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A732
October 15, 2006
2:00 PM - 4:00 PM
Room Hall E, Area L
Influence of Acidosis on Olprinone-Induced Improvement of Fatigued Diaphragmatic Contractility
Masahiro Yagihara, M.D., Aki Uemura, M.D., Ph.D., Makoto Tanaka, M.D., Ph.D.
Anesthesioligy, Tsukuba University, Tsukuba, Ibaraki, Japan
We have reported the phosphodiesterase III inhibitors, olprinone, improves the fatigue-induced changes in guinea-pig diaphragmatic contractility. The present study was designed to determine whether the efficacy of olprinone on diaphragmatic contractility is affected by acidosis.

<Method>

The guinea-pig diaphragm strips stimulated directly were randomly allocated and suspended in HEPES-tyrode solution with pH values adjusted to 7.4, 7.0, or 6.6 (n=5 each). Diaphragmatic contractility was assessed by measuring twitch tension and force at 20Hz and 100Hz stimulation. Diaphragmatic fatigue was induced by generating rhythmic repetitive contractions produced by 20Hz stimulation for 5 min. Then the concentration response relation of diaphragmatic contractility after fatigue-induced changes to oprinone (10-4, 10-5, 0M) were determined.

<Result>

After suspended in HEPES-tyrode solution, diaphragm strips did not contract with pH6.6 compared with pH7.4 and 7.0 (P<0.05). Olplinone 10-4, 10-5M caused an increase in force at both stimuli from fatigued values in a concentration dependent manner at pH7.4 (P<0.05) and only 10-4M caused an increase at pH7.0 (P<0.05). After producing fatigue, titanic force to each stimulus decreased from baseline values at pH7.4 and 7.0.

<Conclusion>

The effect of olprinone on fatigue-induced changes in guinea-pig diaphragmatic contractility by concentration dependent manner were found at pH7.4. Diaphragmatic contractility was significantly depressed at severe acidosis (pH6.6) and mild acidosis (pH7.0), but 10-4M olprinone recovered diaphragmatic contractility at mild acidosis. These results indicate that diaphragmatic contractility is affected by acidosis and the effect of olprinone on fatigue-induced changes in guinea-pig diaphragmatic contractility is also affected by acidosis.[figure1][figure2]

Anesthesiology 2006; 105: A732
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