Effects of prostacyclin and milrinone on pulmonary hemodynamics in newborn lambs with persistent pulmonary hypertension induced by ductal ligation.
Prostacyclin (PGI(2)) stimulates adenyl cyclase to synthesize cAMP within the vascular smooth muscle resulting in vasodilatation. Milrinone inhibits cAMP clearance by phosphodiesterase type III. We studied the dose response of pulmonary and systemic hemodynamics to intratracheal (IT) PGI(2) in newborn lambs with pulmonary hypertension (PH) and whether intravenous milrinone potentiate these effects. IT-PGI(2) at varying doses was administered to lambs with PH induced by prenatal ductal ligation. IT-PGI(2) doses were repeated in the presence of intravenous milrinone (bolus-100 microg/kg followed by infusion at 1 microg/kg/min). Increasing doses of IT-PGI(2) significantly decreased mean pulmonary arterial pressures (PAP) and pulmonary vascular resistance (PVR) and increased pulmonary blood flow (PBF). Intravenous milrinone by itself produced a significant reduction in PVR and a significant increase in PBF. Intravenous milrinone significantly shortened the onset, prolonged the duration and degree of pulmonary vasodilation produced by PGI(2). We conclude that intravenous milrinone potentiates the pulmonary vasodilator effects of PGI(2) at lower doses.
Rashid
Nasir
N
Department of Pediatrics, Center for Developmental Biology of the Lung, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Morin
Frederick C
FC
Swartz
Daniel D
DD
Ryan
Rita M
RM
Wynn
Karen A
KA
Wang
Huamei
H
Lakshminrusimha
Satyan
S
Kumar
Vasanth H
VH
D000818:Animals; D000831:Animals, Newborn; D004373:Ductus Arteriosus / Q000601:surgery; D011464:Epoprostenol / Q000494:pharmacology*; D005333:Fetus / Q000033:anatomy & histology / Q000502:physiology / Q000601:surgery; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000503:physiopathology; D020105:Milrinone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011897:Random Allocation; D012756:Sheep
D010726:Phosphodiesterase Inhibitors; D011464:Epoprostenol; D020105:Milrinone