PT  - JOURNAL ARTICLE
AU  - Reid Hayward
AU  - Tareck O. Nossuli
AU  - Allan M. Lefer
TI  - Heparinase III Exerts Endothelial and Cardioprotective Effects in Feline Myocardial Ischemia-Reperfusion Injury
DP  - 1997 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1032--1038
VI  - 283
IP  - 3
4099  - http://jpet.aspetjournals.org/content/283/3/1032.short
4100  - http://jpet.aspetjournals.org/content/283/3/1032.full
SO  - J Pharmacol Exp Ther1997 Dec 01; 283
AB  - 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