The aim of the present study was to assess the effects of intravenously and topically applied propionyl-L-carnitine (pLc) on microvascular permeability increase and the role of leukocytes into I/R-induced damage in hamster check pouch preparation.

The hamster check pouch microcirculation was visualized by in vivo fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length and capillary red blood cell velocity (VRBC) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescein (DCF), respectively. In control animals, I/R caused a significant increase in permeability and leukocyte adhesion to venules. Capillary perfusion and VRBC decreased. TBARS levels and DCF fluorescence significantly increased. Iv. infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted pLC-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on check pouch produced the same effects as observed with intravenous administration and decreased the E-selectin expression.

In conclusion, pLc prevents microvascular changes induced by I/R injury. The reduction in permeability increase could be mainly due to EDHF and NO release-induced vasodilatation.