Effect of Propionylcarnitine on Changes in Endothelial Function and Plasma Levels of Adhesion Molecules Induced by Acute Exercise in Patients with Intermittent Claudication

Abstract

In patients with intermittent claudication, treadmill exercise may cause acute deterioration of endothelial function and increase in plasma concentrations of adhesion molecules. The authors evaluated the efficacy of intravenously administered propionylcarnitine (PLC) in preventing these phenomena. Thirty-six claudicants with postexercise decrease in brachial artery flow-mediated dilation (FMD) were randomized to either placebo or PLC (600 mg as a single bolus followed by 1 mg/kg/min for 60 minutes). In the 18 patients randomized to placebo, FMD markedly decreased with exercise before (from 6.8 ±0.4% to 4.0 ±0.4%; p<0.001) and after treatment (from 6.5 ±0.4% to 4.4 ±0.5%; p<0.001). By contrast, in the PLC group, FMD significantly decreased with exercise before treatment (from 8.0 ±0.7% to 4.4 ±0.4%; p<0.001), but not after active drug administration (from 7.1 ±0.7% to 6.0 ±0.6%; p=0.067). The difference between treatments was not significant (p=0.099; ANOVA). However, in the PLC group, the authors found that the greater the exercise-induced deterioration in endothelial function before treatment, the greater the capacity of PLC to prevent a postexercise decrease in FMD (r = -0.50, p=0.034). Accordingly, they analyzed data in the 19 patients with a baseline exercise-induced decrease in FMD ≥45% (ie, the median FMD reduction in the entire group of 36 patients), and found that the exercise-induced FMD decrease was less after PLC than after placebo (p=0.046, ANOVA). In the same subgroup, the exercise-induced increase in plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) was significantly higher before than after treatment in patients randomized to PLC (23.4 ±5% vs 15.3 ±7%, p=0.007). In conclusion, in patients with intermittent claudication suffering from a greater endothelial derangement after treadmill, PLC administration provided a protective effect against deterioration of FMD and increase of sVCAM-1 induced by exercise