Fujii Y, Hoshi T, Toyooka H
Department of Anesthesiology, University of Tsukuba Institute of Clinical Medicine, Tsukuba City, Ibaraki, Japan.
Anesth Analg. 2001 Mar;92(3):762-6. doi: 10.1097/00000539-200103000-00039.
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.
Diaphragmatic fatigue is implicated as a cause of respiratory failure in normal subjects and in patients with chronic obstructive lung disease. Colforsin daropate improves contractile properties during diaphragmatic fatigue.
我们研究了水溶性福司可林衍生物可乐福司他对疲劳犬膈肌收缩力的影响。将犬随机分为4组，每组8只。在每组中，通过以20Hz的频率间歇性双侧超强电刺激膈神经30分钟来诱发膈肌疲劳。在产生疲劳的时间段结束后，第1组不给予研究药物，第2组输注小剂量可乐福司他（0.2μg·kg⁻¹·min⁻¹），第3组输注大剂量可乐福司他（0.5μg·kg⁻¹·min⁻¹），第4组在输注可乐福司他（0.5μg·kg⁻¹·min⁻¹）期间输注尼卡地平（5μg·kg⁻¹·min⁻¹）。在产生疲劳的时间段后，每组在低频（20Hz）刺激时的跨膈压（Pdi）较基线值降低（P<0.05），而在高频（100Hz）刺激时Pdi无变化。在第2组和第3组中，在输注可乐福司他期间，每次刺激的Pdi较疲劳值增加（P<0.05）。第3组的Pdi增加幅度大于第2组（P<0.05）。在第4组中，在疲劳的膈肌中，输注尼卡地平后可乐福司他对Pdi的增强作用被消除。各组的膈肌综合电活动均无变化。我们得出结论，可乐福司他通过对跨膜钙转运的作用，以剂量依赖的方式改善疲劳犬膈肌的收缩力。
膈肌疲劳被认为是正常受试者和慢性阻塞性肺疾病患者呼吸衰竭的一个原因。可乐福司他可改善膈肌疲劳时的收缩特性。
