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Preconditioning by isoflurane retains its protection against ischemia-reperfusion injury in postinfarct remodeled rat hearts


Lucchinetti, E; Jamnicki, M; Fischer, G; Zaugg, M (2008). Preconditioning by isoflurane retains its protection against ischemia-reperfusion injury in postinfarct remodeled rat hearts. Anesthesia and Analgesia, 106(1):17-23.

Abstract

BACKGROUND: Postinfarct remodeling in the heart may affect protective signaling. We tested whether isoflurane preconditioning retains its protection in postinfarct remodeled hearts. METHODS: Myocardial remodeling was induced by ligation of the left anterior descending coronary artery in male Wistar rats. Six weeks later, diseased hearts were mounted on a Langendorff apparatus and exposed to 40 min of ischemia followed by 90 min of reperfusion. Isoflurane preconditioning was induced with 1.5 MAC (2.1 vol%) isoflurane for 15 min. Infarct size was determined using 1% triphenyltetrazolium chloride staining and corroborated with measurements of lactate dehydrogenase (LDH) release into the perfusate. In some experiments, the protein kinase B and mitochondrial ATP-dependent potassium channel inhibitors LY294002 (10 microM) or 5-hydroxydecanoate (100 microM), respectively, were concomitantly added with isoflurane. Cardiac function was recorded. RESULTS: Six weeks after permanent coronary artery ligation, infarct rats exhibited a markedly increased heart weight/body weight index (5.41 +/- 0.64 vs 3.60 +/- 0.59 g/kg, P < 0.0001) confirming remodeling with compensatory hypertrophy. Isoflurane preconditioning decreased LDH release and reduced infarct size from 32% +/- 6% to 2% +/- 2% (P < 0.0001). Concomitant administration of LY294002 or 5-hydroxydecanoate with isoflurane completely abolished this protection. Functional assessment also showed significant protection from postischemic stunning by isoflurane preconditioning in remodeled hearts, which was lost in the presence of both blockers. CONCLUSIONS: Myocardial preconditioning with isoflurane retains its protection against ischemia/reperfusion injury in postinfarct remodeled rat hearts via similar signaling pathways, as previously reported in healthy hearts.

BACKGROUND: Postinfarct remodeling in the heart may affect protective signaling. We tested whether isoflurane preconditioning retains its protection in postinfarct remodeled hearts. METHODS: Myocardial remodeling was induced by ligation of the left anterior descending coronary artery in male Wistar rats. Six weeks later, diseased hearts were mounted on a Langendorff apparatus and exposed to 40 min of ischemia followed by 90 min of reperfusion. Isoflurane preconditioning was induced with 1.5 MAC (2.1 vol%) isoflurane for 15 min. Infarct size was determined using 1% triphenyltetrazolium chloride staining and corroborated with measurements of lactate dehydrogenase (LDH) release into the perfusate. In some experiments, the protein kinase B and mitochondrial ATP-dependent potassium channel inhibitors LY294002 (10 microM) or 5-hydroxydecanoate (100 microM), respectively, were concomitantly added with isoflurane. Cardiac function was recorded. RESULTS: Six weeks after permanent coronary artery ligation, infarct rats exhibited a markedly increased heart weight/body weight index (5.41 +/- 0.64 vs 3.60 +/- 0.59 g/kg, P < 0.0001) confirming remodeling with compensatory hypertrophy. Isoflurane preconditioning decreased LDH release and reduced infarct size from 32% +/- 6% to 2% +/- 2% (P < 0.0001). Concomitant administration of LY294002 or 5-hydroxydecanoate with isoflurane completely abolished this protection. Functional assessment also showed significant protection from postischemic stunning by isoflurane preconditioning in remodeled hearts, which was lost in the presence of both blockers. CONCLUSIONS: Myocardial preconditioning with isoflurane retains its protection against ischemia/reperfusion injury in postinfarct remodeled rat hearts via similar signaling pathways, as previously reported in healthy hearts.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Laboratory Animal Science
04 Faculty of Medicine > University Hospital Zurich > Institute of Anesthesiology
05 Vetsuisse Faculty > Institute of Food Safety and Hygiene
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2008
Deposited On:19 Nov 2008 17:42
Last Modified:05 Apr 2016 12:32
Publisher:Lippincott Wiliams & Wilkins
ISSN:0003-2999
Additional Information:Full text at http://www.anesthesia-analgesia.org/cgi/reprint/106/1/17
Publisher DOI:10.1213/01.ane.0000289527.70545.ed
PubMed ID:18165546
Permanent URL: http://doi.org/10.5167/uzh-4833

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