title: Hemodynamic and metabolic effects of a new pediatric dobutamine formulation in hypoxic newborn pigs.
abstract: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans.
  
  
  
  Newborn pigs (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF.
  
  
  
  Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI.
  
  
  
  The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.
authors.affiliation: Experimental Unit, BioCruces Health Research Institute and Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Mielgo
authors.affiliation: Experimental Unit, BioCruces Health Research Institute and Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Adolf
authors.initials: A
authors.lastname: Valls-I-Soler
authors.affiliation: Experimental Unit, BioCruces Health Research Institute and Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Lopez-de-Heredia
authors.affiliation: Academic Department of Paediatrics, Brighton and Sussex Medical School, Brighton, UK.
authors.forename: Heike
authors.initials: H
authors.lastname: Rabe
authors.affiliation: Experimental Unit, BioCruces Health Research Institute and Cruces University Hospital, Barakaldo, Bizkaia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rey-Santano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004280:Dobutamine / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D000860:Hypoxia; D008297:Male; D010100:Oxygen / Q000008:administration & dosage; D010101:Oxygen Consumption; D019265:Spectroscopy, Near-Infrared; D013318:Stroke Volume / Q000187:drug effects*; D034421:Sus scrofa; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D004280:Dobutamine; D010100:Oxygen