Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury

Sevil Korkmaz, Eniko Barnucz, Sivakkanan Loganathan, Shiliang Li, Tamás Radovits, Péter Hegedus, Alina Zubarevich, Kristóf Hirschberg, Alexander Weymann, László G. Puskás, Béla Ózsvári, Nóra Faragó, Iván Kanizsai, Gabriella Fábián, Márió Gyuris, Béla Merkely, Matthias Karck, Csaba Szabo, Gábor Szabó

Research output: Contribution to journalArticle

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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. Methods and Results: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24 h 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) 1 h 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, 1 h after reperfusion, decreased left ventricular systolic pressure, dP/dtmax, dP/dtmin 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. (Circ J 2013; 77: 1817 - 1826).

Original languageEnglish (US)
Pages (from-to)1817-1826
Number of pages10
JournalCirculation Journal
Volume77
Issue number7
DOIs
StatePublished - 2013

Fingerprint

Myocardial Reperfusion Injury
Reperfusion
Zinc
Ischemia
Iron
Heart Transplantation
Reperfusion Injury
Myocardial Ischemia
Heart Injuries
Troponin T
Ventricular Pressure
Chelating Agents
Ligation
Coronary Vessels
Myocardium
Theoretical Models
Up-Regulation
Antioxidants
Adenosine Triphosphate
Phosphates

Keywords

  • Antioxidants
  • Ischemia/reperfusion
  • Myocardial infarction
  • Transplantation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury. / Korkmaz, Sevil; Barnucz, Eniko; Loganathan, Sivakkanan; Li, Shiliang; Radovits, Tamás; Hegedus, Péter; Zubarevich, Alina; Hirschberg, Kristóf; Weymann, Alexander; Puskás, László G.; Ózsvári, Béla; Faragó, Nóra; Kanizsai, Iván; Fábián, Gabriella; Gyuris, Márió; Merkely, Béla; Karck, Matthias; Szabo, Csaba; Szabó, Gábor.

In: Circulation Journal, Vol. 77, No. 7, 2013, p. 1817-1826.

Research output: Contribution to journalArticle

Korkmaz, S, Barnucz, E, Loganathan, S, Li, S, Radovits, T, Hegedus, P, Zubarevich, A, Hirschberg, K, Weymann, A, Puskás, LG, Ózsvári, B, Faragó, N, Kanizsai, I, Fábián, G, Gyuris, M, Merkely, B, Karck, M, Szabo, C & Szabó, G 2013, 'Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury', Circulation Journal, vol. 77, no. 7, pp. 1817-1826. https://doi.org/10.1253/circj.CJ-12-1162
Korkmaz, Sevil ; Barnucz, Eniko ; Loganathan, Sivakkanan ; Li, Shiliang ; Radovits, Tamás ; Hegedus, Péter ; Zubarevich, Alina ; Hirschberg, Kristóf ; Weymann, Alexander ; Puskás, László G. ; Ózsvári, Béla ; Faragó, Nóra ; Kanizsai, Iván ; Fábián, Gabriella ; Gyuris, Márió ; Merkely, Béla ; Karck, Matthias ; Szabo, Csaba ; Szabó, Gábor. / Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury. In: Circulation Journal. 2013 ; Vol. 77, No. 7. pp. 1817-1826.
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T1 - Q50, an iron-chelating and zinc-complexing agent, improves cardiac function in rat models of ischemia/reperfusion-induced myocardial injury

AU - Korkmaz, Sevil

AU - Barnucz, Eniko

AU - Loganathan, Sivakkanan

AU - Li, Shiliang

AU - Radovits, Tamás

AU - Hegedus, Péter

AU - Zubarevich, Alina

AU - Hirschberg, Kristóf

AU - Weymann, Alexander

AU - Puskás, László G.

AU - Ózsvári, Béla

AU - Faragó, Nóra

AU - Kanizsai, Iván

AU - Fábián, Gabriella

AU - Gyuris, Márió

AU - Merkely, Béla

AU - Karck, Matthias

AU - Szabo, Csaba

AU - Szabó, Gábor

PY - 2013

Y1 - 2013

N2 - 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. Methods and Results: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24 h 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) 1 h 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, 1 h after reperfusion, decreased left ventricular systolic pressure, dP/dtmax, dP/dtmin 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. (Circ J 2013; 77: 1817 - 1826).

AB - 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. Methods and Results: Rats underwent 45-min myocardial ischemia by left anterior descending coronary artery ligation followed by 24 h 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) 1 h 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, 1 h after reperfusion, decreased left ventricular systolic pressure, dP/dtmax, dP/dtmin 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. (Circ J 2013; 77: 1817 - 1826).

KW - Antioxidants

KW - Ischemia/reperfusion

KW - Myocardial infarction

KW - Transplantation

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