Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels

The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury.     

Severe perinatal thrombosis in double and triple heterozygous offspring of a family segregating two independent protein S mutations and a protein C mutation

Molecular genetic and phenotypic analyses were performed in a highly unusual case of combined protein S and protein C deficiency manifesting in a family in which a child had died perinatally from renal vein thrombosis. Antenatal diagnosis in a second pregnancy was initially performed by indirect restriction fragment length polymorphism (RFLP) tracking using a neutral dimorphism within the PROS gene and served to exclude severe protein S deficiency. Am umbilical vein blood sample at 22 weeks gestation showed isolated protein C deficiency. This pregnancy proceeded to a full-term delivery without thrombotic complications. Molecular genetic analysis of the PROC and PROS gene segregating in the family then yielded one PROC gene lesion in the father and two PROS gene lesions, one in each parent. These lesions were shown to segregate with the respective deficiency states through the family pedigree. Analysis of DNA from paraffin-embedded liver tissue taken from the deceased child showed the presence of both PROS mutations, as well as the PROC mutation. Genotypic analysis of the second child showed a PROC mutation, but neither PROS mutation consistent with its possession of normal protein S levels and a low/borderline protein C level. Antenatal diagnosis was then performed in a third pregnancy by direct mutation detection. However, although the fetus carried only the paternal PROS and PROC gene lesions, the child developed renal thrombosis in utero. It may be that a further genetic lesion at a third locus still remains to be defined. Alternatively, the intrauterine development of thrombosis in this infant could have been caused, at least in part by a transplacental thrombotic stimulus arising in the protein S-deficient maternal circulation. This analysis may, therefore, serve as a warning against extrapolating too readily from genotype to phenotype in families with a complex thrombotic disorder.     

Direct intracardiac placement of an automatic implantable cardioverter defibrillator coil lead in a small child.

A 3.5-year-old child with hypertrophic obstructive cardiomyopathy and recurrent syncope underwent surgical left-ventricular outflow tract myectomy and implantation of a single-chamber automatic cardioverter defibrillator. A single-coil active fixation lead was introduced via a purse-string suture in the right atrial appendage and the lead tip positioned and fixed in the right-ventricular apex under direct visualization via a small right atriotomy incision. Described configuration may be considered in small children undergoing intracardiac surgery at the time of defibrillator implantation.     

Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy

Objectives/Aim: To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurodevelopmental outcome. Background: Animal models suggest detrimental effects of anesthetic drugs on the developing brain. Whether these results can be extrapolated to human neonates is unclear. Methods/Materials: This is a prospective follow‐up project conducted in Western Canada. In all infants ≤6 weeks of age having surgery for congenital heart disease between April 2003 and December 2006, demographic and perioperative variables were collected prospectively. Sedation/analgesia variables were collected retrospectively. For each drug class (inhalationals, opioids, benzodiazepines, ketamine, and chloral hydrate), we calculated the cumulative dose received during hospitalization, average dose received per day, and cumulative number of days the patient received the drug. The outcomes at 18–24 months were as follows: General Adaptive Composite and motor scaled scores of the Adaptive Behavior Assessment System, significant mental, motor, and vocabulary delay. Multivariable logistic and linear regression was used to analyze the data. Results: One hundred and thirty‐five neonates underwent open heart surgery; 19 died, 16 had chromosomal abnormality, and five were lost to follow up, leaving 95 survivors for analysis. Multiple linear regression analysis found no evidence of an association between sedation/analgesia variables and ABAS‐GAC score or motor scale score. Multiple logistic regression analysis found no evidence of an association between sedation/analgesia variables and significant mental, motor, or vocabulary delay. Conclusion: We found no evidence of an association between dose and duration of sedation/analgesia drugs during the operative and perioperative period and adverse neurodevelopmental outcomes.