragmatic hernia (CDH) and cardiovascular malformations (CVMs) has important clinical, genetic, and developmental implications. Previous examinations of this topic often included patients with genetic syndromes. To correct this potential bias, we undertook an extensive review of the literature and obtained new data. The frequency of CVMs associated with isolated CDH was 11-15%. A careful analysis of CVMs indicates that atrial and ventricular septal defects, conotruncal defects, and left ventricular outflow tract obstructive defects were the most common type of CVMs, but proportional to the frequency of occurrence in the general population. The combination of CVM and CDH results in a poorer prognosis than would be expected with either malformation alone. However, the impact on survival from patients with a genetic syndrome has not been consistently evaluated. We encourage researchers to re-analyze existing series and recommend that future studies distinguish isolated CDH from that which is associated with other malformations, especially as part of genetic syndromes. Therapies should be tailored to maximize cardiac output and systemic oxygen delivery rather than systemic oxygen saturation alone. Although there is speculation about the frequency with which isolated left ventricular "hypoplasia" occurs in patients with CDH, we suggest it results from compression of a pre-load deficient left ventricle by the hypertensive right ventricle, and unlike true hypoplasia, is reversible. Irrespective of the type of severity of CVMs in patients with CDH, the degree of pulmonary hypoplasia and pulmonary vascular disease predicts outcome., ((c) 2007 Wiley-Liss, Inc.)

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease in children. By definition it is a diagnosis of exclusion, and CT of the chest is primarily performed to exclude other causes. Previous studies have defined CT features suggestive of the diagnosis of IPAH, but these have all been limited to the adult population., Objective: Contrast-enhanced chest CT and high-resolution CT findings in IPAH were evaluated in an attempt to define features consistently seen in children with this condition., Materials and Methods: The chest CT scans performed at initial presentation were reviewed in 17 children with echocardiographic or angiographic evidence of IPAH., Result: There were nine boys and eight girls, ranging in age from 1 month to 17 years. The extrapulmonary findings included cardiomegaly with right-sided cardiac enlargement, which was seen in 13 children. The central pulmonary arteries were enlarged in 15 children, with peripheral enlargement in two. In six children this resulted in bronchial compression. In addition, mediastinal and hilar lymphadenopathy was noted in three children. Prominent intrapulmonary features included a peripheral vasculopathy, with enlarged tortuous vessels, seen in eight children. Ill-defined ground-glass centrilobular opacities were also noted in eight children, representing the most common parenchymal abnormality. Other findings included septal lines in five, diffuse ground-glass opacification in four and focal hyperlucent zones in three. Mosaic attenuation was seen in one child., Conclusion: A variety of imaging findings are identified in IPAH. Features particularly consistent with the diagnosis include peripheral vasculopathy and centrilobular opacities in the setting of cardiomegaly and central pulmonary arterial enlargement.

Objectives: Sildenafil, tezosentan, and prostacyclin reduce pulmonary vascular pressures in pulmonary hypertension, but have potential to vasodilate the systemic circulation. Nebulized vasodilators allow targeted drug delivery, high local drug concentrations, less systemic hypotension, and better matching of the lung's ventilation and perfusion. We aimed to estimate pulmonary deposition of these drugs from commonly employed nebulizers using in vitro techniques and to create a mathematical model to predict inspired mass of aerosol., Design: Lung deposition was estimated by characterization of drug output and particle size distribution (PSD) of nebulizers using helium-neon laser diffraction techniques. A mathematical model for each device was created to estimate pulmonary deposition using patients' breathing patterns and was verified with a mechanical-breathing model., Results: Total output and PSD were similar for the Hudson Updraft II and Whisperjet nebulizers, consisting of half the nebulizer's charge, with (1/4) of particles < or = 5 microm, in the respirable fraction (RF). Drug output increased with inspiratory flow for the Pari LC Star. Differences were noted in device performance, depending on the drug tested. Estimated pulmonary deposition (mean, 95% CI) was 8.1 (7.2, 9.0)% of the initial drug charge for the Hudson Updraft II, 6.4 (5.8, 7.0)% for the Whisperjet, and 33.0 (28.3, 37.9)% for the Pari LC Star. A mechanical model was consistent with our mathematical model., Conclusions: All drugs could be nebulized, but expected pulmonary deposition varied depending on the nebulizer and drug.

Our objective was to study exercise capacity and cardiorespiratory response to exertion in survivors of congenital diaphragmatic hernia (CDH). This was a cross-sectional cohort study of 23 CDH survivors, aged 10-16 years, and 23 gender- and age-matched controls. Exercise testing was performed on a cycle ergometer, with cardiac output measurements made using exponential CO2 rebreathing. Pretest cardiorespiratory assessment was done by echocardiography and pulmonary function testing. Statistical analysis was performed using Student's t-test, regression analysis, and longitudinal model computing with spatial covariance structure. No echocardiographic evidence for pulmonary hypertension was found at rest (right ventricular systolic pressures, 27 +/- 6 mmHg). Mean pulmonary artery diameter on the side of the CDH was significantly smaller than contralaterally, but was within normal range (z-score, 0 +/- 1.1 vs. 1.2 +/- 1.6, P < 0.01). Exercise capacity was mildly reduced in CDH compared to controls and predictive data (maximum workload, 77% +/- 12% vs. 91% +/- 16% of predicted, P < 0.01). Cardiorespiratory response to exertion was not significantly different between groups. In conclusion, most adolescent CDH survivors have nearly normal exercise capacity and cardiorespiratory response to exertion. This study may prove useful in comparisons with future cohorts comprising more severely affected individuals now surviving due to improved neonatal care., (Copyright 2006 Wiley-Liss, Inc.)

Background: The impact of "gentle ventilation" (GV) strategies on morbidity and mortality of patients with congenital diaphragmatic hernia (CDH) in our institution has not been determined. This study reviews the primary and secondary outcomes of our patients with CDH treated with the GV approach., Method: We performed a retrospective chart review of respiratory, neurologic, nutritional, and musculoskeletal morbidities in patients with CDH treated at a single institution between 1985 and 1989 with conventional ventilation (CV) compared with those treated from 1996 to 2000 with GV., Results: There were 77 CV-treated and 66 GV-treated patients with CDH, with 51% survival in the CV cohort compared with 80% in the GV group (chi(2), P < .05). At 3-year follow-up, we found no statistically significant differences in the frequency of respiratory (38% of CV patients, 50% of GV patients), neurologic (29% of CV patients, 34% of GV patients), or musculoskeletal morbidity (46% of CV vs 29% of GV-treated patients). There was a difference in nutritional morbidity as indicated by the increased frequency of gastrostomy tube use in the GV-treated patients (34%) compared with the CV patients (8%; chi2, P < .05)., Conclusion: The implementation of GV techniques has significantly decreased mortality in infants with CDH. This has been associated with a documented increase in nutritional morbidity among survivors.

Objective: To review a mortality database, and identify all sudden unexpected deaths in patients followed by the cardiac program., Design: Retrospective review of prospectively maintained database., Results: Over 8 years, we identified 80 sudden unexpected deaths, among which there were sufficient data in 69 (24 females). Patients died at a median age of 17.2 months (28 days-18.8 years). Forty-six patients had 2 functional ventricles and 23 had received palliation for a single-functional ventricle. Patients with a single ventricle died at a younger age (median 120 days; 28 days-17.2 years) and sooner after last assessment (median 27 days; 1-146 days) than patients in the biventricular group (median age 2 years; 43 days-18.8 years; median time since last assessment 49 days, 1 days-1 year) (P < .01; P = .01). Thrombosis was the most common cause (61%) of death in the single-ventricle group. Arrhythmia or presumed arrhythmia was the most common cause (46%) of death in the biventricular group. Fifty-one patients had undergone surgery. Six patients had primary electrophysiological disease, and 5 had cardiomyopathy. Eight deaths occurred in patients with pulmonary vascular disease., Conclusion: Our study demonstrates that sudden unexpected death occurred at a frequency of at least 10 patients per year over an 8-year period with 55,730 patient encounters. We were able to determine a clinical cause of death in most patients. Arrhythmias (30%) and pulmonary vascular disease (13%) are important causes of sudden death. Simple aortic valve disease and hypertrophic cardiomyopathy are rare (4%) causes of sudden death in childhood. Infants and young children with surgical shunts comprise 23% of sudden unexpected deaths that occur within a month of the last evaluation. Close surveillance of these patients is warranted.

Objective: We sought to review the outcome of infants with a functional single ventricle receiving postoperative extracorporeal life support., Methods: We reviewed all patients with a functional single ventricle receiving postoperative extracorporeal life support between January 1997 and May 2003., Results: We supported 25 infants (age range, 2-139 days; median age, 15 days; weight range, 1.9-5.9 kg; median weight, 3.4 kg) with extracorporeal life support. Operative procedures were Norwood stage 1 procedure in 18 patients, modified Blalock-Taussig shunt in 4 patients, bidirectional superior cavopulmonary shunt in 2 patients, and pulmonary vein repair in 1 patient. Indications for extracorporeal life support included cardiac arrest (14/25) and low cardiac output state (11/25). Extracorporeal membrane oxygenation was initiated in 19 patients, with conversion to a ventricular assist device in 7 patients. Ventricular assist device alone was initiated in 6 patients. Survival to decannulation was 76%, with 5 late deaths from multiorgan failure and 56% intensive care unit survival. Survival to hospital discharge was 44%. On univariate analysis, the presence of arrhythmia before extracorporeal life support (P = .005), renal failure (P = .0007), Candida species-induced sepsis (P = .026), and multiorgan failure (P = .0009) were significant risk factors in the nonsurvivors. Median hospital stay was 43.5 days (range, 6-181 days) for the whole group and 93 days (range, 36-181 days) for survivors. Eight patients completed next stage palliation., Conclusions: Twenty percent of patients were supported with a ventricular assist device alone, with 50% conversion to a ventricular assist device from extracorporeal membrane oxygenation. Survival to decannulation was encouraging. Multiorgan failure and risk of invasive infection in the post-extracorporeal membrane oxygenation period mitigate against survival to hospital discharge. Use of extracorporeal life support before cardiac arrest might reduce attrition between decannulation and hospital discharge.

Objectives: Infants with right atrial isomerism have poor outcomes because of a complex combination of cardiac anomalies. Aggressive management of total anomalous pulmonary venous drainage might have a positive effect on the prognosis., Methods: Outcomes of all children with right atrial isomerism from 1994 to the present were reviewed. Management of total anomalous pulmonary venous drainage evolved from no repair or conventional surgical technique to primary sutureless repair on initial palliation. Cox survival models were used to identify variables associated with reduced survival., Results: There were 55 children enrolled in the study. The median age at the initial visit was 2 days. Fifty-one patients had total anomalous pulmonary venous drainage (obstructive in 22 patients). Withdrawal of treatment occurred in 11 (20%) of 55 patients during an interval of institutional bias toward no treatment. Thirteen (24%) of 55 patients had palliations without total anomalous pulmonary venous drainage repair, and 3 (23%) of 13 survived. Thirty-one (56%) of 55 patients had operations that included total anomalous pulmonary venous drainage repair, of whom 13 (42%) of 31 underwent primary sutureless repair for total anomalous pulmonary venous drainage. Sixteen (52%) of 31 survived, and their current status 1 to 10 years (median, 5.8 years) after repair is post-Fontan (7/16 [44%]), postbidirectional Glenn (6/16 [38%]), and others (3 [20%]). In patients who underwent total anomalous pulmonary venous drainage repair (n = 31), 2 risk factors of decreased survival were identified: drainage site obstruction and infracardiac or mixed-type total anomalous pulmonary venous drainage. After adjustment, sutureless repair appeared to be associated with improved survival (hazard ratio, 0.43), but this beneficial effect did not reach significance (P = .19)., Conclusions: Mortality continues to be high; however, aggressive total anomalous pulmonary venous drainage repair for right atrial isomerism has resulted in improved survival. The role of primary sutureless repair for total anomalous pulmonary venous drainage remains to be defined.

Objectives: B-type natriuretic peptide, a cardiac hormone with diuretic, natriuretic, and vasoactive properties, is used in the diagnosis, risk stratification, and management of adult cardiac patients. However, no study has yet determined the prognostic value of B-type natriuretic peptide after surgical intervention for congenital heart disease. The objectives of this study were (1) to determine alterations in B-type natriuretic peptide levels after repair of congenital heart disease with cardiopulmonary bypass and (2) to investigate potential associations between B-type natriuretic peptide levels and outcomes in this patient population., Methods: Fifty-one infants and children undergoing repair of congenital heart disease were studied. B-type natriuretic peptide levels were measured before and after surgical intervention, and the ability of the postoperative 12-hour B-type natriuretic peptide level to predict postoperative outcomes was evaluated., Results: B-type natriuretic peptide levels increased after separation from cardiopulmonary bypass, with an 8-fold peak increase at 12 hours (P < .005). Postoperative 12-hour B-type natriuretic peptide levels were associated with the duration of mechanical ventilation and the presence of a low cardiac output state after surgical intervention. On multivariate analysis, the 12-hour B-type natriuretic peptide level was an independent predictor of the duration of mechanical ventilation. In fact, B-type natriuretic peptide levels of greater than 540 pg/mL predicted mechanical ventilation beyond 48 hours, with a sensitivity of 88.9% and a specificity of 82.5%. In addition, B-type natriuretic peptide levels of greater than 815 pg/mL predicted the presence of a low cardiac output state within 48 hours after surgical intervention, with a sensitivity of 87.5% and a specificity of 90.2%., Conclusions: B-type natriuretic peptide determinations might be a useful tool for clinicians caring for infants and children after surgical intervention for congenital heart disease.

Objective: To determine the impact of rapid advancement to more concentrated formula on weight gain and duration of hospitalization for infants after cardiac surgery., Study Design: We performed a double-blinded, randomized trial of rapid advancement to higher achieved formula concentration for postoperative infants younger than 1 year of age. After transfer to the inpatient ward from the critical care unit, infants were randomly assigned to rapid advancement to a higher achieved formula concentration (2-day transition) or usual care (5-day transition, lower concentration target)., Results: The adequacy of energy intake (expressed as the median percentage of the estimated energy requirement) before discharge from the hospital was 98% in the intervention versus 78% in the usual care group ( P = .01). Before discharge, the median rate of weight gain was greater in the rapid advancement (20 g/d) versus the usual care group (loss of 35 g/d, P < .03). The median postoperative duration of stay on the cardiology inpatient unit was 5 days for the intervention versus 6 days for the usual care group ( P < .05)., Conclusions: Rapid advancement to higher achieved formula concentration significantly improved energy intake and weight gain and decreased duration of postoperative hospital stay in infants after cardiac surgery.

Objectives: We investigated the effects of different CO(2) tensions on oxygenation, pulmonary blood flow (Qp), cerebral blood flow, and systemic blood flow (Qs) after the bidirectional superior cavopulmonary anastomosis (BCPA)., Background: Hypoxemia refractory to management of a high pulmonary vascular resistance index (PVRI) may complicate recovery from the BCPA., Methods: After BCPA, CO(2) was added to the inspired gas of mechanically ventilated patients. The Qp, Qs, PVRI, and systemic vascular resistance index (SVRI) were calculated from oxygen consumption, intravascular pressures, and oxygen saturations. Cerebral blood flow was estimated by near infrared spectroscopy and transcranial Doppler., Results: In nine patients (median age 7.1, range 2 to 23 months), arterial oxygen tension increased significantly (p < 0.005) from 36 +/- 6 mm Hg to 44 +/- 6 to 50 +/- 7 mm Hg at arterial carbon dioxide tensions (PaCO(2)) of 35, 45, and 55 mm Hg, respectively and decreased to 40 +/- 8 mm Hg at PaCO(2) 40 mm Hg. At a PaCO(2) of 55 and 45 compared with 35 mm Hg, Qp, cerebral blood flow, and Qs increased significantly, PVRI, Qp/Qs, and the ratio of Qp to inferior vena caval blood flow were unchanged, but SVRI decreased., Conclusions: We have demonstrated that after the BCPA, systemic oxygenation, Qp, Qs, and cerebral blood flow increased and SVRI decreased at CO(2) tensions of 45 and 55 mm Hg compared with 35 mm Hg. We suggest that hypoxemia after the BCPA is ameliorated by a higher PaCO(2) and that low PaCO(2) or alkalosis may be detrimental. Hypercarbic management strategies may allow earlier progression to the BCPA, which may contribute to reducing the interval morbidity in patients with a functional single ventricle.

Adams-Oliver syndrome (AOS) consists of congenital scalp defects with variable limb defects of unknown pathogenesis. We report on two children with AOS plus additional features including intrauterine growth retardation (IUGR), cutis marmorata telangiectatica congenita (CMTC), pulmonary hypertension (PH), intracranial densities shown in one case to be sites of active bleeding and osteopenia. Autopsy in one case revealed defective vascular smooth muscle cell/pericyte coverage of the vasculature associated with two blood vessel abnormalities. Pericyte absence correlated with vessel dilatation while hyperproliferation of pericytes correlated with vessel stenosis. These findings suggest a unifying pathogenic mechanism for the abnormalities seen in AOS. These and previously reported cases establish that a subset of AOS patients is at high risk for PH.

Effects of inhaled nitric oxide (NO) on human platelet function are controversial. It is uncertain whether intraplatelet cGMP mediates the effect of inhaled NO on platelet function. We investigated the effect of 30 ppm inhaled NO on platelet aggregation and plasma and intraplatelet cGMP in 12 subjects. We performed platelet aggregation studies by using a photooptical aggregometer and five agonists (ADP, collagen, epinephrine, arachidonic acid, and ristocetin). During inhalation, the maximal extent of platelet aggregation decreased by 75% with epinephrine (P < 0.005), 56% with collagen (P < 0.005), and 20% with arachidonic acid (P < 0.05). Responses to ADP (8% P > 0.05) and ristocetin (5% P > 0.05) were unaffected. Platelet aggregation velocity decreased by 64% with collagen (P < 0.005), 60% with epinephrine (P < 0.05), 33% with arachidonic acid (P < 0.05), and 14% with ADP (P > 0.05). Plasma cGMP levels increased from 2.58 +/- 0.43 to 9.99 +/- 5.57 pmol/ml (P < 0.005), intraplatelet cGMP levels were unchanged (means +/- SD: 1.96 +/- 0.58 vs. 2.71 +/- 1.67 pmol/109 platelets; P > 0.05). Inhaled NO inhibits platelet aggregation via a cGMP independent mechanism.

Background: Large symptomatic mediastinal seroma following modified-BT shunts, traditionally required revisional thoracotomy., Objective: We describe percutaneous image-guided pigtail catheter drainage in the successful treatment of early mediastinal seroma secondary to PTFE Blalock-Taussig shunt, avoiding thoracotomy., Materials and Methods: A retrospective review of all relevant clinical and imaging records in five patients was performed., Results: All five presented with intermittent stridor, respiratory distress and/or episodic desaturation within 6 weeks of their surgery. In four of five infants, percutaneous drainage was effective and reoperation was avoided. In one of five, rather than urgent surgical evacuation and BT shunt revision, we were able to perform an elective stage-II bidirectional Glenn SVC-RA anastamosis in a stable infant. There were no complications., Conclusions: Percutaneous image-guided drainage of mediastinal seroma secondary to PTFE-BT shunt is a safe, minimally invasive, and effective treatment. This may avoid BT shunt revision.

Objectives: We have shown that exhaled nitric oxide levels decrease after surgical closure of congenital left-to-right cardiac shunts. It remains unclear whether the change in exhaled nitric oxide levels reflects endothelial injury caused by the use of cardiopulmonary bypass or the decrease in pulmonary blood flow attendant on shunt closure. Transcatheter atrial septal defect closure permits shunt closure without the use of cardiopulmonary bypass. Therefore we compared changes in exhaled nitric oxide levels after surgical and transcatheter device closure of atrial septal defects., Methods: We enrolled sequentially 30 children undergoing atrial septal defect closure. Fifteen patients (age range, 0.4-16 years; median age, 6.5 years) underwent surgical atrial septal defect closure with cardiopulmonary bypass, and 15 patients (age range, 4-17 years; median age, 8.4 years) had device closure of the atrial septal defect in the catheterization laboratory. We measured nitric oxide levels in end-tidal expiratory gas with a rapid-response chemiluminescent analyzer before and after atrial septal defect closure., Results: After surgical repair of the atrial septal defect, exhaled nitric oxide decreased by 21%, from 10.9 +/- 4.4 to 8.4 +/- 3.3 ppb (P <.005), whereas after transcatheter defect closure, exhaled nitric oxide increased by 23%, from 7.6 +/- 2.6 to 9.3 +/- 3.7 ppb (P <.005). Hemoglobin levels in patients undergoing surgical intervention were significantly lower (P =.0001) postoperatively., Conclusions: We confirmed that exhaled nitric oxide, despite a fall in hemoglobin, decreases after surgical closure of atrial septal defects. In contrast, exhaled nitric oxide levels increase after transcatheter closure. Exhaled nitric oxide levels may reflect bypass-induced endothelial cell injury and are independent of changes in pulmonary blood flow.

There have been remarkable advances in our understanding of the pathobiology of pulmonary hypertension. A region on chromosome 2 encoding bone morphogenetic receptor type 2 has been identified to underlie familial and many cases of sporadic primary pulmonary arterial hypertension. The vasoactive mediators, discovered and defined by vascular biologists, have been translated into promising treatments of human disease. Prostacyclin, endothelin receptor blockers, sildenafil, and nitric oxide have been applied therapeutically to limit, and occasionally reverse, the inexorable damage to the pulmonary circulation initiated by recently identified genetic and environmental triggers of pulmonary arterial hypertension.

Background: The historic outcome of the Fontan procedure in children with single ventricle and heterotaxy syndrome has been poor, and in the current era it has been incompletely described., Methods: From January 1993 through April 2000, 30 patients (age range, 5.3 +/- 3.6 years) had total cavopulmonary connection for single ventricle and isomerism and heterotaxy syndrome. Right atrial isomerism and heterotaxy (n = 19) or left atrial isomerism and heterotaxy (n = 11) were associated with a morphologic right ventricle (n = 26), a common atrioventricular valve (n = 25), pulmonary atresia (n = 9) or stenosis (n = 17), anomalous pulmonary venous drainage (partial, n = 7; total, n = 11; obstructed, n = 4), and interrupted inferior vena cava (n = 13). A previous systemic to pulmonary artery shunt had been performed in 21 patients, and 3 patients had previous pulmonary artery banding. The Fontan procedure was staged in all but 3 patients at a median age of 12 months (range, 3 to 114 months). Before the Fontan procedure, atrial arrhythmia was present in 7 patients (23%)., Results: An extracardiac conduit was constructed in 22 patients (median diameter, 20 mm; range, 16 to 27 mm), and a lateral tunnel was constructed in 4 patients. Associated procedures included pulmonary artery augmentation (n = 17), repair of anomalous pulmonary venous drainage (n = 7), and repair of a regurgitant atrioventricular valve (n = 2). The mean cardiopulmonary bypass time was 134 +/- 57 minutes. Cardioplegic cardiac arrest was used in 12 patients for a mean duration of 62 +/- 28 minutes. There were four hospital deaths (13%), three that occurred in children having concomitant repair of anomalous pulmonary venous drainage (previously undetected in one). Thirteen children (41%) developed early postoperative atrial arrhythmias, 11 of the 13 children required temporary pacing. There was one late death. Follow-up (3.4 +/- 2.7 years) was available on 24 of 25 survivors. All but 2 patients were in sinus rhythm., Conclusions: Early and midterm outcomes after the Fontan procedure in this patient group improved and may be further ameliorated by detecting and repairing associated obstruction to pulmonary venous flow and performing atrioventricular valvuloplasty before the Fontan procedure.

Background: Chylopericardium is a rare complication after operation for congenital heart disease. The incidence and clinical outcomes in a large cohort of surgical patients are unknown., Methods: We retrospectively reviewed the clinical records spanning more than 12 years in a single institution of 16 children with chylopericardium after cardiac operation., Results: We identified 16 patients with chylopericardium between 1985 and 1997. Chylopericardium was isolated in 7 patients. Twelve patients required pericardial drainage. Patients with isolated chylopericardium presented late and were treated initially as having postpericardiotomy syndrome. Three patients underwent thoracic duct ligation. There were two late deaths unrelated to the chylothorax. Associated diagnoses were internal jugular vein thrombosis and recurrent pulmonary vein obstruction (1 of 16 patients), an associated syndrome but not Turner or Noonan (10 of 16), superior cavopulmonary or total cavopulmonary anastomosis (7 of 16), atrioventricular septal defect repair (5 of 16), and repair of tetralogy of Fallot (2 of 16)., Conclusions: Percutaneous drainage to relieve tamponade together with a low-fat or medium-chain triglyceride diet results in resolution in most cases of postoperative chylopericardium. If a pericardial effusion enlarges, fails to clear on aspirin therapy, or presents late after hospital discharge, diagnostic pericardial tap and a low-fat diet are indicated.

Objective: We describe the angiographic diagnosis and significance of persistence of the primitive hepatic venous plexus with underdevelopment of the infrahepatic inferior vena cava., Conclusion: We recommend that inferior venacavography be performed in routine assessment before surgery of patients with azygos or hemiazygos continuation of the inferior vena cava, in whom redirection of systemic venous blood to the pulmonary artery is contemplated.

We report a patient with terminal transverse limb defects associated with persistent primitive aorto-pulmonary vascular connections leading to supra-systemic pulmonary artery pressure. It is likely that this patient represents a vascular disruption sequence or as an alternative a form of Adams-Oliver syndrome. These assumptions are based only on the association of vascular abnormalities as an emerging and apparently important association with transverse limb defects despite the absence of aplasia cutis congenita commonly associated with Adams-Oliver syndrome., (Copyright 2000 Wiley-Liss, Inc.)

Objectives: We compared the ability of inhaled nitric oxide (NO), oxygen (O2) and nitric oxide in oxygen (NO+O2) to identify reactive pulmonary vasculature in pulmonary hypertensive patients during acute vasodilator testing at cardiac catheterization., Background: In patients with pulmonary hypertension, decisions regarding suitability for corrective surgery, transplantation and assessment of long-term prognosis are based on results obtained during acute pulmonary vasodilator testing., Methods: In group 1, 46 patients had hemodynamic measurements in room air (RA), 100% O2, return to RA and NO (80 parts per million [ppm] in RA). In group 2, 25 additional patients were studied in RA, 100% O2 and 80 ppm NO in oxygen (NO+O2)., Results: In group 1, O2 decreased pulmonary vascular resistance (PVR) (mean+/-SEM) from 17.2+/-2.1 U.m2 to 11.1+/-1.5 U.m2 (p < 0.05). Nitric oxide caused a comparable decrease from 17.8+/-2.2 U.m2 to 11.7+/-1.7 U.m2 (p < 0.05). In group 2, PVR decreased from 20.1+/-2.6 U.m2 to 14.3+/-1.9 U.m2 in O2 (p < 0.05) and further to 10.5+/-1.7 U.m2 in NO+O2 (p < 0.05). A response of 20% or more reduction in PVR was seen in 22/25 patients with NO+O2 compared with 16/25 in O2 alone (p = 0.01)., Conclusions: Inhaled NO and O2 produced a similar degree of selective pulmonary vasodilation. Our data suggest that combination testing with NO + O2 provides additional pulmonary vasodilation in patients with a reactive pulmonary vascular bed in a selective, safe and expeditious fashion during cardiac catheterization. The combination of NO+O2 identifies patients with significant pulmonary vasoreactivity who might not be recognized if O2 or NO were used separately.

We report a 14 year old boy who presented as a neonate with functional pulmonary atresia due to Uhl's disease with emphasis on the later detection of restrictive right ventricular physiology.

Objectives: We reviewed the factors contributing to or causing death before surgery in neonates with d-transposition of the great arteries (TGA) despite anatomy suitable for the arterial switch operation (ASO) to develop strategies to minimize preoperative attrition., Background: Currently the ASO for neonates with TGA carries a low operative mortality. However, there is a paucity of information regarding the patients who die before the ASO. Strategies to ensure survival to operation are of importance to improve overall outcome., Methods: We reviewed all neonates with TGA and patent forearm ovale (PFO) < or = 2 mm, a birthweight <2 kg, or who died before surgery, between 1988 and 1996., Results: We identified 12 out of 295 neonates with TGA (4.1%) with anatomy suitable for the ASO who died prior to surgery. All had TGA/intact ventricular septum (IVS) and presented with a severely restrictive PFO. In 11 of 12 cases the cause of death was attributed to the sequelae of profound hypoxemia from inadequate mixing. Contributing factors were prematurity, 41.7%; severe respiratory distress syndrome, 25%; and persistent pulmonary hypertension of the newborn (PPHN), 16.7%. All patients received prostaglandin E1 (PGE1) infusion. Urgent balloon atrial sepstostomy (BAS) was performed in 66.7% with improved oxygenation. No cases were diagnosed prenatally. In contrast, all patients with a PFO < or = 2 mm who survived to ASO had a significantly better response to PGE1 infusion (p=0.03) than nonsurvivors. The ASO was accomplished without mortality in four of nine with a weight <2 kg., Conclusions: Of those neonates admitted with TGA, 4.1% died before surgery. Eleven of 12 (3.7%) died due to consequences of inadequate interatrial mixing despite PGE1 infusion. Earlier diagnosis and BAS are critically important in determining survival. Early ASO may improve survival in patients weighing <2 kg. Prenatal diagnosis with delivery in a high-risk obstetrical unit with facilities for immediate BAS and supportive therapy for pulmonary hypertension and ventricular failure may be necessary to salvage this group of patients.

Background: The identification of moderate to severe preoperative truncal valve regurgitation has been synonymous with significant postoperative mortality after neonatal repair of truncus arteriosus. Spurned by the deficiencies of current truncal valve substitutes surgeons are once again reexamining the option of truncal valve reparative techniques., Methods: From May 1996 until June 1997, 8 children underwent correction of truncus arteriosus. A retrospective analysis was conducted., Results: There was one in-hospital death secondary to a postoperative massive coronary air embolism. Moderate-to-severe truncal valve regurgitation was identified clinically and confirmed with cardiac ultrasound in 3 neonates with a mean age of 7 days (range, 4 to 12 days) all with quadracusp truncal valves. Successful truncal valve repair was accomplished in 2 infants, with a third neonate requiring homograft replacement with coronary reimplantation for failure in achieving valvular competence after attempted valvuloplasty. Postoperative echocardiograms in those neonates who underwent truncal valve repair confirmed a functional "tricuspid" valve with only mild to mild-plus regurgitation., Conclusions: We give further credence to the hypothesis that primary neonatal truncal valve repair is feasible and may be successful in the avoidance and delay of serial truncal valve replacements using either mechanical or allograft substitutes.

We describe a technique for transvenous, transatrial selective coronary arteriography, which may prove useful in the diagnostic evaluation of the neonate with pulmonary atresia with intact ventricular septum when right ventriculography and antegrade aortography inadequately define the coronary arterial circulation.

Objective: To determine the effect of inhaled nitric oxide (NO) on clinical outcome in newborns with persistent pulmonary hypertension (PPHN)., Design: A prospective, randomized trial of patients referred to a level 3 nursery in a single large center. Clinicians were not masked to group assignment. Crossover of patients from control to NO treatment was not permitted., Methods: We randomized 49 mechanically ventilated newborns, transferred to our center with clinical and echocardiographic evidence of severe PPHN (arterial oxygen tension [PaO2] <100; fractional inspired oxygen = 1) to treatment with or without NO. Patients with gestational age <34 weeks or with congenital heart disease or diaphragmatic hernia were excluded. High-frequency oscillatory ventilation was used but not allowed concomitantly with NO. Primary outcome variables were oxygenation, mortality, and use of extracorporeal membrane oxygenation (ECMO)., Results: Meconium aspiration syndrome and isolated PPHN were the most common diagnoses (32/49) and were distributed equally between groups. The median age at the time of entry into the study was similar between groups, 25 hours for control patients and 18 hours for NO patients. Median baseline oxygenation index (OI) was similar in 23 control (OI = 29) and 26 NO (OI = 30) patients. Mortality (8%), use of ECMO (33%), median days on mechanical ventilation (9 days), and duration of supplemental oxygen (13 days) were not different between treatment groups. PaO2, oxygen saturation, and OI improved in the NO group compared with baseline and to control patients at 15 minutes. The median percent change in OI (-31%) in the NO group was significantly different from baseline and from the control group. The difference in oxygenation between treatment groups was still apparent 12 hours after baseline. Before cannulation for ECMO, oxygenation was better in the NO group compared with control patients. Among patients who were placed on ECMO, the median time from baseline to ECMO cannulation was 2.4 hours (range, 1 to 12 hours) among control patients and 3.3 hours (range, 2 to 68 hours) for those randomized to receive NO. There was a tendency to observe fewer adverse neurologic events (seizure and intracranial hemorrhage) in the NO group (4/26 vs 8/23). One child with alveolar capillary dysplasia confirmed by postmortem examination could not be weaned from 80 parts per million of NO and transiently developed methemoglobinemia (peak methemoglobin level = 17%). No other side effects were observed., Conclusions: Although mortality and ECMO use were similar for both treatment groups using this study size and design, sustained improvement in oxygenation with NO and better oxygenation at initiation of ECMO may have important clinical benefits. We speculate that modification of treatment to include specific lung expansion strategies with NO treatment and recognition that early improvement of oxygenation may be sustained with NO may lead to reduced use of ECMO in NO treated patients compared with controls.

Objectives: This study was undertaken to investigate the long-term outcome of balloon angioplasty for recurrent coarctation of the aorta in a large series of patients., Background: Balloon angioplasty has become the standard treatment for residual or recurrent aortic coarctation. Despite the widespread use of this treatment modality, there are few data outlining the long-term outcome of a large patient cohort., Methods: Clinical, echocardiographic, hemodynamic and angiographic data on 90 consecutive patients who underwent balloon angioplasty between January 1984 and January 1996 were reviewed., Results: Mean systolic pressure gradients were reduced from 31 +/- 21 to 8 +/- 9 mm Hg after dilation (p = 0.0001). The mean diameter of the stenotic site, measured in the frontal and lateral views, increased by 38% and 35%, respectively (p = 0.001). Neurologic events occurred in two patients, with one death. An aortic tear occurred in one patient, requiring surgical intervention. Optimal results were defined as a postprocedure gradient < 20 mm Hg and were obtained acutely in 88% of patients. At long-term follow-up (12 years), 53 (72%) of 74 patients with an early optimal result remained free from reintervention. Transverse arch hypoplasia, defined as an arch dimension < 2 SD below the mean for age, was the primary predictor of the need for reintervention., Conclusions: Although the majority of patients undergoing percutaneous balloon angioplasty for recoarctation of the aorta will achieve long-term benefit, the need for further surgical intervention in those with transverse arch hypoplasia remains high.

Objectives: We report the clinical course and unique hemodynamic findings after placement of a supraannular mitral valve prosthesis., Background: Children with symptomatic mitral valve disease whose annulus is too small for the smallest prosthesis are difficult to manage. One option is valve replacement with a prosthesis positioned entirely within the left atrium (LA)., Methods: We reviewed 17 patients (median age 10 months) with symptomatic mitral valve disease who underwent placement of a supraannular valve prosthesis between 1980 and 1994., Results: The actuarial survival rates were 88% at 1 month and 71%, 62% and 53% at 1, 2 and 10 years, respectively. Preoperative hemodynamic data (mean +/- SD)) compared with those after placement of the supraannular mitral prosthesis were as follows: "a" wave to left ventricular end-diastolic pressure gradient 17 +/- 5 versus 4 +/- 4 mm Hg (p = 0.003), mean LA pressure 25 +/- 6 versus 20 +/- 6 mm Hg (p = 0.07), "a" wave 30 +/- 6 versus 19 +/- 5 mm Hg (p = 0.006), "v" wave 28 +/- 5 versus 30 +/- 9 mm Hg (p = 0.31), mean pulmonary artery pressure 54 +/- 19 versus 42 +/- 15 mm Hg (p = 0.07) and left ventricular end-diastolic pressure 14 +/- 5 versus 16 +/- 4 mm Hg (p = 0.12)., Conclusions: Supraannular mitral valve replacement provides relief of mitral stenosis or mitral regurgitation. However, LA to left ventricular early diastolic gradients with large atrial "v" waves contribute to elevated mean LA pressures in the absence of prosthetic valve obstruction or regurgitation. As a result of this unexpected finding, associated left heart obstructive lesions and pulmonary and left ventricular end-diastolic hypertension, the outlook remains poor.

Background: We describe the hemodynamic response to initiation and withdrawal of inhaled nitric oxide (NO) in infants with pulmonary hypertension after surgical repair of total anomalous pulmonary venous connection., Methods: Between January 1, 1992, and January 1, 1995, 20 patients underwent repair of total anomalous pulmonary venous connection. Nine patients had postoperative pulmonary hypertension and received a 15-minute trial of inhaled NO at 80 parts per million. Five of these patients received prolonged treatment with NO at 20 parts per million or less., Results: Mean pulmonary artery pressure decreased from 35.6 +/- 2.4 to 23.7 +/- 2.0 mm Hg (mean +/- standard error of the mean) (p = 0.008), and pulmonary vascular resistance decreased from 11.5 +/- 2.0 to 6.4 +/- 1.0 U.m2 (p = 0.03). After prolonged treatment with NO, pulmonary artery pressure increased transiently in all patients when NO was discontinued., Conclusions: After operative repair of total anomalous pulmonary venous connection, inhaled NO selectively vasodilated all patients with pulmonary hypertension. Withdrawal of NO after prolonged inhalation was associated with transient rebound pulmonary hypertension that dissipated within 60 minutes. Appreciation of rebound pulmonary hypertension may have important implications for patients with pulmonary hypertensive disorders when interruption of NO inhalation is necessary or when withdrawal of NO is planned.

We demonstrated selective pulmonary vasodilation in patients with congenital mitral stenosis with inhaled NO, and used NO as prolonged therapy to stabilize the postintervention course of these children. The pulmonary vasoreactivity was greater than that previously reported in adults and may be due to particular sensitivity of pulmonary veins to inhaled NO when pulmonary venous hypertension has been present since birth.

Objectives: We investigated the effect of inhaled nitric oxide and infused acetylcholine in patients with pulmonary hypertension undergoing cardiac catheterization before cardiopulmonary transplantation., Background: The fate of patients under consideration for transplantation of the heart or lungs, or both, is influenced by the evaluation of their pulmonary vascular reactivity., Methods: We evaluated 11 patients who were classified into two groups on the basis of mean left atrial pressure > 15 mm Hg (group I, n = 6) or < or = 15 mm Hg (group II, n = 5). All patients inhaled nitric oxide at 80 ppm. This was preceded by an infusion of 10(-6) mol/liter of acetylcholine in seven consecutive patients (n = 3 in group I, n = 4 in group II)., Results: In group I, inhaled nitric oxide decreased pulmonary artery pressure from (mean +/- SE) 71 +/- 13 to 59 +/- 10 mm Hg (p < 0.05), pulmonary vascular resistance from 14.9 +/- 3.8 to 7.6 +/- 1.7 Um2 (p < 0.05) and intrapulmonary shunt fraction from 17.8 +/- 3.6% to 12.7 +/- 2.1% (p < 0.05). Left atrial pressure tended to increase from 27 +/- 4 to 32 +/- 5 mm Hg (p = 0.07). In group II pulmonary vascular resistance decreased in response to nitric oxide from 36.4 +/- 9.0 to 31.1 +/- 7.9 Um2 (p < 0.05). Cardiac index, systemic pressure and resistance did not change in either group. Seven patients who received acetylcholine had no significant alteration in pulmonary hemodynamic variables., Conclusions: These preliminary observations suggest that nitric oxide is a potent pulmonary vasodilator with minimal systemic effects. It may be useful in discriminating patients needing combined heart and lung transplantation from those requiring exchange of the heart alone.

Objectives: The aim of this study was to assess the morphology of the coronary sinus, its drainage and associated cardiac malformations when there is either complete unroofing of the coronary sinus or atresia of its connection to the right atrium., Background: As more children with complex cardiac anomalies are accepted for primary surgical repair or palliation with cavopulmonary anastomoses, a knowledge of coronary sinus and systemic venous anomalies is important if coronary venous return is to be preserved and residual shunts avoided., Methods: Twenty-six heart-lung specimens without a coronary sinus draining to the right atrium were identified from the Leiden collection of congenital heart malformations. These were classified into specimens with an unroofed coronary sinus and those with atresia of the coronary sinus orifice. Attention was paid to the associated cardiac malformations., Results: In 14 (54%; confidence limits [CL] 35%, 73%) of 26 specimens, there was an unroofed coronary sinus, associated with persistence of the left superior caval vein. An inferoposterior location of an atrial septal defect was detected in 2 (14%; CL -4%, 33%) of 14. Atrial appendage anomalies were seen in 13 (93%; CL 79%, 106%) of 14 specimens, exemplified by both right and left isomerism. These were frequently associated with an atrioventricular septal defect (12 [86%; CL 67%, 104%] of 14). An atretic coronary sinus orifice was seen in 12 (46%; CL 27%, 65%) of 26. Atrial appendage anomalies (2 [17%; CL -4%, 38%] of 12) were rare in these cases. The drainage was then by way of a left superior caval vein or, in its absence, a coronary sinus to left atrial window. Ventricular hypoplasia was seen in both categories of coronary sinus abnormalities. Important ventricular hypoplasia was seen in 12 cases (46%; CL 27%, 65%)., Conclusions: These findings emphasize the need to study coronary sinus drainage before procedures such as ligation or transcatheter coil embolization of a left superior caval vein, venous redirection or closure of a dorsal atrial septal defect are contemplated. These procedures might inadvertently lead to impairment of coronary venous return or persistence of an intracardiac shunt.

We have presented our experience with the use of inhaled nitric oxide in children with congenital heart disease and pulmonary hypertension, which indicates that nitric oxide is a selective pulmonary vasodilator that may improve patient management, particularly after surgical procedures requiring cardiopulmonary bypass. Indeed, we have now seen several patients in whom all resuscitative maneuvers for the treatment of pulmonary hypertensive crises were unsuccessful until inhaled nitric oxide was added to the therapeutic regimen. In addition, our studies using inhaled nitric oxide as an investigational probe point toward endothelial injury as a contributor to post-cardiopulmonary bypass pulmonary vasoconstriction. Inhaled nitric oxide relieves pulmonary vasoconstriction associated both with left atrial or pulmonary venous hypertension and following the relief of mitral valve or pulmonary venous obstruction. Absence of a response on the usually reactive pulmonary vascular bed of the neonate should prompt a careful search for anatomic, and possibly surgically remediable, pulmonary vascular obstruction. In the short term nitric oxide is less effective in the older patient with obliterative pulmonary vascular disease. It is possible that recent experimental work with long-term nitric oxide inhalation might be applicable to this group of patients. Nitric oxide may have a unique role in the management of the patient after lung transplantation, as it both reduces right ventricular afterload and improves intrapulmonary shunting. Is nitric oxide the ideal agent for testing pulmonary vascular reactivity? Nitric oxide is simple to deliver by either mask or ventilator and, as a trial of vasoreactivity over 15 min, remains free of side effects that might be encountered during long-term administration, such as methemoglobinemia or nitrogen dioxide toxicity. Indeed, no patient developed significant methemoglobinemia after a trial of nitric oxide and neither was a level of nitrogen dioxide above 1 ppm registered during the administration. Thus, nitric oxide gas fulfills many of the ideal characteristics, as suggested by Rubin,92 required of a drug to test the acute responsiveness of the pulmonary circulation. It has better pulmonary dilating effects than systemic, a short half-life, and minimal adverse effects and it can be both easily and quickly administered. Whether it is able to reliably predict the effect of long-term administration of orally active agents awaits confirmation. Certainly, inhaled nitric oxide is rapidly becoming the standard agent to test pulmonary vascular reactivity during diagnostic cardiac catheterization at our institution.

Objective: The development of a safe, portable, accurate, and adaptable system to deliver nitric oxide to patients with pulmonary hypertension., Design: A prospective, clinical study., Setting: Tertiary care pediatric intensive care unit and cardiac catheterization laboratory., Patients: One hundred twenty-three patients (median age 11 months, range 1 day to 72 yrs) with pulmonary hypertension who were administered nitric oxide between November 1991 and July 1993. Ninety-one patients were mechanically ventilated (volume-controlled ventilator, n = 53; pressure-controlled ventilator, n = 5; and a pressure-limited, time-cycled infant ventilator, n = 25). The system was adapted to allow high-frequency oscillator (n = 2) or hand ventilation, and for intraoperative use with an anesthesia machine (n = 6). Thirty-two patients were breathing spontaneously through a mask without assistance., Interventions: Nitric oxide was delivered at 10 to 80 parts per million (ppm); the dose was adjusted independently of the FIO2 without altering minute ventilation or tidal volume., Measurements and Main Results: Nitrogen dioxide was continuously monitored and exceeded 3 ppm in only four patients. Methemoglobin concentrations were < 5% in all but four patients. Nitric oxide doses remained stable, independent of minute ventilation and could be changed easily and quickly., Conclusions: Inhaled nitric oxide can be administered precisely and reliably through a variety of delivery systems which can be used in patients of any size. Potential toxicity requires careful monitoring and continued improvement on apparatus design.

Pulmonary hypertension and transient graft dysfunction may complicate the postoperative course of patients undergoing lung transplantation. We report the acute effect of inhaled nitric oxide (80 ppm) on hemodynamics and gas exchange in 6 patients (median age, 14 years; range, 5 to 21 years) after lung transplantation as well as the effect of extended treatment over 40 to 69 hours in 2 patients. In 5 patients with pulmonary hypertension nitric oxide lowered mean pulmonary artery pressure (from 38.4 +/- 1.6 to 29.4 +/- 3.1 mm Hg; p < 0.05), pulmonary vascular resistance index (from 9.3 +/- 1.4 to 6.4 +/- 1.3 Um2; p < 0.05), and intrapulmonary shunt fraction (from 28.6% +/- 8.3% to 21.0% +/- 5.7%; p < 0.05). There was a 28.4% +/- 7.2% reduction in transpulmonary pressure gradient with only minor accompanying effects on the systemic circulation. Mean arterial pressure decreased only 2.7% +/- 5% (from 76.4 +/- 2.2 to 74 +/- 2.3 mm Hg; p = not significant), and systemic vascular resistance index by 4.2% +/- 9.7% (from 21.7 +/- 3.1 to 20.6 +/- 3.6 Um2; p = not significant). Cardiac index was unchanged (from 3.5 +/- 0.8 to 3.6 +/- 0.7 L.min-1.m-2; p = not significant). Nitric oxide caused a sustained improvement in oxygenation and pulmonary artery pressure during extended therapy at doses of 10 ppm. There were no major side effects. However, transient methemoglobinemia (9%) developed in 1 patient after 10 hours of nitric oxide treatment. Nitric oxide may be useful in the treatment of pulmonary hypertension and the impaired gas exchange that occurs after lung transplantation.

The plasma level of the potent vasoconstrictor endothelin-1 was measured in children who underwent cardiac operations. Forty-five patients were divided into two groups, those with a high pulmonary blood flow (HF group; n = 23) and those with a normal or low flow (NF group; n = 22). Seven blood samples were taken: immediately before cardiopulmonary bypass, immediately after removing the aortic cross-clamps, immediately after discontinuing bypass, and at 20 minutes and 3, 6, and 24 hours after termination of bypass. The plasma levels of endothelin-1 were similar in both groups before bypass. From the time the aortic crossclamps were removed, the plasma endothelin-1 levels in both groups increased significantly, to reach a peak level at 3 to 6 hours. The increase was significantly greater in the HF than in the NF group, and the maximum values in the two groups were 12.6 +/- 1.1 and 9.6 +/- 0.8 fmol/ml, respectively (mean +/- standard error of the mean, p < 0.05). The value 20 minutes after bypass showed a positive correlation with the mean pulmonary arterial pressure measured at the preoperative cardiac catheterization study (r = 0.41, p < 0.05). In addition, a significant positive correlation was obtained between endothelin-1 3 hours after bypass and the maximum pulmonary/systemic arterial pressure ratio during the first 12 hours after operation (r = 0.86, p < 0.05). These results suggest that cardiopulmonary bypass is associated with an immediate postoperative increase in circulating endothelin and that patients who had a high pulmonary blood flow before the operation are particularly vulnerable, bypass having a more injurious effect on a lung with preexisting endothelial dysfunction. A high level of circulating endothelin may predispose to pulmonary vascular lability and pulmonary hypertensive crises in the postoperative period.