Beneficial effect of papaverine plus raubasine in peripheral arterial insufficiency

It has been demonstrated that, in most arteriopathic patients, vasodilators induce the vascular steal phenomenon, i.e. the shunting of blood from the ischemic to the normally perfused areas. It is conceivable, therefore, that vasoconstrictors may improve in the opposite way, reducing the blood flow to the normal zones and increasing it to the ischemic. A "reverse vascular steal" caused by the simultaneous IV injection of a vasodilator and a beta-blocker has been previously shown; however, the chronic treatment of arteriopathic patients with beta-adrenoceptor blocking drugs often results in increased evidence of peripheral arterial insufficiency; therefore, the combination of a vasodilating drug with a beta-blocker is limited in the clinical practice. The aim of this study was to investigate the efficacy of the combination of the vasodilator papaverine hydrochloride with a drug having vasoconstrictive action without the undesirable side effects of beta-blockers. Accordingly, raubasine (40 mg) was given p.o. associated with papaverine (300 mg) in 10 arteriopathic patients, who presented a significant reduction of blood flow in the affected limb after the administration of 300 mg p.o. of papaverine alone. The measurements of blood flow were performed by impedance plethysmographic recordings to evaluate papaverine plasma concentrations. Data obtained by this study indicate that papaverine alone induces a significant reduction of blood flow starting from the time of its maximal plasma concentration. Raubasine alone does not induce any change in blood flow, while the combination of the 2 drugs significantly increases the blood supply to the affected limb. These favorable results, probably related to the ability of raubasine to induce a reverse vascular steal, suggest that the combination of this drug with a vasodilator such as papaverine may represent a new approach in the treatment of peripheral arterial insufficiency.