INTRAHEPATOCELLULAR ERYTHROCYTE INCLUSIONS AND INCREASED CALCIUM PRECIPITATION IN CANINE ENDOTOXIC-SHOCK

Aims: To investigate the electron microscopic localization of membrane -bound and exchangeable calcium with specific calcium precipitation te chniques during endotoxic shock in the dog. Methods: Ten pentobarbital anesthetized, mechanically ventilated, and paralyzed dogs were studie d. Sis dogs received 2 mg/kg E.coli endotoxin i.v. followed by a conti nuous 0.9% saline infusion to restore and maintain baseline cardiac fi lling pressures, Four dogs served as time-matched controls, Each exper iment lasted for 3 h, After the completion of study the livers of four endotoxic and two control dogs were fixed by perfusion of 3% glutaral dehyde,ia the portal vein. Liver sections were then prepared for elect ron microscopy and calcium localization studies. Results: Hepatocytes of endotoxic animals completely lost their plasma membrane-bound calci um, The most severely damaged cells showed extensive ''blebbing'' of t he plasma membrane and contained numerous cytoplasmic erythrocyte incl usions, Endotoxin administration also caused excessive calcium precipi tation inside hepatocytes in areas with pronounced sinusoidal damage. Conclusions: In this acute model of fluid-resuscitated endotoxic shock in dogs, the use of specific calcium localization techniques enables the demonstration of disturbances in hepatocellular calcium handling, which appear to be closely related to structural alterations of the he patocyte cell membrane, Erythrocyte uptake by hepatocytes is a previou sly undescribed phenomenon in canine endotoxic shock and may serve as an additional histologic marker of ultrastructural cell (membrane) dam age.