Cerebrovascular response to maternal hyperoxygenation in fetuses with hypoplastic left heart syndrome depends on gestational age and baseline cerebrovascular resistance.

OBJECTIVES: Compared with normal fetuses, fetuses with hypoplastic left heart syndrome (HLHS) have smaller brain volumes and are at higher risk of brain injury, possibly due to diminished cerebral blood flow and oxygen content. By increasing cerebral oxygen delivery, maternal hyperoxygenation (MH) might improve brain development and reduce the risk of brain injury in these fetuses. This study investigated whether gestational age and baseline cerebrovascular resistance affect the response to MH in fetuses with HLHS. METHODS: The study population comprised 43 fetuses with HLHS or HLHS variant referred for fetal echocardiography between January 2004 and September 2008. Middle cerebral artery (MCA) pulsatility index (PI), a surrogate measure of cerebrovascular resistance, was assessed between 20 and 41 weeks' gestation at baseline in room air (RA) and after 10 min of MH. Z-scores of MCA-PI were generated. A mixed-effects model was used to determine whether change in MCA-PI depends upon gestational age and baseline MCA-PI. RESULTS: In RA and following MH, MCA-PI demonstrated a curvilinear relationship with gestational age in fetuses with HLHS, peaking at around 28 weeks and then falling more steeply near term. MCA-PI Z-score declined in a linear manner, such that it was 1.4 SD below that in normal fetuses at 38 weeks. Increase in MCA-PI Z-score after MH was first seen at ≥ 28 weeks. A baseline MCA-PI Z-score ≤ -0.96 was predictive of an increase in cerebrovascular resistance in response to MH. CONCLUSION: In fetuses with HLHS, MCA-PI first increases in response to MH at ≥ 28 weeks' gestation. A baseline MCA-PI Z-score ≤ -0.96 predicts an increase in cerebrovascular resistance in response to MH. These results may have implications for clinical trials utilizing MH as a neuroprotective agent. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Perinatal and early surgical outcome for the fetus with hypoplastic left heart syndrome: a 5-year single institutional experience.

OBJECTIVES: To review our experience with the prenatal diagnosis of hypoplastic left heart syndrome (HLHS). Our goal was to establish the benchmark for perinatal and early surgical outcome in the current era, from a center with an aggressive surgical approach and a cohort with a high level of intention-to-treat. METHODS: Outcome was assessed in fetuses with HLHS following stratification into high-risk and standard-risk categories. High risk was defined as the presence of any of the following: extracardiac, genetic or chromosomal anomalies; prematurity of < 34 weeks' gestation; additional cardiac findings such as intact or highly restrictive atrial septum, severe degree of tricuspid regurgitation or severe ventricular dysfunction. Standard risk was defined as absence of these risk factors. RESULTS: Of 240 fetuses evaluated over 5 years, 162 (67.5%) were in the standard-risk group and 78 (32.5%) were in the high-risk group. Of the 240 sets of parents, 38 (15.8%) chose termination or non-intervention at birth at initial prenatal counseling and 185 of the neonates (77.1%) underwent first-stage Norwood surgery with 155 surviving and 30 deaths, giving an overall Norwood operative survival of 83.8%. Breakdown by risk class reveals a significant Norwood operative survival advantage for the standard-risk group (92.8%) over the high-risk group (56.5%) (P < 0.001). CONCLUSIONS: Following prenatal diagnosis of HLHS, families should be strongly encouraged to undertake comprehensive prenatal evaluation in order to obtain an accurate prognosis. One-third have additional risk factors that limit survival outcome, however two-thirds do not and have an excellent chance of early survival.

Survival after reconstructive surgery for hypoplastic left heart syndrome: A 15-year experience from a single institution.

BACKGROUND: There are limited data regarding the long-term survival of patients who have undergone reconstructive surgery for hypoplastic left heart syndrome (HLHS). We reviewed the 15-year experience at our institution to examine survival in the context of continued improvements in early operative results. METHODS AND RESULTS: Between 1984 and 1999, 840 patients underwent stage I surgery for HLHS. From review of medical records and direct patient contact, survival status was determined. The 1-, 2-, 5-, 10-, and 15-year survival for the entire cohort was 51%, 43%, 40%, 39%, and 39%, respectively. Late death occurred in 14 of the 291 patients discharged to home after the Fontan procedure, although only 1 patient has died beyond 5 years of age. Heart transplantation after stage I reconstruction was performed in 5 patients. Later era of stage I surgery was associated with significantly improved survival (P:<0.001). Three-year survival for patients undergoing stage I reconstruction from 1995 to 1998 was 66% versus 28% for those patients undergoing surgery from 1984 to 1988. Age >14 days at stage I and weight <2.5 kg at stage I were also associated with higher mortality (P:=0.004 and P:=0.01, respectively). Other variables, including anatomic subtype, heterotaxia, and age at subsequent staging procedures, were not associated with survival. CONCLUSIONS: Over the 15-year course of this study, early- and intermediate-term survival for patients with HLHS undergoing staged palliation increased significantly. Late death and the need for cardiac transplantation were uncommon.

Permanent epicardial pacing in pediatric patients: seventeen years of experience and 1200 outpatient visits.

BACKGROUND: The purpose of this study was to evaluate the long-term outcome of all pediatric epicardial pacing leads. METHODS AND RESULTS: All epicardial leads and 1239 outpatient visits between January 1, 1983, and June 30, 2000, were retrospectively reviewed. Pacing and sensing thresholds were reviewed at implant, at 1 month, and at subsequent 6-month intervals. Lead failure was defined as the need for replacement or abandonment due to pacing or sensing problems, lead fracture, or phrenic/muscle stimulation. A total of 123 patients underwent 207 epicardial lead (60 atrial/147 ventricular, 40% steroid) implantations (median age at implant was 4.1 years [range 1 day to 21 years]). Congenital heart disease was present in 103 (84%) of the patients. Epicardial leads were followed for 29 months (range 1 to 207 months). The 1-, 2-, and 5-year lead survival was 96%, 90%, and 74%, respectively. Compared with conventional epicardial leads, both atrial and ventricular steroid leads had better stimulation thresholds 1 month after implantation; however, only ventricular steroid leads had improved chronic pacing thresholds (at 2 years: for steroid leads, 1.9 muJ [from 0.26 to 16 mu]; for nonsteroid leads, 4.7 muJ [from 0.6 to 25 muJ]; P<0.01). Ventricular sensing was significantly better in steroid leads 1 month after lead implantation (at 2 years: for steroid leads, 8 mV [from 4 to 31 mV]; for nonsteroid leads, 4 mV [from 0.7 to 10 mV]; P<0.01). Neither congenital heart disease, lead implantation with a concomitant cardiac operation, age or weight at implantation, nor the chamber paced was predictive of lead failure. CONCLUSIONS: Steroid epicardial leads demonstrated relatively stable acute and chronic pacing and sensing thresholds. In this evaluation of >200 epicardial leads, lead survival was good, with steroid-eluting leads demonstrating results similar to those found with historical conventional endocardial leads.

What factors are important to parents making decisions about neonatal research?

BACKGROUND: Although parents of neonates with congenital heart disease are often asked permission for their neonates to participate in research studies, little is known about the factors parents consider when making these decisions. OBJECTIVE: To determine the reasons for parents' decisions about participation in research studies. METHODS: Qualitative analysis of the unsolicited comments of 34 parents regarding reasons for agreeing or declining to participate in research studies. Parents' comments were offered spontaneously during interviews about clinical care decisions for neonates with congenital heart disease. RESULTS: Parents cited five types of reason for or against permitting their newborn to participate in research studies: societal benefit (n = 18), individual benefit for their infant (n = 16), risk of study participation (n = 10), perception that participation posed no harm (n = 9), and anti-experimentation views (n = 4). CONCLUSION: Addressing parental decision making in the light of these reasons could enhance the parental permission process for parents of critically ill neonates.

Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal membrane oxygenation.

OBJECTIVE: To describe the outcome and treatment of two patients with recombinant factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal membrane oxygenation (ECMO). DESIGN: Case report. SETTING: A 38-bed pediatric intensive care unit and 20-bed pediatric cardiac intensive care unit at a tertiary care children's hospital. PATIENT: Two patients with life-threatening hemorrhagic complications associated with ECMO requiring massive transfusion of blood products. INTERVENTIONS: Administration of repeated doses of rFVIIa at 90 microg/kg/dose. MEASUREMENT AND MAIN RESULTS: PATIENT 1 was an 11-yr-old male with a dilated cardiomyopathy who had undergone an orthotopic heart transplant treated with venoarterial ECMO postoperatively for right ventricular dysfunction. PATIENT 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary failure from necrotizing staphylococcal pneumonia. Both patients had severe hemorrhage from the cannulation sites and thoracostomy tubes requiring massive transfusion to maintain intravascular blood volume and replace clotting factors. Both patients were treated with rFVIIa every 2-4 hrs and attained hemostasis. PATIENT 1 was administered three doses and PATIENT 2 was administered ten doses. No evidence of abnormal thrombus formation was noted in their respective ECMO circuits. CONCLUSIONS: The efficacy of rFVIIa in reducing intractable bleeding postcardiac surgery and in other coagulopathic states is being investigated. Despite theoretical concerns of thrombosis, these cases illustrate that there may be a role for the cautious use of rFVIIa in treating severe and intractable hemorrhage associated with ECMO.

Outcome of children with pulmonary hypertension referred for lung or heart and lung transplantation.

We reviewed our institutional experience with 24 children with pulmonary hypertension, who were referred for lung or heart and lung transplantation. Diagnosis, age, and previously published predictive survival scores calculated at the time of referral were analyzed as predictors of pretransplant death. Among the 24 children, 7 did not meet criteria for listing and 17 were listed for transplantation. Of those listed, eight died waiting, two await transplantation, and seven were transplanted and are alive and well 7-20 months after transplantation. Poor functional status (New York Heart Association class 3 or 4) at the time of referral was significantly associated with death before transplant (P=0.05) in univariate analysis. Analysis of the predictive scores was possible in 21 of 24 patients; lower predictive scores were significantly associated with death before transplantation and shorter duration of survival without transplantation in univariate analysis. Multivariate analysis (Cox regression) confirmed that lower scores were significantly associated with poor survival. We conclude that children with pulmonary hypertension are often referred for transplantation too late in the course of their disease. Early complete hemodynamic evaluation before the onset of severe symptoms, followed by serial evaluations of disease progression and consultation with a transplant center, should result in earlier, more appropriate time of listing and improved survival. A systematic study of pretransplant mortality among all children listed for lung transplantation would provide a basis for clinical decision making and policies affecting organ allocation.

Pediatric lung transplantation--are there surgical contraindications?

Lung transplantation has evolved as a successful treatment for end-stage cardiopulmonary disease in children; however, clear guidelines regarding surgical exclusion criteria for pediatric lung transplant candidates have not been well-established. Since December 1994, we have performed 10 bilateral lung transplants and 1 heart-lung transplant in 10 recipients (mean age, 7 years; range, 3 months to 19 years). Indications for transplantation included pulmonary vascular disease (n=6), bronchiolitis obliterans (n=2), bronchopulmonary dysplasia (n=1), graft failure due to viral pneumonitis (n=1), and cystic fibrosis (n=1). Among the 10 patients, 4 were evaluated elsewhere for lung transplantation; of these, 3 were rejected by 1 or more programs because of "high-risk" characteristics. We considered 8 of the 10 patients to have 1 or more "high-risk" characteristics, as follows: previous chest operations other than open lung biopsy (n=6 patients having 1-4 previous operations), ventilator-dependence with tracheostomy and high-dose corticosteroids (n=4), redo lung transplant (n=2), concomitant intracardiac repair (n=6), portal hypertension (n=1), and the use of extracorporeal membrane oxygenation (ECMO) at the time of transplant (n=1). Our standard operative approach was a bilateral thoracosternotomy. Cardiopulmonary bypass was used for explant of the recipient lungs and implant of the donor lungs, and during repair of coexisting congenital heart defects. Aprotinin and fresh whole blood were administered during the procedure to aid in hemostasis. Concomitant procedures were frequently performed and included repair of an intra-atrial baffle leak (prior Mustard procedure), closure of an atrial septal defect, repair of partial anomalous pulmonary venous return, reconstruction of the pulmonary venous confluence, ECMO decannulation, and splenectomy. There were no operative deaths, and no patient required re-exploration for bleeding. One patient had primary graft failure due to adenovirus infection of the donor lungs, and required prolonged mechanical ventilation and eventually ECMO support until retransplantation was performed. The mean hospital stay after transplant was 25+/-13 days (range, 10-56 days). All patients were discharged with a natural airway. Airway complications consisted of one bronchial anastomotic stricture which required dilation, for a complication rate of 5% per anastomoses at risk. One patient required reoperation for stenosis of the superior vena cava. There have been no late deaths, with a mean follow-up of 7+/-4 months (range, 1-13 months). We attribute this 100% operative and short-term survival in these "high-risk" pediatric lung transplant recipients to our operative methods, a multidisciplinary approach to postoperative management, and the enormous physiologic reserve of pediatric patients. Therefore, the standard exclusion criteria used for adult lung transplantation may not be applicable to the pediatric age group. We hope to use these data to expand the use of lung transplantation in pediatric patients.

Usefulness of intraoperative transesophageal echocardiography in predicting the degree of mitral regurgitation secondary to atrioventricular defect in children.

The objectives of this study were to determine the validity of the grade of mitral regurgitation (MR) as imaged by intraoperative transesophageal echocardiography (TEE) in predicting the grade of MR at follow-up. Intraoperative TEE and corresponding follow-up transthoracic studies were retrospectively reviewed and the regurgitant jet area to left atrial area ratio was used to quantify the MR. Patient records were reviewed to identify factors contributing to the development of a certain grade of MR. Intraoperative TEE was useful in detecting severe MR that required further repair at the same time. However, discrepancy in the grade of MR at follow-up was noted in 47% of patients (21 of 47) and unchanged grade of MR was found only in 53% of patients (26 of 47). Blood pressures were significantly lower and heart rates higher intraoperatively. Initial preoperative grade of MR and type of atrioventricular canal defect did not predispose for a particular grade of MR at follow-up. The grade of MR by intraoperative TEE does not predict the grade of MR at follow-up as imaged by transthoracic echocardiography.

Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass.

OBJECTIVE: Our objective was to test the hypothesis that use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function in children. METHODS: Twenty-one infants undergoing cardiopulmonary bypass were instrumented with ultrasonic dimension transducers, to measure the anteroposterior minor axis diameter, and a left ventricular micromanometer. Patients were randomized to modified ultrafiltration (n = 11, age 226 +/- 355 days, weight 6.7 +/- 3.1 kg) or control (n = 10, age 300 +/- 240 days, weight 7.0 +/- 2.5 kg) (all differences p > 0.05 between groups). Left ventricular systolic function was assessed by means of the slope of the preload-recruitable stroke work index. Myocardial cross-sectional area was measured by echocardiography. Data were acquired immediately after separation from bypass, at steady state, and during transient vena caval occlusion. Data acquisition was repeated after 13 +/- 5 minutes of modified ultrafiltration or after 12 +/- 5 minutes without modified ultrafiltration in the control group. Inotropic drug support was the same at both study points. RESULTS: In the modified ultrafiltration group, the filtrate volume was 363 +/- 262 ml. The hematocrit value increased from 26.0% +/- 2.7% to 36.7% +/- 9.5% (p = 0.018), myocardial cross-sectional area decreased from 3.72 +/- 0.35 cm2 to 3.63 +/- 0.36 cm2 (p = 0.04), end-diastolic length increased from 25.6 +/- 9.0 mm to 28.8 +/- 9.9 mm (p = 0.01), and end-diastolic pressure fell from 5.6 +/- 0.8 mm Hg to 4.2 +/- 0.8 mm Hg (p = 0.005), suggesting an improved diastolic compliance. In the control group, the hematocrit value, myocardial cross-sectional area, end-diastolic length, and pressure did not change (all p > 0.05). Mean ejection pressure increased in the ultrafiltration group (p = 0.001) but did not change in the control group (p = 0.22). The slope of the preload-recruitable stroke work index increased after ultrafiltration from 52.3 +/- 52.0 to 74.2 +/- 66.0 (10[3] erg/cm3) (p = 0.02) but did not change in the control group (p = 0.07). One patient from each group died in the postoperative period. Patients in the ultrafiltration group received less inotropic drug support in the first 24 hours after the operation (156.62 +/- 92.31 microg/kg in 24 hours) than patients in the control group (865.33 +/- 1772.26 microg/kg in 24 hours, p = 0.03). CONCLUSIONS: Use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function, improves diastolic compliance, increases blood pressure, and decreases inotropic drug use in the early postoperative period.

Outcome after operations for pulmonary atresia with intact ventricular septum.

OBJECTIVE: Pulmonary atresia with intact ventricular septum is an anatomically heterogeneous anomaly with a variety of surgical strategies possible. We sought to compare the outcome of patients with a single ventricle approach to those with a biventricular repair and to compare outcome of patients with coronary abnormalities to those with normal coronary arteries. METHODS: A retrospective review of our surgical database revealed 67 patients with pulmonary atresia with intact ventricular septum operated on between 1981 and 1998. Patients were categorized on the basis of initial surgical strategy: strategy A, aortopulmonary shunt alone (n = 31); strategy B, right ventricular recruitment (n = 32); strategy C, heart transplantation (n = 4). Tricuspid valve size (Z-score) and coronary anatomy were determined. Right ventricular-coronary artery dependency was noted in 8 patients. RESULTS: Overall actuarial survivals at 1, 5, and 8 years were 82%, 76%, and 76%. Mortality was highest in infancy (10 of 16 deaths). Outcome was equivalent for all 3 strategies. There was no difference in tricuspid valve size between survivors and nonsurvivors (mean Z-score -2.0 (2.5) vs -2.0 (1.9), P =.83). There was no difference in survival based on severity of coronary abnormality. Only one third of patients had a successful biventricular repair, and the tricuspid valve was significantly larger in these than in patients who had Fontan operation (mean Z-score -0.53 [1.6], range -3.5 to 1, versus mean Z-score -3.03 [2.7], range -5.5 to 0, P =.002). CONCLUSIONS: Surgical outcome for patients born with pulmonary atresia with intact ventricular septum is satisfactory. The strategies of biventricular repair, single ventricle palliation, and heart transplantation allow for equal outcome among all anatomic subtypes.

Delayed right heart failure following lung transplantation.

Dynamic right ventricular outflow tract obstruction (RVOTO) has been reported following lung transplantation for pulmonary hypertension, usually in association with the use of inotropic agents. This report describes delayed severe right-sided heart failure associated with right ventricular outflow tract obstruction following sequential bilateral lung transplantation and closure of a ventricular septal defect. The patient had no evidence of outflow tract obstruction in the early posttransplant period but developed progressive right heart failure more than 2 months later. Catheterization revealed dynamic RVOTO and an elevated right ventricular end-diastolic pressure. The patient was treated with metoprolol tartrate and diltiazem hydrochloride with resolution of the outflow tract obstruction and heart failure. This case demonstrates that RVOTO can occur in the late posttransplant period and must be included in the differential diagnosis for patients who develop right-sided heart failure.

Long-term outcome of infants with single ventricle and total anomalous pulmonary venous connection.

BACKGROUND AND METHODS: Between January 1, 1984, and December 1, 1997, 73 infants with functional single ventricle and total anomalous pulmonary venous connection were admitted to our institution. A retrospective review was undertaken to determine factors influencing survival. RESULTS: Heterotaxy syndrome was present in 52 patients and hypoplastic left heart syndrome in 14. Obstructed total anomalous pulmonary venous connection was present in 21 patients. The pulmonary venous connection was supracardiac in 32 patients, cardiac in 21 patients, infracardiac in 13, and mixed in 7. Twelve patients died before the operation. The remaining 61 patients underwent surgery at a median age of 5 days (range 1 day-2. 5 years). Overall survival was 45% at 6 months of age, 37% at 1 year, and 19% at 5 years. Survival for patients undergoing surgery was 54% at 6 months of age, 44% at 1 year, and 23% at 5 years. By univariate analysis with the Cox proportional hazards model, younger age at the time of the initial operation and repair of total anomalous pulmonary venous connection were predictors of mortality. Lung tissue from 14 patients was available for histologic examination. The pulmonary veins were dilated and wall thickness was increased. Increased muscularization of the arteries was seen in 11 patients. CONCLUSIONS: The long-term prognosis for children undergoing staged reconstructive operations for single ventricle and total anomalous pulmonary venous connection is poor. Early mortality is high and late death is a continuing risk. Development of the pulmonary vasculature, especially the pulmonary veins, is abnormal, even in children without clinical evidence of pulmonary venous obstruction.

Assessment of pulmonary/systemic blood flow ratio after first-stage palliation for hypoplastic left heart syndrome: development of a new index with the use of doppler echocardiography.

OBJECTIVE: Circulatory maldistribution is believed to be a major cause of early death after first-stage palliation for hypoplastic left heart syndrome. Flow reversal in the reconstructed aorta may reflect the pulmonary/systemic blood flow ratio. The purpose of our study was to investigate the utility of arterial PO (2), arterial oxygen saturation, and a newly developed Doppler-derived flow index in predicting the pulmonary/systemic flow ratio after first-stage palliation for hypoplastic left heart syndrome. METHODS: Twenty-four infants who underwent first-stage palliation for hypoplastic left heart syndrome or a variant were studied. Superior vena cava blood samples were drawn to estimate the mixed venous saturation and permit calculation of the pulmonary/systemic blood flow ratio. Fifty-four samples were evaluated within the first 24 hours after surgery. Simultaneous blood draw and Doppler echocardiography were performed with interrogation in the distal aspect of the arch reconstruction. The ratio of the Doppler velocity-time integral of retrograde flow to the velocity-time integral of forward flow was calculated and compared with the pulmonary/systemic blood flow ratio RESULTS: The median mixed venous saturation for the 54 samples was low (38.5%; range, 18%-64%). The median calculated pulmonary/systemic blood flow ratio was 1.4:1 (range, 0.3:1 to 4. 2:1). Pulse pressure, mixed venous saturation, and arterial PO (2) were not statistically significant predictors of the measured pulmonary/systemic blood flow ratio. Although both aortic oxygen saturation (R (2) = 0.84, P <.01) and Doppler flow reversal ratio (R (2) = 0.94, P <.001) were significantly associated with the measured pulmonary/systemic blood flow ratio, the model coefficient of determination was greatest for Doppler flow reversal ratio. CONCLUSION: Measures of arterial oxygen saturation and arterial PO (2) may be misleading in assessing the circulatory status of infants after first-stage palliation for hypoplastic left heart syndrome. Doppler echocardiography, through use of the Doppler flow reversal ratio, provides a more useful measure of pulmonary/systemic blood flow ratio. Low mixed venous saturation after surgery may be due to factors other than pulmonary overcirculation, such as ventricular dysfunction and low cardiac output.

Modified ultrafiltration improves cerebral metabolic recovery after circulatory arrest.

Modified ultrafiltration uses hemofiltration of the patient and bypass circuit after separation from cardiopulmonary bypass to reverse hemodilution and edema. This study investigated the effect of modified ultrafiltration on cerebral metabolic recovery after deep hypothermic circulatory arrest. Twenty-six 1-week-old piglets (2 to 3 kg) were supported by cardiopulmonary bypass (37 degrees C) at 100 ml.kg-1.min-1 and cooled to 18 degrees C. Animals underwent 90 minutes of circulatory arrest followed by rewarming to 37 degrees C. After being weaned from cardiopulmonary bypass, animals were divided into three groups: controls (n = 10); modified ultrafiltration for 20 minutes (n = 9); transfusion of hemoconcentrated blood for 20 minutes (n = 7). Global cerebral blood flow was measured by xenon 133 clearance methods: stage I--before cardiopulmonary bypass; stage II--5 minutes after cardiopulmonary bypass; and stage III--25 minutes after cardiopulmonary bypass. Cerebral metabolic rate of oxygen consumption, cerebral oxygen delivery, and hematocrit value were calculated for each time point. At point III, the hematocrit value (percent) was elevated above baseline in the ultrafiltration and transfusion groups (44 +/- 1.8, 42 +/- 1.8 versus 28 +/- 1.7, 30 +/- 0.7, respectively, p < 0.05). Cerebral oxygen delivery (ml.100 gm-1.min-1) increased significantly above baseline at point III after ultrafiltration (4.98 +/- 0.32 versus 3.85 +/- 0.16, p < 0.05) or transfusion (4.59 +/- 0.17 versus 3.89 +/- 0.06, p < 0.05) and decreased below baseline in the control group (2.77 +/- 0.19 versus 3.81 +/- 0.16, p < 0.05). Ninety minutes of deep hypothermic circulatory arrest resulted in impaired cerebral metabolic oxygen consumption (ml.100 gm-1.min-1) at point III in the control group (1.95 +/- 0.15 versus 2.47 +/- 0.07, p < 0.05) and transfusion group (1.72 +/- 0.10 versus 2.39 +/- 0.15, p < 0.05). After modified ultrafiltration, however, cerebral metabolic oxygen consumption at point III had increased significantly from baseline (3.12 +/- 0.24 versus 2.48 +/- 0.13, p < 0.05), indicating that the decrease in cerebral metabolism immediately after deep hypothermic circulatory arrest is reversible and may not represent permanent cerebral injury. Use of modified ultrafiltration after cardiopulmonary bypass may reduce brain injury associated with deep hypothermic circulatory arrest.

Rabbit antithymocyte globulin decreases acute rejection after lung transplantation: results of a randomized, prospective study.

STUDY OBJECTIVES: The efficacy of antithymocyte induction therapy in lung transplantation is controversial, and its use varies from center to center. We hypothesized that rabbit antithymocyte globulin (RATG) induction therapy would decrease acute rejection after lung transplantation, and we designed a single-center, randomized, prospective study to test this hypothesis. DESIGN: A total of 44 single or bilateral adult lung transplant recipients were randomly assigned to receive either RATG induction therapy (dosage, 1.5 mg/kg/d for 3 days) at the time of transplantation, along with conventional immunosuppression (cyclosporine, azathioprine, and prednisone), or conventional immunosuppression alone with no induction therapy. RESULTS: Although a similar number of biopsies were performed in each group, the number of patients experiencing biopsy-proven grade II or greater acute rejection was significantly reduced in the group receiving RATG induction therapy (23% incidence), as compared to the patients treated with conventional immunosuppression alone (55% incidence; p = 0.03). In addition, there was a nonsignificant reduction in the incidence of bronchiolitis obliterans syndrome at the conclusion of the study in patients who received RATG induction (20%), as compared to patients in the control group (38%). The incidence of posttransplant infections and malignancies were similar between the two groups. CONCLUSION: Induction therapy with RATG significantly reduces the incidence of acute allograft rejection after lung transplantation.

Cardiopulmonary bypass and circulatory arrest increase endothelin-1 production and receptor expression in the lung.

BACKGROUND: Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung. METHODS AND RESULTS: Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC50 value (effective concentration causing 50% of the maximum response) of about 1 x 10(-8) mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02). CONCLUSIONS: Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production.

Left ventricular adaptation to aortic regurgitation in conscious dogs.

OBJECTIVE: Cardiac failure as a result of valvular heart disease remains a major clinical problem that frequently leads to ventricular dysfunction, myocardial failure, and even death. The development of irreversible myocardial damage may be especially insidious in volume overload as a result of aortic or mitral regurgitation. METHODS AND RESULTS: Left ventricular wall volume, ventricular function, and myocardial performance were assessed in 10 chronically instrumented conscious dogs before and after creation of aortic regurgitation. Left ventricular wall volume was measured by serial echocardiography. Left ventricular function was assessed by total cardiac output, stroke work, the slope of the Frank-Starling relationship, and the slope of the end-systolic pressure-volume relationship. Myocardial performance was assessed by the slope of the myocardial power output versus end-diastolic strain relationship. End-diastolic wall stress and volume both increased acutely and remained elevated after creation of aortic regurgitation. Peak systolic wall stress increased initially (1 to 3 weeks) from 336 +/- 30 to 369 +/- 55 mm Hg but returned to control values as left ventricular wall volume increased from 78 +/- 13 to 88 +/- 16 ml after development of compensatory hypertrophy. Left ventricular systolic function remained constant or increased and was maintained initially by increased myocardial performance, which returned to baseline levels after the development of compensatory hypertrophy. CONCLUSIONS: Myocardial performance and ventricular function vary independently in aortic regurgitation. Measures of myocardial performance such as the myocardial power output versus end-diastolic strain relationship may be useful in clinical assessment of aortic regurgitation.

Modifications to the cavopulmonary anastomosis do not eliminate early sinus node dysfunction.

OBJECTIVE: To determine whether operations that theoretically jeopardize the sinus node (hemi-Fontan and/or lateral tunnel Fontan procedures) are associated with a greater risk of sinus node dysfunction than those that theoretically spare the sinus node (bidirectional Glenn and/or extracardiac conduit). METHODS: Between January 1, 1996, and December 31, 1999, a prospective cohort study was conducted evaluating the incidence of sinus node dysfunction in patients undergoing a bidirectional Glenn or hemi-Fontan procedure and those in whom the Fontan repair was completed with either an extracardiac conduit or a lateral tunnel. Sinus node dysfunction was defined (1) as a heart rate more than 2 SD below age-adjusted norms or (2) as a predominant junctional rhythm and/or a sinus pause of more than 3 seconds as determined by the resting electrocardiogram and/or ambulatory monitoring at hospital discharge. RESULTS: Fifty-one patients had a bidirectional Glenn shunt (mean age 7.8 +/- 5.1 months) and 79 a hemi-Fontan procedure (mean age 6.9 +/- 2.8 months). The incidence of sinus node dysfunction on postoperative day 1 was significantly higher after the hemi-Fontan (36%) than after the bidirectional Glenn shunt (9.8%); however, by hospital discharge this difference was no longer apparent (hemi-Fontan [8%]; bidirectional Glenn [6%]; P = not significant). No difference in early sinus node dysfunction was discernible after the extracardiac conduit (4/30 [13%]) compared with the lateral tunnel Fontan procedure (6/46 [13%]) (P = not significant). No diagnostic or perioperative variables were predictive of sinus node dysfunction. CONCLUSIONS: Avoidance of surgery near the sinus node has no discernible effect on the development of early sinus node dysfunction. Thus, concerns about early sinus node dysfunction should not override patient anatomy or surgeon preference as determinants of which cavopulmonary anastomosis to perform.

pH-stat cooling improves cerebral metabolic recovery after circulatory arrest in a piglet model of aortopulmonary collaterals.

Cardiopulmonary bypass with deep hypothermic circulatory arrest increases the risk of neurologic injury in patients with aortopulmonary collaterals. Experimental studies have demonstrated that such collaterals decrease the rate of cerebral cooling before arrest and cerebral metabolic recovery after circulatory arrest. Use of pH-stat blood gas management has been shown to increase cerebral blood flow during cooling. The current study was designed to test whether cooling with pH-stat blood gas management can decrease the cerebral metabolic impact of aortopulmonary collaterals. Twenty 4- to 6-week-old piglets underwent placement of a shunt between the left subclavian artery and main pulmonary artery. In control animals (n = 10) the shunts were immediately ligated, whereas in the shunt animals (n = 10) the shunts were left patent. All animals were supported with cardiopulmonary bypass, cooled to 18 degrees C by means of either alpha-stat (five control and five shunt animals) or pH-stat (five control and five shunt animals) blood gas management, subjected to circulatory arrest for 90 minutes, and rewarmed to 37 degrees C. The cerebral metabolic rate of oxygen consumption (a marker for neurologic function) was significantly lower after circulatory arrest in the shunt animals cooled with alpha-stat blood gas management than in the control animals subjected to alpha-stat management (1.2 +/- 0.2 vs 2.3 +/- 0.2 ml oxygen per 100 gm/min, p < 0.05). By contrast, there was no difference between the pH-stat shunt animals and either control group (2.1 +/- 0.2 vs 2.3 +/- 0.2 [alpha-stat] and 2.0 +/- 0.3 [pH-stat] ml oxygen per 100 gm/min, p = not significant). pH-Stat cooling protected the brain from shunt-related injury. When circulatory arrest is used in the presence of aortopulmonary collaterals, the use of pH-stat blood gas management during cooling results in better cerebral protection than alpha-stat blood gas management.