title: Cardiopulmonary effects of the novel neuromuscular blocking drug GW280430A (AV430A) in dogs.
abstract: BACKGROUND
  This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles.
  
  
  METHODS
  The ED95 for GW280430A was first determined in four animals. These data were then used to guide bolus dosing in multiples of ED95 in six dogs instrumented for hemodynamic measurements as well as inspiratory pressure and pulmonary compliance. Cardiopulmonary data were compared before and after the conclusion of a 60- to 90-min GW280430A infusion and in response to subsequent incremental bolus dosing starting with 3.125 x ED95. An adverse response was regarded as an alteration of 10% or greater in any variable. Arterial blood was obtained for histamine analysis before and 1 min after each dose.
  
  
  RESULTS
  The ED95 of GW280430A was 0.064 +/- 0.01 mg/kg, and stable neuromuscular blockade was maintained with infusion of 0.012 +/- 0.002 mg.kg(-1).min(-1). With the exception of a late 14% increase in heart rate, there were no cardiopulmonary changes during infusion. Bolus dosing produced no cardiopulmonary change until a decrease in mean arterial pressure was elicited in four of six dogs at 25 x ED95. This response was modest, transient, and associated with a concomitant increase in plasma histamine concentration. There were no accompanying changes indicative of direct myocardial depression, pulmonary vasoconstriction, or bronchospasm.
  
  
  CONCLUSIONS
  These data indicate that GW280430 does not produce demonstrable cardiovascular effects in the anesthetized dog until doses far in excess of the ED95 are administered as a bolus.
authors.affiliation: Department of Anesthesiology, Weill Medical College of Cornell University, New York, New York 10021, USA. pmheerd@mail.med.cornell.edu
authors.forename: Paul M
authors.initials: PM
authors.lastname: Heerdt
authors.forename: Richard
authors.initials: R
authors.lastname: Kang
authors.forename: Andrew
authors.initials: A
authors.lastname: The'
authors.forename: Mir
authors.initials: M
authors.lastname: Hashim
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mook
authors.forename: John J
authors.initials: JJ
authors.lastname: Savarese
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006632:Histamine / Q000097:blood; D007546:Isoquinolines / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D006632:Histamine; C451919:gantacurium