Intermittent high altitude hypoxia protects the heart against lethal Ca2+ overload injury.

Abstract

Adaptation to intermittent high altitude (IHA) hypoxia can protect the heart against ischemia-reperfusion injury. In view of the fact that both Ca2+ paradox and ischemia-reperfusion injury are associated with the intracellular Ca2+ overload, we tested the hypothesis that IHA hypoxia may protect hearts against Ca2+ paradox-induced lethal injury if its cardioprotection bases on preventing the development of intracellular Ca2+ overload. Langendorff-perfused hearts from normoxic and IHA hypoxic rats were subjected to Ca2+ paradox (5 min of Ca2+ depletion followed by 30 min of Ca2+ repletion) and the functional, biochemical and pathological changes were investigated. The Ca2+ paradox incapacitated the contractility of the normoxic hearts, whereas the IHA hypoxic hearts significantly preserved contractile activity. Furthermore, the normoxic hearts subjected to Ca2+ paradox exhibited a marked reduction in coronary flow, increase in lactate dehydrogenase release, and severe myocyte damage. In contrast, these changes were significantly prevented in IHA hypoxic hearts. We, then, tested and confirmed our hypothesis that the protective mechanisms are mediated by mitochondria ATP-sensitive potassium channels (mitoKATP) and Ca2+/calmodulin-dependent protein kinase II (CaMKII), as the protective effect of IHA hypoxia was abolished by 5-hydroxydecanoate, a selective mitoKATP blocker, and significantly attenuated by KN-93, a CaMKII inhibitor. In conclusion, our studies offer for the first time that IHA hypoxia confers cardioprotection against the lethal injury of Ca2+ paradox and give biochemical evidence for the protective mechanism of IHA hypoxia. We propose that researches in this area may lead a preventive regimen against myocardial injury associated with Ca2+ overload.

• Authors: Yan Xie, Wei-Zhong Zhu, Yi Zhu, Le Chen, Zhao-Nian Zhou, Huang-Tian Yang
• Journal: Life sciences (Life Sci) Vol. 76 Issue 5 Pg. 559-72 (Dec 17 2004) ISSN: 0024-3205 [Print] Netherlands
• PMID: 15556168 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Potassium Channels
• L-Lactate Dehydrogenase
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Calcium-Calmodulin-Dependent Protein Kinases
• Calcium

Topics

• Adaptation, Physiological
• Altitude
• Animals
• Body Weight (physiology)
• Calcium (metabolism)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Calcium-Calmodulin-Dependent Protein Kinases (metabolism)
• Hypoxia (physiopathology)
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (enzymology, metabolism, ultrastructure)
• Organ Size (physiology)
• Potassium Channels (metabolism)
• Rats
• Rats, Sprague-Dawley
• Time Factors
• Ventricular Function, Left (physiology)