Quantitative assessment of a circulating depolarizing factor in shock.

Area of Science:

• Physiology
• Biochemistry
• Pathophysiology

Background:

• Cell membrane depolarization and edema are hallmarks of circulatory shock.
• These cellular changes likely contribute to hypovolemia and dysfunction.
• A circulating factor has been hypothesized to mediate these shock-induced effects.

Purpose of the Study:

• To confirm the existence of a circulating depolarizing factor (CDF) in different forms of shock.
• To investigate the role of CDF in causing cell membrane depolarization during shock.

Main Methods:

• Plasma samples from animals in hemorrhagic shock, burn shock, sepsis, and after cardiopulmonary bypass were collected.
• Depolarizing activity was quantified using a microelectrode assay on isolated rat diaphragm.
• In vitro depolarizing effects were compared to in situ shock conditions.

Main Results:

• Circulating depolarizing factor (CDF) activity was confirmed across multiple shock models (hemorrhagic, burn, sepsis, cardiopulmonary bypass).
• In vitro CDF activity mirrored the magnitude of depolarization observed in vivo during shock.
• CDF's depolarizing effect was dose-dependent, saturable, and reversible with Ringer's solution or control plasma.
• CDF emerged rapidly after burn injury and increased over time.
• Resuscitation successfully eliminated CDF in hemorrhaged pigs but not in burned sheep.

Conclusions:

• Circulating depolarizing factor (CDF) is a key mediator of cell membrane depolarization in various forms of circulatory shock.
• CDF can fully account for the observed membrane depolarization during shock states.
• The presence and clearance of CDF may differ based on the type of shock and resuscitation effectiveness.