Cardiac troponin I in neonates undergoing the arterial switch operation

BACKGROUND: Cardiac troponin I (TnI) is a sensitive and specific marker of myocardial injury, but little is known about its release after complex congenital heart surgery. We investigated whether TnI correlates with early clinical outcome in neonates undergoing the arterial switch operation (ASO) for transposition of the great arteries (TGA). METHODS: Troponin I was measured serially up to 48 hours postoperatively in 31 neonates undergoing the ASO alone (simple TGA) and 9 neonates undergoing the ASO combined with other procedures (complex TGA) (eg, closure of a ventricular septal defect) and correlated with intraoperative and postoperative clinical parameters. RESULTS: There was no mortality. Troponin I peaked at either 4 or 12 hours postoperatively in all patients (median for simple TGA = 3.4 ng/mL, interquartile range 2.4 to 4.6; median for complex TGA = 4.7 ng/mL, interquartile range 3.2 to 6.8, p = 0.20). Peak TnI correlated with the durations of inotropic support (r = 0.54, p < 0.001), ventilation (r = 0.51, p < 0.01), and intensive care unit stay (r = 0.50, p < 0.01). The duration of cardiopulmonary bypass, aortic cross-clamping, and circulatory arrest did not correlate with the peak or total TnI release. The duration of aortic cross-clamping correlated poorly with the duration of inotropic support (r = 0.40, p < 0.05). The complex TGA group had longer aortic cross-clamp times, required more postoperative inotropic support, and had significantly higher total TnI release compared with the simple TGA group. CONCLUSIONS: There are weak but statistically significant correlations between peak TnI and clinical outcome. Complexity of the defect and ischemic times may be as useful to predict outcome in this group of patients.     

The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk

The DNA repair protein xeroderma pigmentosum complementation group D (XPD) is involved in the nucleotide excision repair of DNA lesions induced by many tobacco and environmental carcinogens. In order to study the functional impact of the common polymorphisms in XPD exon 10 (G > A, Asp312Asn) and exon 23 (A > C, Lys751Gln), we have genotyped 185 Swedish lung cancer cases (97 smokers and 88 never-smokers) and 162 matched population controls (83 smokers and 79 never-smokers). Presence of one or two variant alleles was associated with increased risk for lung cancer among never-smokers only, in particular younger (<70 years) never-smokers [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.1-6.5 for exon 10; OR = 3.2, 95% CI = 1.3-8.0 for exon 23, adjusted for age, gender and environmental tobacco smoke]. Aromatic DNA adduct level (AL) in peripheral lymphocytes was found to be similar between cases and controls, but significantly increased by current or recent smoking. Overall, there was a significant trend for increasing AL with increasing number of variant alleles in exon 10 (P = 0.02) or in exon 23 (P = 0.001). In addition, subjects with the combined exon 10 AA and exon 23 CC genotype showed a significantly higher AL compared with all those with any of the other genotypes (P = 0.02). We conclude that the XPD variant alleles may be associated with reduced repair of aromatic DNA adducts in general and increased lung cancer risk among never-smokers.     

Effect of thalidomide on the skeletal muscle in experimental heart failure

BACKGROUND: Tumour Necrosis Factor alpha (TNFalpha) has been shown to contribute to heart failure (CHF) progression. AIMS: We have tried to antagonise the detrimental effects of TNFalpha on skeletal muscle apoptosis, by using thalidomide, a drug that inhibits its biosynthesis. METHODS: CHF was induced in 20 rats by injecting monocrotaline, which determines right ventricle (RV) failure. After 2 weeks, when CHF developed, 12 rats were treated with thalidomide 3.5.mg/kg per day for 2 weeks. Eight had saline and served as CHF controls. RESULTS: Thalidomide failed to decrease TNFalpha and its second messenger sphingosine (SPH), but was able to prevent the shift toward the fast myosin heavy chains. In the Tibialis Anterior muscle of the thalidomide group, the degree of atrophy, the number of apoptotic nuclei and the levels of caspases, were similar to those of the CHF controls. CONCLUSIONS: Thalidomide, at the doses used in this study, which are the same employed for the treatment of tubercolosis, leprosy, AIDS and cancer in humans, did not lower either TNFalpha or SPH and only marginally influenced the apoptosis-induced muscle atrophy. Since other TNFalpha blockers are under investigation for improving the clinical status of patients with CHF, the present data could be relevant in the design of randomised clinical trials in humans.     

Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene mutations. Study of aneural and innervated cultured myotubes

Mutations in the sarcoglycan (SG) genes cause autosomal recessive muscular dystrophies. The absence of each SG complex component in muscle impairs the proper assembly of the entire SG complex, resulting in sarcolemmal damage. We investigated the consequences of beta-SG gene mutations in cultured muscle from two beta-SG mutated patients, and analysed each individual SG protein expression by cross-sectional immunocytochemistry and Western blot in aneural and innervated myotubes. Patients' muscle biopsy showed total loss of SG complex; however, a limited amount of beta-SG was detected in aneural and innervated myotubes, where the protein was localized to the plasma membrane. This paradoxical beta-SG expression can be attributable to antibody cross-reaction or to the expression of an unknown SG isoform specific of immature muscle. In our cultured myotubes, the other components of the SG complex were absent, suggesting that beta-SG gene mutations result in a defective assembly of the entire SG complex in early stages of muscle development, and that the role of beta-SG is crucial for the normal structure and/or function of the SG complex in the sarcolemma.     

Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound

Cerebral emboli detected by transcranial Doppler imaging wererecorded in 20 patients undergoing multiple-vessel coronaryartery bypass surgery, either with or without cardiopulmonarybypass, in a prospective unblinded comparative study. Emboliwere recorded continuously from the time of pericardial incisionuntil 10 min after the last aortic instrumentation. The numbersof coronary grafts and of aortic clampings were also documented.Patients undergoing revascularization with cardiopulmonary bypasshad more emboli (median 79, range 38–876) per case comparedwith patients having off-pump surgery (median 3, range 0–18).No clinically detectable neurological deficits were seen ineither group. Beating heart surgery is associated with feweremboli than coronary surgery with cardiopulmonary bypass. Furtherresearch is necessary to determine whether a smaller numberof emboli alters the incidence of neurological deficit aftercardiac surgery.     

Localization of FMRFamide-like immunoreactivity in the brain of the viviparous skink (Chalcides chalcides)

Neuroanatomical distribution of FMRFamide-like immunoreactivity was investigated in the brain and olfactory system of the viviparous skink, Chalcides chalcides. In the adult brain FMRFamide immunoreactive (ir) perikarya were observed in the diagonal band of Broca, medial septal nucleus, accumbens nucleus, bed nucleus of the anterior commissure, periventricular hypothalamic nucleus, lateral forebrain bundle, and lateral preoptic, subcommissural, suprachiasmatic and lateral hypothalamic areas. This pattern was seen in both male and female brains. Though all major brain areas showed FMRFamide-ir innervation, the densest ir fiber network was observed in the hypothalamus. During development, ir elements were observed for the first time in embryos at mid-pregnancy. FMRFamide perikarya were located along the ventral surface of the vomeronasal nerve, in the olfactory peduncle mediobasally, as well as in the anterior olfactory nucleus and olfactory tubercle. Furthermore, some ir neurons were observed in the rhombencephalic reticular substance; however, the ir fiber network was poorly developed. Later in development FMRFamide-ir neurons appeared also in the bed nucleus of the anterior commissure as well as the rhombencephalic nucleus of solitary tract and the dorsal motor nucleus of vagus nerve. In juveniles, the distribution profile of FMRFamide immunoreactivity was substantially similar to that of the adults, with a less widespread neuronal distribution and a more developed fiber network. Ontogenetic presence of FMRFamide immunoreactivity in the nasal area has been linked to the presence of a nervus terminalis in this reptile.     

Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study

OBJECTIVE: Coronary artery bypass grafting on the beating heart through median sternotomy is a relatively new treatment, which allows multiple revascularization without the use of cardiopulmonary bypass. A prospective randomized study was designed to investigate the effect of coronary bypass with or without cardiopulmonary bypass on postoperative blood loss and transfusion requirement. METHODS: Two hundred patients with coronary artery disease were prospectively randomized to (1) on-pump treatment with conventional cardiopulmonary bypass and cardioplegic arrest and (2) off-pump treatment on the beating heart. Postoperative blood loss identified as total chest tube drainage, transfusion requirement, and related costs together with hematologic indices and clotting profiles were analyzed. RESULTS: There was no difference between the groups with respect to preoperative and intraoperative patient variables. The mean ratio of postoperative blood loss and 95% confidence interval between groups was 1.64 and 1.39 to 1.94, respectively, suggesting on average a postoperative blood loss 1.6 times higher in the on-pump group compared with the off-pump group. Seventy-seven patients in the off-pump group required no blood transfusion compared with only 48 in the on-pump group (P <.01). Furthermore, less than 5% of patients in the on-pump group required fresh frozen plasma and platelet transfusion compared with 30% and 25%, respectively, in the on-pump group (both P <.05). Mean transfusion cost per patient was higher in the on-pump compared with that in the off-pump group ($184.8 +/- $35.2 vs $21.47 +/- $6.9, P <.01). CONCLUSIONS: Coronary artery bypass grafting on the beating heart is associated with a significant reduction in postoperative blood loss, transfusion requirement, and transfusion-related cost when compared with conventional revascularization with cardiopulmonary bypass and cardioplegic arrest.     

Late failure of double-inlet left ventricle septation: treatment by orthotopic heart transplantation

We report a patient in whom orthotopic heart transplantation was performed after late failure of ventricular septation for double-inlet left ventricle. This case shows that orthotopic heart transplantation represents a valid therapeutic alternative in children with previous correction of complex congenital heart defects not amenable to further intracardiac repair.