A fetal-instrumented model to study age-specific responses to leukotriene D4 and prostaglandin D2 in unsedated newborn lambs.
Sequential studies of the pulmonary vascular response to leukotriene D4 (LTD4) and prostaglandin D2 (PGD2) in the immediate newborn period were performed in lambs, instrumented in utero and delivered vaginally. Compounds were tested in fully conscious 1.5-day-old lambs and the study was repeated 1 week later. Bolus injections of PGD2 (0.05-2.0 micrograms/kg) or LTD4 (0.01-1.0 micrograms/kg) were made into the main pulmonary artery or aorta while pulmonary blood flow and aortic, pulmonary artery, and left and right atrial pressures were monitored continuously. PGD2 was a systemic constrictor regardless of age. In lambs 1.5 days of age, it decreased pulmonary vascular pressure and resistance by 6% (p less than 0.05) and 15% (p less than 0.05), respectively, while 1 week later it increased pulmonary vascular resistance by 18% (p less than 0.05). In contrast, LTD4 was a pulmonary and systemic vasoconstrictor in both the early and late newborn, the threshold dose being between 0.01 and 0.05 micrograms/kg at either age. The decrease in pulmonary blood flow and the increase in pressure and resistance were greater in older animals. In lambs 1.5 days of age, LTD4 (1 micrograms/kg) increased pulmonary vascular resistance by 66.1% (p less than 0.05) and 1 week later by 210% (p less than 0.001). These sequential observations in the same animal indicate that unlike PGD2, LTD4 is a pulmonary vasoconstrictor regardless of age, and its effectiveness increases significantly with age. These results support previous reports that PGD2 action in the pulmonary circulation changes shortly after birth from dilation to constriction.
Coe
J Y
JY
Research Institute, Hospital for Sick Children, Toronto, Ont., Canada.
Olley
P M
PM
Coceani
F
F
D000375:Aging / Q000502:physiology*; D000758:Anesthesia; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000502:physiology*; D008954:Models, Biological; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000494:pharmacology*; D013189:SRS-A / Q000494:pharmacology*; D012756:Sheep; D013997:Time Factors
D013189:SRS-A; D015230:Prostaglandin D2