Effect of torbafylline on muscle blood flow, performance, and capillary supply in ischemic muscles subjected to varying levels of activity.

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.

Phosphodiesterase inhibitory profile of some related xanthine derivatives pharmacologically active on the peripheral microcirculation.

The cyclic nucleotide phosphodiesterase (PDE) inhibitory profile of four related xanthine derivatives: pentoxifylline (BL 191), propentofylline (HWA 285), torbafylline (HWA 448) and albifylline (HWA 138), pharmacologically active on the peripheral and/or cerebral microcirculation was established using the four main PDE isoforms present in rat heart cytosol. HPLC on a Mono Q ion-exchange column resolved four separate cyclic nucleotide PDE activities: a calmodulin-activated fraction (PDE I), a cGMP-stimulated fraction (PDE II), a cAMP-specific rolipram-sensitive fraction (PDE IV) and a cGMP-inhibited fraction (PDE III). Among the four compounds studies, only torbafylline and pentoxifylline inhibited more efficiently the calcium plus calmodulin-stimulated than the basal activity of PDE I.

Correlation of function and energy metabolism in rat ischemic skeletal muscle by 31P-NMR spectroscopy: effects of torbafylline.

The aim of this study was to correlate function of rat ischemic skeletal muscle directly with energy metabolism, to investigate the effects of torbafylline, a novel xanthine derivative potentially useful for the treatment of peripheral vascular occlusive disease and other ailments of skeletal muscle, and to get insight into its mechanism of action. Phosphocreatine (PCr), inorganic phosphate (Pi) and pH were estimated at rest, during induced contractions and during the recovery phase after cessation of electrical stimulation in rat hind limb muscles with two weeks unilateral chronic ligation of the femoral artery. Concomitantly, contraction force was measured in terms of tension developed during the stimulation interval.

Effects of torbafylline on muscle atrophy: prevention and recovery.

The effects of torbafylline on the prevention of and the recovery from 5 weeks of hindlimb suspension induced atrophy were analyzed in rat soleus and extensor digitorum longus muscles. Muscle alterations were investigated by determining a suite of electrophysiological, histochemical, and muscle ultrastructural characteristics. Administration of torbafylline during the suspension period was ineffective in preventing any of the observed muscle atrophic changes.

Skeletal muscle microcirculation: the effects of limited blood supply and treatment with torbafylline.

The effects of one and two week arterial occlusion on the microcirculation of fast glycolytic skeletal muscle (rat tibialis anterior) were assessed by direct observation. Ligation of the right common iliac artery resulted in a greater proportion of the capillary population exhibiting intermittent flow, and reduction of capillary diameters. Terminal arterioles showed a lack of responsiveness to acute contractions of the muscle, while those in control muscles dilated.