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Myocardial Ischemia and Preconditioning pp 465–480Cite as

Role of Lipid Peroxidation in Myocardial Ischemic Injury

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 6))

Summary

Extensive studies show that myocardial ischemia and reperfusion is associated with increased generation of reactive oxygen species (ROS). However, the contribution of oxidative stress to ischemic injury has not been fully assessed and the mechanisms by which ROS or their secondary products cause myocardial injury and dysfunction remain unclear. Although ROS could affect several cell constituents, unsaturated lipids appear to be their most vulnerable targets, therefore, oxidative injury in the ischemic heart may be, in part, due to the generation of toxic end products of lipid peroxidation. Because they are more stable than their radical precursors, the lipid peroxidation products could amplify oxidative injury and extend the duration of the pathological consequences of increased free radical generation in the heart. These products, particularly the unsaturated aldehydes, are highly toxic and disrupt several myocardial processes, including surface excitability and ATP generation. Moreover, the lipid-derived aldehydes form covalent adducts with phospholipids, proteins and DNA and hence may be responsible for the long-term dysfunction of the post-ischemic heart. Our studies show that global ischemia in isolated perfused rat hearts is associated with the appearance of several proteins with increased immunoreactivity to antibodies raised against protein adducts of 4-hydroxy trans-2-nonenal (HNE) which is the major cytotoxic aldehyde generated during lipid peroxidation. These studies provide unambiguous evidence that ischemia increases myocardial lipid peroxidation. To delineate the contribution of lipid-derived aldehydes to ischemic injury, we examined the biochemical pathways involved in the myocardial metabolism and detoxification of HNE. Our results suggest that aldose reductase, aldehyde dehydrogenase, and glutathione-S-transferases catalyze the major biochemical transformations of HNE in the heart. Because they regulate the effective concentration of aldehydes in the heart, these metabolic pathways are likely to be key determinants of ischemic injury and may represent an integral component of antioxidant defense against secondary products of oxidative stress.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Jewish Cardiowascular Research Centre, University of Louisville, 500 South Floyd Street, 40202, Louisville, Kentucky, USA

    Matthew West, Sanjay Srivastava & Aruni Bhatnagar Ph.D

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  1. Matthew West
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  2. Sanjay Srivastava
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  3. Aruni Bhatnagar Ph.D
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Correspondence to Aruni Bhatnagar Ph.D .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) & Anton Lukas PhD (Associate Professor) (Distinguished Professor and Director) &  (Associate Professor)

  2. Aoto Hospital, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Nobuakira Takeda MD, PhD (Associate Professor) (Associate Professor)

  3. Dept. of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, India

    Manjeet Singh PhD (Professor & Head) (Professor & Head)

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West, M., Srivastava, S., Bhatnagar, A. (2003). Role of Lipid Peroxidation in Myocardial Ischemic Injury. In: Dhalla, N.S., Takeda, N., Singh, M., Lukas, A. (eds) Myocardial Ischemia and Preconditioning. Progress in Experimental Cardiology, vol 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0355-2_32

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