Studies of fetal cardiac bypass

Abstract

In their elegant studies of fetal cardiopulmonary bypass (CPB), Carotti and colleagues1Carotti A, Emma F, Picca S, Iannace E, Albanese SB, Grigioni M, et al. Inflammatory response to cardiac bypass in ewe fetuses: effects of steroid administration or continuous hemodiafiltration. J Thorac Cardiovasc Surg. 203;126:1839-50.Google Scholar use time-dated pregnant sheep of 120 to 130 days' gestation. Indeed, in all published studies, the preferred animals for studying fetal CPB have been near-term fetal sheep (mean, approximately 126 days' gestation; term, 148 days' gestation). However, this age does not agree with the now-accepted window for effective fetal therapy in the clinical setting: 21 to 29 weeks' human gestation. Therefore we propose that all investigators conduct future fetal CPB studies at clinically relevant gestational ages (83-112 days' gestation in sheep; see below). This is of great import when considering the vast changes taking place in the uteroplacental and umbilical-placental vascular beds during pregnancy. For example, the uterine weight, uterine blood flow (UBF), and UBF per gram of uterine weight increase significantly from 90 days onward. Indeed, this final phase in the growth of UBF is exponential and associated with a 3-fold increase in fetal weight that occurs after 110 days in sheep and beyond 30 weeks in human subjects.2Rosenfeld C.R. Consideration of the uteroplacental circulation in intrauterine growth.Semin Perinatol. 1984; 8: 42-51PubMed Google Scholar Similarly, blood flow distribution during this period changes substantially; nearly half the UBF is diverted away from endometrium-myometrium to the placenta. These changes reflect significant alterations in placental vascular resistance, which affect studies of fetal CPB. Finally, similar gestational differences in physiology affect other experimental features, such as fetal responses to steroids.3Byrne G.C. Perry Y.S. Winter J.S. Kinetic analysis of adrenal 3 beta-hydroxysteroid dehydrogenase activity during human development.J Clin Endocrinol Metab. 1985; 60: 934-939Crossref PubMed Scopus (26) Google Scholar We would like to caution investigators, however, against using direct gestational equivalence (human 280 days = sheep 148 days). Differences in fetal growth rates between species can lead to large errors when assuming direct equivalence, as we discovered during our research involving early-gestation lambs. Therefore, we developed an equation to successfully translate gestational equivalence between species on the basis of previous studies of sheep4Koong L.J. Garrett W.N. Rattray P.V. A description of the dynamics of fetal growth in sheep.J Anim Sci. 1975; 41: 1065-1068PubMed Google Scholar and human5O'Rahilly R. Early human development and the chief sources of information on staged human embryos.Eur J Obstet Gynecol Reprod Biol. 1979; 9: 273-280Abstract Full Text PDF PubMed Scopus (98) Google Scholar embryos that have established the gestational age for completion of specific Carnegie stages of development. We translated these stages into developmental equivalence at specific times during gestation. Using the age for each species at equivalent Carnegie stages and assuming full-term pregnancy, we derived a second-degree polynomial equation:Sheep gestation day = − 0.003 × Human gestation day2 + 0.6296 − Human gestation day, with a correlation coefficient (R2) equal to 0.9973. Comparing our developmentally based gestational age with that determined by direct equivalence reveals a difference as large as 14%, which can significantly affect experimental design. For example, a 5-day difference in gestational age (eg, 78 vs 83 days for 21 weeks' human gestation) can lead to a difference of 180 g for a singleton fetus (720 vs 900 g). These weight differences can have substantial implications in surgical technique. At the latter part of the range (29 weeks' human gestation), when the fetus is growing more rapidly, the difference is even larger; for a 107-day (2.23 kg) versus 112-day (2.71 kg) singleton fetus, the difference is about 500 g. Finally, calculations based on these variations can also greatly influence results. For example, calculation of satisfactory fetal CPB flow rates (on the basis of milliliters per kilogram per hour) can be substantially different and potentially inadequate when using the wrong gestational age and fetal weight. Inflammatory response to cardiac bypass in ewe fetuses: effects of steroid administration or continuous hemodiafiltrationThe Journal of Thoracic and Cardiovascular SurgeryVol. 126Issue 6PreviewWe sought to investigate the effectiveness of glucocorticoid administration or continuous venovenous hemodiafiltration on endothelin and corticotropin-releasing factor release or clearance during prolonged fetal cardiac bypass and on the overall performance of fetuses. Full-Text PDF Reply to the editor:The Journal of Thoracic and Cardiovascular SurgeryVol. 129Issue 1PreviewWe appreciate the comments of Drs Sedgwick and Eghtesady. Full-Text PDF