Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury.

Abstract

Myocardial ischemia-reperfusion injury is at least partially mediated by oxygen-derived free radicals. Catalase is a major enzyme involved in the detoxification of hydrogen peroxide. The activity of catalase in the heart is very low, which may be a factor responsible for the high sensitivity of the heart to ischemia-reperfusion injury. The present study was undertaken to determine whether elevation of catalase specifically in the heart of transgenic mice can provide protection against ischemia-reperfusion injury. Hearts isolated from transgenic mice in which catalase in the heart was elevated approximately 60-fold higher than that in nontransgenic heart and from the non-transgenic littermates were subjected to 50 min of warm (37 degrees C) zero-flow ischemia followed by 90 min reflow. Compared with nontransgenic controls, transgenic hearts showed significantly improved recovery of contractile force (75 vs. 25% at the end of 90 min reperfusion, P < 0.01). Efflux of creatine kinase was reduced by approximately 50%, and the zone of myocardial infarction as demarcated by triphenyltetrazolium at the end of reperfusion was reduced by approximately 40% in transgenic hearts compared with nontransgenic controls. These findings support the view that hydrogen peroxide is an important cause of ischemia-reperfusion damage and suggest that protection may be provided by elevation of catalase activity.

• Authors: G Li, Y Chen, J T Saari, Y J Kang
• Journal: The American journal of physiology (Am J Physiol) Vol. 273 Issue 3 Pt 2 Pg. H1090-5 (Sep 1997) ISSN: 0002-9513 [Print] United States
• PMID: 9321793 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Catalase
• Creatine Kinase

Topics

• Animals
• Catalase (biosynthesis, genetics)
• Creatine Kinase (analysis)
• Heart (physiology, physiopathology)
• Heart Rate
• In Vitro Techniques
• Mice
• Mice, Inbred Strains
• Mice, Transgenic
• Myocardial Contraction
• Myocardial Infarction (physiopathology, prevention & control)
• Myocardial Ischemia (physiopathology)
• Myocardial Reperfusion Injury (enzymology, physiopathology, prevention & control)
• Myocardium (enzymology)