Sustained depolarization of cell membranes and cellular edema are known to
accompany various forms of circulatory shock and probably contribute to hyp
ovolemia and cellular dysfunction. It has been proposed that a circulating
protein is responsible for these effects. In the present study we have conf
irmed the existence of a circulating depolarizing factor (CDF) in hemorrhag
ic shock, burn shock, sepsis, and cardiopulmonary bypass. Plasma samples fr
om pigs or sheep in shock were quantitatively assayed for depolarizing acti
vity using a microelectrode method on rat diaphragm in vitro. The depolariz
ing effect of CDF in vitro was similar in magnitude to that of shock in sit
u. We conclude that CDF can entirely account for membrane depolarization du
ring shock. The depolarizing effect of CDF was dose-dependent and saturable
; it could be reversed by rinsing the diaphragm with Ringer's or control pl
asma. CDF activity was detectable in plasma within 5 min after a severe sca
ld and gradually increased over the next 25 min. Resuscitation of hemorrhag
ed pigs, but not burned sheep, eliminated plasma CDF activity.