Dose-response effects of milrinone on hemodynamics of newborn pigs with hypoxia-reoxygenation.
OBJECTIVE
Neonatal asphyxia causes cardiogenic shock and pulmonary hypertension with decreased brain perfusion. We examined the dose-response of milrinone on systemic, pulmonary, and carotid circulations in a model of neonatal hypoxia-reoxygenation.


METHODS
Controlled, block-randomized study in a university research laboratory.


METHODS
Mixed breed piglets (1-3 days, 1.5-2.3 kg).


METHODS
In acutely instrumented piglets normocapnic alveolar hypoxia (10-15% oxygen) was induced for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). At 2 h of reoxygenation after a volume loading (10 ml/kg) either saline or milrinone (bolus and infusion at 0.25, 0.5, or 0.75 microg/kg per minute) was given for 2 h in a blinded-randomized fashion (n = 7/group).


RESULTS
All milrinone-treated groups had higher cardiac output and stroke volume than those of saline-treated hypoxic controls, which showed progressive decline in these measurements. At 2 h of infusion plasma milrinone levels were significantly correlated with cardiac output (r = 0.6), which increased from pretreatment value in the group receiving 0.75 microg/kg per minute. Milrinone maintained mean arterial pressure; heart rate and pulmonary arterial pressure did not differ between groups. Milrinone prevented continued increases in systemic and pulmonary vascular resistances after hypoxia-reoxygenation. Milrinone infusion at higher doses increased common carotid flow. Milrinone-treated piglets had increased systemic and carotid oxygen delivery, with no difference in plasma and myocardial lactate levels among groups.


CONCLUSIONS
When used to treat shock in newborn piglets with hypoxia-reoxygenation, milrinone improved cardiac output and carotid flow while maintaining systemic blood pressure. Pulmonary hypertension was not aggravated. Further studies are needed to confirm these findings in asphyxiated neonates.
Joynt
Chloë
C
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Bigam
David L
DL
Charrois
Gregory
G
Jewell
Laurence D
LD
Korbutt
Gregory
G
Cheung
Po-Yin
PY
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D000860:Hypoxia / Q000188:drug therapy*; D007262:Infusions, Intravenous; D007773:Lactates / Q000097:blood; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D007773:Lactates; D014665:Vasodilator Agents; D020105:Milrinone; D010100:Oxygen