Universität zu Köln

Goltz, D., Huss, S., Ramadori, E., Buettner, R., Diehl, L. and Meyer, R. (2015). Immunomodulation by splenectomy or by FTY720 protects the heart against ischemia reperfusion injury. Clin. Exp. Pharmacol. Physiol., 42 (11). S. 1168 - 1178. HOBOKEN: WILEY-BLACKWELL. ISSN 1440-1681

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Abstract

The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an inflammatory response in the myocardium undergoing reperfusion. Modulation of this response by splenectomy constitutes an option to protect the heart from MI/R. To mimic the effect of splenectomy in a pharmacological approach, the sphingosine-1-phosphate agonist FTY720 was applied at the onset of reperfusion. In a closed chest model of MI/R, infarct size was assessed by triphenyltetrazolium chloride staining after 1h of ischemia and 24h of reperfusion, and by Masson trichrome staining 21days after reperfusion in splenectomised mice, mice post-conditioned with FTY720 IP (1mg/kg), and controls. In addition, hemodynamic parameters were recorded after 24h and 21days by catheterization. Infarct size, and immune cell invasion of phagocytic monocytes investigated by FACS after 24h of reperfusion were significantly reduced by both splenectomy, and FTY720 treatment. Evaluation after 21days of reperfusion revealed that FTY720 treated animals had an improved hemodynamic outcome compared to placebo treated as well as splenectomised animals. FTY720 treatment reduced cell injury as effectively as splenectomy by lowering the number of phagocytic monocytes invading the myocardium and ameliorated hemodynamic outcome within the first 21days.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goltz, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huss, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ramadori, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diehl, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-389107
DOI:	10.1111/1440-1681.12465
Journal or Publication Title:	Clin. Exp. Pharmacol. Physiol.
Volume:	42
Number:	11
Page Range:	S. 1168 - 1178
Date:	2015
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1440-1681
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MYOCARDIAL-INFARCTION; ISCHEMIA/REPERFUSION INJURY; SPLENIC RESERVOIR; MODULATOR FTY720; SPHINGOSINE-1-PHOSPHATE; MONOCYTES; MICE; SPHINGOSINE; CARDIOPROTECTION; IDENTIFICATION Multiple languages Pharmacology & Pharmacy; Physiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/38910