The effect of 7-(2'-oxopropyl)-1,3-di-n-butyl-xanthine (BRL 30892) on ischaemic skeletal muscle pO2, pH and contractility in cats and rats.
The purpose of the present investigation was to study in animal experiments whether 7-(2'-oxopropyl)-1,3-di-n-butyl-xanthine (BRL 30892) could be of potential value for the treatment of peripheral vascular disease (PVD). In order to obtain information on oxygen supply, energy metabolism and function of ischaemic calf muscle in rats and cats, muscle pO2, pH and contractility were measured before and after dosing of BRL 30892. In cats, pO2 histograms of the ischaemic gastrocnemius muscle demonstrate an improved supply after dosing of BRL 30892. A dosage of 0.1 mg/kg intraduodenally (i.d.) increased tissue pO2 by an average of 6 Torr. Dose-effect relationships showed BRL 30892 to be of high potency, the lowest effective dose being 0.025 mg/kg i.d. BRL 30892 also increased pO2 in the ischaemic rat gastrocnemius. Furthermore, an increase in pH in this tissue was seen, a dosage of 0.2 mg/kg increasing pH by ca. 0.1 unit. Contractility of the cat ischaemic calf muscle was increased by 13% after 0.0125 mg/kg i.v. and by nearly 50% after 0.3 mg/kg i.d. BRL 30892. Pentoxifylline used as a reference compound showed qualitatively similar effects to BRL 30892 but pentoxifylline was ca. 100 times less potent. Furthermore, pentoxifylline produced lower maximum effects than BRL 30892. Thus, BRL 30892 could be a useful compound for the treatment of PVD.
D000818:Animals; D002415:Cats; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006863:Hydrogen-Ion Concentration; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009132:Muscles / Q000098:blood supply* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010431:Pentoxifylline / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity; D014970:Xanthines
D011688:Purinones; D014970:Xanthines; C043898:denbufylline; D010431:Pentoxifylline