Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction

Adam B. Stein, Yiru Guo, Wei Tan, Wen Jian Wu, Xiaoping Zhu, Qianhong Li, Cheng Luo, Buddhadeb Dawn, Tony R. Johnson, Roberto Motterlini, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato) ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24:h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120:h later, underwent a 30-min coronary occlusion followed by 24:h of reperfusion. Pretreatment with CORM-3 24:h prior to coronary occlusion markedly reduced infarct size (24.8% ± 2.9% of the risk region vs. 43.8% ± 4.4% with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72:h after administration of the CO donor (20.4% ± 3.7% of the risk region vs. 41.9% ± 2.5% with inactive CORM-3) but was no longer apparent at 120:h. Both at 24 and 72:h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0% ± 2.9% and 30.3% ± 3.9% of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72:h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72:h in the mouse.

Original languageEnglish (US)
Pages (from-to)127-134
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume38
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

Fingerprint

Carbon Monoxide
Myocardial Infarction
Coronary Occlusion
tricarbonylchloro(glycinato)ruthenium(II)
Ischemic Preconditioning
Reperfusion
Phenotype
Water

Keywords

  • Carbon monoxide-releasing molecules
  • Myocardial infarction
  • Preconditioning

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. / Stein, Adam B.; Guo, Yiru; Tan, Wei; Wu, Wen Jian; Zhu, Xiaoping; Li, Qianhong; Luo, Cheng; Dawn, Buddhadeb; Johnson, Tony R.; Motterlini, Roberto; Bolli, Roberto.

In: Journal of Molecular and Cellular Cardiology, Vol. 38, No. 1, 01.2005, p. 127-134.

Research output: Contribution to journalArticle

Stein, AB, Guo, Y, Tan, W, Wu, WJ, Zhu, X, Li, Q, Luo, C, Dawn, B, Johnson, TR, Motterlini, R & Bolli, R 2005, 'Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction', Journal of Molecular and Cellular Cardiology, vol. 38, no. 1, pp. 127-134. https://doi.org/10.1016/j.yjmcc.2004.10.006
Stein, Adam B. ; Guo, Yiru ; Tan, Wei ; Wu, Wen Jian ; Zhu, Xiaoping ; Li, Qianhong ; Luo, Cheng ; Dawn, Buddhadeb ; Johnson, Tony R. ; Motterlini, Roberto ; Bolli, Roberto. / Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. In: Journal of Molecular and Cellular Cardiology. 2005 ; Vol. 38, No. 1. pp. 127-134.
@article{b035bba29efb4684a48bf2a055247757,
title = "Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction",
abstract = "Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato) ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24:h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120:h later, underwent a 30-min coronary occlusion followed by 24:h of reperfusion. Pretreatment with CORM-3 24:h prior to coronary occlusion markedly reduced infarct size (24.8{\%} ± 2.9{\%} of the risk region vs. 43.8{\%} ± 4.4{\%} with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72:h after administration of the CO donor (20.4{\%} ± 3.7{\%} of the risk region vs. 41.9{\%} ± 2.5{\%} with inactive CORM-3) but was no longer apparent at 120:h. Both at 24 and 72:h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0{\%} ± 2.9{\%} and 30.3{\%} ± 3.9{\%} of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72:h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72:h in the mouse.",
keywords = "Carbon monoxide-releasing molecules, Myocardial infarction, Preconditioning",
author = "Stein, {Adam B.} and Yiru Guo and Wei Tan and Wu, {Wen Jian} and Xiaoping Zhu and Qianhong Li and Cheng Luo and Buddhadeb Dawn and Johnson, {Tony R.} and Roberto Motterlini and Roberto Bolli",
year = "2005",
month = "1",
doi = "10.1016/j.yjmcc.2004.10.006",
language = "English (US)",
volume = "38",
pages = "127--134",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction

AU - Stein, Adam B.

AU - Guo, Yiru

AU - Tan, Wei

AU - Wu, Wen Jian

AU - Zhu, Xiaoping

AU - Li, Qianhong

AU - Luo, Cheng

AU - Dawn, Buddhadeb

AU - Johnson, Tony R.

AU - Motterlini, Roberto

AU - Bolli, Roberto

PY - 2005/1

Y1 - 2005/1

N2 - Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato) ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24:h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120:h later, underwent a 30-min coronary occlusion followed by 24:h of reperfusion. Pretreatment with CORM-3 24:h prior to coronary occlusion markedly reduced infarct size (24.8% ± 2.9% of the risk region vs. 43.8% ± 4.4% with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72:h after administration of the CO donor (20.4% ± 3.7% of the risk region vs. 41.9% ± 2.5% with inactive CORM-3) but was no longer apparent at 120:h. Both at 24 and 72:h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0% ± 2.9% and 30.3% ± 3.9% of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72:h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72:h in the mouse.

AB - Mounting evidence suggests that carbon monoxide (CO) exerts powerful cytoprotective actions. CO-releasing molecules (CORMs) offer an effective means of delivering CO to tissues in vivo. The goal of the present study was to determine whether a water-soluble CORM, tricarbonylchloro(glycinato) ruthenium(II) (CORM-3), induces delayed protection against myocardial infarction 24:h later and to explore the duration of this protection. Mice received a 60-min i.v. infusion of CORM-3 or inactive CORM-3 (which does not release CO) and then, 24, 72, or 120:h later, underwent a 30-min coronary occlusion followed by 24:h of reperfusion. Pretreatment with CORM-3 24:h prior to coronary occlusion markedly reduced infarct size (24.8% ± 2.9% of the risk region vs. 43.8% ± 4.4% with inactive CORM-3). The infarct-sparing effect of CORM-3 was still evident 72:h after administration of the CO donor (20.4% ± 3.7% of the risk region vs. 41.9% ± 2.5% with inactive CORM-3) but was no longer apparent at 120:h. Both at 24 and 72:h, the protective effects of CORM-3 were equivalent to those afforded by the late phase of ischemic preconditioning (PC; 27.0% ± 2.9% and 30.3% ± 3.9% of the risk region, respectively). We conclude that the novel CO-releasing compound, CORM-3, induces delayed protection against myocardial infarction which is similar to that afforded by the late phase of ischemic PC, and that this salubrious effect is sustained for 72:h. To our knowledge, this is the first report that exposure to CO causes the heart to shift to a preconditioned phenotype. In addition, this study provides the first evidence that the cardioprotective actions of ischemic PC persist for 72:h in the mouse.

KW - Carbon monoxide-releasing molecules

KW - Myocardial infarction

KW - Preconditioning

UR - http://www.scopus.com/inward/record.url?scp=19944371683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944371683&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2004.10.006

DO - 10.1016/j.yjmcc.2004.10.006

M3 - Article

VL - 38

SP - 127

EP - 134

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 1

ER -