Accession Number : ADA336783

Title :   Prevention of Membrane Depolarization of Shock

Descriptive Note : Final rept 1 Feb 94-30 Jun 96

Corporate Author : MARYLAND UNIV BALTIMORE

Personal Author(s) : Gann, Donald S.

PDF Url : ADA336783

Report Date : JUL 1996

Pagination or Media Count : 30

Abstract : Severe hemorrhage is associated with increased intracellular accumulation of sodium and water, reflecting membrane depolarization i.e. decreased activity of the sodium pump. Since others have described normal or increased ATP during this depolarization, we hypothesize that Na/K ATPase is inhibited in shock. Since the defect is seen in red blood cells, a circulating factor appears to be involved. We have identified this factor as the 33amino acid C-terminal fragment of Plasminogen Activator Inhibitor type-1 (PAI-1) generated by the cleavage of PAI-1 at its Arg-Met active center by plasminogen activators. Synthetic 33aa fragment causes dose-dependent inhibition of Na/K ATPase in membrane vesicles. (We call the fragment Sodium Pump Inhibiting Peptide, SPIP). We have measured SPIP in the plasma of rats in hemorrhagic shock and have found the apparent concentration to be sufficient to inhibit completely membrane Na/K ATPase (compared to ouabain). We conclude that hemorrhage elevates a form of PAI-1 that is bound and cleaved by plasminogen activators producing SPIP. SPIP, in turn, inhibits membrane Na/K ATPase producing cell depolarization and increased cell sodium and water, contributing to the development of hemorrhagic shock.

Descriptors :   *DEPOLARIZATION, *HEMORRHAGIC SHOCK, RATS, WATER, SODIUM, MEMBRANES, ERYTHROCYTES, CELLS(BIOLOGY), CIRCULATION, POTASSIUM, AMINO ACIDS, BLOOD PLASMA, PEPTIDE HYDROLASES, PLASMIN.

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE