title: Addition of alinidine, a specific bradycardic agent, to dobutamine in a canine model of endotoxic shock.
abstract: METHODS
  Alinidine is a recently developed antiarrhythmic medication that acts directly on the cardiac pacemaker cells to reduce heart rate (HR). At effective doses, alinidine might have cardiodepressant actions that could be hazardous in the presence of hemodynamic instability. On the other hand, one limitation of the use of catecholamines is tachycardia, and alinidine could be beneficial in situations such as septic shock, where adrenergic agents are commonly required. The present study explored the hemodynamic and gasometric effects of alinidine during dobutamine administration in a canine model of septic shock induced by endotoxin administration. In ten pentobarbital-anesthetized, mechanically ventilated dogs (weight 28 +/- 4 kg), Escherichia coli endotoxin (3 mg/kg) injection was followed 30 mins later by saline infusion to restore and maintain pulmonary artery occlusion pressure at the baseline value. Sixty minutes after the endotoxin administration, a dobutamine infusion was started at a rate of 10 micrograms/kg/min. Thirty minutes later, alinidine was administered as a bolus dosage of 1 mg/kg in five dogs; the other five dogs served as a control group.
  
  
  RESULTS
  Alinidine administration resulted in a decrease in HR from 157 +/- 20 to 138 +/- 27 beats/min (p less than .01) and a nonsignificant increase in cardiac output from 5.2 +/- 3.0 to 6.8 +/- 2.8 L/min, as a consequence of increases in stroke volume from 31.9 +/- 15.3 to 49.2 +/- 13.9 mL (p less than .01) and in left ventricular stroke work from 32.1 +/- 20.0 to 57.4 +/- 32.1 g.m (p less than .05).
  
  
  CONCLUSIONS
  During experimental septic shock, alinidine administration can reverse dobutamine-induced tachycardia and simultaneously improve ventricular function.
authors.affiliation: Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
authors.forename: J C
authors.initials: JC
authors.lastname: Preiser
authors.forename: D
authors.initials: D
authors.lastname: Moulart
authors.forename: J L
authors.initials: JL
authors.lastname: Vincent
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D003000:Clonidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004280:Dobutamine / Q000627:therapeutic use*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D011446:Prospective Studies; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000889:Anti-Arrhythmia Agents; D004280:Dobutamine; C022192:alinidine; D003000:Clonidine