Colforsin daropate improves contractility in fatigued canine diaphragm

We studied the effects of colforsin daropate, a water-soluble forskoline de rivative, 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 a ta frequency of 20 Hz applied for 30 min. Immediately after the end of a fa tigue-producing period, Group 1 received no study drug, Group 2 was infused with small-dose colforsin daropate (0.2 mug . kg(-1) . min(-1)), Group 3 w as infused with large-dose colforsin daropate (0.5 mug . kg(-1) . min(-1)), and Group 4 was infused with nicardipne (5 mug . kg(-1) . min(-1)) during colforsin daropate (0.5 mug . kg(-1) . min(-1)) administration. After the f atigue-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) stimulatio n. In Groups 2 and 3, during colforsin daropate administration, Pdi to each stimulus increased from fatigued values (P < 0.05). The increase in Pdi wa s larger in Group 3 than in Group 2 (P < 0.05). In Group 4, the augmentatio n 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 impro ves, in a dose-dependent manner, contractility in fatigued canine diaphragm via its effect on transmembrane calcium movement.