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. 2010 Jun;71(3):154–161. doi: 10.1016/j.curtheres.2010.06.001

Effects of dibutyryl cyclic adenosine monophosphate on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs

Yoshitaka Fujii 1,*, Aki Uemura 2
PMCID: PMC3967283  PMID: 24683261

Abstract

Background: Hypercapnia is associated with diaphragm muscle dysfunction that causes a reduction of diaphragmatic force generated for a constant elective myographic activity. No published data are available concerning hypercapnic depression of diaphragmatic contractility during dibutyryl cyclic adenosine monophospate (DBcAMP) administration.

Objective: The aim of this study was to assess the effects of DBcAMP on hypercapnic depression of diaphragmatic contractility in pentobarbital-anesthetized dogs.

Methods: This experimental study was conducted from July to December 2008 at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Adult (aged >5 years) mongrel dogs weighing 10 to 15 kg were randomly divided into 3 equal groups. Hypercapnia (80–90 mm Hg) was induced with 10% carbon dioxide added to the inspired gas. When hypercapnia was established, group 1 was infused with low-dose DBcAMP (0.05 mg/kg/min); group 2 was infused with high-dose DBcAMP (0.2 mg/kg/min); and group 3 received placebo (saline). Study drug was administered intravenously for 60 minutes. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at baseline, induction of hypercapnia, and study drug administration.

Results: Twenty-one dogs were divided into 3 groups of 7. There were no significant differences observed at baseline. In the presence of hypercapnia, Pdi (mean [SD], cm H2O) at low- (20-Hz) and high-frequency (100-Hz) stimulation was significantly decreased from baseline in each group (all, P = 0.001). In groups 1 and 2, Pdi at both stimuli was significantly increased during DBcAMP administration compared with hypercapnia-induced values (group 1: 20-Hz, 13.5 [2.2] vs 15.0 [2.4], respectively, P = 0.001, 100-Hz, 21.2 [1.6] vs 22.5 [1.6], P = 0.001; group 2: 20-Hz, 13.7 [1.4] vs 19.2 [1.7], P = 0.001, 100-Hz, 21.0 [2.4] vs 27.2 [2.5], P = 0.001). The Pdi at both stimuli during DBcAMP administration was significantly higher in group 2 than in group 1 (20-Hz, 19.2 [1.7] vs 15.0 [2.4], P = 0.001, 100-Hz, 27.2 [2.5] vs 22.5 [1.6], P = 0.003). In group 3, Pdi did not significantly change in regard to either stimulus from hypercapnia-induced values.

Conclusion: DBcAMP, in a dose-dependent manner, was associated with improved hypercapnic depression of diaphragmatic contractility in these pentobarbital-anesthetized dogs.

Key words: muscle, diaphragm, contractility, hypercapnia, dibutyryl cyclic adenosine monophosphate (DBcAMP)

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