Selective A2A adenosine receptor activation reduces skin pressure ulcer formation and inflammation

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 281; no. 1; p. H67
• Main Authors: Peirce, Shayn M, Skalak, Thomas C, Rieger, Jayson M, Macdonald, Timothy L, Linden, Joel
• Format: Journal Article
• Language: English
• Published: 01.07.2001
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.281.1.h67

Departments of 1  Biomedical Engineering, 2  Chemistry, and 3  Cardiovascular Medicine, University of Virginia, Charlottesville, Virginia 22908 Activation of A 2A adenosine receptors (A 2A -AR) by ATL-146e (formerly DWH-146e) prevents inflammatory cell activation and adhesion. Recurrent ischemia-reperfusion (I/R) of the skin results in pressure ulcer formation, a major clinical problem. ATL-146e was evaluated in a novel reproducible rat model of pressure ulcer. A 9-cm 2 region of dorsal rat skin was cyclically compressed at 50 mmHg using a surgically implanted metal plate and an overlying magnet to generate reproducible tissue necrosis. Osmotic minipumps were implanted into 24 rats divided into four equal groups to infuse vehicle (control), ATL-146e (0.004 µg · kg 1 · min 1 ), ATL-146e plus an equimolar concentration of A 2A antagonist, ZM-241385, or ZM-241385 alone. Each group received 10 I/R cycles. In non-I/R-treated skin, ATL-146e has no effect on blood flow. I/R-treated skin of the ATL-146e group compared with the vehicle group had 65% less necrotic area, 31% less inhibition of average skin blood flow, and fewer extravasated leukocytes (23 ± 3 vs. 49 ± 6 per 500 µm 2 ). These data suggest that ATL-146e, acting via an A 2A -AR, reduces leukocyte infiltration and is a potent prophylactic for I/R injury in skin. ischemia-reperfusion; leukocyte extravasation; magnetic force; skin necrosis