TY - JOUR T1 - Heparinase III Exerts Endothelial and Cardioprotective Effects in Feline Myocardial Ischemia-Reperfusion Injury JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1032 LP - 1038 VL - 283 IS - 3 AU - Reid Hayward AU - Tareck O. Nossuli AU - Allan M. Lefer Y1 - 1997/12/01 UR - http://jpet.aspetjournals.org/content/283/3/1032.abstract N2 - The initial phase of neutrophil (PMN) adherence in the pathophysiology of myocardial ischemia-reperfusion (MI/R) injury depends on the selectins, particularly P- and L-selectin. Several ligands for these selectins have been identified, one of which may be a heparan sulfate proteoglycan (HSPG). Cats subjected to 90 min of MI and 270 min of R were given either heparinase III (0.033, 0.33 or 3.33 IU/kg/min) or its vehicle beginning 10 min before R and continuing throughout the 270-min R period. Heparinase III at 3.33 IU/kg/min provided a marked cardioprotective effect compared with cats receiving only vehicle as evidenced by a significant attenuation in myocardial necrosis (P < .01). In addition, endothelium-dependent vasorelaxation to acetylcholine in coronary artery rings isolated from MI/R cats treated with heparinase III was significantly preserved (P < .01). Adherence of PMNs to the coronary vascular endothelium after 270 min of R was also significantly attenuated in heparinase III-treated cats compared with vehicle (P < .01). At 0.33 IU/kg/min, heparinase III exerted modest, significant cardioprotective effects, whereas at 0.033 IU/kg/min, no significant beneficial effects were observed. Our results indicate that heparinase III is cardioprotective in a dose-dependent manner, preserves endothelial function and attenuates PMN adherence to the coronary vascular endothelium. The American Society for Pharmacology and Experimental Therapeutics ER -