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Updated: Aug 10, 2026
Standardized Hemorrhagic Shock Induction Guided by Cerebral Oximetry and Extended Hemodynamic Monitoring in Pigs
Published on: May 21, 2019
Quantitative assessment of a circulating depolarizing factor in shock
B Button1, R D Baker, R A Vertrees
1Department of Physiology, The University of Texas Medical Branch, Galveston 77555-0801, USA.
Insights
Researchers confirmed a circulating depolarizing factor (CDF) in various shock types. This factor causes cell membrane depolarization and edema, contributing to cellular dysfunction during 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.
Abstract:
Sustained depolarization of cell membranes and cellular edema are known to accompany various forms of circulatory shock and probably contribute to hypovolemia and cellular dysfunction. It has been proposed that a circulating protein is responsible for these effects. In the present study we have confirmed the existence of a circulating depolarizing factor (CDF) in hemorrhagic shock, burn shock, sepsis, and cardiopulmonary bypass. Plasma samples from pigs or sheep in shock were quantitatively assayed for depolarizing activity using a microelectrode method on rat diaphragm in vitro. The depolarizing effect of CDF in vitro was similar in magnitude to that of shock in situ. We conclude that CDF can entirely account for membrane depolarization during shock. The depolarizing effect of CDF was dose-dependent and saturable; it could be reversed by rinsing the diaphragm with Ringer's or control plasma. CDF activity was detectable in plasma within 5 min after a severe scald and gradually increased over the next 25 min. Resuscitation of hemorrhaged pigs, but not burned sheep, eliminated plasma CDF activity.
