A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion

Oliver Dewald, Nikolaos G. Frangogiannis, M. P. Zoerlein, G. D. Duerr, G. Taffet, L. H. Michael, A. Welz, M. L. Entman

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Repetitive brief myocardial ischemia has been implicated in the pathogenesis of the ventricular dysfunction associated with ischemic cardiomyopathy and myocardial hibernation. In this study we examine the effects of repetitive ischemia and reperfusion (I/R) on murine myocardium. Methods: C57/BL6 mice underwent daily 15 min left anterior descending coronary occlusions followed by reperfusion. After 3, 5, 7, 14, 21 and 28 days, echocardiographic studies were performed, and hearts of I/R and sham-operated animals were processed for histological examination. Results: Histological studies showed no evidence of myocardial necrosis in the ischemic region. Quantitative assessment of collagen revealed a marked persistent interstitial deposition of collagen after seven days I/R in the anterior left ventricular wall (sham 4.6 ± 2.0%, I/R 21.5 ± 6.5%, p < 0.05). Echocardiographic studies showed persistent regional anterior wall dysfunction in I/R animals. Histological evaluation showed absence of neovessel formation. After discontinuation of the I/R protocol, fibrosis and regional ventricular dysfunction decreased within 60 days. Conclusions: Repetitive brief murine myocardial I/R induces reversible fibrotic remodeling and ventricular dysfunction, without myocardial infarction and necrosis, and may play a role in the pathogenesis of ischemic cardiomyopathy and myocardial hibernation.

Original languageEnglish (US)
Pages (from-to)305-311
Number of pages7
JournalThoracic and Cardiovascular Surgeon
Volume52
Issue number5
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Cardiomyopathies
Reperfusion
Ischemia
Ventricular Dysfunction
Myocardial Stunning
Myocardial Ischemia
Necrosis
Collagen
Myocardial Reperfusion
Coronary Occlusion
Myocardium
Fibrosis
Myocardial Infarction

Keywords

  • Hibernation
  • Ischemia
  • Myocardium
  • Reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion. / Dewald, Oliver; Frangogiannis, Nikolaos G.; Zoerlein, M. P.; Duerr, G. D.; Taffet, G.; Michael, L. H.; Welz, A.; Entman, M. L.

In: Thoracic and Cardiovascular Surgeon, Vol. 52, No. 5, 10.2004, p. 305-311.

Research output: Contribution to journalArticle

Dewald, O, Frangogiannis, NG, Zoerlein, MP, Duerr, GD, Taffet, G, Michael, LH, Welz, A & Entman, ML 2004, 'A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion', Thoracic and Cardiovascular Surgeon, vol. 52, no. 5, pp. 305-311. https://doi.org/10.1055/s-2004-821153
Dewald, Oliver ; Frangogiannis, Nikolaos G. ; Zoerlein, M. P. ; Duerr, G. D. ; Taffet, G. ; Michael, L. H. ; Welz, A. ; Entman, M. L. / A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion. In: Thoracic and Cardiovascular Surgeon. 2004 ; Vol. 52, No. 5. pp. 305-311.
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abstract = "Background: Repetitive brief myocardial ischemia has been implicated in the pathogenesis of the ventricular dysfunction associated with ischemic cardiomyopathy and myocardial hibernation. In this study we examine the effects of repetitive ischemia and reperfusion (I/R) on murine myocardium. Methods: C57/BL6 mice underwent daily 15 min left anterior descending coronary occlusions followed by reperfusion. After 3, 5, 7, 14, 21 and 28 days, echocardiographic studies were performed, and hearts of I/R and sham-operated animals were processed for histological examination. Results: Histological studies showed no evidence of myocardial necrosis in the ischemic region. Quantitative assessment of collagen revealed a marked persistent interstitial deposition of collagen after seven days I/R in the anterior left ventricular wall (sham 4.6 ± 2.0{\%}, I/R 21.5 ± 6.5{\%}, p < 0.05). Echocardiographic studies showed persistent regional anterior wall dysfunction in I/R animals. Histological evaluation showed absence of neovessel formation. After discontinuation of the I/R protocol, fibrosis and regional ventricular dysfunction decreased within 60 days. Conclusions: Repetitive brief murine myocardial I/R induces reversible fibrotic remodeling and ventricular dysfunction, without myocardial infarction and necrosis, and may play a role in the pathogenesis of ischemic cardiomyopathy and myocardial hibernation.",
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AU - Michael, L. H.

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