Hudlicka O, Egginton S, Brown M D, Okyayuz-Baklouti I
Department of Physiology, University of Birmingham, United Kingdom.
Can J Physiol Pharmacol. 1994 Jul;72(7):811-7. doi: 10.1139/y94-115.
Torbafylline, a novel xanthine derivative, was given to rats by gavage (2 x 25 mg.kg-1.day-1, morning and evening) to study its effect upon fast muscles (tibialis anterior and extensor digitorum longus) made ischemic by unilateral ligation of the common iliac artery and subjected to two types of activity imposed by chronic electrical stimulation at 10 Hz: (i) strenuous, 6 h.day-1 as 3 x 2 h with 90- to 120-min intervals or (ii) mild, 105 min.day-1 as 7 x 10-15 min with 90- or 85-min intervals for 12-14 days. Some of the deleterious effects on ischemic muscles of strenuous activity (reduced blood flow during contractions, less resistance to fatigue) were remedied by torbafylline treatment, and values normalized. Most notably, torbafylline significantly reduced the degree of capillary endothelial cell swelling. In addition, the degree of atrophy was reduced and fatigue resistance improved in muscles contralateral to ischemic, which had been impaired with the strenuous regime. Torbafylline treatment had little further effect on ischemic muscles subjected to mild stimulation, which on its own improved functional hyperemia, resistance to fatigue, and the capillaries per fibre ratio in tibialis anterior, although it did significantly increase the capillary per fibre ratio in extensor digitorum longus. These data indicate a possible role for torbafylline as an adjunct to exercise therapy for chronic muscle ischemia.
托巴茶碱是一种新型黄嘌呤衍生物，通过灌胃给予大鼠（2×25毫克·千克⁻¹·天⁻¹，早晚各一次），以研究其对因单侧结扎髂总动脉而缺血的快肌（胫前肌和趾长伸肌）的影响，这些肌肉还受到10赫兹慢性电刺激施加的两种活动的影响：（i）剧烈活动，每天6小时，分3次，每次2小时，间隔90至120分钟；或（ii）轻度活动，每天105分钟，分7次，每次10至15分钟，间隔90或85分钟，持续12至14天。托巴茶碱治疗纠正了剧烈活动对缺血肌肉的一些有害影响（收缩期间血流减少、抗疲劳能力降低），并使各项指标恢复正常。最值得注意的是，托巴茶碱显著降低了毛细血管内皮细胞肿胀的程度。此外，在剧烈运动方案中受损的缺血对侧肌肉的萎缩程度降低，抗疲劳能力提高。托巴茶碱治疗对轻度刺激的缺血肌肉几乎没有进一步影响，轻度刺激本身改善了功能性充血、抗疲劳能力以及胫前肌每根纤维的毛细血管比例，尽管它确实显著增加了趾长伸肌每根纤维的毛细血管比例。这些数据表明托巴茶碱可能作为慢性肌肉缺血运动疗法的辅助药物发挥作用。
