The involvement of polymorphonuclear leukocytes (PMN) in reperfusion-mediated
vascular injury was studied in a model of
ischemia and reperfusion in rabbit hindlimb.
Ischemia was induced by 4-h occlusion of the left iliac artery followed by 4-h reperfusion. Plasma
creatine kinase (CK) and
lactate dehydrogenase (LDH) activities, hindlimb vascular resistance (HVR), and
myeloperoxidase (MPO) activity in the postischemic extensor digitorum longus (EDL) muscle were measured to evaluate the extent of vascular and skeletal muscle injury. In addition, the
ischemia/reperfusion-induced injury of the hindlimb vasculature was evaluated by electron microscopy.
Ischemia and reperfusion (n = 10) was associated with an increase in CK (6,380 +/- 1,346 U/L, p < 0.05) and LDH (552 +/- 76 U/L, p < 0.05) activities which were significantly greater than those observed in
sham-operated control animals (CK 1,651 +/- 207 U/L, LDH 246 +/- 14 U/L; n = 6). HVR in
sham-operated animals decreased by 20 +/- 3%, but increased in the ischaemic group by 56 +/- 16% (p < 0.05). MPO activity of EDL muscle increased from 7.3 +/- 3.9 U per muscle (
sham) to 28.0 +/- 5.9 U per muscle (p < 0.05) after
ischemia and reperfusion. Morphologic analysis did not show any alteration in the microvascular bed of the hindlimb. Moreover, 1 mg/kg/h intravenous (i.v.)
cloricromene, an antithrombotic drug that inhibits
superoxide anion production as well as PMN adhesion to endothelium, reduced the increase in plasma CK and LDH and the increase in MPO and HVR observed in animals subjected to hindlimb
ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)