Zymosan-induced resistance to endotoxin and hemorrhagic shock

Improved surgical techniques and judicial use of available antibiotics have reduced the number of postoperative complications over the past decade. However, septic and hemorrhagic shock occur all too frequently, and each carries with it an appreciable morbidity and mortality. Endotoxins and hemorrhage are both known to suppress the phagocytic activity of the reticuloendothelial system (RES). On the other hand, zymosan, a yeast (Saccharomyces cerevisiae) cell wall preparation administered intravenously, results in temporary RES hyperplasia and increased phagocytic activity. Dogs were pretreated with zymosan to determine the degree of RES stimulation and protection against endotoxin and hemorrhagic shock attainable. Twenty-five dogs received intravenous zymosan (10 mg/kg) on days 1, 2, and 3. Another 24 dogs served as controls. On day four, one-half the animals in each group received E coli endotoxin (1.5 mg/kg) intravenously. The other animals underwent two hours of hemorrhagic shock at a mean blood pressure of 40 mm Hg. Seventy-two hour survival was as follows: Endotoxin treated, 66.7% (8/12); endotoxin control, 27% (3/11); hemorrhagic treated, 53.3% (8/15); and hemorrhagic control, 28.6% (4/14). Hemodynamic, metabolic, and lysosomal enzyme parameters were evaluated. No zymosan toxicity was observed. These findings suggest that an RES stimulant such as zymosan could be incorporated as preoperative adjunctive therapy to induce resistance to these shock syndromes in the elective surgical patient.