title: The dose-related efficacy of diltiazem for enhancing diaphragmatic fatigability in dogs.
abstract: Nicardipine, a calcium channel blockade, enhances the production of diaphragmatic fatigue. We studied the dose-related effects of diltiazem, another calcium channel blockade, on diaphragmatic fatigability in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. During this fatigue-producing period, Group I received no study drug, Group II was infused with diltiazem 0.1 mg. kg(-1). h(-1), and Group III was infused with diltiazem 0.5 mg. kg(-1). h(-1). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in Group I, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups II and III, with an infusion of diltiazem, Pdi at both stimuli decreased from baseline values (P < 0.05). The decrease in Pdi to each stimulus was more in Group III than in Group II (P < 0.05). We conclude that diltiazem causes a dose-related augmentation of fatigability in the diaphragm of dogs.
  
  
  CONCLUSIONS
  Diaphragmatic muscle fatigue is implicated as a cause of respiratory failure. Diltiazem, a calcium channel blockade, enhances diaphragmatic fatigability in dogs in a dose-related manner.
authors.affiliation: Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, 2-1-1 Amakubo, Tsukuba City, Ibaraki 305-8576, Japan. yfujii@igaku.md.tsukuba.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Aki
authors.initials: A
authors.lastname: Uemura
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyooka
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006439:Hemodynamics / Q000187:drug effects; D018763:Muscle Fatigue / Q000187:drug effects*; D010791:Phrenic Nerve / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D004110:Diltiazem