Different Effects of Beta-1-Adrenergic Blocking Agents With ISA or Without ISA on Peripheral Blood Flow

Abstract

Until recently beta-adrenergic blocking agents were considered contraindicated in peripheral arterial occlusive disease (PAOD). However, in recent years several studies have failed to show negative effects on peripheral blood flow. It was the aim of this study to compare the effects of celiprolol, a beta-1-adrenergic blocking agent with intrinsic sympathomimetic activity (ISA), and of metoprolol, a beta-1-adrenergic blocking agent without ISA, on peripheral blood flow of patients with and without PAOD. In an acute trial 24 patients (group I: 12 patients with PAOD stage I and II; group II: 12 patients without PAOD received a single dose of 200 mg celiprolol or 200 mg metoprolol in a double-blind crossover design. Celiprolol induced no significant changes in calf and skin blood flow at rest or during reactive hyperemia. Basal vascular resistance (BVR) and minimal vascular resistance (MVR) were not affected. Metoprolol, however, significantly reduced muscle blood flow and increased BVR in both groups. Subsequently the patients were treated in a randomized double-blind design with a daily dose of 200 mg celiprolol or metoprolol for three weeks. In long-term treatment skin and muscle blood flow at rest and during reactive hyperemia, BVR, and MVR were not affected by celiprolol. Metoprolol significantly lowered calf blood flow at rest in patients with PAOD; other parameters remained unchanged. In patients without PAOD, metoprolol caused a significant decrease of calf blood flow at rest and an increase of BVR. Calf blood flow during reactive hyperemia, as well as skin blood flow at rest and during reactive hyperemia, showed no significant changes. Our results suggest that celiprolol— owing to its ISA or other mechanisms not yet clarified—in contrast to other beta-1-adrenergic blocking agents without ISA, neither reduces muscle blood flow nor increases BVR.