Alterations in cell function with ischemia and shock and their correction.
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.
D000255:Adenosine Triphosphate / Q000627:therapeutic use; D000818:Animals; D001777:Blood Coagulation; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D008274:Magnesium / Q000627:therapeutic use; D015636:Magnesium Chloride; D008564:Membrane Potentials; D009943:Organophosphorus Compounds / Q000378:metabolism; D012769:Shock / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy
D009943:Organophosphorus Compounds; D015636:Magnesium Chloride; D000255:Adenosine Triphosphate; D008274:Magnesium