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Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury Davani, Ehsan Y.; Brumme, Zabrina L.; Singhera, Gurpreet K.; Côté, Hélène C. F.; Harrigan, Paul Richard; Dorscheid, Delbert R.

Abstract

Introduction: Ischemia/reperfusion occurs in myocardial infarction, cardiac dysfunction during sepsis, cardiac transplantation and coronary artery bypass grafting, and results in injury to the myocardium. Although reperfusion injury is related to the nature and duration of ischemia, it is also a separate entity that may jeopardize viable cells and ultimately may impair cardiac performance once ischemia is resolved and the organ heals. Method: The present study was conducted in an ex vivo murine model of myocardial ischemia/reperfusion injury. After 20 min of ischemia, isolated hearts were perfused for up to 2 hours with solution (modified Kreb's) only, solution plus insulin-like growth factor (IGF)-1, or solution plus tumor necrosis factor (TNF)-α. Cardiac contractility was monitored continuously during this period of reperfusion. Results: On the basis of histologic evidence, IGF-1 prevented reperfusion injury as compared with TNF-α; TNF-α increased perivascular interstitial edema and disrupted tissue lattice integrity, whereas IGF-1 maintained myocardial cellular integrity and did not increase edema. Also, there was a significant reduction in detectable creatine phosphokinase in the perfusate from IGF-1 treated hearts. By recording transduced pressures generated during the cardiac cycle, reperfusion with IGF-1 was accompanied by markedly improved cardiac performance as compared with reperfusion with TNF-α or modified Kreb's solution only. The histologic and functional improvement generated by IGF-1 was characterized by maintenance of the ratio of mitochondrial to nuclear DNA within heart tissue. Conclusion: We conclude that IGF-1 protects ischemic myocardium from further reperfusion injury, and that this may involve mitochondria-dependent mechanisms.

Item Metadata

Title
Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury
Creator
Davani, Ehsan Y.; Brumme, Zabrina L.; Singhera, Gurpreet K.; Côté, Hélène C. F.; Harrigan, Paul Richard; Dorscheid, Delbert R.
Contributor
James Hogg iCAPTURE Centre (University of British Columbia)
Publisher
BioMed Central
Date Issued
2003-10-10
Description
Introduction: Ischemia/reperfusion occurs in myocardial infarction, cardiac dysfunction during sepsis, cardiac transplantation and coronary artery bypass grafting, and results in injury to the myocardium. Although reperfusion injury is related to the nature and duration of ischemia, it is also a separate entity that may jeopardize viable cells and ultimately may impair cardiac performance once ischemia is resolved and the organ heals. Method: The present study was conducted in an ex vivo murine model of myocardial ischemia/reperfusion injury. After 20 min of ischemia, isolated hearts were perfused for up to 2 hours with solution (modified Kreb's) only, solution plus insulin-like growth factor (IGF)-1, or solution plus tumor necrosis factor (TNF)-α. Cardiac contractility was monitored continuously during this period of reperfusion. Results: On the basis of histologic evidence, IGF-1 prevented reperfusion injury as compared with TNF-α; TNF-α increased perivascular interstitial edema and disrupted tissue lattice integrity, whereas IGF-1 maintained myocardial cellular integrity and did not increase edema. Also, there was a significant reduction in detectable creatine phosphokinase in the perfusate from IGF-1 treated hearts. By recording transduced pressures generated during the cardiac cycle, reperfusion with IGF-1 was accompanied by markedly improved cardiac performance as compared with reperfusion with TNF-α or modified Kreb's solution only. The histologic and functional improvement generated by IGF-1 was characterized by maintenance of the ratio of mitochondrial to nuclear DNA within heart tissue. Conclusion: We conclude that IGF-1 protects ischemic myocardium from further reperfusion injury, and that this may involve mitochondria-dependent mechanisms.
Subject
Apoptosis; Mitochondrial DNA; Myocardium; Reperfusion injury; Sepsis
Genre
Article
Type
Text
Language
eng
Date Available
2016-01-09
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223215
URI
http://hdl.handle.net/2429/56337
Affiliation
Other UBC; Non UBC; Medicine, Faculty of; Medicine, Department of
Citation
Critical Care. 2003 Oct 10;7(6):R176
Publisher DOI
10.1186/cc2375
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Davani et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)