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J Thorac Cardiovasc Surg 2005;129:235a-236
© 2005 The American Association for Thoracic Surgery

Letters to the Editor

Studies of fetal cardiac bypass

Department of Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45244
Department of Surgery, University of Cincinnati, Cincinnati, OH 45221

To the Editor:

In their elegant studies of fetal cardiopulmonary bypass (CPB), Carotti and colleagues¹ 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.² 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.³

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 sheep⁴ and human⁵ 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 x 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.

References

1. Carotti 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..
   
2. Rosenfeld CR. Consideration of the uteroplacental circulation in intrauterine growth. Semin Perinatol. 1984;8:42-51.[Medline]
   
3. Byrne GC, Perry YS, Winter JS. Kinetic analysis of adrenal 3 beta-hydroxysteroid dehydrogenase activity during human development. J Clin Endocrinol Metab. 1985;60:934-939.[Abstract/Free Full Text]
   
4. Koong LJ, Garrett WN, Rattray PV. A description of the dynamics of fetal growth in sheep. J Anim Sci. 1975;41:1065-1068.
   
5. O'Rahilly R. Early human development and the chief sources of information on staged human embryos. Eur J Obstet Gynecol Reprod Biol. 1979;9:273-280.[Medline]
   

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Pirooz Eghtesady Permission Requests Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sedgwick, J. A. Articles by Eghtesady, P. Search for Related Content PubMed Articles by Sedgwick, J. A. Articles by Eghtesady, P. Related Collections Cardiac - other Congenital - acyanotic Congenital - cyanotic Extracorporeal circulation