title: Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury.
abstract: BACKGROUND
  Reperfusion of ischemic myocardium may contribute to substantial cardiac tissue damage, but the addition of iron chelators, zinc or zinc complexes has been shown to prevent heart from reperfusion injury. We investigated the possible beneficial effects of an iron-chelating and zinc-complexing agent, Q50, in rat models of ischemia/reperfusion (I/R)-induced myocardial infarction and on global reversible myocardial I/R injury after heart transplantation.
  
  
  RESULTS
  Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24h reperfusion. Vehicle or Q50 (10 mg/kg, IV) were given 5 min before reperfusion. In a heart transplantation model, donor rats received vehicle or Q50 (30 mg/kg, IV) 1h before the onset of ischemia. In myocardial infarcted rats, increased left ventricular end-systolic and end-diastolic volumes were significantly decreased by Q50 post treatment as compared with the sham group. Moreover, in I/R rat hearts, the decreased dP/dtmax and load-independent contractility parameters were significantly increased after Q50. However, Q50 treatment did not reduce infarct size or have any effect on increased plasma cardiac troponin-T-levels. In the rat model of heart transplantation, 1h after reperfusion, decreased left ventricular systolic pressure, dP/dt(max), dP/dt(min) and myocardial ATP content were significantly increased and myocardial protein expression of superoxide dismutase-1 was upregulated after Q50 treatment.
  
  
  CONCLUSIONS
  In 2 experimental models of I/R, administration of Q50 improved myocardial function. Its mechanisms of action implicate in part the restoration of myocardial high-energy phosphates and upregulation of antioxidant enzymes.
authors.affiliation: Laboratory of Cardiac Surgery, Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. korkmaz@uni-heidelberg.de
authors.forename: Sevil
authors.initials: S
authors.lastname: Korkmaz
authors.forename: Enikő
authors.initials: E
authors.lastname: Barnucz
authors.forename: Sivakkanan
authors.initials: S
authors.lastname: Loganathan
authors.forename: Shiliang
authors.initials: S
authors.lastname: Li
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
authors.forename: Péter
authors.initials: P
authors.lastname: Hegedus
authors.forename: Alina
authors.initials: A
authors.lastname: Zubarevich
authors.forename: Kristóf
authors.initials: K
authors.lastname: Hirschberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Weymann
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
authors.forename: Béla
authors.initials: B
authors.lastname: Ózsvári
authors.forename: Nóra
authors.initials: N
authors.lastname: Faragó
authors.forename: Iván
authors.initials: I
authors.lastname: Kanizsai
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fábián
authors.forename: Márió
authors.initials: M
authors.lastname: Gyuris
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabó
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D020107:Troponin T / Q000097:blood; D015032:Zinc
chemical_list: D007502:Iron Chelating Agents; D020107:Troponin T; D015032:Zinc