title: Increased susceptibility of the left compared to the right ventricle to remote ischemia/reperfusion injury in human C1-inhibitor-overexpressing transgene mice.
abstract: Acute myocardial injury has been demonstrated as a remote sequela of severe lower torso ischemia-reperfusion (I/R) due to proinflammatory events. In a model of I/R injury, administration of C1 esterase inhibitor (C1-Inh) reduces myocardial necrosis. We investigated the susceptibility of the left (LV) versus right ventricle (RV) and the protective effect of transgenic C1-Inh-overexpressing mice. Two groups of mice (n = 6) underwent a 2-h lower torso ischemia followed by 3 h of reperfusion: transgenic and wild type with sham-operated controls. Animals were then injected with (125)I bovine albumin. Heart was removed and samples from right and left ventricular free wall were harvested, weighted, and radioactivity was determined. Permeability index for wild-type animals in the RV was 0.22 +/- 0.04, compared to 0.17 +/- 0.07 in controls (NS), and in the LV 0.36 +/- 0.08, compared to 0.21 +/- 0.05 in controls (p <.01). The LV showed a significantly higher value compared to the right (0.22 +/- 0.04 vs. 0.36 +/- 0.08, p <.01). No difference was seen in the RV between transgenic and wild-type mice; however, in the LV the values decreased significantly in transgenic animals (p <.015). Thus, remote myocardial injury after lower torso I/R is present in both ventricles; however, the LV seems to be more susceptible as assessed by albumin permeability. Inhibition of the classic complement cascade may be a promising therapeutic approach for myocardial protection in reperfusion injury.
authors.affiliation: Clinic for Cardiovascular Surgery, University Hospital, Zürich, Switzerland. jurg.grunenfelder@chi.usz.ch
authors.forename: Jürg
authors.initials: J
authors.lastname: Grünenfelder
authors.forename: Daniel
authors.initials: D
authors.lastname: Inderbitzin
authors.forename: Gregor
authors.initials: G
authors.lastname: Zünd
authors.forename: Itzhak
authors.initials: I
authors.lastname: Avital
authors.forename: Tobias
authors.initials: T
authors.lastname: Burkhardt
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Marko
authors.initials: M
authors.lastname: Turina
mesh_terms: D000208:Acute Disease; D000418:Albumins / Q000378:metabolism; D000818:Animals; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D003171:Complement Pathway, Classical / Q000502:physiology; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D015843:Serpins / Q000235:genetics*; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000235:genetics; D018497:Ventricular Dysfunction, Right / Q000209:etiology* / Q000235:genetics
chemical_list: D000418:Albumins; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D015843:Serpins