title: Meclofenamate increases ventilation in lambs.
abstract: To investigate the effects of the prostaglandin synthetase inhibitor, meclofenamate, on postnatal ventilation, we studied 11 unanaesthetised, spontaneously-breathing lambs at an average age of 7.9 +/- 1.1 days (SEM; range 5-14 days) and an average weight of 4.9 +/- 0.5 kg (range 3.0-7.0 kg). After a 30-min control period we infused 4.23 mg/kg meclofenamate over 10 min and then gave 0.23 mg/h per kg for the remainder of the 4 h. Ventilation increased progressively from a control value of 515 +/- 72 ml/min per kg to a maximum of 753 +/- 100 ml/min per kg after 3h of infusion (P less than 0.05) due to an increased breathing rate; the effects were similar during both high- and low-voltage electrocortical activity. There were no significant changes in tidal volume, heart rate, blood pressure, arterial pH or PaCO2, the increased ventilation resulted from either an increase in dead space ventilation or an increase in CO2 production. This study indicates that meclofenamate causes an increase in ventilation in lambs but no changes in pH of PaCO2. The mechanism and site of action remain to be defined.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco.
authors.forename: F A
authors.initials: FA
authors.lastname: Guerra
authors.forename: R D
authors.initials: RD
authors.lastname: Savich
authors.forename: R I
authors.initials: RI
authors.lastname: Clyman
authors.forename: J A
authors.initials: JA
authors.lastname: Kitterman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002245:Carbon Dioxide / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D008168:Lung / Q000502:physiology; D008469:Meclofenamic Acid / Q000494:pharmacology*; D011458:Prostaglandins E / Q000502:physiology; D012119:Respiration / Q000187:drug effects*; D012126:Respiratory Dead Space / Q000187:drug effects; D012756:Sheep; D013990:Tidal Volume; D014797:Vital Capacity / Q000187:drug effects; D014939:Work of Breathing / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D011458:Prostaglandins E; D062367:ortho-Aminobenzoates; D002245:Carbon Dioxide; D008469:Meclofenamic Acid; D015232:Dinoprostone