We studied the effects of
colforsin daropate, a water-soluble forskoline derivative, on contractility in fatigued canine diaphragm. Dogs were randomly divided into 4 groups of 8 each. In each group, diaphragmatic
fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Immediately after the end of a
fatigue-producing period, Group 1 received no study
drug, Group 2 was infused with small-dose
colforsin daropate (0.2 microg. kg(-1). min(-1)), Group 3 was infused with large-dose
colforsin daropate (0.5 microg. kg(-1). min(-1)), and Group 4 was infused with nicardipne (5 microg. kg(-1). min(-1)) during
colforsin daropate (0.5 microg. kg(-1). min(-1)) administration. After the
fatigue-producing period, in each group transdiaphragmatic pressure (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 2 and 3, during
colforsin daropate administration, Pdi to each stimulus increased from fatigued values (P < 0.05). The increase in Pdi was larger in Group 3 than in Group 2 (P < 0.05). In Group 4, the augmentation of Pdi by
colforsin daropate was abolished in fatigued diaphragm with an infusion of
nicardipine. The integrated diaphragmatic electric activity did not change in any of the groups. We conclude that
colforsin daropate improves, in a dose-dependent manner, contractility in fatigued canine diaphragm via its effect on transmembrane
calcium movement.
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