Pulmonary vascular resistance in neonatal swine: response to right pulmonary artery occlusion, isoproterenol, and prostaglandin E1.
The pulmonary physiological response of adults to unilateral pulmonary artery (PA) occlusion has been well-characterized as resulting in a decrease in the pulmonary vascular resistance (PVR), in order to maintain the same PA pressure and accommodate the entire cardiac output (CO). We evaluated the response of the neonate to unilateral PA occlusion and how this response is altered by infusions of Isoproterenol (Isuprel) and prostaglandin E1 (PGE1) in the neonatal swine model. Twenty farm piglets (five at 1 day, three at 5 days, seven at 14 days, and five at 60 days as controls) underwent left lateral thoracotomy and measurement of PA and left atrial (LA) pressures, CO, and PVR with the right PA open and occluded. To determine if neonatal PVR could be influenced by a vasodilator (indicating the vascular capacity is not fixed) or by an inotrope (indicating the lung is not maximally recruited) this experiment was then repeated with infusions of PGE1 (a vasodilator) at doses of 0.1, 0.5, and 1.0 micrograms/kg/min and subsequently with Isuprel (an inotrope and vasodilator) at doses of 0.1, 0.5, 1.0 micrograms/kg/min. Control measurements taken without unilateral PA occlusion showed that PVR is high at 1 day of age but progressively decreases to a level 89% lower by 60 days of age. The vascular capacity of the neonatal lung is fixed and responds to unilateral PA occlusion with a dramatic increase in PVR. This response cannot be altered by either a vasodilator (PGE1) or an inotrope (Isuprel) thereby limiting the utility of these drugs in treating neonatal pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Crombleholme
T M
TM
Fetal Treatment Program, University of California, San Francisco 94143.
Adzick
N S
NS
Longaker
M T
MT
Bradley
S M
SM
Duncan
B W
BW
Jennings
R
R
Verrier
E D
ED
Harrison
M R
MR
D000527:Alprostadil / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D003250:Constriction; D004305:Dose-Response Relationship, Drug; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology* / Q000627:therapeutic use; D011651:Pulmonary Artery; D011652:Pulmonary Circulation / Q000187:drug effects*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects*
D000527:Alprostadil; D007545:Isoproterenol