Götz von Bernuth

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.

Anatomical risk factors for mortality and cardiac morbidity after arterial switch operation

BACKGROUND The arterial switch operation (ASO) is the treatment of choice for transposition of the great arteries. METHODS Anatomical risk factors on mortality and morbidity were analyzed retrospectively in 312 patients who underwent ASO between 1982 and 1997. RESULTS Survival was 95%, 92%, and 92% after 30 days, 5, and 10 years, respectively. Operative survival improved after 1990 to 97% (p < 0.001). Risk factors for operative mortality were complex anatomy (p = 0.018), coronary anomalies (p = 0.008), and prolonged bypass time (p < 0.001). Determinants of late mortality were coronary distribution (p = 0.03), position of the great arteries (p = 0.0095), bypass time (p = 0.047), and aortic coarctation (p = 0.046). After a follow-up of 3.6 +/- 2.7 years (0.1 to 14.9 years), 98% had good left ventricle function, 94% were in sinus rhythm, 2.4% had moderate to severe pulmonary stenosis, 0.3% had significant aortic regurgitation, and 1% had coronary stenosis. Freedom from reoperation was 100%, 96%, and 94% after 1, 5, and 10 years, respectively. No preoperative anatomic parameter correlated with long-term morbidity. CONCLUSIONS ASO can be performed with low operative mortality (< 5%) and long-term morbidity. Malformations associated with complex transposition of the great arteries influence early and late mortality.

Neurodevelopmental outcome related to cerebral risk factors in children after neonatal arterial switch operation

Abstract Background . Neurodevelopmental outcome after neonatal arterial switch operation for complete transposition of the great arteries is an important topic needing prospective assessment. Methods . A group of 33 unselected children (3.0 to 4.6 years) operated on as neonates with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass and a control group of 32 age-matched healthy children (3.0 to 4.8 years) underwent evaluation of socioeconomic and clinical neurological status and a standardized test comprising all areas of child development. Results of patients were related to those of the control group, to population norms, and to preoperative, perioperative, and postoperative cerebral risk factors. Results . Clinical neurological status was normal in 26 patients (78.8%) and reduced in 7 (21.2%). Complete developmental score and the subscores for motor function, visual perception, learning and memory, cognitive function, language, and socioemotional functions were not different compared to population norms. Compared to the patients, the children of the control group scored higher on tests of complete development, cognition, and language, but also on socioeconomic status. Complete developmental score and the scores for motor, cognitive, and language functions were weakly inversely related to the duration of circulatory arrest, but not to the duration of bypass. Cerebral risk factors such as serum levels of the neuron-specific enolase, perinatal acidosis, perinatal asphyxia, peri- and postoperative cardiocirculatory insufficiency, or clinical seizures were not correlated to the test results. Conclusions . Neonatal arterial switch operation with combined circulatory arrest and low flow bypass is associated with neurological impairment, but not with reduced development as assessed by formal testing of motor, cognitive, language, and behavioral functions. Perioperative serum level of the neuron-specific enolase is not a valid marker for later developmental impairment.

Correlations between Indices of Heart Rate Variability in Healthy Children and Children with Congenital Heart Disease

Heart rate variability, as determined from 24-hour Holter recordings, represents a noninvasive parameter for studying the autonomic control of the heart. It decreases with certain disease states characterized by autonomic dysfunction such as congestive heart failure. No study in healthy or cardiac children has been performed to determine the correlations between and within time and frequency domain indices of heart rate variability. We examined five time domain (SDNN, SDNNi, SDANNi, rMSSD and pNN50) and five frequency domain measures (ULF, VLF, LF, HF and balance LF/HF) in 200 healthy children and 200 children with congenital heart disease, aged 3 days to 14 years. All measures were significantly correlated with each other. However, the strength of correlation varied greatly. Our data show that variables strongly dependent on vagal tone (rMSSD, pNN50 and HF) were highly correlated (r value > 0.90), as well as SDNN and SDANNi. We conclude that certain time and frequency domain indices correlate so strongly with each other that they can act as surrogates for each other.

Long-Term Results of Cardiac and General Health Status in Children After Neonatal Arterial Switch Operation

BACKGROUND The purpose of this study was to assess cardiac and general health status 8 to 14 years after neonatal arterial switch operation for transposition of the great arteries. METHODS Sixty unselected children with intact ventricular septum (78.3%) or ventricular septal defect (21.7%) without or with aortic isthmic stenosis (5.1%) were examined 10.5 +/- 1.6 (mean +/- SD) years after neonatal switch and 5.3 +/- 1.6 years after mid-term evaluation. Complete clinical examination, standard and 24-hour Holter electrocardiogram, M-mode, 2D-, Doppler, and color Doppler echocardiography were performed. Results were compared with normal values and to mid-term follow-up results. RESULTS Rates of reoperation after arterial switch operation and operation to correct concomitant coarctation were 3.3% and 5.1%, respectively. No patient needed medication, and 93.3% had no limitation of physical activity. All children had normal height and weight; 31.6% had abnormal thoracic configuration after median sternotomy. Most patients (91.7%) were in sinus rhythm. Incidence of complete right bundle branch block (10.0%) was unchanged, as was prevalence of ectopic activity (occasional atrial ectopy 20.0%, ventricular ectopy: occasional 21.7%; frequent 1.7%). Left ventricular dimensions and shortening fraction did not change over time. Diameters of neo-aortic valve annulus and neo-aortic root did not increase, and z-scores decreased between mid-term and present evaluation. Incidence of neo-aortic insufficiency was 13.3% and remained unchanged in comparison with the pre-examination value. Neo-aortic stenosis was not seen. Compared with mid-term follow-up, incidence (41.6%) and degree of supravalvular pulmonary stenosis increased. CONCLUSIONS Good cardiac results persist 10 years after neonatal arterial switch operation for transposition of the great arteries. Encouraging findings include preservation of left ventricular function, low incidence of rhythm disturbances, lack of further neo-aortic root dilatation, and unchanged incidence of neo-aortic insufficiency compared with mid-term follow-up. Increased incidence and degree of supravalvular pulmonary stenosis are of concern.

Moderate Hypothermia During Cardiopulmonary Bypass Reduces Myocardial Cell Damage and Myocardial Cell Death Related to Cardiac Surgery

OBJECTIVES The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha (TNFalpha). METHODS Twelve young pigs were assigned to a temperature (T degrees ) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB. RESULTS Synthesis of IL10 was significantly higher, while that of TNFalpha was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively. CONCLUSIONS Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

Surgical correction of coarctation in early infancy: Does surgical technique influence the result?

Between 1979 and 1988, a total of 53 infants less than 1 year of age underwent repair of coarctation. Thirty-seven patients (70%) were younger than 3 months. Median age was 0.9 month. Four different surgical techniques were used: resection with end-to-end anastomosis, patch enlargement, subclavian flap aortoplasty, and subclavian displacement aortoplasty (Meier-Mendonca technique). Hospital mortality was 7.5% and was limited to patients with additional complex intracardiac defects. Neither age nor surgical technique had an influence on the operative risk. Follow-up averaged 15 to 43 months for the four different groups. Restenosis developed in 9 (19%) of 47 patients regularly followed up, 5 (11%) of whom have had reoperation. Age at operation was not a predictor for restenosis, which occurred in 17.4% of patients less than 1 month and 20.8% of those greater than 1 month of age at operation. Patch enlargement and the subclavian displacement technique demonstrated the highest restenosis rates (42% and 43%, respectively). However, patients who underwent patch enlargement had less favorable pathological conditions. It is concluded that results of coarctation repair in early infancy do not depend as much on the operative method itself as on the specific pathological aspect, which largely determines the method of treatment. Some reservation must be made in regard to the subclavian displacement technique.

Aortopexy in severe tracheal instability: short-term and long-term outcome in 29 infants and children

BACKGROUND Tracheal instability is a hazardous situation after operation for esophageal atresia. In cases with life-threatening apneas, aortopexy is a therapeutic option. To assess efficacy, short-term and long-term outcome was analyzed retrospectively. METHODS Between 1985 and 2000, 29 patients (age, 1.5 months to 5.2 years) were operated on. A flaccid trachea after operation for esophageal atresia was the cause for life-threatening apneas in 27, and there was external vascular compression in 2 patients. The operative procedure consisted of ventropexy of the aortic arch to the sternum and ventral thoracic wall. RESULTS There was neither early nor late mortality. A reversible lesion of the phrenic nerve was observed in 2 patients, a pneumothorax in 3, and secondary wound healing in 1. In all but 1 patient symptoms improved markedly or disappeared within days or within the first 3 months postoperatively. An increased susceptibility to respiratory infections was observed in long-term follow-up. CONCLUSIONS Aortopexy can be performed with no mortality and low morbidity. Aortopexy is effective to prevent further life-threatening apneas, but does not prevent an increased susceptibility to respiratory infections.

Results of the Bruce treadmill test in children after arterial switch operation for simple transposition of the great arteries

Children who underwent arterial switch operation for simple transposition of the great arteries in the neonatal period are now reaching an age when exercise testing becomes feasible. This study was conducted to assess exercise tolerance and electrocardiographic response to exercise stress in 50 asymptomatic children, aged 4 to 9 years, using the Bruce walking treadmill protocol to voluntary exhaustion. Heart rate and blood pressure response to exercise stress, endurance time, and electrocardiographic changes were analyzed and compared with those of age-matched normal children. Forty-seven patients had normal exercise capacity and parameters. One patient, whose coronary angiogram showed occlusion of the left main coronary artery, developed electrocardiographic signs of myocardial ischemia during exercise. In 1 patient with a single right coronary artery ostium and in another, who underwent a neonatal internal mammary bypass graft for obstruction of the right coronary artery, the resting electrocardiogram showed ventricular premature complexes and exercise stress-induced salvos of ventricular tachycardia. We conclude that most of the children who underwent the neonatal arterial switch operation for simple transposition of the great arteries have a normal exercise capacity. Exercise testing appears to be useful in detecting ischemic damage or exercise-induced arrhythmias possibly secondary to reduced coronary flow reserve.

Systemic right ventricular failure after atrial switch operation: midterm results of conversion into an arterial switch

BACKGROUND Failure of the systemic right ventricle after atrial switch operation can be treated by conversion into an arterial switch operation. METHODS Four patients, age 38 to 59 months, presented with right ventricular failure after Senning operation and ventricular septal defect closure. One patient had elevated left ventricular pressure; in the other three patients the left ventricle was retrained to a left ventricular/right ventricular pressure ratio of 0.8 or greater by pulmonary artery banding in 12 to 24 months. RESULTS Postoperative course after arterial switch operation was prolonged, but clinical condition was good at discharge. Fractional shortening ranged from 20% to 28%. Trace-to-moderate aortic regurgitation was present; only 1 patient had preserved sinus rhythm. After a mean follow-up of 43.5 months 1 patient had died due to left ventricular dysfunction. The survivors are in New York Heart Association functional class I to II. Fractional shortening has improved (29% to 37%); aortic regurgitation has not increased. No patient has undisturbed sinus rhythm. CONCLUSIONS Conversion of an atrial into an arterial switch is an alternative to cardiac transplantation in childhood. However, the procedure is demanding. Long-term morbidity is caused by rhythm disturbances. Aortic valve performance and left ventricular function require close observation.