Porcine Model of the Arterial Switch Operation: Implications for Unique Strategies in the Management of Hypoplastic Left Ventricles.

There are no reports on the performance of the arterial switch operation (ASO) in a normal heart with normally related great vessels. The objective of this study was to determine whether the ASO could be performed in a healthy animal model. Cardiopulmonary bypass (CPB) and coronary translocation techniques were used to perform ASO in neonatal piglets or a staged ASO with prior main pulmonary artery (PA) banding. Primary ASO was performed in four neonatal piglets. Coronary translocation was effective with angiograms confirming patency. Piglets could not be weaned from CPB due to right ventricle (RV) dysfunction. To improve RV function for the ASO, nine piglets had PA banding. All survived the procedure. Post-banding RV pressure increased from a mean of 20.3 ± 2.2 mmHg to 36.5 ± 7.3 mmHg (p = 0.007). At 58 ± 1 days post-banding, piglets underwent cardiac MRIs revealing RV hypertrophy, and RV pressure overload with mildly reduced RV function. Catheterization confirmed RV systolic pressures of 84.0 ± 6.7 mmHg with LV systolic pressure 83.3 ± 6.7 mmHg (p = 0.43). The remaining five PA banded piglets underwent ASO at 51 ± 0 days post-banding. Three of five were weaned from bypass with patent coronary arteries and adequate RV function. We were able to successfully perform an arterial switch with documented patent coronary arteries on standard anatomy great vessels in a healthy animal model. To our knowledge this is the first time this procedure has been successfully performed. The model may have implications for studying the failing systemic RV, and may support a novel approach for management of borderline, pulsatile left ventricles.

Mechanical hemolysis in pediatric patients associated with rapid transfusion and one-way valve.

BACKGROUND: Four similar transfusion reactions involving infants were reported in less than 1 year. After transfusion of red blood cells (RBCs) via syringe in the operating room, each patient experienced discolored urine, laboratory evidence of hemolysis, and acute kidney injury. Clerical and serologic investigations were unremarkable. Mechanical hemolysis was considered. STUDY DESIGN AND METHODS: Simulated syringe transfusions were performed. Measurements included hematocrit (Hct), free hemoglobin, and visual hemolysis index. Washed and unwashed RBCs were tested with or without a recently introduced one-way valve, using a 24- or 16-gauge intravenous catheter. Constant manual pressure (1.43 ± 0.49 mL/sec) or syringe pump (2 mL/min) was used and a subset was timed. RESULTS: The valve increased hemolysis during manual transfusion using both catheters with washed and unwashed RBCs. With the 24-gauge catheter, the change in Hct was -3.53 ± 0.69% with the valve and 0.22 ± 0.13% without (p < 0.00001). Comparing the individual valves tested, differences in hemolysis were observed (change in Hct, p < 0.0001). During manual transfusion with 24-gauge catheter and unwashed RBCs, the degree of hemolysis was greater when it took longer to transfuse with a valve (change in Hct versus time, r = -0.75, p < 0.0001) compared to a slight increase in hemolysis for samples that took less time to transfuse without a valve (change in Hct versus time, r = 0.58, p = 0.23). CONCLUSIONS: Mechanical hemolysis should be considered when investigating possible hemolytic transfusion reactions, especially with high rates of transfusion and use of a valve. During rapid manual transfusion with the valve, greater resistance was associated with increased hemolysis.

Minimizing the risk of preoperative brain injury in neonates with aortic arch obstruction.

OBJECTIVE: To determine whether prenatal diagnosis lowers the risk of preoperative brain injury by assessing differences in the incidence of preoperative brain injury across centers. STUDY DESIGN: From 2 prospective cohorts of newborns with complex congenital heart disease studied by preoperative cerebral magnetic resonance imaging, one cohort from the University Medical Center Utrecht (UMCU) and a combined cohort from the University of California San Francisco (UCSF) and University of British Columbia (UBC), patients with aortic arch obstruction were selected and their imaging and clinical course reviewed. RESULTS: Birth characteristics were comparable between UMCU (n = 33) and UCSF/UBC (n = 54). Patients had a hypoplastic aortic arch with either coarctation/interruption or hypoplastic left heart syndrome. In subjects with prenatal diagnosis, there was a significant difference in the prevalence of white matter injury (WMI) between centers (11 of 22 [50%] at UMCU vs 4 of 30 [13%] at UCSF/UBC; P < .01). Prenatal diagnosis was protective for WMI at UCSF/UBC (13% prenatal diagnoses vs 50% postnatal diagnoses; P < .01), but not at UMCU (50% vs 46%, respectively; P > .99). Differences in clinical practice between prenatally diagnosed subjects at UMCU vs UCSF/UBC included older age at surgery, less time spent in the intensive care unit, greater use of diuretics, less use of total parenteral nutrition (P < .01), and a greater incidence of infections (P = .01). In patients diagnosed postnatally, the prevalence of WMI was similar in the 2 centers (46% at UMCU vs 50% at UCSF/UBC; P > .99). Stroke prevalence was similar in the 2 centers regardless of prenatal diagnosis (prenatal diagnosis: 4.5% at Utrecht vs 6.7% at UCSF/UBC, P = .75; postnatal diagnosis: 9.1% vs 13%, respectively, P > .99). CONCLUSION: Prenatal diagnosis can be protective for WMI, but this protection may be dependent on specific clinical management practices that differ across centers.

Tezosentan increases nitric oxide signaling via enhanced hydrogen peroxide generation in lambs with surgically induced acute increases in pulmonary blood flow.

We have previously shown that acute increases in pulmonary blood flow (PBF) are limited by a compensatory increase in pulmonary vascular resistance (PVR) via an endothelin-1 (ET-1) dependent decrease in nitric oxide synthase (NOS) activity. The mechanisms underlying the reduction in NO signaling are unresolved. Thus, the purpose of this study was to elucidate mechanisms of this ET-1-NO interaction. Pulmonary arterial endothelial cells were acutely exposed to shear stress in the presence or absence of tezosentan, a combined ET(A) /ET(B) receptor antagonist. Shear increased NO(x) , eNOS phospho-Ser1177, and H(2) O(2) and decreased catalase activity; tezosentan enhanced, while ET-1 attenuated all of these changes. In addition, ET-1 increased eNOS phospho-Thr495 levels. In lambs, 4 h of increased PBF decreased H(2) O(2) , eNOS phospho-Ser1177, and NO(X) levels, and increased eNOS phospho-Thr495, phospho-catalase, and catalase activity. These changes were reversed by tezosentan. PEG-catalase reversed the positive effects of tezosentan on NO signaling. In all groups, opening the shunt resulted in a rapid increase in PBF by 30 min. In vehicle- and tezosentan/PEG-catalase lambs, PBF did not change further over the 4 h study period. PVR fell by 30 min in vehicle- and tezosentan-treated lambs, and by 60 min in tezosentan/PEG-catalase-treated lambs. In vehicle- and tezosentan/PEG-catalase lambs, PVR did not change further over the 4 h study period. In tezosentan-treated lambs, PBF continued to increase and LPVR to decrease over the 4 h study period. We conclude that acute increases in PBF are limited by an ET-1 dependent decrease in NO production via alterations in catalase activity, H(2) O(2) levels, and eNOS phosphorylation.

Rosiglitazone preserves pulmonary vascular function in lambs with increased pulmonary blood flow.

BACKGROUND: Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect. METHODS: An aorta-to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR-γ agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk. Lung tissue from five normal 4-wk-old lambs was used for comparisons. RESULTS: At 4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled nitric oxide (NO) in RG- and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated, shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177 eNOS protein, and eNOS activity were increased, and NADPH activity, rac1, superoxide levels, and 3-NT levels were decreased, as compared with vehicle-treated shunt lambs. PPAR-γ protein expression was lower in vehicle-treated shunt lambs than in normal and RG-treated shunt lambs. CONCLUSION: The PPAR-γ agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.

Single-ventricle anatomy predicts delayed microstructural brain development.

BACKGROUND: Term newborns with congenital heart disease (CHD) show delayed brain development as early as the third trimester, especially in single-ventricle physiology (SVP). Mechanisms causing delayed brain development in CHD are uncertain but may include impaired fetal brain blood flow. Our objective was to determine if cardiac anatomy associated with obstruction to antegrade flow in the ascending aorta is predictive of delayed brain development as measured by diffusion tensor imaging and magnetic resonance spectroscopic (MRS) imaging. METHODS: Echocardiograms from 36 term newborns with SVP were reviewed for the presence of aortic atresia and the diameter of the ascending aorta. Quantitative magnetic resonance imaging parameters measuring brain microstructural (fractional anisotropy (FA) and average diffusivity (Dav)) or metabolic development (N-acetylaspartate (NAA) and lactate/choline (Lac/Cho)) were recorded. RESULTS: Increasing NAA/Cho and white matter (WM) FA, and decreasing Dav and Lac/Cho characterize normal brain development. Consistent with the hypothesis that delayed brain development is related to impaired brain perfusion, smaller ascending aortic diameter and aortic atresia were associated with higher Dav and lower WM FA. Echocardiogram variables were not associated with brain metabolic measures. CONCLUSIONS: These observations support the hypothesis that obstruction to fetal cerebral blood flow impairs brain microstructural development.

Pulmonary interstitial glycogenosis: an unrecognized etiology of persistent pulmonary hypertension of the newborn in congenital heart disease?

BACKGROUND: Pulmonary interstitial glycogenosis (PIG) arises from a developmental disorder of the pulmonary mesenchyme and presents clinically with reversible neonatal respiratory distress and/or persistent pulmonary hypertension of the newborn (PPHN). OBJECTIVE: We report two cases of PIG in patients with congenital heart disease (CHD) and evidence of PPHN. RESULTS: Both cases demonstrated the hallmark PIG histologic finding of diffuse, uniform interstitial thickening due to the presence of immature interstitial cells containing abundant cytoplasmic glycogen. CONCLUSIONS: We report the second and third patients with PIG associated with CHD. Because histologic examination is required to establish the diagnosis, we speculate that PIG, although rare, may be underrecognized in neonates presenting with PPHN in the setting of CHD.

Prenatal diagnosis of atrial restriction in hypoplastic left heart syndrome is associated with decreased 2-year survival.

OBJECTIVE: To compare the course of hypoplastic left heart syndrome (HLHS) patients diagnosed prenatally with any degree of atrial restriction with those without evidence of atrial restriction. DESIGN: Retrospective, cohort. METHODS: Prenatally diagnosed HLHS patients from August 1999 to January 2009 were categorized as nonrestrictive versus restrictive, defined by left atrial hypertension on pulmonary venous Doppler and/or an intact interatrial septum. RESULTS: Of 73 total fetal patients identified, 49 were live-born. Survival at 2 years was 29/35 [83% confidence interval (CI): 59.5%-88.9%] for the nonrestrictive group and 6/14 (43% CI: 17.7%-6.0%) for the restrictive group (p<0.0001). Of those who underwent stage 1 palliation (35 with nonrestrictive and 10 with restrictive atrial septa), both groups had a similar incidence of preoperative acidosis and need for ventilation and inotropic support. Postoperatively, there was no difference between groups in ventilator days, length of stay, or survival to discharge. There was decreased survival at 2 years in the restrictive group, 60% (CI: 26.2%-87.8%) versus 83% (CI: 66.4%-93.4%) in the nonrestrictive group. Furthermore, a disproportionate number of interstage deaths was evident in the restrictive group. CONCLUSIONS: Prenatal presence of any degree of atrial septal restriction in the setting of HLHS confers a significant survival disadvantage, with increases in both early and late mortality.

Surgical management of left ventricular outflow tract obstruction.

BACKGROUND: Left ventricular outflow tract obstruction (LVOTO) is caused by a spectrum of lesions. This study was performed to determine the outcomes of surgical management of LVOTO. METHODS: All patients who had surgery of the LVOT between 2002 and 2010 were retrospectively reviewed. RESULTS: There were 103 consecutive patients with median age 6.8 years (range 8 days to 62 years). Fourteen patients had simple subaortic membrane. Eighty-nine patients had complex LVOTO including fibromuscular obstruction (n = 53), tunnel obstruction (n = 22), hypertrophic cardiomyopathy/muscular obstruction (n = 15), and anomalies of the mitral subvalvar apparatus (n = 13). There were no early deaths. Mean LVOT gradient decreased from 33 mmHg (range 1 to 108 mmHg) to 6 mmHg (range 0 to 45 mmHg) (p < 0.001). Median follow-up was 3.8 years (range 0.9 to 8.5 years). There were three late deaths. Cumulative survival at one, three, and five years was 96% (95% CI 89% to 99%). All patients are in New York Heart Association classes I-II. Ten patients required reoperation (three for recurrent/residual LVOTO). Freedom from reoperation was 94%, 90%, and 78% at one, three, and five years (95% CI 86% to 98%, 80% to 95%, and 59% to 89%, respectively). No patient with complex LVOTO who had release of the fibrous trigones required reoperation [0% (0/26) vs. 16% (10/63) (p = 0.031)]. Factors associated with increased reoperation risk were interrupted aortic arch (OR 6.4, p = 0.22), atrioventricular septal defect (OR 15.4, p = 0.008), and higher mean LVOT gradient at discharge (OR 1.08, p = 0.023). CONCLUSIONS: Utilizing a multitude of operative strategies for surgery of the LVOT results in favorable early and midterm outcomes. Residual LVOTO and original cardiac diagnosis are associated with increased reoperation risk. Release of the fibrous trigones decreases reoperation risk in patients with complex LVOTO.

Ross-Konno and endocardial fibroelastosis resection after hybrid stage I palliation in infancy: successful staged left-ventricular rehabilitation and conversion to biventricular circulation after fetal diagnosis of aortic stenosis.

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction.

Aortic stenosis in a patient with Hurler's syndrome after bone marrow transplantation.

We describe a case of severe aortic stenosis in a 16-year-old male with Hurler's syndrome who had prior bone marrow transplantation. The excised aortic valve leaflets showed characteristic pathologic findings of Hurler's syndrome. This is the first case report of aortic valve replacement in a patient with Hurler's syndrome treated with bone marrow transplantation that demonstrates progression of the aortic valve disease despite treatment.

Infection and white matter injury in infants with congenital cardiac disease.

More than 60% of newborns with severe congenital cardiac disease develop perioperative brain injuries. Known risk factors include: pre-operative hypoxemia, cardiopulmonary bypass characteristics, and post-operative hypotension. Infection is an established risk factor for white matter injury in premature newborns. In this study, we examined term infants with congenital cardiac disease requiring surgical repair to determine whether infection is associated with white matter injury. Acquired infection was specified by site - bloodstream, pneumonia, or surgical site infection - according to strict definitions. Infection was present in 23 of 127 infants. Pre- and post-operative imaging was evaluated for acquired injury by a paediatric neuroradiologist. Overall, there was no difference in newly acquired post-operative white matter injury in infants with infection (30%), compared to those without (31%). When stratified by anatomy, infants with transposition of the great arteries, and bloodstream infection had an estimated doubling of risk of white matter injury that was not significant, whereas those with single ventricle anatomy had no apparent added risk. When considering only infants without stroke, the estimated association was higher, and became significant after adjusting for duration of inotrope therapy. In this study, nosocomial infection was not associated with white matter injury. Nonetheless, when controlling for risk factors, there was an association between bloodstream infection and white matter injury in selected sub-populations. Infection prevention may have the potential to mitigate long-term neurologic impairment as a consequence of white matter injury, which underscores the importance of attention to infection control for these patients.

Anisotropic Polytetrafluoroethylene Cardiovascular Conduits Spontaneously Expand in a Growing Lamb Model.

BACKGROUND: Insertion of conduits from the right ventricle (RV) to the pulmonary artery (PA) is a commonly used technique for repair of congenital heart defects. The vast majority of infants and children will require reoperation and/or re-intervention to replace the conduit. Some children may require multiple reoperations, with the risk of death and morbidity increasing significantly with each subsequent operation. We evaluated the feasibility and performance of a relatively novel anisotropic conduit for cardiovascular repair in the growing lamb model. MATERIALS AND METHODS: Lambs were allocated into a control (n = 3) or test (n = 4, anisotropic) conduit group. Control conventional polytetrafluoroethylene (PTFE) conduits or test anisotropic expanded PTFE (ePTFE) based test conduits measuring 10-11 mm in diameter were sewn as interpositional grafts in the main pulmonary artery (MPA) and followed up to 6 months. Clinical and echocardiographic evaluations were performed monthly with hemodynamic and angiographic assessment at 3 and 6 months. RESULTS: Control conduits did not expand, all 3 animals developed one or more adverse events including tachypnea, ascites, inappetence, lethargy, and mortality due to severe right heart failure and significantly higher peak trans-conduit gradients (48.5 ± 5.1 p = 0.02). The test conduits spontaneously expanded up to 14.8 ± 0.8 mm in diameter, no adverse events were observed in any animals and trans-conduit gradients were significantly lower (27.0 ± 8.3, p = 0.02). CONCLUSIONS: Anisotropic ePTFE conduits can be safely implanted in growing lambs with stable hemodynamics. This spontaneously expanding anisotropic conduit may represent a novel approach to congenital heart repairs that would avoid the need for reoperation or multiple operations.

Feasibility Study of Catheter-Based Interventions for Anisotropic Expanded Polytetrafluoroethylene Cardiovascular Conduits in a Growing Lamb Model.

BACKGROUND: Cardiovascular repair in children often requires implant of conduits which do not have growth potential and will require reoperation. In the current study we sought to determine the feasibility of catheter-based interventions of anisotropic conduits inserted as interposition grafts in the main pulmonary artery (MPA) of growing lambs. METHODS: Lambs underwent interpositional implant of either an anisotropic expanded polytetrafluoroethylene (ePTFE) (Test) conduit or conventional PTFE (Control) conduit. In the postoperative period, lambs were anesthetized and underwent catheter-based interventions consisting of hemodynamic and angiographic data collection, balloon dilation and/or stenting of the conduit at 3, 6 or 9 month postoperative time point. RESULTS: At 3 months, control lambs showed significant increases in right ventricular pressures and trans-conduit gradients in comparison to test lambs. Test conduit diameters were significantly larger compared to controls due to spontaneous radial expansion of the anisotropic conduit. Balloon dilation of test conduits at 3 and 6 months showed a reduction in RV pressure and statistically significant improvement in the RV outflow tract gradient as well as significant increase in graft diameter, compared to both control and pre-dilation conditions. Furthermore, the test conduit diameter increased significantly compared to the pre-balloon and control conditions at each time point. Necropsy of test conduits showed no evidence of tears, perforations, or clot and smooth interiors with well-healed anastomoses. CONCLUSIONS: Anisotropic conduits implanted as interposition grafts in the MPA show spontaneous expansion, and can safely and effectively undergo catheter-based interventions, with significant increases in graft diameter occurring after balloon dilation.

Abnormal brain development in newborns with congenital heart disease.

BACKGROUND: Congenital heart disease in newborns is associated with global impairment in development. We characterized brain metabolism and microstructure, as measures of brain maturation, in newborns with congenital heart disease before they underwent heart surgery. METHODS: We studied 41 term newborns with congenital heart disease--29 who had transposition of the great arteries and 12 who had single-ventricle physiology--with the use of magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) before cardiac surgery. We calculated the ratio of N-acetylaspartate to choline (which increases with brain maturation), the ratio of lactate to choline (which decreases with maturation), average diffusivity (which decreases with maturation), and fractional anisotropy of white-matter tracts (which increases with maturation). We compared these findings with those in 16 control newborns of a similar gestational age. RESULTS: As compared with control newborns, those with congenital heart disease had a decrease of 10% in the ratio of N-acetylaspartate to choline (P=0.003), an increase of 28% in the ratio of lactate to choline (P=0.08), an increase of 4% in average diffusivity (P<0.001), and a decrease of 12% in white-matter fractional anisotropy (P<0.001). Preoperative brain injury, as seen on MRI, was not significantly associated with findings on MRS or DTI. White-matter injury was observed in 13 newborns with congenital heart disease (32%) and in no control newborns. CONCLUSIONS: Term newborns with congenital heart disease have widespread brain abnormalities before they undergo cardiac surgery. The imaging findings in such newborns are similar to those in premature newborns and may reflect abnormal brain development in utero.

Use of virtual reality for pre-surgical planning in separation of conjoined twins: A case report.

We describe the use of virtual reality technology for surgical planning in the successful separation of thoracopagus conjoined twins. Three-dimensional models were created from computed tomography angiograms to simulate the patient's anatomy on a virtual stereoscopic display. Members of the surgical teams reviewed the anatomical models to localize an interatrial communication that allowed blood to flow between the two hearts. The surgical plan to close the 1-mm interatrial communication was significantly modified based on the pre-procedural spatial awareness of the anatomy presented in the virtual visualization. The virtual stereoscopic display was critical for the surgical team to successfully separate the twins and provides a useful case study for the use of virtual reality technology in surgical planning. Both twins survived the operation and were subsequently discharged from the hospital.

Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects.

BACKGROUND AND PURPOSE: Brain injury is common in newborns with congenital heart disease (CHD) requiring neonatal surgery. The purpose of this study is to define the risk factors for preoperative and postoperative brain injuries and their association with functional cardiac anatomic groups. METHODS: Sixty-two neonates with CHD were studied with preoperative MRI, and 53 received postoperative scans. Clinical and therapeutic characteristics were compared in newborns with and without newly acquired brain injuries. A subset of 16 consecutive patients was monitored with intraoperative cerebral near-infrared spectroscopy. RESULTS: Brain injury was observed in 56% of patients. Preoperative brain injury, seen in 39%, was most commonly stroke and was associated with balloon atrial septostomy (P=0.002). Postoperative brain injury, seen in 35%, was most commonly white matter injury and was particularly common in neonates with single-ventricle physiology and aortic arch obstruction (P=0.001). Risk factors associated with acquired postoperative brain injury included cardiopulmonary bypass (CPB) with regional cerebral perfusion (P=0.01) and lower intraoperative cerebral hemoglobin oxygen saturation during the myocardial ischemic period of CPB (P=0.008). In a multivariable model, new postoperative white matter injury was specifically associated with low mean blood pressure during the first postoperative day (P=0.04). CONCLUSIONS: Specific modifiable risk factors can be identified for preoperative and postoperative white matter injury and stroke associated with neonatal surgery for CHD. The high incidence of postoperative injury observed despite new methodologies of CPB indicates the need for ongoing evaluation to optimize neurological outcome.

Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs.

OBJECTIVE: The objective of the study was to determine alterations in cGMP, soluble guanylate cyclase (sGC), phosphodiesterase type 5 (PDE5), and B-type natriuretic peptide (BNP), in an animal model of a congenital cardiac defect with increased pulmonary blood flow. DESIGN: Prospective, comparative, experimental study. SUBJECTS: Lambs, from birth until 8 weeks of age. METHODOLOGY: Late gestation fetal lambs underwent in utero placement of an 8 mm aortopulmonary vascular graft (shunt). In shunted and normal age-matched control lambs, at 2, 4, and 8 weeks of age, cGMP and BNP levels were measured, and sGC subunit and PDE5 protein expression were determined by Western blot analysis and immunohistochemistry. RESULTS: In shunted lambs, tissue and plasma cGMP levels were greater than normal throughout the 8-week study period (P < 0.05). sGCalpha protein was greater at 2 and 4 weeks (P < 0.05), and sGCbeta and PDE5 protein were greater at 4 weeks in shunted lambs (P < 0.05). Plasma BNP levels did not change in normal lambs but increased in shunted lambs by 8 weeks of age (P < 0.05). BNP levels were greater in shunted lambs than normal at 4 and 8 weeks (P < 0.05). CONCLUSIONS: Alterations in sGC subunit protein expression during the first post-natal month, and increased BNP levels during the second post-natal month contribute to elevations in plasma and lung tissue cGMP in lambs with increased pulmonary blood flow.

Regional and central venous oxygen saturation monitoring following pediatric cardiac surgery: concordance and association with clinical variables.

OBJECTIVE: To compare changes in regional cerebral or flank oxygen saturation measured by near-infrared spectroscopy with changes in central venous oxygen saturation (ScvO2) and to determine clinical variables associated with these changes. DESIGN: Prospective observational cohort study. SETTING: University tertiary care center, pediatric cardiac intensive care unit. PATIENTS: Seventy postoperative congenital cardiac surgical patients (median age 0.3 yrs; interquartile range 0.02-0.46 yrs). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured temporally correlated regional oxygen saturation (rSO2) with hematologic (hematocrit), biochemical (arterial blood gas, ScvO2, and lactate) and physiologic (temperature, heart rate, mean blood pressure, and pulse oximetry) variables in the first postoperative day. Cerebral and flank rSO2 were strongly correlated with ScvO2, in both cyanotic or acyanotic patients and single- or two-ventricle physiology with and without aortic arch obstruction (all p < .001). However, individual values had wide limits of agreement on Bland-Altman analysis. The correlations of change in these measurements were weaker but still significant (all p < .0001), again with wide limits of agreement. Similar direction of change in cerebral rSO2 and ScvO2 was present 64% (95% confidence interval, 55-73%) of the time. Change in arterial pressure of carbon dioxide (delta PaCO2) was associated with cerebral delta rSO2 (delta PaCO2 beta = 0.35, p < .0001) but not flank delta rSO2 or delta ScvO2. A pattern of relative cerebral desaturation (flank rSO2 > cerebral rSO2) was noted in a majority of patients (81%) with two-site monitoring regardless of bypass method or age. CONCLUSIONS: Neither individual values nor changes in rSO2 are interchangeable measures of ScvO2 in postoperative pediatric cardiac patients. The unique relationship between changes in PaCO2 and cerebral rSO2 supports the hypothesis that cerebral near-infrared spectroscopy monitors regional cerebral oxygenation. Clinical application of this monitor must include recognition of the clinical variables that affect regional brain oxygenation.

Undiagnosed coronary fistula causing low cardiac output syndrome after pediatric heart surgery.

A patient with preoperative pulmonary hypertension and a large left to right intracardiac shunt underwent surgical correction of a complex cardiac anomaly and required extracorporeal life support for unexplained ventricular dysfunction following the procedure. Following recovery, a fistulous connection between the right coronary artery and main pulmonary artery was demonstrated. Implications and management strategies of unsuspected coronary fistula in pediatric heart surgery are discussed.