Alterations in cell function with ischemia and shock and their correction
I. H. Chaudry, M. G. Clemens and A. E. Baue
Progressive cell injury occurs with shock and ischemia, beginning with
functional changes in the cell and cell membrane. Membrane transport and
potential decrease, Na+ enters and K+ leaves cells; N+-K+ adenosine
triphosphatase is activated, adenosine triphosphate (ATP) is used, and
mitochondria are stimulated as increased lactate produces acidosis. Energy
and cyclic adenosine monophosphate levels decrease, Ca2+ regulation is
compromised, and nuclear function and protein synthesis are depressed. The
cell swells, and further membrane changes occur with altered hormonal
effects and mitochondrial uncoupling. Finally, lysosomes leak,
intracellular and mitochondria disruption occurs, and the cell is
destroyed. Based on these changes, attempts were made to directly support
cell function during low-flow states. After volume replacement and
vasoactive agents, other modalities, eg, substrates, membrane-stabilizing
solutions, osmotic agents, and energy compounds were used. The use of
ATP-MgCl2 was helpful in many experimental low-flow states, with an
improvement in cell function mediated by micro-circulatory, cell membrane,
or energy-recycling effects. Clinical examples of altered cell and organ
function with ischemia and shock are numerous and play a critical role in
the development of multiple systems failure. The potential for biochemical
support and correction of these problems is now recognized. Benefits have
already been achieved in myocardial preservation during cardiac operations,
kidney preservation for transplantation, and circulatory and metabolic
support of the injured and septic patient.
