Altered Calcium Homeostasis and Membrane Integrity in Myocardial Cell Injury

  • L. Maximilian Buja
  • Karen P. Burton
  • Kenneth R. Chien
  • James T. Willerson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 232)


Coronary occlusion leads to contractile arrest of ischemic myocardium and progressive metabolic derangements and ultrastructural alterations, which if of sufficient duration and severity, lead to irreversible myocardial injury. Based on a number of experimental observations, we and others have put forward the following general hypothesis regarding the pathogenesis of irreversible myocardial injury1,2. Myocardial ischemia causes oxygen deprivation which leads to depressed energy metabolism resulting in a reduced ATP level, increased lactate, and decreased pH. The metabolic changes are followed by discrete alterations in energy dependent membrane transport systems which lead to altered ionic composition of the cell, including an increase in cytosolic calcium. These membrane alterations may include altered ionic flux across the sarcolemma as well as release of calcium from mitochondria and sarcoplasmic reticulum. The elevated cytosolic calcium concentration has the potential to activate catabolic enzymes, including phospholipases. This may lead to acceleration phosphlipid degradation, increased membrane permeability, and further electrolyte derangements, including calcium accumulation. The excess cellular calcium load may also lead to ATP depletion by activation of calcium-dependent ATPases as well as by mitochondrial calcium accumulation which occurs at the expense of continued energy production. Thereafter, a vicious cycle of membrane injury and ATP depletion may ensue which terminates in irreversible cell injury. Observations pertinent to this hypothesis are reviewed in this chapter.


Coronary Occlusion Total Phospholipid Calcium Overload Membrane Injury Irreversible Injury 
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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • L. Maximilian Buja
    • 1
  • Karen P. Burton
    • 1
  • Kenneth R. Chien
    • 1
  • James T. Willerson
    • 1
  1. 1.Departments of Pathology, Physiology, and Internal Medicine (Cardiology Division)The University of Texas Health Science Center at DallasDallasUSA

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