title: Intestinal hemodynamic effects of milrinone in asphyxiated newborn pigs after reoxygenation with 100% oxygen: a dose-response study.
abstract: Neonatal asphyxia can result in poor perfusion, vasoconstriction, and decreased oxygen delivery in the intestine. Milrinone increases myocardial contractility and causes peripheral vasodilatation. We examined the dose-response of milrinone on the intestinal circulation, oxygen metabolism, and injury in a newborn piglet model of asphyxia-reoxygenation. Piglets (aged 1-3 days, weighing 1.5-2.3 kg) were acutely instrumented to measure superior mesenteric artery (SMA) flow and oxygen delivery. After stabilization, hypoxia (inspired oxygen concentration, 0.08-0.15) was induced for 2 h followed by reoxygenation with 100% O2 for 1 h then 21% O2 for 3 h. At 2 h of reoxygenation, saline or milrinone infusion at doses of 0.25, 0.5, or 0.75 microg/kg per min was given for 2 h in a blinded randomized fashion (n = 7 per group). Hemodynamic and oxygen transport parameters were analyzed at predefined time points. Intestinal tissue lactate concentrations, plasma milrinone levels, and intestinal glutathione redox status were determined at the end of the experiment. In the intestinal tract, milrinone significantly increased SMA flow and oxygen delivery while decreasing vascular resistance at a dose of 0.75 microg/kg per min (P < 0.05, ANOVA). A modest increase in SMA flow and oxygen delivery was found with milrinone at 0.5 microg/kg per min. Plasma milrinone levels correlated with SMA flow and vascular resistance (r = 0.5 and r = -0.6, respectively, P < 0.05). Intestinal lactate concentrations and histopathology were not significantly different among groups. Oxidized glutathione correlated with SMA vascular resistance and negatively with milrinone levels (r = 0.6 and r = -0.5, P < 0.05). When used to treat shock in a newborn model of asphyxia-reoxygenation, milrinone dose-dependently increases SMA flow and oxygen delivery with a significantly decreased SMA vascular resistance at higher doses.
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Chloë
authors.initials: C
authors.lastname: Joynt
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Gregory
authors.initials: G
authors.lastname: Charrois
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Jewell
authors.forename: Gregory
authors.initials: G
authors.lastname: Korbutt
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D017538:Mesenteric Artery, Superior / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020105:Milrinone / Q000493:pharmacokinetics / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D019344:Lactic Acid; D005978:Glutathione; D020105:Milrinone; D010100:Oxygen