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Cardiovascular Drugs and Therapy

, Volume 22, Issue 6, pp 437–442 | Cite as

A Single Intravenous sTNFR-Fc Administration at the Time of Reperfusion Limits Infarct Size—Implications in Reperfusion Strategies in Man

  • Marie-Claire Toufektsian
  • Vanessa Robbez-Masson
  • Drissa Sanou
  • Marie-Gabrielle Jouan
  • Olivier Ormezzano
  • Joël de Leiris
  • François Boucher
Article

Abstract

Background

Reperfusion of the ischemic myocardium is associated with increased inflammatory processes that can exert deleterious effects and therefore contribute to cardiac dysfunction. The aim of the present study was to verify whether the administration of sTNFR-Fc, a scavenger of the pro-inflammatory cytokine TNF-α, at the time of reperfusion would protect against myocardial infarction and reduce the severity of early mechanical dysfunction.

Methods

Male Wistar rats were subjected to 60 min coronary occlusion followed by reperfusion. A bolus of sTNFR-Fc (10 µg/kg, i.v.) (MI + sTNFR-Fc group) or a placebo (MI group) was injected prior to reperfusion. Cardiac geometry was assessed by echocardiography 1, 3 and 7 days after reperfusion. Eight days after reperfusion, left ventricular (LV) function was evaluated under basal conditions and during an experimental challenge of volume overload. Finally, infarct size was measured after euthanasia.

Results

sTNFR-Fc administration markedly reduced infarct size (P < 0.01) and decreased LV dilation as assessed by the echocardiographic measurement of the LV end diastolic area, 7 days post-MI (P < 0.01). Moreover, LV end-diastolic pressure was significantly preserved by sTNFR-Fc 1 week after myocardial infarction, under basal conditions (P < 0.05) as well as during cardiac overload (P < 0.05).

Conclusion

A single administration of sTNFR-Fc at the time of reperfusion after myocardial infarction is able to limit infarct size and to reduce early LV diastolic dysfunction in rats. These findings suggest that intravenous neutralization of TNF-α during surgical cardiac reperfusion might improve the outcome of myocardial infarction in humans.

Key words

Transient ischemia TNF-α sTNFR-Fc Cardiac dysfunction Remodelling 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Marie-Claire Toufektsian
    • 1
  • Vanessa Robbez-Masson
    • 1
    • 2
  • Drissa Sanou
    • 3
  • Marie-Gabrielle Jouan
    • 1
  • Olivier Ormezzano
    • 4
  • Joël de Leiris
    • 1
  • François Boucher
    • 1
  1. 1.TIMC-PRETA CNRS (UMR 5525), Equipe Coeur & NutritionUniversité de GrenobleGrenobleFrance
  2. 2.UMR 1154 INRAUniversité Paris Sud XIParisFrance
  3. 3.Département de PhysiologieUniversité de OuagadougouOuagadougouBurkina-Faso
  4. 4.Service de CardiologieCHU MichallonGrenobleFrance

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