ION GRADIENTS AND METABOLIC ENERGY IN ANIMAL TISSUE

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We had earlier shown that the gradients of inorganic ions between the intra and extracellular phases of the cell, and with that the water distribution and electrical potential of the cell can be changed simply by changing to cell's metabolic substrate. An example is the change in resting electrical potential of hepatocytes brought about when the liver metabolizes ethanol (Veech, R.L. et al, Alcoholism, Clin. Exptl. Stud. 18: 1040-1056, 1994). These insights can be extended to the acute treatment of severely injured patients. When a cell is injured by any means, it immediately undergoes a series of stereotyped reactions where it gains sodium and calcium, looses potassium and swells. This reaction occurs because the living cell constitutes a Gibbs-Donnan system in which the gradients of the major inorganic ions are in near equilibrium with the energy of hydrolysis of ATP, the electric potential between the phases and each other (Masuda, T. et al, J.Biol.Chem. 265: 20321-20334, 1990). We have now shown that simple metabolic means may alter the energy of ATP hydrolysis (Kashiwaya, Y. et al, Am. J. Cardiol. 80: 50A-64A, 1997), and with that, restore the normal gradients of inorganic ions in patients with severe injuries or burns. By altering replacement therapy to include metabolic as well as simple volumetric considerations, one should be able to decrease both morbidity and mortality of acute hemorrhage and burns. These concepts will be the topic of a meeting to be held at the Academy of Medicine on Sept 16-18, 1998.