title: Ischemia/reperfusion injury: effect of simultaneous inhibition of plasma cascade systems versus specific complement inhibition.
abstract: Ischemia/reperfusion injury (IRI) may occur from ischemia due to thrombotic occlusion, trauma or surgical interventions, including transplantation, with subsequent reestablishment of circulation. Time-dependent molecular and structural changes result from the deprivation of blood and oxygen in the affected tissue during ischemia. Upon restoration of blood flow a multifaceted network of plasma cascades is activated, including the complement-, coagulation-, kinin-, and fibrinolytic system, which plays a major role in the reperfusion-triggered inflammatory process. The plasma cascade systems are therefore promising therapeutic targets for attenuation of IRI. Earlier studies showed beneficial effects through inhibition of the complement system using specific complement inhibitors. However, pivotal roles in IRI are also attributed to other cascades. This raises the question, whether drugs, such as C1 esterase inhibitor, which regulate more than one cascade at a time, have a higher therapeutic potential. The present review discusses different therapeutic approaches ranging from specific complement inhibition to simultaneous inhibition of plasma cascade systems for reduction of IRI, gives an overview of the plasma cascade systems in IRI as well as highlights recent findings in this field.
authors.affiliation: Department of Clinical Research, University of Bern, Murtenstrasse 50, P.O. Box 44, CH-3010 Bern, Switzerland; Graduate School of Cellular and Biomedical Sciences, University of Bern, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Duehrkop
authors.affiliation: Department of Clinical Research, University of Bern, Murtenstrasse 50, P.O. Box 44, CH-3010 Bern, Switzerland. Electronic address: robert.rieben@dkf.unibe.ch.
authors.forename: Robert
authors.initials: R
authors.lastname: Rieben
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002986:Clinical Trials as Topic; D003169:Complement Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D007705:Kinins / Q000037:antagonists & inhibitors / Q000276:immunology; D015427:Reperfusion Injury / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D007705:Kinins; D003165:Complement System Proteins; D013925:Thromboplastin
keywords: Complement system; Ischemia/reperfusion injury; Plasma cascade systems; Therapy