Cariporide (HOE 642) attenuates leukocyte activation in ischemia and reperfusion

Citation
M. Redlin et al., Cariporide (HOE 642) attenuates leukocyte activation in ischemia and reperfusion, ANESTH ANAL, 93(6), 2001, pp. 1472-1479
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ANESTHESIA AND ANALGESIA
ISSN journal
0003-2999 → ACNP
Volume
93
Issue
6
Year of publication
2001
Pages
1472 - 1479
Database
ISI
SICI code
0003-2999(200112)93:6<1472:C(6ALA>2.0.ZU;2-6
Abstract
Cariporide (HOE 642) ameliorates myocardial ischemia/reperfusion (I/R) inju ry, by the well established reduction of cytosolic [Ca2+] in cardiac myocyt es through inhibition of Na+/H+ exchange. However, postischemic inflammatio n also contributes to I/R injury. We tested the hypothesis that cariporide also modulates the inflammatory response. The effect of cariporide on L-sel ectin expression by human leukocytes in vitro and leukocyte adhesion and em igration in the reperfused rat cremaster muscle in vivo were studied. The r at cremaster muscle was exteriorized for intravital videomicroscopy, induct ion of ischemia (90 min), and reperfusion (90 min). Eleven rats were pretre ated with cariporide (9 mg/kg body weight IV) whereas 11 rats received sali ne. Leukocyte adhesion was quantified offline. Human venous blood was incub ated with cariporide (3 mu mol/L) or saline, stimulated with formylmethioni ne-leucine-phenylalanine (10(-10)-10(-6) mol/ L), and granulocyte L-selecti n expression was analyzed by flow cytometry. Cariporide reduced leukocyte r olling and adhesion by approximately 35% and 45%, respectively, after 30 mi n of reperfusion. Leukocyte extravasation was decreased by approximately 85 % after 90 min. Cariporide increased L-selectin shedding at each formyl-met hionine-leucine-phenylalanine concentration, reducing the 50% effective dos e from 9.95 to 4.68 nmol/L. Thus, cariporide may ameliorate I/R injury not only by the known reduction of cytosolic [Ca2+] in cardiomyocytes, but also by attenuating leukocyte-dependent inflammatory responses. Promotion of L- selectin shedding from activated leukocytes may present a mechanism underly ing this newly detected effect.