The Effect of Pentoxifylline on Ischemia and Reperfusion Injury in the Rat Cremaster Muscle

ABSTRACT

The accumulation of leukocytes is believed to contribute to reperfusion injury following ischemia. The purpose of this study was to determine if pentoxifylline (PTX) would ameliorate reperfusion injury by preventing activation of leukocytes. Male Wistar rats received 40 mg/kg of PTX orally in water for 6 days, and a single dose of PTX (30 mg/kg) intraarterially before experiments. Control measurements of red-cell velocity and inside diameter were made in first-through-third-order arterioles (1A-3A) of the cremaster muscle, along with the number of rolling and sticking leukocytes (WBC) in venules and the density of flowing capillaries, by intravital microscopy. The muscles were then subjected to total ischemia for 2 hr by arterial clamping, followed by a repeat of the measurements during reperfusion. The number of both rolling and sticking WBCs was not different between the two groups during the control period but, following reperfusion, there were significantly fewer WBCs rolling and sticking in the venules of the PTX group at the measured times (immediately, 1,2, and 3 hr after reperfusion). Arteriolar blood flow was lower than initial values during the first hour of reperfusion in both groups. But while blood flow decreased further in the untreated group, it significantly improved in the PTX group. There were no significant differences in arteriolar diameter or density of flowing capillaries between the two groups at any time. Treatment with PTX prevented accumulation of rolling and sticking leukocytes following reperfusion. This may contribute to the improved arteriolar blood flow following 2 hr of ischemia.