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 >or=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.

Effects of oral N-acetylcysteine on walking capacity, leg reactive hyperemia, and inflammatory and angiogenic mediators in patients with intermittent claudication

“…Prior studies have shown that flow-mediated dilation (FMD) of the brachial artery is markedly reduced following maximal exercise in these patients (56,57). Intravenous infusion of vitamin C prevents the reduction in FMD, which indicates that this abnormal response is mediated, at least in part, by oxidative stress (57).…”

“…Another possibility is that, if present, the impairment in leg vascular function following exercise is very brief. In the studies of Silvestro and coworkers (56,57), the postexercise assessment of FMD was performed shortly after the maximal exercise bout, while our measurements of postocclusive hyperemia were conducted 30 min following the completion of the exercise bout. Additional studies are warranted to determine the time course of changes in vascular function in response to exercise in these patients.…”

The association of acute exercise-induced ischaemia with systemic vasodilator function in patients with peripheral arterial disease

“…It was derived from previous observations that FMD additionally decreased in PAD patients shortly after exercise-induced maximal tolerable leg ischaemia. 5,6 To assess the duration of this phenomenon, we extended the observation time to 4 hours. Therefore, we followed the time course of changes in FMD of the clinically unaffected brachial artery after acute exercise-induced leg ischaemia in PAD patients.…”

Propionyll-carnitine: intermittent claudication and peripheral arterial disease

“…In 15 patients with IC, exercise-induced increases in serum levels of E-selectin, P-selectin, L-selectin, and other chemokines were significantly reduced with the administration of oral propionyl L-carnitine 2 g/day for 2 months [51]. In a more recent study [52], a single intravenous (i.v.) dose of propionyl L-carnitine 600 mg in 18 claudicants significantly attenuated the exercise-induced decrease in FMD, whereas administration of placebo had no effect on this parameter.…”

“…Propionyl L-carnitine provides protection from the effects of oxidative stress and inflammation in ischemic tissue endothelium by reducing the plasma release of leukocyteendothelial adhesion cells [51,52], improving arteriolar function [53], and increasing arterial flow-mediated dilation (FMD) [52]. In 15 patients with IC, exercise-induced increases in serum levels of E-selectin, P-selectin, L-selectin, and other chemokines were significantly reduced with the administration of oral propionyl L-carnitine 2 g/day for 2 months [51].…”