Cardiopulmonary bypass in neonates and infants: advantages of high flow high hematocrit bypass strategy-clinical practice review.

Cardiopulmonary bypass is an integral and indispensable part of surgical repair of congenital heart defects. While the complications and morbidity secondary to the use of cardiopulmonary bypass has decreased considerably, there remains a significant incidence of clinically relevant renal and neurological injury. To provide more physiological delivery of oxygenated blood to the end-organs, our center has been successfully using a high-flow, high hematocrit cardiopulmonary bypass strategy since 2006. The essential components of this strategy include maintaining high flows (typically 200 mL/kg/min in neonates, 150-175 mL/kg/min in older infants weighing <10 kg, and 2.6 L/min/m2 in older children) throughout the duration of cardiopulmonary bypass irrespective of patient temperature, as well as maintaining a hematocrit of at least 32% on cardiopulmonary bypass. The incidence of post-operative acute kidney injury (around 3%) and clinical acute neurological events (<1%) with this strategy is considerably less when compared to other contemporary publications using the conventional cardiopulmonary bypass strategy. In this review, we discuss the rationale behind our approach and present evidence to support the high-flow, high-hematocrit strategy. We also discuss the practical aspects of our strategy and describe the adjuncts we use to derive additional benefits. These adjuncts include the use of a hybrid pH/alpha stat strategy during cooling/rewarming, aggressive use of conventional ultrafiltration during cardiopulmonary bypass, a terminal hematocrit of 40-45%, and avoidance of milrinone and albumin in the early peri-operative period. This results in a very low incidence of post-operative bleeding, facilitates chest closure in the operating room even in most neonates, helps in reducing the need for post-operative blood product transfusion and helps in achieving a favorable post-operative fluid balance early after surgery.

Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression.

Antibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal antibody preparation that causes antibody-mediated immunosuppression (AMIS), thereby preventing maternal immune responses against fetal RBCs. Despite the success of RhIg, it is only effective against 1 alloantigen. The lack of similar interventions that mitigate immune responses toward other RBC alloantigens reflects an incomplete understanding of AMIS mechanisms. AMIS has been previously attributed to rapid antibody-mediated RBC removal, resulting in B-cell ignorance of the RBC alloantigen. However, our data demonstrate that antibody-mediated RBC removal can enhance de novo alloimmunization. In contrast, inclusion of antibodies that possess the ability to rapidly remove the target antigen in the absence of detectable RBC clearance can convert an augmented antibody response to AMIS. These results suggest that the ability of antibodies to remove target antigens from the RBC surface can trigger AMIS in situations in which enhanced immunity may otherwise occur. In doing so, these results hold promise in identifying key antibody characteristics that can drive AMIS, thereby facilitating the design of AMIS approaches toward other RBC antigens to eliminate all forms of HDFN.

Incidence of Acute Neurological Events in Neonates and Infants Undergoing Cardiac Surgery Using a High-Hematocrit/ High-Flow Bypass Strategy.

Background: The incidence of new acute neurological injury occurring in neonates and infants during cardiac surgery utilizing cardiopulmonary bypass is reportedly 3% to 5%. In 2013, we adopted a high flow rate, and high hematocrit bypass strategy, and sought to assess the incidence of early neurological injuries associated with this strategy. Methods: Neonates and infants undergoing cardiopulmonary bypass between January 2013 and December 2019 (n = 714) comprise the study. Adverse neurological events (ANEs) were defined as any abnormality of pupils, delayed awakening, seizures, focal neurological deficits, concerns prompting neurological consultation, or any abnormality on neurological imaging in the postoperative period. Our bypass strategy included a high flow rate (150-200 mL/kg/min), without reduction of flow rates during cooling and maintaining a target hematocrit on bypass > 32% with a terminal hematocrit of > 42%. Results: Median weight at the time of the procedure was 4.6 kg (IQR 3.6-6.1 kg) with the smallest patient weighing 1.36 kg. There were 46 premature patients (6.4%). There were 149 patients (20.9%) patients who underwent deep hypothermic circulatory arrest with a median time of 26 min (IQR 21-41 min). Hospital mortality was 3.5% (24/714, 95% CI: 2.28-5.13). The incidence of neurological events as defined above was 0.84% (6/714, 95% CI: 0.31-1.82). Neurological imaging identified ischemic injury in 4 patients and intraventricular hemorrhage in 2. Conclusions: High flow/high hematocrit bypass strategy was associated with a low incidence of ANE in this vulnerable population.

Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice.

INTRODUCTION: The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC-induced alloantibody production and others failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens. METHODS: RBCs expressing two distinct model antigens, HEL-OVA-Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion. Transfused donor RBC survival was assessed within 24 h of transfusion, while IgM and IgG antibody production were assessed 5 and 14 days after transfusion. RESULTS: Stored HOD or KEL RBCs retained similar HEL or KEL antigen levels, respectively, as fresh RBCs, but did exhibit enhanced RBC clearance with increased storage age. Storage enhanced IgG antibody formation against HOD, while the oppositive outcome occurred following transfusion of stored KEL RBCs. The distinct impact of storage on HOD or KEL alloimmunization did not appear to reflect intrinsic differences between HOD or KEL RBCs, as transfusion of stored HOD × KEL RBCs resulted in increased IgG anti-HOD antibody development and reduced IgG anti-KEL antibody formation. CONCLUSIONS: These data demonstrate a dichotomous impact of storage on immunization to distinct RBC antigens, offering a possible explanation for inconsistent clinical experience and the need for additional studies on the relationship between RBC storage and alloimmunization.

Purification of Recombinant Galectins from Different Species Using Distinct Affinity Chromatography Methods.

Galectins are lectins having the capacity to recognize ß-galactose-containing glycan structures and are widely distributed among various taxa. However, the exact physiological and biochemical functions mediated by galectins that necessitate their wide occurrence among diverse species have not yet been delineated in a precise manner. Purification of recombinant galectins in active form is a fundamental requirement to elucidate their biological function. In this chapter, we are describing methods to recombinantly express and purify galectins using three different methods of affinity purification, i.e., lactosyl-Sepharose chromatography for fungal galectin Coprinopsis cinerea galectin 2 (CGL2), nickel-chromatography for histidine-tagged human galectin-7, and glutathione-Sepharose chromatography for Glutathione S-transferase-tagged (GST-tagged) human galectin-7. Step-by-step instructions are provided for obtaining the above-mentioned recombinant galectins that retain carbohydrate-binding activity and are suitable for conducting biochemical experiments.

Are We Forgetting About IgA? A Re-examination of Coronavirus Disease 2019 Convalescent Plasma.

BACKGROUND: While convalescent plasma (CP) may benefit patients with COVID-19, fundamental questions remain regarding its efficacy, including the components of CP that may contribute to its therapeutic effect. Most current serological evaluation of CP relies on examination of total immunoglobulin or IgG-specific anti-SARS-CoV-2 antibody levels. However, IgA antibodies, which also circulate and are secreted along the respiratory mucosa, represent a relatively uncharacterized component of CP. STUDY DESIGN AND METHODS: Residual samples from patients and CP donors were assessed for IgM, IgG, and IgA anti-SARS-CoV-2 antibody titers against the receptor-binding domain responsible for viral entry. Symptom onset was obtained by chart review. RESULTS: Increased IgA anti-SARS-CoV-2 antibody levels correlated with clinical improvement and viral clearance in an infant with COVID-19, prompting a broader examination of IgA levels among CP donors and hospitalized patients. Significant heterogeneity in IgA levels was observed among CP donors, which correlated weakly with IgG levels or the results of a commonly employed serological test. Unlike IgG and IgM, IgA levels were also more likely to be variable in hospitalized patients and this variability persisted in some patients >14 days following symptom onset. IgA levels were also less likely to be sustained than IgG levels following subsequent CP donation. CONCLUSIONS: IgA levels can be very heterogenous among CP donors and hospitalized patients and do not necessarily correlate with commonly employed testing platforms. Examining isotype levels in CP and COVID-19 patients may allow for a tailored approach when seeking to fill specific gaps in humoral immunity.

Marginal zone B cells mediate a CD4 T-cell-dependent extrafollicular antibody response following RBC transfusion in mice.

Red blood cell (RBC) transfusions can result in alloimmunization toward RBC alloantigens that can increase the probability of complications following subsequent transfusion. An improved understanding of the immune mechanisms that underlie RBC alloimmunization is critical if future strategies capable of preventing or even reducing this process are to be realized. Using the HOD (hen egg lysozyme [HEL] and ovalbumin [OVA] fused with the human RBC antigen Duffy) model system, we aimed to identify initiating immune factors that may govern early anti-HOD alloantibody formation. Our findings demonstrate that HOD RBCs continuously localize to the marginal sinus following transfusion, where they colocalize with marginal zone (MZ) B cells. Depletion of MZ B cells inhibited immunoglobulin M (IgM) and IgG anti-HOD antibody formation, whereas CD4 T-cell depletion only prevented IgG anti-HOD antibody development. HOD-specific CD4 T cells displayed similar proliferation and activation following transfusion of HOD RBCs into wild-type or MZ B-cell-deficient recipients, suggesting that IgG formation is not dependent on MZ B-cell-mediated CD4 T-cell activation. Moreover, depletion of follicular B cells failed to substantially impact the anti-HOD antibody response, and no increase in antigen-specific germinal center B cells was detected following HOD RBC transfusion, suggesting that antibody formation is not dependent on the splenic follicle. Despite this, anti-HOD antibodies persisted for several months following HOD RBC transfusion. Overall, these data suggest that MZ B cells can initiate and then contribute to RBC alloantibody formation, highlighting a unique immune pathway that can be engaged following RBC transfusion.

Generation and Use of Recombinant Galectins.

Galectins are soluble carbohydrate binding proteins that can bind ß-galactose-containing glycoconjugates by means of a conserved carbohydrate recognition domain (CRD). In mammalian systems, galectins have been shown to mediate very important roles in innate and adaptive immunity as well as facilitating host-pathogen relationships. Many of these studies have relied on purified recombinant galectins to uncover key features of galectin biology. A major limitation to this approach is that certain recombinant galectins purified using standard protocols are easily susceptible to loss of glycan-binding activity. As a result, biochemical studies that employ recombinant galectins can be misleading if the overall activity of a galectin remains unknown in a given assay condition. This article examines fundamental considerations when purifying galectins by lactosyl-sepharose and nickel-NTA affinity chromatography using human galectin-4N and -7 as examples, respectively. As other approaches are also commonly applied to galectin purification, we also discuss alternative strategies to galectin purification, using human galectin-1 and -9 as examples. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Purification of galectins using lactosyl-sepharose affinity chromatography Basic Protocol 2: Purification of human galectin-7 using a nickel-NTA affinity chromatography column Alternate Protocol 1: Iodoacetamide alkylation of free sulfhydryls on galectin-1 Alternate Protocol 2: Purification of human galectin-9 using lactosyl-sepharose column chromatography.

Antigen density dictates RBC clearance, but not antigen modulation, following incompatible RBC transfusion in mice.

Incompatible red blood cell (RBC) transfusion can result in life-threatening transfusion complications that can be challenging to manage in patients with transfusion-dependent anemia. However, not all incompatible RBC transfusions result in significant RBC removal. One factor that may regulate the outcome of incompatible RBC transfusion is the density of the incompatible antigen. Despite the potential influence of target antigen levels during incompatible RBC transfusion, a model system capable of defining the role of antigen density in this process has not been developed. In this study, we describe a novel model system of incompatible transfusion using donor mice that express different levels of the KEL antigen and recipients with varying anti-KEL antibody concentrations. Transfusion of KEL+ RBCs that express high or moderate KEL antigen levels results in rapid antibody-mediated RBC clearance. In contrast, relatively little RBC clearance was observed following the transfusion of KEL RBCs that express low KEL antigen levels. Intriguingly, unlike RBC clearance, loss of the KEL antigen from the transfused RBCs occurred at a similar rate regardless of the KEL antigen density following an incompatible transfusion. In addition to antigen density, anti-KEL antibody levels also regulated RBC removal and KEL antigen loss, suggesting that antigen density and antibody levels dictate incompatible RBC transfusion outcomes. These results demonstrate that antibody-induced antigen loss and RBC clearance can occur at distinct antigen density thresholds, providing important insight into factors that may dictate the outcome of an incompatible RBC transfusion.

Comparison of Antibody Class-Specific SARS-CoV-2 Serologies for the Diagnosis of Acute COVID-19.

Accurate diagnosis of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for appropriate management of patients with this disease. We examined the possible complementary role of laboratory-developed class-specific clinical serology in assessing SARS-CoV-2 infection in hospitalized patients. Serological tests for immunoglobulin G (IgG), IgA, and IgM antibodies against the receptor binding domain (RBD) of SARS-CoV-2 were evaluated using samples from real-time reverse transcription-quantitative PCR (qRT-PCR)-confirmed inpatient coronavirus disease 2019 (COVID-19) cases. We analyzed the influence of timing and clinical severity on the diagnostic value of class-specific COVID-19 serology testing. Cross-sectional analysis revealed higher sensitivity and specificity at lower optical density cutoffs for IgA in hospitalized patients than for IgG and IgM serology (IgG area under the curve [AUC] of 0.91 [95% confidence interval {CI}, 0.89 to 0.93] versus IgA AUC of 0.97 [95% CI, 0.96 to 0.98] versus IgM AUC of 0.95 [95% CI, 0.92 to 0.97]). The enhanced performance of IgA serology was apparent in the first 2 weeks after symptom onset and the first week after PCR testing. In patients requiring intubation, all three tests exhibit enhanced sensitivity. Among PCR-negative patients under investigation for SARS-CoV-2 infection, 2 out of 61 showed clear evidence of seroconversion IgG, IgA, and IgM. Suspected false-positive results in the latter population were most frequently observed in IgG and IgM serology tests. Our findings suggest the potential utility of IgA serology in the acute setting and explore the benefits and limitations of class-specific serology as a complementary diagnostic tool to PCR for COVID-19 in the acute setting.

Impact of Different Cardiopulmonary Bypass Strategies on Renal Injury After Pediatric Heart Surgery.

BACKGROUND: The purpose of this study is to compare the incidence and severity of acute kidney injury (AKI) after open heart surgery in neonates and infants for two different cardiopulmonary bypass (CPB) strategies. METHODS: In all, 151 infants undergoing cardiac surgery were prospectively enrolled between June 2017 and June 2018 at two centers, one using conventional CPB (2.4 L · min-1 · m-2, 150 mL · kg-1 · min-1) with reduction of flow rates with moderate hypothermia and with a targeted hematocrit greater than 25% (center 1, n = 91), and the other using higher bypass flow rates (175 to 200 mL · kg-1 · min-1) and higher minimum hematocrit (greater than 32%) CPB (center 2, n = 60). The primary endpoint was the incidence of postoperative AKI as defined by Acute Kidney Injury Network criteria and risk factors associated with AKI. RESULTS: Preoperative characteristics and complexity of surgery were comparable between centers. The overall incidence of early postoperative AKI was 10.6% (16 of 151), with 15.4% (14 of 91) in center 1 and 3.3% (2 of 60) in center 2 (P = .02). Mean lowest flow rates on CPB were 78 mL · kg-1 · min-1 vs 118 mL · kg-1 · min-1 and mean highest hematocrit on separation from CPB were 33% vs 43% at center 1 and 2, respectively (P < .001). Center 1 used less packed red blood cells but more fresh frozen plasma than center 2 (P = .001). By multivariate analysis, only lower flows on CPB (78 vs 96 mL · kg-1 · min-1, P = .043) and lower hematocrit at the end of CPB (33% vs 37%, P = .007) were associated with AKI. CONCLUSIONS: In this contemporary comparative study, higher flow rates and higher hematocrit during cardiopulmonary bypass were associated with better preservation of renal function.

Single Institution Experience With International Referrals for Pediatric Cardiac Surgery.

BACKGROUND: Pediatric cardiac surgery in developing countries poses many challenges. The practice of referring patients from abroad via nongovernmental organizations has occurred for many years. We describe our experience with international referrals for pediatric cardiac surgery via Gift of Life Mid-South to the Heart Institute, Le Bonheur Children's Hospital in Memphis, Tennessee. METHODS: We performed a retrospective descriptive review of data collected in our Society of Thoracic Surgeons Congenital Heart Surgery Database (STS CHSD) along with data from our electronic medical record from January 1, 2007, to December 31, 2017. Available data included patient demographics, diagnoses, surgical procedure, entire inpatient length of stay (LOS), complications, and operative mortality. Cardiac surgeries were grouped according to the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT Mortality Categories). Complications were defined according to the STS CHSD. RESULTS: In this retrospective descriptive study, case complexity level varied; however, 38% cardiac surgeries were in STAT Mortality Category 3 or 4. Honduras was the most common referral source with a total of 18 countries represented. Operative mortality remained very low (1 [1.4%] of 71 cardiac surgeries) despite patients being referred beyond infancy. There were an increasing number of complications and longer inpatient LOS (with greater variance) in STAT Mortality Category 4. CONCLUSIONS: International patients referred for congenital heart surgery can be successfully treated with an acceptable mortality rate despite late referrals. Inpatient LOS is related to surgical complexity. Follow-up studies are needed to determine the long-term outcomes of these patients.

Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation.

Anti-factor VIII (fVIII) alloantibodies, which can develop in patients with hemophilia A, limit the therapeutic options and increase morbidity and mortality of these patients. However, the factors that influence anti-fVIII antibody development remain incompletely understood. Recent studies suggest that Fc gamma receptors (FcγRs) may facilitate recognition and uptake of fVIII by recently developed or pre-existing naturally occurring anti-fVIII antibodies, providing a mechanism whereby the immune system may recognize fVIII following infusion. However, the role of FcγRs in anti-fVIII antibody formation remains unknown. In order to define the influence of FcγRs on the development of anti-fVIII antibodies, fVIII was injected into WT or FcγR knockout recipients, followed by evaluation of anti-fVIII antibodies. Anti-fVIII antibodies were readily observed following fVIII injection into FcγR knockouts, with similar anti-fVIII antibody levels occurring in FcγR knockouts as detected in WT mice injected in parallel. As antibodies can also fix complement, providing a potential mechanism whereby anti-fVIII antibodies may influence anti-fVIII antibody formation independent of FcγRs, fVIII was also injected into complement component 3 (C3) knockout recipients in parallel. Similar to FcγR knockouts, C3 knockout recipients developed a robust response to fVIII, which was likewise similar to that observed in WT recipients. As FcγRs or C3 may compensate for each other in recipients only deficient in FcγRs or C3 alone, we generated mice deficient in both FcγRs and C3 to test for potential antibody effector redundancy in anti-fVIII antibody formation. Infusion of fVIII into FcγRs and C3 (FcγR × C3) double knockouts likewise induced anti-fVIII antibodies. However, unlike individual knockouts, anti-fVIII antibodies in FcγRs × C3 knockouts were initially lower than WT recipients, although anti-fVIII antibodies increased to WT levels following additional fVIII exposure. In contrast, infusion of RBCs expressing distinct alloantigens into FcγRs, C3 or FcγR × C3 knockout recipients either failed to change anti-RBC levels when compared to WT recipients or actually increased antibody responses, depending on the target antigen. Taken together, these results suggest FcγRs and C3 can differentially impact antibody formation following exposure to distinct alloantigens and that FcγRs and C3 work in concert to facilitate early anti-fVIII antibody formation.

Experience of a single institution with femoral vein homograft as right ventricle to pulmonary artery conduit in stage 1 Norwood operation.

OBJECTIVE: Femoral vein homograft can be used be used as valved right ventricle to pulmonary artery conduit in the Norwood operation. We describe the results of this approach, including pulmonary artery growth and ventricular function. METHODS: A retrospective chart review of 24 consecutive neonates with hypoplastic left heart syndrome or complex single ventricle undergoing this approach between June 2012 and December 2017 was performed. Conduit valve competency and ventricular function were estimated using transthoracic echocardiogram, and pulmonary artery growth was measured using Nakata's index. Changes in ventricular function pre-Glenn and at latest follow-up were assessed by ordinal logistic regression with a general linear model to account for the correlation within the same patient over time. RESULTS: Median age at surgery was 4 days, and mean weight was 3 kg. There was no interstage mortality. A total of 21 patients have undergone Glenn operation, and 9 patients have completed the Fontan operation. None of the conduits developed thrombosis. Sixty-three percent of conduits remained competent in the first month, and 33% remained competent after 3 months of operation. Catheter interventions on conduits were necessary in 14 patients. Median Nakata index at pre-Glenn catheterization was 228 mm2/m2 (interquartile range, 107-341 mm2/m2). Right ventricular function was preserved in 83% of patients at a median follow-up of 34 (interquartile range, 10-46) months. CONCLUSIONS: Femoral vein homograft as a right ventricle to pulmonary artery conduit in the Norwood operation is safe and associated with good pulmonary artery growth and preserved ventricular function as assessed by subjective echocardiography. Catheter intervention of the conduit may be necessary.

High acetylsalicylic acid dosing in infants after modified Blalock-Taussig shunt.

OBJECTIVE: Shunt-related adverse events are frequent in infants after modified Blalock-Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock-Taussig. METHODS: In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock-Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose. RESULTS: There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2-23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3-71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7-10), p=0.16] was not associated with decrease in these events. CONCLUSIONS: High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock-Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock-Taussig.

Femoral vein homograft as Sano shunt results in improved pulmonary artery growth after Norwood operation.

OBJECTIVE: To evaluate differences in interstage growth of pulmonary arteries between use of polytetrafluoroethylene and femoral vein homograft as Sano shunt during stage-I Norwood palliation. METHODS: A retrospective review of all patients who survived to the second stage following Norwood-Sano operation at two institutions was performed. Either polytetrafluoroethylene or the valved segment of femoral vein homograft was used for construction of the Sano shunt. The size of pulmonary arteries was compared at pre-Glenn catheterisation. RESULTS: A total of 48 neonates with the diagnosis of hypoplastic left heart syndrome or its variants comprised the study population. Femoral vein homograft of 5-6 mm diameter was used in 14 and polytetrafluoroethylene graft of 5 mm was used in 34 patients. The two groups were comparable in terms of preoperative demographics and age at time of pre-Glenn catheterisation (3.9±0.7 versus 3.4±0.8 months, p=0.06). Patients who received femoral vein homograft demonstrated a significantly higher pre-Glenn Nakata index [264 (130-460) versus 165 (108-234) mm2/m2, p=0.004]. The individual branch pulmonary arteries were significantly larger in the femoral vein group (right, 7.8±3.6 versus 5.0±1.2, p=0.014; left, 7.2±2.1 versus 5.6±1.9, p=0.02). There were no differences in cardiac index, Qp:Qs, ventricular end-diastolic pressure or systemic oxygen saturations. CONCLUSIONS: Utilisation of a valved segment of femoral vein homograft as right ventricle to pulmonary artery conduit during Norwood-Sano operation confers better interstage growth of the pulmonary arteries. Further studies are needed to evaluate the impact of femoral vein homograft on single ventricle function.

Optimum position of transthoracic intracardiac line following cardiac surgery.

OBJECTIVES: The transthoracic intracardiac line placed in the right atrium provides a convenient access to the central venous system following cardiac surgery. However, it is associated with risks such as migration and bleeding. We conducted a retrospective study to determine whether position of transthoracic line with respect to site of exit from the chest makes a difference in the rate of complications. METHODS: All infants receiving a transthoracic intracardiac line in the right atrium following cardiac surgery between June 2012 and December 2015 were part of the study. A 3.5-Fr double-lumen umbilical venous catheter was placed directly into the right atrium. The lines exited the thorax either above in the suprasternal notch (upper transthoracic line) or below the diaphragm across the abdominal wall (lower transthoracic line). Patients were analysed for complications such as catheter migration, bleeding upon removal, atrial thrombus, line occlusion, premature removal and failed removal. RESULTS: A total of 131 patients received a transthoracic intracardiac line during the study period. Of the total patients, 88 patients received the upper transthoracic line and 43 patients received the lower transthoracic line. The upper transthoracic line was associated with significantly lower incidence of catheter migration (1% vs 14%) and this held by multivariable logistic regression, adjusting for age and duration of the line (P = 0.003). There was no difference in the rate of other complications including bleeding. CONCLUSIONS: The upper transthoracic line is associated with significantly lower incidence of catheter migration and offers a more optimum position for central access following cardiac surgery.

Effect of thyroid hormone on cardiac function following orthotopic heart transplantation in piglets.

Studies in adult HT have demonstrated improved cardiac function in the recipient following administration of T3 to the donor. The purpose of this experiment was to assess the effects of T3 on the function of the immature donor heart following HT in a piglet model. A total of 32 piglets were divided into 16 donors and 16 recipients. Following creation of brain death, half of the donor piglets were randomized to receive three doses of T3 (0.2 µg/kg) along with hydrocortisone (1 mg/kg). The donor hearts were then transplanted into the recipient piglets on CPB. Duration of survival off CPB, inotrope score, and EF of heart following CPB were evaluated. There were no differences between the two groups in age, weight, pre-brain death EF, T3 levels, and CPB times. Post-CPB survival times were inversely related to the ischemic times in both groups (Pearson r=-0.80, P<.001), and this relationship was not influenced by T3. There was no difference in inotrope score, EF, or biochemical assessment between the two groups. Administration of T3 in combination with hydrocortisone to the brain-dead donor confers no beneficial effect on myocardial function or survival following HT in a piglet model.

Influence of weight at the time of first palliation on survival in patients with a single ventricle.

BACKGROUND: Numerous advances in surgical techniques and understanding of single-ventricle physiology have resulted in improved survival. We sought to determine the influence of various demographic, perioperative, and patient-specific factors on the survival of single-ventricle patients following stage 1 palliation at our institution. METHODS: We conducted a retrospective study of all single-ventricle patients who had undergone staged palliation at our institution over an 8-year period. Data were collected from the Society of Thoracic Surgeons Congenital Heart Surgery database and from patient charts. Information on age, weight at stage 1 palliation, prematurity, genetic abnormalities, non-cardiac anomalies, ventricular dominance, and type of palliation was collected. Information on mortality and unplanned reinterventions was also collected. RESULTS: A total of 72 patients underwent stage 1 palliation over an 8-year period. There were 12 deaths before and one death after stage 2 palliation. There was no hospital mortality following Glenn or Fontan procedures. On univariate analysis, low weight at the time of stage 1 palliation and prematurity were found to be risk factors for mortality following stage 1 palliation. However, multivariable Cox regression analysis revealed weight at stage 1 palliation to be a strong predictor of mortality. The type of stage 1 palliation did not have any influence on the outcome. No difference in survival was noted following the Glenn procedure. CONCLUSION: Low weight has a deleterious impact on survival following stage 1 palliation. This is mitigated by stage 2 palliation. The type of stage 1 palliation itself has no bearing on the outcome.

Vasopressin After the Fontan Operation.

BACKGROUND: Prolonged pleural effusion following Fontan operation is common and increases morbidity and hospital length of stay. Vasopressin (VP), a neurohypophysial hormone, has numerous effects on the cardiovascular system. The most notable is increased peripheral vascular resistance, but it may also reduce capillary leakage by tightening endothelial intercellular junctions and reducing capillary hydrostatic pressure We reviewed our experience with the perioperative administration of VP following Fontan operation. METHODS: We retrospectively reviewed the records of 62 consecutive patients who underwent Fontan operation from January 2004 to June 2014. In January 2010, VP was introduced as part of the standard perioperative management of patients undergoing Fontan operation at our center. For this retrospective observational study, patients were grouped according to the use (VP; N = 40) or nonuse (non-VP; N = 22) of VP (0.3-0.5 mU/kg/min) in the perioperative period. The primary end point analyzed was chest tube output. Secondary end points analyzed included fluid balance and length of hospital stay, with groups compared using Mann-Whitney U test. RESULTS: There was no hospital mortality. Median total chest tube output was 22 mL/kg in the VP group and 68 mL/kg in the non-VP group (P < .001). The median total duration of chest tube indwelling time was five days in the VP group and was 11 days in the non-VP group (P < .001). Median fluid balance on first postoperative day was 13 and 38 mL/kg, respectively (P < .001). Median hospital stay for VP and non-VP groups was 9 and 16 days, respectively (P = .002). CONCLUSIONS: The more recent group of patients undergoing Fontan operations, all of whom received VP perioperatively, had less chest tube output and shorter duration of chest tube drainage after the Fontan operation relative to the earlier patient group whose perioperative management did not include VP. They also experienced less positive fluid balance in the early postoperative period and shorter hospital length of stay than the patients from the earlier era.