title: Improved right ventricular function after intracoronary administration of a C1 esterase inhibitor in a right heart transplantation model.
abstract: OBJECTIVE
  Myocardial injury from ischemia can be augmented after reperfusion due to proinflammatory events including complement activation, leukocyte adhesion, and release of various chemical mediators. It has been shown that intracoronary administration of a C1 esterase inhibitor (C1 INH) significantly reduces myocardial necrosis in an experimental model of ischemia. Our study addresses the question whether the most susceptible region of the heart for ischemic injury, the right ventricle (RV), can benefit from the protective effects of C1 esterase inhibition after transplantation.
  
  
  METHODS
  To precisely control RV volume in vivo an isovolumic model was used in which the RV volume was regulated using an intracavity high compliance balloon inserted into donor hearts of domestic pigs (34+/-4 kg). After 4 h of ischemia, donor hearts were transplanted into recipient pigs (44+/-4 kg). Treatment groups, each with six animals, consisted of C1 INH treatment or control. After opening the cross clamp, the C1 INH group animals received 20 IU/kg body weight of C1 INH intracoronary over a 5 min period. The control animals received no drug therapy. The hearts were reperfused for 60 min, and thereafter the RV balloon volume was increased in 10 ml increments until RV failure occurred. These measurements were repeated after 120 min of reperfusion.
  
  
  RESULTS
  There was no significant difference in maximal RV developed pressure between the two groups (after 1 h, 35.7+/-5.9 vs. 40.6+/-12.7 mm Hg; after 2 h, 41.5+/-10.7 vs. 46.3+/-15.2 mm Hg; for C1 INH and control animals, respectively). However, the RV could be loaded with a significantly higher volume after both 1 h (60.0+/-20.0 ml (C1 INH) vs. 46.7+/-13.7 ml (control) balloon volume, P<0.05), and 2 h of reperfusion (70.0+/-8.9 ml vs. 60.0+/-6.3 ml; C1 INH and control animals, respectively; P<0.05).
  
  
  CONCLUSIONS
  Intracoronary administration of a C1 INH significantly improves right ventricular function in an experimental transplant model. Thus, inhibition of the classic complement cascade may be a promising therapeutic approach for effective protection of myocardium from reperfusion injury after transplantation.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany. klima@thg-mh.hannover.de
authors.forename: U
authors.initials: U
authors.lastname: Klima
authors.forename: I
authors.initials: I
authors.lastname: Kutschka
authors.forename: G
authors.initials: G
authors.lastname: Warnecke
authors.forename: P
authors.initials: P
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Strüber
authors.forename: M
authors.initials: M
authors.lastname: Kirschfink
authors.forename: A
authors.initials: A
authors.lastname: Haverich
mesh_terms: D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003165:Complement System Proteins / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects*; D007269:Injections, Intra-Arterial; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D016278:Ventricular Function, Right / Q000187:drug effects / Q000502:physiology*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D003174:Complement C1 Inactivator Proteins; D003165:Complement System Proteins; D003402:Creatine Kinase