Postoperative Hyperglycemia and 4-Year Neurodevelopmental Outcome in Children Operated for Congenital Heart Disease.

OBJECTIVES: To study the long-term neurodevelopmental effects of hyperglycemia in infant bypass surgery for congenital heart disease (CHD). STUDY DESIGN: Prospective cohort study on neurodevelopmental outcome after infant cardiac bypass surgery. EXCLUSION CRITERIA: age older than 1 year at first surgery, genetic comorbidity, and birth weight <2000 g. Of 167 eligible infants, follow-up examination at 4 years was completed in 150 children (90%). Intraoperative and postoperative highest and lowest glucose levels within 24 hours after bypass surgery were prospectively collected. Neurodevelopmental outcome at 4 years of age was assessed using standardized IQ tests and the Movement Assessment Battery for Children-second version for motor outcome assessment. RESULTS: Mean age at surgery was 2.8 months (0.1-10.7 months), 33% of children had an acyanotic CHD and 67% a cyanotic CHD. Glucose levels were elevated (>8 mmol/L) in 21 (14%) children in the first 24 postoperative hours. Glucose levels normalized in all children within 48 hours, 7 children (4%) received insulin infusions. Mean total IQ was within the normal range, but significantly lower than the normal population (92.5 [SD 15.0], P < .001). Higher postoperative glucose levels were related to better cognitive performance in the univariate analysis (P < .03), but not when other risk factors were taken into account. Independent risk factors for adverse outcome were lower socioeconomic status, higher risk adjustment for congenital heart surgery score, and longer duration of intensive care stay. CONCLUSION: Hyperglycemia is common in the early postoperative course after infant bypass surgery for CHD and normalizes within 48 hours. Hyperglycemia has no adverse effect on long-term neurodevelopmental outcome.

Oral everolimus inhibits neointimal proliferation in prosthetic pulmonary valved stents in pigs.

BACKGROUND AND AIM OF THE STUDY: Growth factor-dependent cell proliferation can cause in-stent neointimal hyperplasia. The study aim was to evaluate whether oral everolimus inhibits the intimal proliferation associated with the implantation of prosthetic pulmonary valved stents. METHODS: Prosthetic pulmonary valves were implanted in 12 pigs (mean bodyweight 25 kg) using a transcatheter technique. Tricuspid valves were prepared from a titanium-coated polymer and sewn into a self-expanding nitinol stent (diameter 20 mm). Valved stents were implanted in the pulmonary position, where they remained for three months. In six animals, treatment with 2 mg/kg everolimus (Certican; Novartis) per day was started three days before implantation and continued throughout the course of the experiment. The other six pigs acted as controls. Adjuvant anticoagulation treatment consisted of acetylsalicylic acid and oral clopidogrel. After three months, hemodynamic valve function was investigated at catheterization and with MRI. At postmortem investigation the valved stents were explanted and subjected to macroscopic, histological and electron microscopic examination. RESULTS: There were no adverse side effects due to everolimus treatment. The overall mean everolimus plasma level during the study was 4.2 +/- 2.4 ng/ml. MRI revealed intact valve function with a regurgitation fraction of 7.3 +/- 4.2% in controls and 4.3 +/- 3.1% in the everolimus group (p <0.01). On macroscopic inspection and histological examination, the everolimus group showed only a thin tissue coverage of the stent struts. The valve cusps were free from intimal thickening, and electron microscopy showed a thin continuous cellular coating. In contrast, substantial neointimal formation was noted in controls. Tissue neogenesis was pronounced at the base of the valve, extended to the valve cusps, and caused valve thickening and foreshortening. CONCLUSION: The oral administration of everolimus effectively inhibits tissue neogenesis in pulmonary valved stents in pigs.

Magnetic resonance imaging-guided balloon angioplasty of coarctation of the aorta: a pilot study.

BACKGROUND: MRI guidance of percutaneous transluminal balloon angioplasty (PTA) of aortic coarctation (CoA) would be desirable for continuous visualization of anatomy and to eliminate x-ray exposure. The aim of this study was (1) to determine the suitability of MRI-controlled PTA using the iron oxide-based contrast medium Resovist (ferucarbotran) for catheter visualization and (2) to subsequently apply this technique in a pilot study with patients with CoA. METHODS AND RESULTS: The MRI contrast-to-noise ratio and artifact behavior of Resovist-treated balloon catheters was optimized in in vitro and animal experiments (pigs). In 5 patients, anatomy of the CoA was evaluated before and after intervention with high-resolution respiratory-navigated 3D MRI and multiphase cine MRI. Position monitoring of Resovist-treated catheters was realized with interactive real-time MRI. Aortic pressures were continuously recorded. Conventional catheterization was performed before and after MRI to confirm interventional success. During MRI, catheters filled with 25 micromol of iron particles per milliliter of Resovist produced good signal contrast between catheters and their background anatomy but no image distortion due to susceptibility artifacts. All MRI procedures were performed successfully in the patient study. There was excellent agreement between the diameters of CoA and pressure gradients as measured during MRI and conventional catheterization. In 4 patients, PTA resulted in substantial widening of the CoA and a decrease in pressure gradients. In 1 patient, PTA was ineffective. CONCLUSIONS: The MRI method described represents a potential alternative to conventional x-ray fluoroscopy for catheter-based treatment of patients with CoA.

Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis.

Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart. This adaptive process produces changes in specific signaling pathways for mitochondrial proteins and heat-shock response. To further test for hypothermic modulation of other signaling pathways such as apoptosis, we used various molecular techniques, including cDNA arrays. Isolated rabbit hearts were perfused and exposed to ischemic cardioplegic arrest for 2 h at 34 degrees C [ischemic group (I); n = 13] or at 30 degrees C before and during ischemia [hypothermic group (H); n = 12]. Developed pressure, the maximum first derivative of left ventricular pressure, oxygen consumption, and pressure-rate product (P < 0.05) recovery were superior in H compared with in I during reperfusion. mRNA expression for the mitochondrial proteins, adenine translocase and the beta-subunit of F1-ATPase, was preserved by hypothermia. cDNA arrays revealed that ischemia altered expression of 13 genes. Hypothermia modified this response to ischemia for eight genes, six related to apoptosis. A marked, near fivefold increase in transformation-related protein 53 in I was virtually abrogated in H. Hypothermia also increased expression for the anti-apoptotic Bcl-2 homologue Bcl-x relative to I but decreased expression for the proapoptotic Bcl-2 homologue bak. These data imply that hypothermia modifies signaling pathways for apoptosis and suggest possible mechanisms for hypothermia-induced myocardial protection.

Physical models aiding in complex congenital heart surgery.

PURPOSE: Our aim was to improve spatial imagination of complex congenital cardiac abnormalities for subsequent surgical intervention. DESCRIPTION: Magnetic resonance imaging data of a patient with complex congenital heart malformations was post-processed with software developed at our institution. The resulting virtual surface data sets were printed out three-dimensionally by rapid prototyping techniques. EVALUATION: We present the first patient operated on with intraoperative use of physical models representing the intracardiac volumes (RepliCast) or muscle and vessel walls (RepliCardio). The courses of the coronary arteries were visible on the RepliCast, whereas the RepliCardio showed intracardiac views a surgeon could never obtain intraoperatively in the relaxed heart. Other than on virtual reconstructions presented on computer screens, physical models vastly improve the spatial imagination and give precise information regarding localization and actual size of abnormal structures. The self-explanatory utility of these models shortened preparation and expedited orientation on the open heart. CONCLUSIONS: The additional spatial information provided by RepliCast and RepliCardio models may enable even high-risk correction procedures in patients with complex congenital heart disease.

Hypothermia preserves myocardial function and mitochondrial protein gene expression during hypoxia.

Hypothermia before and/or during no-flow ischemia promotes cardiac functional recovery and maintains mRNA expression for stress proteins and mitochondrial membrane proteins (MMP) during reperfusion. Adaptation and protection may occur through cold-induced change in anaerobic metabolism. Accordingly, the principal objective of this study was to test the hypothesis that hypothermia preserves myocardial function during hypoxia and reoxygenation. Hypoxic conditions in these experiments were created by reducing O2 concentration in perfusate, thereby maintaining or elevating coronary flow (CF). Isolated Langendorff-perfused rabbit hearts were subjected to perfusate (Po2 = 38 mmHg) with glucose (11.5 mM) and perfusion pressure (90 mmHg). The control (C) group was at 37 degrees C for 30 min before and 45 min during hypoxia, whereas the hypothermia (H) group was at 29.5 degrees C for 30 min before and 45 min during hypoxia. Reoxygenation occurred at 37 degrees C for 45 min for both groups. CF increased during hypoxia. The H group markedly improved functional recovery during reoxygenation, including left ventricular developed pressure (DP), the product of DP and heart rate, dP/dtmax, and O2 consumption (MVo2) (P < 0.05 vs. control). MVo2 decreased during hypothermia. Lactate and CO2 gradients across the coronary bed were the same in C and H groups during hypoxia, implying similar anaerobic metabolic rates. Hypothermia preserved MMP betaF1-ATPase mRNA levels but did not alter adenine nucleotide translocator-1 or heat shock protein-70 mRNA levels. In conclusion, hypothermia preserves cardiac function after hypoxia in the hypoxic high-CF model. Thus hypothermic protection does not occur exclusively through cold-induced alterations in anaerobic metabolism.