[Early repair of congenital cardiopathies under extracorporeal circulation. Apropos of 158 surgical cases under the age of 5]. / La réparation précoce sous circulation extracorporelle des cardiopathies congénitales. A propos de 158 opérés de moins de 5 ans

A great number of congenital heart diseases are now amenable to treatment before school age. A homogeneous experience of 158 cases operated upon made it possible to make the follow remarks:--The operative mortality before the age of 1 year remains high, in view of the difficulties of ressuscitation, but mainly because of the severity of the heart disease to treat. --Between the ages of 1 and 5 years, the risk decreased with experience, and for the heart diseases most frequently encountered, lethality fell to 2.8% for the last 4 years. One may thus accept to perform, not only necessity operations, but principle operations before school age. The schematic indications in relation with each heart disease were analysed.

Use of human and animal liver microsomes in drug metabolic studies.

A bank of readily available well-characterized human and animal hepatic microsomal fractions has been established. By using these "in vitro" models, we evidenced large interspecies variabilities for various compounds including digoxin, minaprine and two vincaalkaloïds (navelbine, vinblastine). Therefore, extrapolation from animal to human appeared limited and we focused our interest on human liver microsomes. Enzymatic characteristics of human microsomes from 35 different livers were determined using specific monooxygenase (i.e. erythromycin, aniline, aminopyrin...) and UDP-glucuronosyltransferase substrates (i.e. p-nitrophenol, monodigitoxoside digitoxigenin...). A wide variability was thus ascertained between individual for both phase I and phase II metabolic processes. Microsomal fractions were also shown to be of great interest for assessing the P450 cytochrome isoform(s) involved in the biotransformation of a given drug. For instance, using inhibitory experiments, we showed the implication of P450IID in minaprine metabolism. We also demonstrated that P450IIIA is probably involved in vindesine biotransformation. Drug metabolic interactions between cyclosporin A and macrolides were studied using the same model. These results demonstrating that erythromycin is a much more potent inhibitor of cyclosporin A biotransformation than spiramycin, agree closely with "in vivo" data. In conclusion, liver microsomes are powerful tools in studying: i) interspecies and interindividual variabilities, ii) metabolic drug interactions.