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Research Article Free access | 10.1172/JCI108888

Lanthanum Probe Studies of Cellular Pathophysiology Induced by Hypoxia in Isolated Cardiac Muscle

Karen P. Burton, Herbert K. Hagler, Gordon H. Templeton, James T. Willerson, and L. Maximilian Buja

Department of Pathology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Physiology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Find articles by Burton, K. in: PubMed | Google Scholar

Department of Pathology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Physiology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Find articles by Hagler, H. in: PubMed | Google Scholar

Department of Pathology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Physiology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Find articles by Templeton, G. in: PubMed | Google Scholar

Department of Pathology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Physiology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Find articles by Willerson, J. in: PubMed | Google Scholar

Department of Pathology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Physiology, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Department of Internal Medicine, Southwestern Medical School, University of Texas Health Science Center at Dallas, Dallas, Texas 75235

Find articles by Buja, L. in: PubMed | Google Scholar

Published December 1, 1977 - More info

Published in Volume 60, Issue 6 on December 1, 1977
J Clin Invest. 1977;60(6):1289–1302. https://doi.org/10.1172/JCI108888.
© 1977 The American Society for Clinical Investigation
Published December 1, 1977 - Version history
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Abstract

This study was undertaken to evaluate directly the relationship between evolution of irreversible myocardial injury induced by hypoxia in an isolated papillary muscle preparation and the development of pathophysiological alterations related to severely impaired membrane function. An ionic lanthanum probe technique was employed as a cytochemical marker to monitor the progression of cellular injury, and data from this cytologic technique were correlated with ultrastructure and measurements of contractile parameters in a total of 67 muscles subjected to control conditions or to graded intervals of hypoxia with or without reoxygenation. Marked depression of developed tension and rate of tension development occurred after 30 min of hypoxia. Contractile function showed significant recovery with reoxygenation after 1 h and 15 min of hypoxia but remained depressed when reoxygenation was provided after 2 or 3 h of hypoxia. Examination by transmission and analytical electron microscopy (energy dispersive X-ray microanalysis) revealed lanthanum deposition only in extracellular regions of control muscles and muscles subjected to 30 min of hypoxia. After hypoxic intervals of over 1 h, abnormal intracytoplasmic and intramitochondrial localization of lanthanum were detected. After 1 h and 15 min of hypoxia, abnormal intracellular lanthanum accumulation was associated with only minimal ultrastructural evidence of injury; muscle provided reoxygenation after 1 h and 15 min of hypoxia showed improved ultrastructure and did not exhibit intracellular lanthanum deposits upon exposure to lanthanum during the reoxygenation period. After 2 to 3 h of hypoxia, abnormal intracellular lanthanum accumulation was associated with ultrastructural evidence of severe muscle injury which persisted after reoxygenation. Thus, the data support the conclusion that cellular and membrane alterations responsible for abnormal intracellular lanthanum deposition precede the development of irreversible injury but evolve at a transitional stage in the progression from reversible to irreversible injury induced by hypoxia in isolated feline papillary muscles.

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