Altered right ventricular function in the long-term follow-up evaluation of patients after delayed aortic reimplantation of the anomalous left coronary artery from the pulmonary artery.

This study aimed to evaluate regional and global ventricular functions in the long term after aortic reimplantation of the anomalous left coronary artery from the pulmonary artery (ALCAPA) and to assess whether the time of surgical repair influences ventricular performance.The study examined 20 patients with a median age of 15 years (range 3-37 years) who had a corrected ALCAPA and 20 age-matched control subjects using echocardiography and tissue Doppler imaging (TDI). The median follow-up period after corrective surgery was 6 years (range 2.6-15 years). Seven patients underwent surgery before the age of 3 years (early-surgery group), whereas 13 patients had surgery after that age (late-surgery group). The TDI-derived myocardial strain of the interventricular septum (IVS), lateral wall of the left ventricle (LV), and lateral wall of the right ventricle (RV) in the basal and mid regions were examined, and a mean was calculated. The pulsed Doppler-derived Tei index was used to assess global left ventricular function. No significant differences were found between the early-surgery group and the control group regarding the regional myocardial strain or the Tei index. Compared with the early-surgery group, the late-surgery group had a significantly higher Tei index (mean 0.37; range 0.31-0.42 vs. mean 0.52; range 0.39-0.69; p < 0.005), a lower strain percentage of the lateral wall of the LV (mean 29; range 17-30 vs. mean 9; range 7-23), IVS (mean 23; range 21-31 vs. mean 19; range 13-25), and lateral wall of the RV (mean 23; range 21-31 vs. mean 19; range 13-25). The age at operation correlated significantly with the Tei index (r = 0.84, p < 0.001) and inversely with the mean strain of the lateral wall of the LV (r = -0.53, p = 0.028), IVS (r = -0.68, p = 0.003), and lateral wall of the RV (r = -0.68, p = 0.003). At the midterm follow-up evaluation after corrective surgery of ALCAPA, not only the left but also the right ventricular function seemed to be affected in patients with delayed diagnosis and late surgical repair but preserved among the younger patients with early diagnosis and corrective surgery.

Hypothermia suppresses inflammation via ERK signaling pathway in stimulated microglial cells.

Hypothermic perfusion is a standard method for neuroprotection during cardiac surgery in children. However, the cellular responses underlying these mechanisms have not been clearly elucidated. In the present study we demonstrated that the inflammatory response of stimulated microglial cells is significantly reduced after moderate hypothermia. Continuous hypothermia caused a diminished NO release. Moderate hypothermia and rewarming caused a downregulation of phosphorylated MEK, ERK and iNOS-expression, diminished cytokine release and reduced CD-11a and ICAM-1 expression. Thus, neuroprotection offered by hypothermia could be attributed to reduced cytotoxic products released from stimulated microglial cells mediated by the MEK/ERK signal transduction pathway.

S100B modulates IL-6 release and cytotoxicity from hypothermic brain cells and inhibits hypothermia-induced axonal outgrowth.

Brain protection is essential during neonatal and pediatric cardiac surgery. Deep hypothermia is still the most important method for achieving neuroprotection during cardiopulmonary bypass. Previously, we could demonstrate that deep hypothermia induces substantial cytotoxicity in brain cells as well as increased release of the pro-inflammatory cytokine interleukin-6 (IL-6), which plays an important role in neuroprotection and neuroregeneration. Deep hypothermia is also associated with increased levels of the astrocytic protein S100B in the serum and cerebrospinal fluid of patients. Since S100B may modulate pro-inflammatory cytokines and may stimulate neurite outgrowth, we have tested the hypothesis that nanomolar concentrations of S100B may increase IL-6 release from brain cells and support axonal outgrowth from organotypic brain slices under hypothermic conditions. S100B administration substantially reduced neuronal and glial cytotoxicity under hypothermic conditions. In the presence of S100B hypothermia-induced IL-6 release in primary astrocytes was significantly increased but reduced in BV-2 microglial cells and primary neurons. Surprisingly, deep hypothermia increased axonal outgrowth from brain slices and--in contrast to our hypothesis--this hypothermia-induced neurite outgrowth was inhibited by S100B. These data suggest that S100B differentially influences cytokine release and cytotoxicity from distinct brain cells and may inhibit neuroregeneration by suppressing hypothermia-induced axonal outgrowth.

Detection of left ventricular asynchrony in patients with right bundle branch block after repair of tetralogy of Fallot using tissue-Doppler imaging-derived strain.

OBJECTIVES: We aimed to investigate whether patients after tetralogy of Fallot (TOF) repair with right bundle branch block have left ventricular (LV) asynchrony and to assess the influence of ventricular asynchrony on regional and global LV function. BACKGROUND: Patients after TOF repair usually have right bundle branch block. However, no data regarding LV asynchrony in this group are available. METHODS: Twenty-five patients after TOF repair and 25 age-matched healthy control subjects were studied. The regional myocardial deformation of the interventricular septum (IVS) and the LV lateral wall were examined using tissue-Doppler-derived strain. The time interval between the onset of QRS complex and the peak strain was measured for each wall. According to the difference between LV and septum time intervals among the normal subjects, a normal range (mean +/- 2 SD) was plotted, and TOF patients in whom the difference was beyond the normal range were considered to have LV asynchrony. The Tei index was used to assess global LV function. RESULTS: Thirteen (52%) of the examined patients after TOF repair had LV asynchrony. Patients after TOF repair with LV asynchrony had a significantly reduced regional septal systolic strain (p < 0.001) and significantly elevated Tei index (p < 0.001) compared with those without. CONCLUSIONS: Left ventricular asynchrony may exist in patients after TOF repair with right bundle branch block. This LV asynchrony is associated with a reduction of both regional and global LV function.

[The competence network for congenital heart defects. Networking instead of isolated efforts for optimized research and care]. / Das Kompetenznetz Angeborene Herzfehler (KN AHF): Vernetzung statt Insellösungen für optimierte Forschung und Versorgung.

Congenital heart defects (CHD) are the most common congenital malformation; there is no clearly defined clinical picture. Although, thanks to medical progress, most of those affected survive into adulthood, they remain chronically ill throughout their lives and require specific care. By enabling nationwide cooperation and interdisciplinary research, the Competence Network for Congenital Heart Defects can provide and optimize this care. Clinical studies concerning clinical manifestations and recent diagnostic and treatment options can make use of the collected data. Being the core project of the Network, the National Register for congenital heart defects (registered association) registers all patients with a CHD throughout Germany. This data provides a basis for epidemiologic studies concerning quality of life and psychosocial aspects. Thus, integral care and swift transfer of knowledge between science and practice can be achieved. Meanwhile, pediatric guidelines could be developed and raised to S2 level. Additionally, the Register's results allow an assessment of the present situation of cardiac malformations, which is to be further evaluated in current studies. Particular attention is paid to the prevalence of CHD and adult patients' needs. In the long term, the concept of integrated care, and especially the idea of multidisciplinarity, is to be realized within the scope of a "health care database". All in all, the Competence Network for Congenital Heart Defects plays a substantial part in detecting needs and deficits of the current care for patients with CHD and helps developing strategies for an adequate and efficient care, while guaranteeing a high degree of transparency for those concerned.

Genome-wide array analysis of normal and malformed human hearts.

BACKGROUND: We present the first genome-wide cDNA array analysis of human congenitally malformed hearts and attempted to partially elucidate these complex phenotypes. Most congenital heart defects, which account for the largest number of birth defects in humans, represent complex genetic disorders. As a consequence of the malformation, abnormal hemodynamic features occur and cause an adaptation process of the heart. METHODS AND RESULTS: The statistical analysis of our data suggests distinct gene expression profiles associated with tetralogy of Fallot, ventricular septal defect, and right ventricular hypertrophy. Applying correspondence analysis, we could associate specific gene functions to specific phenotypes. Furthermore, our study design allows the suggestion that alterations associated with primary genetic abnormalities can be distinguished from those associated with the adaptive response of the heart to the malformation (right ventricular pressure overload hypertrophy). We provide evidence for the molecular transition of the hypertrophic right ventricle to normal left ventricular characteristics. Furthermore, we present data on chamber-specific gene expression. CONCLUSIONS: Our findings propose that array analysis of malformed human hearts opens a new window to understand the complex genetic network of cardiac development and adaptation. For detailed access, see the online-only Data Supplement.

Adult patients with congenital heart disease and pulmonary arterial hypertension: first open prospective multicenter study of bosentan therapy.

BACKGROUND: Endothelin receptor antagonism has been introduced as an effective oral therapy of patients with idiopathic pulmonary arterial hypertension. In view of the pathophysiologic and histologic similarities between idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD), there is a rationale for treating these patients with the oral dual (ET(A)/ET(B)) endothelin receptor antagonist bosentan. METHODS: Thirty-three patients with PAH-CHD (43 +/- 14 years, 23 with Eisenmenger syndrome) were treated with bosentan for a mean of 2.1 +/- 0.5 years. Efficacy was assessed by a panel of tests, including New York Heart Association functional class, 6-minute walking distance, and echocardiographic and hemodynamic parameters. RESULTS: Mean 6-minute walking distance increased from 362 +/- 105 to 434 +/- 68 m (P = .001). New York Heart Association class also improved significantly (3.1 to 2.4, P = .0001). This was associated with slight trends in improvements of transcutaneous oxygen saturation (86% +/- 7% to 88% +/- 7%, P = .13) and maximum oxygen uptake (13.2 +/- 4.0 to 14.9 +/- 2.5, P = .18). Right ventricular systolic pressure measured by echocardiographic decreased from 111 +/- 32 to 106 +/- 22 mm Hg (P = .001). Bosentan treatment was well tolerated by all patients. CONCLUSIONS: Long-term bosentan treatment in adult patients with PAH-CHD was well tolerated and improved functional status as well as exercise capacity. These findings have to be corroborated by controlled studies that are presently ongoing.

Comparison between cerebral tissue oxygenation index measured by near-infrared spectroscopy and venous jugular bulb saturation in children.

OBJECTIVE: To compare the cerebral tissue oxygenation index (TOI) measured by near-infrared spectroscopy (NIRS) with venous oxygen saturation in the jugular bulb (SjO(2)) during elective cardiac catheterization in children. DESIGN AND SETTING: Prospective observational clinical study in a catheterization laboratory for pediatric cardiology. PATIENTS: Sixty children with congenital heart defects admitted to the catheterization laboratory. MEASUREMENTS AND RESULTS: TOI measured noninvasively by NIRS was compared to SjO(2) measured in the jugular bulb during cardiac catheterization. Patients were divided into two groups regarding body weight: below (n=29) and above 10 kg (n=31). Linear regression analysis and Pearson's correlation coefficient were calculated. Bland-Altman analysis, sensitivity, and specificity calculation for spatially resolved near-infrared spectroscopy with a cutoff level of 60% were performed. Simultaneously measured values for SjO(2) (67.3+/-9.8%, 40-84.1%) and TOI (65.7+/-7.2%, 39-80%) showed a significant correlation; the correlation in children weighing under 10 kg was stronger in children weighing over 10 kg. Bland-Altman analysis showed a mean bias of -1.8% with limits of agreement between 11.7% and -15.3% for all children. Sensitivity and specificity of the SRS method were 46% and 91%, respectively, for all children and 53% and 83% respectively in infants weighing under 10 kg. CONCLUSIONS: The results demonstrate that despite a significant correlation, sensitivity of spatially resolved spectroscopy is poor, and it is questionable whether TOI can be used reliably to detect low SjO(2).

Clinical course and complications of infective endocarditis in patients growing up with congenital heart disease.

BACKGROUND: Although a high number of patients with congenital heart disease (CHD) undergo surgical palliation or definite correction up to adolescence, adult congenital heart disease (ACHD) may remain a potential lifelong risk factor for infective endocarditis (IE) in patients growing up with congenital heart disease (GUCH). METHODS: In a retrospective case study of a tertiary care center long-term clinical course and complications of patients with IE and GUCH were analysed. RESULTS: Data of 52 patients with CHD, who fulfilled the Saiman criteria for infective endocarditis and were treated between April 1986 and March 2001, were identified: Risk factors for infective endocarditis were previous cardiovascular operation (51.9%), use of foreign material (38.5%), dental or other surgical procedures without recommended antibiotic prophylaxis (25.0%), or cardiac catheterization (5.8%). Staphylococcal (38.9%) or streptococcal species (35.2%) were cultivated in most cases as causative microorganisms. Complications were: recurrence of IE (7.7%), septic embolisms (30.8%) leading to central nervous complications (7.7%), embolism of pulmonary arteries (7.7%), renal arteries (1.9%), arteries of the extremities (9.6%), or infarction of spleen (1.9%). Other cardiac (23.1%) or extracardiac (13.5%) complications were frequent. The need of re-operations during or after IE was high (67.3%). The hospital mortality was 1.9%, late mortality was 7.7%. CONCLUSIONS: Patients with IE and CHD show a broad clinical spectrum of cardiac and extracardiac complications. They may lead to a complicative short- and long-term course with the potential risk of death and a high number of re-operation. Efforts have to be made to improve long-term outcome of patients with ACHD by an interdisciplinary cooperation.

Pneumatic pulsatile ventricular assist devices in children under 1 year of age.

OBJECTIVE: Although considerable progress has been made on ventricular assist devices (VAD) for adults, pneumatic pulsatile circulatory support in young infants is still limited. There is a need for long-term ventricular assist devices to bridge the failing myocardium of young children until recovery or transplantation. Miniaturized devices and innovative modalities need to be optimized. We report on our experience. METHODS: From 1/1992 to 6/2004, 18 infants (6 male/12 female) under 1 year of age were treated with the Berlin Heart Excor VAD. The infants were divided into two groups, depending on the year of treatment. Group A consists of eight infants resuscitated and supported with a pulsatile pneumatic ventricular assist device between 1992 and 1998 and group B consists of 10 infants treated between 1999 and 6/2004. With the pediatric-sized Berlin Heart we used miniaturized extracorporeal pneumatically driven blood pumps, the lowest stroke volume being 10 ml. RESULTS: In 18 children, age 3-345 (median 147) days, artificial replacement of heart function was applied for long-term support (1-64, median 10 days) as a life-saving measure in our hospital. Nine had LVAD and nine BVAD support. All were in cardiogenic shock with multiorgan failure; three had fulminant myocarditis, four cardiomyopathy, and one chronic stage of congenital heart disease. Five children were weaned from the system, three reached heart transplantation, and 10 died on the VAD. There were no differences between groups A and B regarding age, body weight or diagnosis, but the duration of mechanical support differed: Group A, median 2, range 1-16 days; group B, median 12, range 1-100 days. Since 1999 (group B), the survival rate of our small infants has increased to 70% whereas none of the infants in group A survived to be discharged. CONCLUSIONS: The outcome of VAD support in small infants is no longer inferior to that of adult support, now optimized cannulas, modified anticoagulation and optimized surgical and intensive care management have been established.

Paralysis of the phrenic nerve as a risk factor for suboptimal Fontan hemodynamics.

OBJECTIVE: The introduction of the Fontan operation for single ventricle physiology was based on the dual principle of the pulmonary blood flow. It is postulated that normal breathing movements are necessary for passive blood flow into the lungs. We compared patients with and without palsy of the phrenic nerve regarding the sufficiency of Fontan hemodynamics. METHODS: We analyzed 85 consecutive patients, who were available for follow-up after completion of their total cavopulmonary connection (TCPC) between February 1992 and February 2003. The median age at TCPC completion was 4.3 (range 1.3-37) years. Sixty were operated on with an extracardiac conduit and 25 with a lateral tunnel. Fifty patients underwent postoperative heart catheterization with contrast angiography. The diagnosis of diaphragm paralysis was made using echocardiography, fluoroscopy and X-ray examination. Surgical diaphragm plication was performed in 13 patients (Four before and nine after Fontan operation) at a median of 2.2 years after the diagnosis. RESULTS: Twenty-one patients developed fixed palsy of the phrenic nerve during a total of 225 operations before and including completion of TCPC. There were no differences in the incidence of phrenic nerve paralysis between small children (aged <3 years) and older patients or between patients with the extracardiac and intracardiac Fontan procedures. There were no differences in the duration of mechanical ventilation. However, prolonged pleural effusions and a hospital stay of longer than 2 weeks were noted more frequently in patients with palsy (P<0.05). During the median follow-up of 4.6 (range: 0.7-11.4) years significantly more patients with phrenic nerve palsy developed chronic ascites compared to those without palsy (8 of 20 vs. 2 of 65; P<0.001). CONCLUSIONS: Phrenic nerve palsy was recognized as a risk factor for suboptimal Fontan hemodynamics due to the hindrance of passive venous blood flow. Patients with phrenic nerve palsy have a longer hospital stay and a higher incidence of prolonged pleural effusions and of chronic ascites, than those without. Early diaphragm plication may be favorable to optimize the Fontan circuit in these patients. Completion of the TCPC in patients with diaphragm paralysis should be viewed critically.

Emergency hospital admissions and three-year survival of adults with and without cardiovascular surgery for congenital cardiac disease.

OBJECTIVE: This study determined the quantity and nature of emergencies leading to unscheduled hospital admissions of adults with congenital cardiac disease and their mid-term survival. RESULTS: During 1 year, 429 adults with congenital cardiac diseases were admitted 571 times, and 124 admissions (22%) of 95 patients (22%) were emergency admissions. Fifteen of the 95 patients were seen for the first time in 1 of the participating centers. The underlying anomalies were Fallot's tetralogy and pulmonary atresia (n = 26/7), univentricular heart after Fontan procedure (n = 25), atrial septal defect (n = 18), Eisenmenger syndrome (n = 12), complete transposition (n = 11), and others (n = 25). Indications for admission were cardiovascular complications (n = 103; 83%) (arrhythmia, cardiac failure, syncope, pacemaker problems, pericardial tamponade, and sudden death), infections (n = 8, 6%) (endocarditis, pacemaker infection, pneumonia, and cerebral abscess), acute chest pain (n = 7; 6%), and acute abdominal pain (n = 4; 3%). All patients required immediate emergency care, and 16 patients (17%) required urgent cardiovascular or abdominal surgery. Six patients died during the hospital stay. During a follow-up of 2.9 years (SD 0.8), 16 (18%) of the discharged patients died, and 2 additional patients underwent heart or heart-lung transplantation. CONCLUSION: Adults with congenital cardiac disease often experience serious emergency situations with a high in-hospital and mid-term post-hospital mortality. Care given by physicians with special expertise is important in this specific group of patients.

Assessment of symptoms and exercise capacity in cyanotic patients with congenital heart disease.

OBJECTIVES: Patients with cyanotic congenital heart disease are generally thought to be limited by hypoxemia. To correlate exercise tolerance to the severity of the cardiac abnormality and to further characterize dyspnea in affected patients, we examined 25 adults with uncorrected cyanotic congenital heart disease. DESIGN AND SETTING: Cohort study at a university hospital. METHODS: Symptom-limited cardiopulmonary exercise testing (CPX) was performed on a treadmill. Expiratory gas was analyzed breath by breath for evaluation of maximal exercise performance, ventilation, and ventilatory efficiency in combination with blood gas analysis during rest and exercise. Symptoms were assessed by the ability index and New York Heart Association class, and the results were compared to 101 healthy volunteers. RESULTS: PaO(2) decreased by 26 +/- 8% (mean +/- SD) with exercise (from 49 +/- 12 to 36 +/- 10 mm Hg), while PaCO(2) was only slightly decreased compared to control subjects. Peak oxygen uptake (O(2)) was significantly reduced when compared to control subjects: 16.7 +/- 6.6 mL/kg/min vs 36.1 +/- 7.7 mL/kg/min. Ventilatory efficiency was markedly impaired at rest (minute ventilation [E]/carbon dioxide output [CO(2)] ratio of 70 +/- 18; control subjects, 53 +/- 11; p < 0.005) and during exercise (E vs CO(2) slope, 58 +/- 31; control subjects, 26 +/- 4; p < 0.005). At rest, ventilatory efficiency was correlated to resting pH and PaO(2), while during exercise it was linked to PaO(2). Ventilatory efficiency during exercise had the strongest correlation with observed symptoms, while hypoxemia and peak O(2) were not significantly associated with symptomatic state. CONCLUSION: CPX in patients with cyanotic congenital heart disease provides helpful parameters that better define the symptomatic state of these patients. The summation of disease-related factors is best reflected by ventilatory efficiency. This parameter offers additional and independent information when compared to peak O(2) and the extent of cyanosis alone.

Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device.

BACKGROUND: Mechanical support with a pulsatile pneumatic ventricular assist device (VAD) is a complex rescue procedure performed in children with untreatable cardiogenic shock. Its impact on early and long-term survival after subsequent heart transplantation (HTx) remains to be determined. METHODS: We reviewed retrospectively the course of 95 children (median age, 8 years; range, 8 days-17 years; body weight, 24 kg; range, 3-110 kg) who underwent HTx. Group A, the elective-HTx group, consists of 33 children who were treated as outpatients before transplantation. Group B, the emergency-HTx group, has 44 children who were critically ill and hospitalized before transplantation but without ventricular assist devices, whereas Group C, the VAD-HTx group, consists of 18 children resuscitated and supported with pulsatile pneumatic VADs for a median time of 20 days. RESULTS: Overall actuarial survival after cardiac transplantation was 86% at 1 month, 82% at 1 year, and 78% at 5 years, without significant differences among the 3 sub-groups. Group A had the best long-term survival rate, 88% at 1 month, 88% at 1 year, and 80% at 5 years. Group B had a survival rate of 88% at 1 month, 82% at 1 year, and 79% at 5 years. Group C had a survival rate of 72% at 1 month, 72% at 1 year, and 72% at 5 years. We found no differences in neurologic outcome, acute cardiac rejection, or transplant failure. The survival rate was significantly better in the children with cardiomyopathy compared with those with congenital heart defects (p = 0.014). CONCLUSIONS: Bridging to HTx with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After HTx, overall survival of these children is similar to that of patients who were bridged with inotropes or who were awaiting heart transplantation electively.

Release patterns of astrocytic and neuronal biochemical markers in serum during and after experimental settings of cardiac surgery.

OBJECTIVE: Brain injury and altered psychomotor development in infants, children and adults after cardiac surgery using cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) is still a matter of concern. Early diagnosis and identification of brain injury that has occurred or is ongoing by measurement of biochemical markers in serum may have diagnostic and prognostic value. The aim of the experimental studies in an animal model was therefore to investigate the release patterns of astroglial and neuronal markers in serum and to determine the morphological and immunohistochemical changes in the brain of animals undergoing similar perfusion conditions of CPB and a period of DHCA. METHODS: Fourteen New Zealand rabbits, (weight, 3.1 +/- 0.25 kg) were anesthetized, intubated and mechanically ventilated. Four animals were sham operated and served as controls. After median sternotomy the animals were connected to CPB by cannulation of the aorta and right atrium. Full flow CPB (200-250 ml/kg/min) was initiated to achieve homogeneous systemic cooling. Circulatory arrest of 60 minutes was induced when rectal and nasopharyngeal temperature of 14 degrees C was achieved. After rewarmed reperfusion and establishment of stable cardiac ejection the animals were weaned from CPB and monitored for 6 hours. Then the animals were killed, the brain was immediately removed and cut in standardized sections. These were fixated, embedded in paraffin and stained for further quantitative histological studies. In the brain astrocyte reactivity for S-100B was assessed immunocytochemically (DPC Immustain Los Angeles, USA). Monoclonal mouse anti-human neurospecific enolase (NSE) antibody was used for the localization of NSE in the fixed and paraffin embedded brain (NSE-DAKO, H14). The concentrations of S-100B protein and neurospecific enolase (NSE) in the serum were analyzed using a commercially available immunoluminometric assay (LIA-mat, Sangtec 100, Byk-Sangtec). Immunospecific monoclonal anti-parvalbumin antibody was used for the detection of parvalbumin in the brain. Serum concentrations of parvalbumin were analyzed using a newly developed ELISA method. RESULTS: In all experimental animals a significant increase of the serum concentration of the astroglial protein S-100B was found immediately after reperfusion and the termination of CPB. In contrast the serum levels of the neuronal proteins parvalbumin and NSE were not increased, but rather decreased. Light microscopy and electron microscopy revealed perivascular astrocytic swelling and minor neuronal cell injury. In comparison to the sham operated animals, increased immunohistochemical staining of S-100B was found. This increased reactivity of S100B antibody was found in the astrocytic processes with immediate connection to the perivascular space and around the perivascular oedema. The immunocytochemical stainings for NSE and parvalbumin in the neuronal cells was not different from that of sham-operated animals and indicated well preserved neurons.

Effect of increasing doses of magnesium in experimental pulmonary hypertension after acute pulmonary embolism.

OBJECTIVE: To investigate the dose-related effects of magnesium on pulmonary vascular resistance and associated changes in cardiac output in porcine micro-embolic pulmonary hypertension. DESIGN: Prospective, interventional animal study. SETTING: University animal laboratory. SUBJECTS: Forty anaesthetised and ventilated piglets. INTERVENTIONS: Right heart catheterisation for the measurement of cardiac output, pulmonary artery pressure, central venous pressure and pulmonary capillary wedge pressure; arterial cannulation for measurement of arterial pressures and ionised magnesium levels; calculation of pulmonary and systemic vascular resistance before and after induction of acute pulmonary micro-embolism, and without or with the administration of magnesium (0.5, 1.0, 2.0 mmol/kg bolus and 1 mmol/kg bolus followed by 1 mmol/kg per h continuous infusion). MEASUREMENTS AND MAIN RESULTS: The bolus administration of increasing doses of magnesium (0.5, 1.0, 2.0 mmol/kg) was associated with an increase in ionised serum magnesium levels and a dose-dependent decrease of mean pulmonary arterial pressure, an increase of cardiac output and a decrease of pulmonary vascular resistance. This effect was sustained after bolus administration (1 mmol/kg) followed by a continuous infusion of magnesium (1 mmol/kg per h). CONCLUSIONS: Magnesium has a directly dose-dependent beneficial effect on the circulation in acute embolic pulmonary hypertension and improves cardiocirculatory impairment in massive pulmonary embolism (PE).

Relation of cerebral tissue oxygenation index to central venous oxygen saturation in children.

OBJECTIVE: To evaluate the relationship between the cerebral tissue oxygenation index measured by near-infrared spectroscopy and central venous oxygen saturation (SvO2) after corrective surgery of congenital heart defects in children. DESIGN: Prospective observational clinical study. SETTING: A tertiary neonatal and paediatric intensive care unit for paediatric cardiology. PATIENTS: Neonates and children consecutively admitted to the paediatric cardiology intensive care unit after corrective surgery of non-cyanotic congenital heart defects. MEASUREMENTS AND RESULTS: Forty-three children were studied. Cerebral tissue oxygenation index, measured non-invasively by near-infrared spectroscopy, was compared to SvO2, measured by a catheter placed in the right atrium, and to haemodynamic and respiratory parameters. Pearson's correlation coefficients and p values were calculated. Simultaneously measured values for SvO2 (62.2+/-9.8%, 39.8-80.4%) and cerebral tissue oxygenation index (56.7+/-8.8%, 35.8-71.2%) showed a significant correlation ( r=0.52, p<0.001). CONCLUSION: Cerebral tissue oxygenation index and SvO2 are not interchangeable parameters, but cerebral tissue oxygenation index reflects the haemodynamic influence on cerebral oxygenation after cardiovascular surgery. Further work is necessary to confirm the clinical role of continuous non-invasive measurement of cerebral tissue oxygenation index with regard to the variations of global systemic oxygen consumption after cardiac surgery in children.

Consumption of blood products during mechanical circulatory support in children: comparison between ECMO and a pulsatile ventricular assist device.

OBJECTIVE: Different mechanical circulatory support (MCS) systems are used in children with intractable heart failure. However, the need for anticoagulation leads to hemorrhage with subsequent use of blood products. We compared the coagulation disorders and the need for blood products in children treated either with extracorporeal membrane oxygenation (ECMO) or with the Berlin Heart pulsatile pneumatic ventricular assist device. PATIENTS: We retrospectively reviewed the first 8-day course of 64 children who were on MCS for more than 2 days between 1990 and 2002. Thirty children (median age 7.4 years, weight 25.5 kg) received Berlin Heart support and 34 children (median age 1.8 years, weight 9.2 kg) ECMO. Anticoagulation was accomplished by continuous infusion of heparin. Red blood cell count, platelet count, aPTT, AT III, fibrinogen, and ACT were measured regularly. Depending on blood loss and the coagulation disorder, red blood cells, fresh frozen plasma, platelets, and AT III were substituted. RESULTS: There were no preoperative differences in hematological parameters between the two groups. In the Berlin Heart group platelet transfusion was 4.3 ml x kg x day vs 24.6 ml x kg x day in the ECMO group. Red blood cell substitution was 17.2 vs 60.3 ml.kg.day. Fresh frozen plasma substitution was 8.5 ml x kg x day vs 46.9 ml x kg x day (P<0.001). Even in the congenital heart defect subgroups, when MCS was implanted without recent cardiotomy, the differences were significant. Nevertheless, the mean daily values for hemoglobin, platelets, and fibrinogen were lower in the ECMO group. There was lower overall mortality in the Berlin Heart group. CONCLUSIONS: Compared to ECMO, use of the Berlin Heart in children results in less blood loss and lower consumption of red blood cells, platelets, and fresh frozen plasma.

Novel growth stent for the permanent treatment of vessel stenosis in growing children: an experimental study.

Stent implantation in stenotic vessels of infants and small children is problematic because there is no ideal stent model that is small enough to be easily introduced into the infant femoral vein or artery and, at the same time, large enough to be dilated during growth to adult vessel diameters. To overcome this problem, we designed a new stent, the growth stent. This growth stent is a balloon-expandable metal stent. Two longitudinal halves are connected with bioabsorbable sutures so that a circular stent is created. It was postulated that after absorption of the sutures the stent would not impede growth. Twenty of these stents were implanted in the aorta, pulmonary arteries, and inferior vena cava of piglets (average weight 6.9 kg). After 18 weeks (14-23 weeks) and a mean weight gain of 59 kg, none of the stented vessels showed any significant stenosis or pressure gradient, documented by angiography and catheter pullback. During fluoroscopy, the two halves of the stent were clearly separated in all animals. The growth stent has the potential to be nonrestrictive during vessel growth, and thus is a promising new device for the permanent treatment of stenotic vessels in infancy and childhood.

Influence of cold storage on renal ischemia reperfusion injury after non-heart-beating donor explantation.

BACKGROUND: Due to the increasing need for kidney donors, transplantation from non-heart-beating donors (NHBD) is currently being practiced more extensively. As detailed studies on the reperfusion injury of these kidneys do not exist so far, a comparison of renal ischemia reperfusion injury scores immediately after organ explantation with injury scores after NHBD organ explantation with subsequent cold storage would be useful. METHODS: Non-stored kidneys were compared to a group of kidneys stored for 6.9 +/- 1.8 h. Functional analyses were made during 145 min of ex vivo perfusion. Quantitative histological analyses were performed in all kidneys after termination of perfusion. RESULTS: During ex vivo reperfusion, renal vascular resistance was elevated, while creatinine clearance, filtration fraction, renal oxygen consumption, and sodium reabsorption were below normal after non-heart-beating explantation and further decreased after subsequent washing and cold storage. In the kidneys subjected to cold preservation, histologically tubular damage was enhanced, and the total count, as well that for the intraglomerular neutrophil granulocytes were also elevated. CONCLUSIONS: Explantation from NHBD causes renal ischemia reperfusion injury. Cold storage augmented deterioration of the kidney as histologically and functionally demonstrated. Thus, preservation times for non-heart-beating kidneys should be carefully reappraised.