Complement and polymorphonuclear leukocyte activation each play a role in determining myocardial ischemia-reperfusion injury.
Cobra venom factor (CVF) transiently activates polymorphonuclear leukocytes (PMN) by complement activation, followed by rapid complement depletion and gradual reversal of PMN activation. Utilizing these sequential changes caused by CVF, the individual and combined effects of complement and PMNs on myocardial infarct size (IS) were investigated. Rats were treated with CVF, and/or anti-PMNs. Complement was depleted, but circulating PMNs were being activated at 4h after CVF administration, and at 36h after, complement was depleted, but PMNs were in a near basal condition. Under anesthesia, the rats had a 30-min coronary occlusion followed by 6h of reperfusion. The IS was assessed by tetrazolium staining. CVF, as well as anti-PMNs, reduced myeloperoxidase (MPO) activity in the risk area and the reduced MPO resulted in a reduced IS, which was also the effect of anti-PMNs, but complement depletion by CVF, during which circulating PMNs were activated, failed to reduce the IS despite low MPO activity. These results suggest that complement and the condition of PMNs each play a role in determining the IS, and ischemic reperfusion injury might be produced even by relatively low myocardial MPO activity.
Atsuumi
T
T
First Department of Internal Medicine, Fukushima Medical University, Japan.
Yaoita
H
H
Shichishima
T
T
Maehara
K
K
Fujita
T
T
Maruyama
Y
Y
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D003165:Complement System Proteins / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000008:administration & dosage / Q000494:pharmacology; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D004546:Elapid Venoms; D018836:Inflammation Mediators; C016310:cobra venom factor; D003165:Complement System Proteins