Response of germfree animals to shock

Many current models of septic shock in conventional (CV) rats utilize cecal ligation and perforation. That germfree (GF) status offered no increased protection in shock, compared with the effect on CV controls, was shown in early studies. Appropriate fluid therapy, however, did increase survival. Our laboratory's efforts to determine the influence of the GF rat's enlarged cecum on its early response to hemorrhagic shock can be summarized as follows. Ten litters of 8 GF rats each were randomly divided into four groups with two animals/group: CV control, GF control, CV cecectomized and GF cecectomized. Littermates were cecectomized at seven weeks and bled at 14 weeks. Under methoxyflurane anesthesia, the rats were cannulated (femoral artery), heparinized, restrained, and allowed to awaken. Blood pressure was maintained at 60 mmHg for 1 hr and at 50 mmHg for 3 hr by adjusting the height of a burette reservoir. In the GF cecectomized rats, 95% (19/20) survived, whereas only 50% (10/20) of the other three categories survived. Cecectomized GF rats required only 3% of their shed blood, whereas, the other three groups needed 10 to 15%. Cecum from the GF rat contains a 5-fold greater quantity of bioactive and vasoactive substances than the cecum of its CV control, and may cause these changes in basic cardiovascular parameters in GF control rats: decreased cardiac output, blood volume, heart weight, and vasoconstriction to epinephrine in mesenteric arterioles, plus increased hemoconcentration and blood viscosity. In cecectomised GF rats, these parameters return to the CV levels and help to protect the animal during the early hypovolemic trauma. Clearly, the rat's cecum produces significant cardiovascular effects that need to be considered when evaluating experimental models for trauma or stress.