Socio-demographic parameters and non-cardiac comorbidity related to self-perceived quality of life in young adults after neonatal arterial switch operation for transposition of the great arteries.

Evaluating the relation of non-cardiac comorbidity and socio-demographic factors to physical and mental health-related quality of life (QOL) which has been partially found at elevated risk in young adults after neonatal arterial switch operation (ASO) for transposition of the great arteries (TGA). In a prospective reassessment study, results of 92 unselected young adults (22.8 ± 2.6 years) having undergone evaluation of QOL (SF-36) were related to non-cardiac comorbidity with special respect to neurologic and psychiatric comorbidity and to socio-demographic parameters. Neurologic (14%) contrary to psychiatric comorbidities (6.5%) were more frequent than in the general population. The educational level was higher, the rate of unemployment was double as high compared to the average German population. Significant inverse relations (p = 0.006 to 0.033) existed between physical health domains (physical functioning and general health perception) and non-cardiac, neurologic, and psychiatric comorbidity, as well as correlations between the latter domains and socio-economic status, educational level, and worse employment status (Spearman 0.22-0.41, p < 0.0001 to 0.036). Mental health domains (vitality, social functioning, psychical health) were significantly inversely related with neurologic and psychiatric comorbidity (p = 0.002 to 0.048) and correlated with higher educational level (Spearman 0.25, p = 0.019). Neurologic and psychiatric comorbidities and socio-demographic parameters are significant risk factors for a reduced QOL concerning physical and mental health in young adults with TGA after ASO. Standardized QOL measurement should be part of routine screening programs to detect subclinical physical, neurodevelopmental, and psychosocial comorbidity.

Long-Term Outcome Up To 40 Years after Single Patch Repair of Complete Atrioventricular Septal Defect in Infancy or Childhood.

OBJECTIVES: Patients with repaired complete atrioventricular septal defect (CAVSD) represent an increasing portion of grown-ups with congenital heart disease. For repair of CAVSD, the single-patch technique has been employed first. This technique requires division of the bridging leaflets, thus, among other issues, long-term function of the atrioventricular valves is of particular concern. METHODS: Between 1978 and 2001, 100 consecutive patients with isolated CAVSD underwent single-patch repair in our institution. Hospital mortality was 11%. Primary endpoints were clinical status, atrioventricular valve function, and freedom from reoperation in long term. Follow-up was obtained contacting the patient and/or caregiver, and the referring cardiologist. RESULTS: Eighty-three patients were eligible for long-term follow-up (21.0 ± 8.7, mean ± standard deviation [21.5; 2.1-40.0, median; min-max] years after surgical repair). Actual long-term mortality was 3.4%. Quality of life (QoL; self- or caregiver-reported in patients with Down syndrome) was excellent or good in 81%, mild congestive heart failure was present in 16%, moderate in 3.6% as estimated by New York Heart Association classification. Echocardiography revealed normal systolic left ventricular function in all cases. Regurgitation of the right atrioventricular valve was mild in 48%, mild-moderate in 3.6%, and moderate in 1.2%. The left atrioventricular valve was mildly stenotic in 15% and mild to moderately stenotic in 2%; regurgitation was mild in 54%, mild to moderate in 13%, and moderate in 15% of patients. Freedom from left atrioventricular-valve-related reoperation was 95.3, 92.7, and 89.3% after 5, 10, and 30 years, respectively. Permanent pacemaker therapy, as an immediate result of CAVSD repair (n = 7) or as a result of late-onset sick sinus syndrome (n = 5), required up to six reoperations in single patients. Freedom from pacemaker-related reoperation was 91.4, 84.4, and 51.5% after 5, 10, and 30 years, respectively. CONCLUSION: Up to 40 years after single-patch repair of CAVSD, clinical status and functional results are promising, particularly, in terms of atrioventricular valve function. Permanent pacemaker therapy results in a life-long need for surgical reinterventions.

Expression of inflammation in myocardial tissue of rabbits: comparison of two miniaturized heart-lung machines.

The majority of cases involving the surgical treatment of congenital heart disease require implementation of cardiopulmonary bypass (CPB). However, neonates and infants are particularly prone to serious complications associated with CPB as a result of capillary leak due to cardiovascular failure. These complications are related to the transfusion of foreign blood, the disproportionately large area of contact between the patient's blood and foreign material, as well as the systemic inflammatory response induced by hemolysis. To attenuate these risks, we developed a novel, highly integrative, miniaturized heart-lung machine (MiniHLM) with a static priming volume of only 102 mL. This prototype was tested in comparison with a conventional heart-lung machine (static priming volume 213 mL) using a rabbit animal model. The animals were anesthetized, sternotomized, and connected to CBP via the aorta and right atrium. The aorta was cross-clamped for 1 h. Blood samples for examination were taken at regular intervals. Biopsies of the right atrial appendage (RAA) were removed directly after initiation and after cessation of CPB. After gradual reduction of perfusion with the HLM, all rabbits were successfully weaned from CPB, and the sternum was closed. Foreign blood was not administered in all cases. After cryopreservation of the RAA tissue, de novo transcription of inflammatory cytokines was measured by means of real-time polymerase chain reaction using the comparative CT method. No significant differences in the expression of the inflammatory parameters of the myocardial tissue samples were found between the study groups.

Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect.

Background: Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERß- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role. Patients and Methods: Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome. Results: ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p = 0.032), higher PaO2/FiO2 ratio at 4 h po (p = 0.059), lower fluid retention at 4 h po (p = 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p = 0.047). A higher ERß-mRNA expression was also correlated with lower fluid retention at 24 h po (p = 0.048). Patients in whom the levels of ERα- and ERß-mRNA were >P50 had lower troponin T (p = 0.003, respectively) and lower AST concentrations at 24 h po (p = 0.043, respectively) than the others. Conclusions: The expression of ERα- and ERß-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.

Proximal Aortic Dilatation and Pulmonary Valve Replacement in Patients with Repaired Tetralogy of Fallot: Is There a Relationship? A Cardiac Magnetic Resonance Imaging Study.

Aortopathy is a known complication whose incidence is growing within the population of tetralogy of Fallot (TOF) patients. Its pathology and relationship with other comorbidities remain unclear. This study was designed to determine the prevalence and predictors of proximal aortic dilatation after TOF repair. We retrospectively investigated all patients who underwent follow-up cardiac magnetic resonance imaging (CMR; at least 4 years after TOF repair) between March 2004 and December 2019. The dimensions at the ascending aorta (AAo) and sinus of Valsalva (SoV) levels were measured. Aortic dilatation was defined as an internal aortic diameter that was >2 standard deviation of the previously published normal values. We included 77 patients (mean age 28.9 ± 10.5 years, 41.5% female, mean follow-up of 24.5 ± 8.1 years). AAo and SoV were dilated in 19 (24.6%) and 43 (55.8%) patients, respectively. Patients with dilated AAo and SoV were older during the corrective surgery (p < 0.001 and p = 0.004, respectively) and during CMR (p = 0.002 and 0.024, respectively) than patients without AAo and SoV dilatation. Patients of the dilated AAo group were more likely to have prior palliative shunt (p = 0.008), longer shunt duration (p = 0.005), and a higher degree of aortic valve regurgitation (AR) fraction (p < 0.001) and to undergo pulmonary (PVR) and/or aortic valve replacement (p < 0.001 and p = 0.013, respectively). PVR (p = 0.048, odds ratio = 6.413, and 95% CI = 1.013-40.619) and higher AR fraction (p = 0.031, odds ratio = 1.194, and 95% CI = 1.017-1.403) were independent predictors for AAo dilatation. Aortopathy is a common progressive complication that may require reintervention and lifelong follow-up. Our study shows that proximal aortic dilatation may be attributed to factors that increase the volume overload across the proximal aorta, including late corrective surgery and palliative shunt. We also found that PVR and higher AR fraction are independent predictors of AAo dilatation.

A newly developed miniaturized heart-lung machine--expression of inflammation in a small animal model.

Cardiopulmonary bypass may cause severe inflammatory reactions and multiorgan failure, especially in premature and low-weight infants. This is due in part to the large area of contact with extrinsic surfaces and the essential addition of foreign blood. Thus, we developed a new miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102mL (including arterial and venous lines) and tested it in a small animal model. Seven Chinchilla Bastard rabbits were perfused with the MiniHLM (dynamic priming volume 127mL). Seven animals serving as a control were perfused using Dideco Kids and a Stöckert roller pump (modified dynamic priming volume 149mL). The rabbits were anesthetized and sternotomized, followed by cannulation of the aorta and the right atrium. The aorta was clamped for 1h. Blood for examination of inflammation (TNF-α, IL-1ß, IL-6, IL-8, and IL-10) and blood gas analysis were taken before skin incision, 5min before opening of the aorta, 15min after opening of the aorta, and 4 h after the initiation of cardiopulmonary bypass. The parameters of inflammation were expressed by means of the comparative C(T) method (ΔΔC(T) method). After gradual reduction of perfusion with the HLM, the heart was decannulated, and the sternum was closed. All rabbits were successfully weaned from cardiopulmonary bypass. Blood gas analysis was unremarkable in all cases. Foreign blood was not administered. Although statistical significance was not achieved, there was a reduced expression of inflammatory markers in the MiniHLM group. The newly developed MiniHLM prototype was tested successfully in a small animal model in terms of technical function and expression of inflammation. Upcoming tests with the industrially manufactured MiniHLM may reveal the advantages of the MiniHLM in comparison with the conventional HLM.

The Aachen MiniHLM--a miniaturized heart-lung machine for neonates with an integrated rotary blood pump.

The operation of congenital heart defects in neonates often requires the use of heart-lung machines (HLMs) to provide perfusion and oxygenation. This is prevalently followed by serious complications inter alia caused by hemodilution and extrinsic blood contact surfaces. Thus, one goal of developing a HLM for neonates is the reduction of priming volume and contact surface. The currently available systems offer reasonable priming volumes for oxygenators, reservoirs, etc. However, the necessary tubing system contains the highest volumes within the whole system. This is due to the use of roller pumps; hence, the resulting placement of the complete HLM is between 1 and 2 m away from the operating table due to connective tubing between the components. Therefore, we pursued a novel approach for a miniaturized HLM (MiniHLM) by integrating all major system components in one single device. In particular, the MiniHLM is a HLM with the rotary blood pump centrically integrated into the oxygenator and a heat exchanger integrated into the cardiotomy reservoir which is directly connected to the pump inlet. Thus, tubing is only necessary between the patient and MiniHLM. A total priming volume of 102 mL (including arterial filter and a/v line) could be achieved. To validate the overall concept and the specific design we conducted several in vitro and in vivo test series. All tests confirm the novel concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce known complications related to cardiopulmonary bypass in neonates (e.g., inflammatory reaction and capillary leak syndrome).

Right Atrial Myocardial Remodeling in Children With Atrial Septal Defect Involves Inflammation, Growth, Fibrosis, and Apoptosis.

Introduction: Myocardial remodeling due to large atrial septum defect (ASD) is macroscopically characterized by dilation of the right-sided cardiac cavities secondary to volume overload, the cellular mechanisms of which are not yet understood. We postulated that inflammation, fibrosis, and cell death are actors of right atrial remodeling secondary to ASD. Patients and Methods: In 12 children with large ASD (median age: 63 months), expression of genes coding for proteins involved in the response to cell stress and -protection, inflammation, growth and angiogenesis, fibrosis, and apoptosis was assessed by RT-PCR in right atrial myocardial biopsies taken during cardiac surgery. The presence of cytokines in myocardial cells was confirmed by immunohistochemistry and effective apoptosis by TUNEL assay. Results: In all patients investigated, a cellular response to early mechanical stress with the initiation of early protective mechanisms, of inflammation (and its control), -growth, and -angiogenesis, of fibrosis and apoptosis was present. The apoptotic index assessed by TUNEL assay averaged 0.3%. Conclusions: In children with large ASD, macroscopic right atrial remodeling relates to cellular mechanisms involving the expression of numerous genes that either still act to protect cells and tissues but that also harm as they initiate and/or sustain inflammation, fibrosis, and cell death by apoptosis. This may contribute to long term morbidity in patients with ASD.

The Aachen miniaturized heart-lung machine--first results in a small animal model.

Congenital heart surgery most often incorporates extracorporeal circulation. Due to foreign surface contact and the administration of foreign blood in many children, inflammatory response and hemolysis are important matters of debate. This is particularly an issue in premature and low birth-weight newborns. Taking these considerations into account, the Aachen miniaturized heart-lung machine (MiniHLM) with a total static priming volume of 102 mL (including tubing) was developed and tested in a small animal model. Fourteen female Chinchilla Bastard rabbits were operated on using two different kinds of circuits. In eight animals, a conventional HLM with Dideco Kids oxygenator and Stöckert roller pump (Sorin group, Milan, Italy) was used, and the Aachen MiniHLM was employed in six animals. Outcome parameters were hemolysis and blood gas analysis including lactate. The rabbits were anesthetized, and a standard median sternotomy was performed. The ascending aorta and the right atrium were cannulated. After initiating cardiopulmonary bypass, the aorta was cross-clamped, and cardiac arrest was induced by blood cardioplegia. Blood samples for hemolysis and blood gas analysis were drawn before, during, and after cardiopulmonary bypass. After 1 h aortic clamp time, all animals were weaned from cardiopulmonary bypass. Blood gas analysis revealed adequate oxygenation and perfusion during cardiopulmonary bypass, irrespective of the employed perfusion system. The use of the Aachen MiniHLM resulted in a statistically significant reduced decrease in fibrinogen during cardiopulmonary bypass. A trend revealing a reduced increase in free hemoglobin during bypass in the MiniHLM group could also be observed. This newly developed Aachen MiniHLM with low priming volume, reduced hemolysis, and excellent gas transfer (O(2) and CO(2)) may reduce circuit-induced complications during heart surgery in neonates.

Aortopexy offers surgical options for a variety of pathological tracheal conditions in paediatric patients.

OBJECTIVES: Aortopexy is widely used; however, many surgeons still regard it with suspicion. To date, there are only a few large series and minimal long-term data. Against this background, our goal was to report our experience, particularly with regard to the recent expansion of indications and modification of diagnostic routine and surgical strategy. METHODS: Between 1994 and 2012, 53 patients (mean age: 1.1 years; 5 weeks-10.2 years) were operated on. Tracheomalacia after the operation for oesophageal atresia was the main indication for aortopexy (74%), followed by tracheal compression by the innominate artery (17%) and other selected indications (9%). Computed tomography angiography has emerged in recent years as the method of choice for preoperative diagnosis. Median sternotomy has replaced lateral thoracotomy, and intraoperative bronchoscopy has become the standard. RESULTS: In contrast to magnetic resonance imaging, computed tomography angiography resulted in perfect visualization of the condition. Median sternotomy and simultaneous bronchoscopy led to immediate readjustment of the aortopexy sutures in 6 patients. There were no surgical deaths or serious morbidities. The mean follow-up was 4.9 (0.3-14.9) years. Two patients with additional complex diseases died during the follow-up period. In all survivors, symptoms improved markedly or disappeared. However, we observed an increased susceptibility to lower respiratory tract infections over the long-term (32%). CONCLUSIONS: Aortopexy is effective for treating tracheomalacia of different origins and other pathological conditions as well. Preoperative computed tomography angiography offers excellent visualization of the condition. Median sternotomy and intraoperative bronchoscopy provide a combination for reliable operative and long-term results. However, many patients still have an increased susceptibility to lower respiratory tract infections.

The use of moderate hypothermia during cardiac surgery is associated with repression of tumour necrosis factor-alpha via inhibition of activating protein-1: an experimental study.

INTRODUCTION: The use of moderate hypothermia during experimental cardiac surgery is associated with decreased expression of tumour necrosis factor (TNF)-alpha in myocardium and with myocardial protection. In order to identify the cellular mechanisms that lead to that repression, we investigated the effect of hypothermia during cardiac surgery on both main signalling pathways involved in systemic inflammation, namely the nuclear factor-kappaB (NF-kappaB) and activating protein-1 pathways. METHOD: Twelve female pigs were randomly subjected to standardized cardiopulmonary bypass with moderate hypothermia or normothermia (temperature 28 degrees C and 37 degrees C, respectively; six pigs in each group). Myocardial probes were sampled from the right ventricle before, during and 6 hours after bypass. We detected mRNA encoding TNF-alpha by competitive RT-PCR and measured protein levels of TNF-alpha, inducible nitric oxide synthase and cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF-kappaB and activating protein-1, as well as phosphorylation of p38 mitogen-activated protein kinase by electrophoretic mobility shift assay with super shift and/or Western blot. RESULTS: During and after cardiac surgery, animals subjected to hypothermia exhibited lower expression of TNF-alpha and cyclo-oxygenase-2 but not of inducible nitric oxide synthase. This was associated with lower activation of p38 mitogen-activated protein kinase and of its downstream effector activating protein-1 in hypothermic animals. In contrast, NF-kappaB activity was no different between groups. CONCLUSION: These findings indicate that the repression of TNF-alpha associated with moderate hypothermia during cardiac surgery is associated with inhibition of the mitogen-activated protein kinase p38/activating protein-1 pathway and not with inhibition of NF-kappaB. The use of moderate hypothermia during cardiac surgery may mitigate the perioperative systemic inflammatory response and its complications.

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects.

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved. BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium. METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively. RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD. CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant's myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.

Does cardiac surgery in newborn infants compromise blood cell reactivity to endotoxin?

INTRODUCTION: Neonatal cardiac surgery is associated with a systemic inflammatory reaction that might compromise the reactivity of blood cells against an inflammatory stimulus. Our prospective study was aimed at testing this hypothesis. METHODS: We investigated 17 newborn infants with transposition of the great arteries undergoing arterial switch operation. Ex vivo production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), of the regulator of the acute-phase response IL-6, and of the natural anti-inflammatory cytokine IL-10 were measured by enzyme-linked immunosorbent assay in the cell culture supernatant after whole blood stimulation by the endotoxin lipopolysaccharide before, 5 and 10 days after the operation. Results were analyzed with respect to postoperative morbidity. RESULTS: The ex vivo production of TNF-alpha and IL-6 was significantly decreased (P < 0.001 and P < 0.002, respectively), whereas ex vivo production of IL-10 tended to be lower 5 days after the operation in comparison with preoperative values (P < 0.1). Ex vivo production of all cytokines reached preoperative values 10 days after cardiac surgery. Preoperative ex vivo production of IL-6 was inversely correlated with the postoperative oxygenation index 4 hours and 24 hours after the operation (P < 0.02). In contrast, postoperative ex vivo production of cytokines did not correlate with postoperative morbidity. CONCLUSION: Our results show that cardiac surgery in newborn infants is associated with a transient but significant decrease in the ex vivo production of the pro-inflammatory cytokines TNF-alpha and IL-6 together with a less pronounced decrease in IL-10 production. This might indicate a transient postoperative anti-inflammatory shift of the cytokine balance in this age group. Our results suggest that higher preoperative ex vivo production of IL-6 is associated with a higher risk for postoperative pulmonary dysfunction.

Atrial fibrillation-induced atrial contractile dysfunction: a tachycardiomyopathy of a different sort.

OBJECTIVE: Although AF-induced atrial contractile dysfunction has significant clinical implications the underlying intracellular mechanisms are poorly understood. METHODS: From the right atrial appendages of 59 consecutive patients undergoing mitral valve surgery (31 in SR, 28 in chronic AF) thin muscle preparations (diameter<0.7 mm) were isolated. Isometric force of contraction was measured in the presence of different concentrations of Ca(2+) and isoprenaline. To assess the function of the sarcoplasmic reticulum, the force-frequency relationship and the post-rest potentiation were studied. The myocardial density of the ryanodine-sensitive calcium release channel (CRC) of the sarcoplasmic reticulum was determined by [3H]ryanodine binding. Myocardial content of SR-Ca(2+)-ATPase (SERCA), phospholamban (Plb), calsequestrin (Cals) and the Na(+)/Ca(2+)-exchanger (NCX) were analyzed by Western blot analysis. Adenylyl cyclase activity was measured with a radiolabeled bioassay using [32P]ATP as a tracer. RESULTS: In 72 muscle preparations of SR patients contractile force was 10.9+/-1.8 mN/mm(2) compared to 3.3+/-0.9 mN/mm(2) (n=48, P<0.01) in AF patients. The positive inotropic effect of isoprenaline was diminished but the stimulatory effect on relaxation and the adenylyl cyclase were not altered in AF patients. The force-frequency relation and the post-rest potentiation were enhanced in atrial myocardium of AF patients. The protein levels of CRC, SERCA, Plb, and Cals were not different between the two groups. In contrast, the Na(+)/Ca(2+)-exchanger was upregulated by 67% in atria of AF patients. CONCLUSIONS: AF-induced atrial contractile dysfunction is not due to beta-adrenergic desensitization or dysfunction of the sarcoplasmic reticulum and thus is based on different cellular mechanisms than a ventricular tachycardia-induced cardiomyopathy. Instead, downregulation or altered function of the L-type Ca(2+)-channel and an increased Ca(2+) extrusion via the Na(+)/Ca(2+)-exchanger seem to be responsible for the depressed contractility in remodeled atria.

Gene expression of cytokines, growth factors and apoptosis regulators in a neonatal model of pulmonary stenosis.

BACKGROUND: Right ventricular remodeling due to pulmonary stenosis increases morbidity in children. Its pathophysiology needs to be clarified. METHODS: Six newborn lambs underwent pulmonary arterial banding, seven sham operation. mRNA encoding for cytokines, growth factors and regulators of apoptosis was sequentially measured in myocardium and blood before and up to 12 weeks postoperatively. RESULTS: Experimental animals showed hypertrophy and fibrosis of the right ventricular myocardium, myocardial over-expression of CT-1-mRNA and higher blood concentrations of mRNA encoding for VEGF, TGF-ß, Bak and BcL-xL than controls, respectively. CONCLUSION: Neonatal pulmonary stenosis leads to myocardial hypertrophy that is associated with CT-1 gene expression and with activation of growth- and apoptosis pathways in blood cells.

Moderate hypothermia during cardiopulmonary bypass increases intramyocardial synthesis of heat shock protein 72.

OBJECTIVES: This study was undertaken to test the hypothesis that the myocardial protective effect of moderate hypothermia during cardiopulmonary bypass involves upward regulation of heat shock protein 72. METHODS: Sixteen young pigs were randomly assigned to a temperature regimen during standardized cardiopulmonary bypass of normothermia or moderate hypothermia (temperatures 37 degrees C and 28 degrees C, respectively, n = 8 per group). Myocardial probes were sequentially sampled from the right ventricle before and during bypass and 6 hours after bypass. Messenger RNA encoding for heat shock protein 72 was assessed by competitive reverse transcriptase-polymerase chain reaction, and heat shock protein 72 synthesis was assessed by Western blot and immunohistochemical methods. Induction of apoptosis was assessed by gene expression of apoptosis-regulating proteins (Bcl-xL, Bak, and Fas) according to competitive reverse transcriptase polymerase chain reaction. Apoptotic cells were identified with an in situ apoptosis-detection kit (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) in combination with morphologic criteria. Necrotic cells were detected by standard histologic methods. RESULTS: Moderate hypothermia rather than normothermia was associated with earlier and higher gene expression and synthesis of heat shock protein 72 in the myocardium during and after cardiac surgery. In the hypothermia group both heat shock protein 72 and the messenger RNA encoding it were detected as soon as 30 minutes after initiation of bypass and before aortic clamping, whereas in the normothermia group they were not detected before aortic clamping. Immunohistochemical methods showed localization of heat shock protein 72 in the cardiomyocytes, endothelial cells, and macrophages. Although the percentage of necrotic cells in the myocardium was lower in the hypothermic group, the induction of apoptosis regulatory proteins and the percentage of apoptotic cells did not differ between the groups. CONCLUSIONS: These results suggest that the myocardial protective effect of moderate hypothermia during cardiopulmonary bypass involves upward regulation of heat shock protein 72 and inhibition of necrosis but not of apoptosis.

Production of proinflammatory cytokines and myocardial dysfunction after arterial switch operation in neonates with transposition of the great arteries.

OBJECTIVE: Neonates undergoing cardiac surgery have a systemic inflammatory reaction with release of proinflammatory cytokines, which could be responsible for myocardial dysfunction as a result of myocardial cell damage. The purpose of this study was to test the hypothesis that the production of proinflammatory cytokines during cardiac surgery would be associated with myocardial dysfunction after the arterial switch operation in neonates. METHODS: A total of 63 neonates with transposition of the great arteries were operated on with combined deep hypothermic circulatory arrest and low-flow cardiopulmonary bypass at a median age of 7 days. Perioperative plasma concentrations of interleukins 6 and 8 were correlated with myocardial dysfunction, as assessed clinically and by echocardiography within 24 hours after the operation, and with perioperative cardiac troponin T blood levels as a marker of myocardial cell damage. RESULTS: Myocardial dysfunction was observed in 11 patients (17.5%), and 2 of them died. Durations of cardiopulmonary bypass and aortic crossclamping, but not of circulatory arrest, were correlated with myocardial dysfunction. Patients with myocardial dysfunction had significantly higher cardiac troponin T blood levels at the end of cardiopulmonary bypass and 4 and 24 hours after the operation than did patients without myocardial dysfunction. Patients with myocardial dysfunction also had higher interleukin 6 plasma concentrations after cardiopulmonary bypass and 4 hours after the operation, as well as higher interleukin 8 plasma concentrations 4 and 24 hours after the operation, than did those without myocardial dysfunction. Postoperative interleukin 6 and 8 plasma concentrations were significantly correlated with postoperative cardiac troponin T blood levels. Multivariable analysis of independent risk factors for myocardial dysfunction comprising cytokine and troponin levels and bypass duration revealed interleukin 6 levels 4 hours after the operation as significant (P =.047). CONCLUSIONS: Cardiac operations in neonates stimulate the production of proinflammatory cytokines, which may contribute to myocardial cell damage and myocardial dysfunction.

Injury of the common peroneal nerve after cardiothoracic operations.

BACKGROUND: To assess incidence, etiology, and clinical relevance of common peroneal nerve injury (CPNI) in patients after cardiothoracic surgery. METHODS: In an 11-year period, CPNI was detected in 39 out of 20,718 patients (0.19%): 38 times after cardiopulmonary bypass (CPB) (38 of 12,726; 0.30%) and in 1 patient after a non-CPB procedure (1 of 7,992; 0.013%). These patients underwent intensive physiotherapeutic treatment. As the majority of CPNI occurred after CPB (97.4%), data of these patients were compared with a 1-year set of 1,032 patients who underwent CPB procedures. RESULTS: Patients with CPNI were older, had a higher percentage of subnormal body weight, and had considerable comorbidity such as peripheral arteriosclerotic disease, diabetes mellitus, and arrhythmias. Follow-up was complete (mean: 5.2 years; 0.4 to 10.7 years). Twenty-eight patients were free of symptoms; 10 patients complained of moderate symptoms, but were not limited in their everyday life; 1 patient still suffers from severe sensorimotor symptoms. CONCLUSIONS: CPNI after cardiothoracic surgery is rare. Duration of the operative procedure, an increased comorbidity, and a subnormal body weight are assumed to have an etiologic impact. Prognosis is mostly good, but early physiotherapeutic treatment is crucial for prognosis.

Cytokine balance in infants undergoing cardiac operation.

BACKGROUND: The control of the systemic inflammatory response taking place during cardiac operations depends on adequate antiinflammatory reaction. In this prospective study we tested the hypothesis that cytokine balance during pediatric cardiac surgical procedures would be influenced by the patients' preoperative clinical condition, defined as hypoxemia or heart failure. METHODS: Twenty infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left shunt (group 1, n = 10) or with heart failure because of intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective primary corrective operation, were enrolled. Plasma levels of the proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers of the acute-phase response, C-reactive protein and procalcitonin, were sequentially measured before, during, and after cardiac operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the individual's antiinflammatory cytokine balance. RESULTS: Group 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein and procalcitonin were not detectable. In group 1, preoperative IL-6 levels inversely correlated with preoperative oxygen saturation (Spearman correlation coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients, postoperative IL-6 levels were positively correlated with duration of inotropic support and serum creatinine value and inversely correlated with oxygenation index and diuresis. CONCLUSIONS: Infants with hypoxemia show a preoperative inflammatory state with low antiinflammatory cytokine balance in contrast to those with heart failure. This in turn is associated with lower perioperative antiinflammatory cytokine balance and might contribute to postoperative morbidity.