In situ perfusion in the rabbit: effects of different umbilical flow rates on placental transfer of compounds.
The effects of different umbilical flow rates on the placental transfer of compounds were studied in order to optimize an in situ placental perfusion model in the rabbit for establishing the most suitable perfusion flow rate range and assessing alterations in the placental architecture related to the umbilical flow. Placental transfer of a tool compound theophylline (TH) at different umbilical flow rates was compared with that of antipyrine (AP), the commonly used indicator of placental exchange, in maternal arterial drug steady-state conditions after a two-step infusion program. Placentas of six rabbits were perfused for 250 min with Earle's enriched bicarbonate buffer at 0.5, 1, 1.5, 2, 3, and 4 mL/min flow rates. Plasma and placental perfusate effluent biochemical parameters, gas exchange, body temperature, and electrocardiogram were recorded. Umbilical arterial perfusion pressure was controlled throughout the experiments. A detailed pharmacokinetic analysis of unbound maternal plasma, perfusate TH, and AP concentrations was made. Placental clearance of TH and AP rose up to the 3 mL/min flow rate and then remained constant. Placental clearance was linear up to 2.0 mL/min for TH and 1.5 mL/min for AP. The umbilical flow rate limit was 1.76 +/- 0.29 mL/min for TH and 1.72 +/- 0.49 mL/min for AP. The clearance index was 0.71 +/- 0.04. The correlation between umbilical flow and perfusion pressure was linear, with mean values from 4 to 25 mmHg. Placental resistances did not change significantly at all flow rates with mean values between 6 and 9 mmHg/mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)
Barzago
M M
MM
Perinatal Clinical Pharmacology Unit, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Omarini
D
D
Aramayona
J J
JJ
Bonati
M
M
D000704:Analysis of Variance; D000818:Animals; D000983:Antipyrine / Q000097:blood; D005260:Female; D007700:Kinetics; D008431:Maternal-Fetal Exchange; D010477:Perfusion / Q000379:methods*; D011247:Pregnancy; D011817:Rabbits; D013806:Theophylline / Q000097:blood; D014469:Umbilical Arteries / Q000502:physiology*
D013806:Theophylline; D000983:Antipyrine