Heparinase III exerts endothelial and cardioprotective effects in feline myocardial ischemia-reperfusion injury.
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.
Hayward
R
R
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Nossuli
T O
TO
Lefer
A M
AM
D000818:Animals; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D019763:Heparin Lyase / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology
D019763:Heparin Lyase