Short term effects of intra-arterial propionyl-L-carnitine on isolated canine hind-limbs.
Treatment with propionyl-L-carnitine has been shown to increase the walking capacity of patients with peripheral vascular disease, but the mechanisms responsible for the effect are unknown. To study the effects of propionyl-L-carnitine on musculocutaneous vascular beds and the related mechanisms, a preparation of constant-pressure blood-perfused dog hind-limb was used. Since the propionyl-L-carnitine solution had a pH less than 4 the contralateral limb simultaneously received acidified saline. The substances were injected into the perfused arteries in 2 minutes or in 20 minutes, and the cumulative dose of propionyl-L-carnitine was 20 mg/kg for each administration. The preparation was well suited for this study, because there were no major systemic effects of propionyl-L-carnitine, nor signs of cross-circulation between the isolated limbs. Propionyl-L-carnitine increased flow by 130% in 2 minute infusions and by 49% in 20 minute infusions. Acidified saline increased flow by 47% in 2 minute infusions and by 34% in 20 minute infusions. The difference between propionyl-L-carnitine and acidified saline was significant in 2 minute infusions. The 2 minute infusions of propionyl-L-carnitine increased venous PO2 by 34% and PCO2 by 22% while pH decreased by 0.07. The 20 minute infusions of propionyl-L-carnitine increased PO2 by 22% and PCO2 by 24% while pH decreased 0.10 units. Acidified saline increased only venous PO2 in 2 minute infusions (16%). Calculated oxygen consumption of the perfused limbs increased in 2 minute infusions of propionyl-L-carnitine, but not significantly. It was concluded that propionyl-L-carnitine has a direct vasodilator effect in musculocutaneous vascular beds at high doses and probably enhances tissue metabolism.
Cevese
A
A
Institute of Human Physiology, University of Verona, Italy.
Schena
F
F
Poltronieri
R
R
Cerutti
G
G
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects*; D010477:Perfusion
C003223:propionylcarnitine; D002331:Carnitine