title: Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction.
abstract: The pathophysiology of ischemic myocardial injury involves cellular events, reactive oxygen species, and an inflammatory reaction cascade. The zinc complex of acetylsalicylic acid (Zn(ASA)2) has been found to possess higher anti-inflammatory and lower ulcerogenic activities than acetylsalicylic acid (ASA). Herein, we studied the effects of both ASA and Zn(ASA)2 against acute myocardial ischemia. Rats were pretreated with ASA (75 mg/kg) or Zn(ASA)2 (100 mg/kg) orally for five consecutive days. Isoproterenol (85 mg/kg, subcutaneously [s.c.]) was applied to produce myocardial infarction. After 17-22 h, animals were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally [i.p.]) and both electrical and mechanical parameters of cardiac function were evaluated in vivo. Myocardial histological and gene expression analyses were performed. In isoproterenol-treated rats, Zn(ASA)2 treatment normalized significantly impaired left-ventricular contractility index (Emax 2.6 ± 0.7 mmHg/µL vs. 4.6 ± 0.5 mmHg/µL, P < 0.05), increased stroke volume (30 ± 3 µL vs. 50 ± 6 µL, P < 0.05), decreased systemic vascular resistance (7.2 ± 0.7 mmHg/min/mL vs. 4.2 ± 0.5 mmHg/min/mL, P < 0.05) and reduced inflammatory infiltrate into the myocardial tissues. ECG revealed a restoration of elevated ST-segment (0.21 ± 0.03 mV vs. 0.09 ± 0.02 mV, P < 0.05) and prolonged QT-interval (79.2 ± 3.2 ms vs. 69.5 ± 2.5 ms, P < 0.05) by Zn(ASA)2. ASA treatment did not result in an improvement of these parameters. Additionally, Zn(ASA)2 significantly increased the mRNA-expression of superoxide dismutase 1 (+73 ± 15%), glutathione peroxidase 4 (+44 ± 12%), and transforming growth factor (TGF)-β1 (+102 ± 22%). In conclusion, our data demonstrate that oral administration of zinc and ASA in the form of bis(aspirinato)zinc(II) complex is superior to ASA in preventing electrical, mechanical, and histological changes after acute myocardial ischemia. The induction of antioxidant enzymes and the anti-inflammatory cytokine TGF-β1 may play a pivotal role in the mechanism of action of Zn(ASA)2.
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Sevil
authors: S
authors: Korkmaz
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Ayhan
authors: A
authors: Atmanli
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Shiliang
authors: S
authors: Li
authors: Heart Center, Semmelweis University, 1122 Budapest, Hungary.
authors: Tamás
authors: T
authors: Radovits
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany Heart Center, Semmelweis University, 1122 Budapest, Hungary.
authors: Peter
authors: P
authors: Hegedűs
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany Heart Center, Semmelweis University, 1122 Budapest, Hungary korkmaz@uni-heidelberg.de.
authors: Enikő
authors: E
authors: Barnucz
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Kristóf
authors: K
authors: Hirschberg
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Sivakkanan
authors: S
authors: Loganathan
authors: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 607-8414 Kyoto, Japan.
authors: Yutaka
authors: Y
authors: Yoshikawa
authors: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 607-8414 Kyoto, Japan.
authors: Hiroyuki
authors: H
authors: Yasui
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Matthias
authors: M
authors: Karck
authors: Department of Cardiac Surgery, University of Heidelberg, 69120 Heidelberg, Germany.
authors: Gábor
authors: G
authors: Szabó
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D056831:Coordination Complexes / Q000008:administration & dosage*; D004562:Electrocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000139:chemically induced / Q000150:complications / Q000473:pathology; D017202:Myocardial Ischemia / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020107:Troponin T / Q000097:blood; D015032:Zinc / Q000008:administration & dosage
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D056831:Coordination Complexes; D020107:Troponin T; C000606758:bis(aspirinato)zinc(II); D015032:Zinc; D007545:Isoproterenol; D001241:Aspirin
keywords: Myocardial ischemia; acetylsalicylic acid; antioxidant; cardiac function; isoproterenol; zinc complex of acetylsalicylic acid