The Relationship of Circulating Endogenous Endotoxin to Hemorrhagic Shock in the Baboon

Abstract

Experiments were carried out to test the hypothesis that during hemorrhagic shock endotoxin enters the circulation from ischemic bowel by way of the portal venous system and is then associated with irreversibility of the hemorrhagic shock state. After placement of sampling catheters in the portal vein, right atrium, and aorta, 14 awake, restrained baboons were subjected to 1 hour of hemorrhagic shock at a mean arterial pressure (MAP) of 60 torr followed by a second hour at 40 torr MAP. Six animals were resuscitated with Ringers lactate and their shed blood; 8 were maintained hypotensive until death. Serial blood samples were analyzed for the presence of endotoxin. Endotoxemia was found infrequently, with no greater incidence (p > 0.6) in portal venous samples than in systemic blood, so these data were pooled for further analysis. Furthermore, endotoxemia was no more frequent (p > 0.6) late in shock than it was in early shock or during the baseline period. Autopsy showed no evidence of ischemic damage to the splanchnic viscera. It was concluded that spontaneous endogenous entotoxemia is not a common feature of hemorrhagic shock in baboons and is not related to the duration or degree of severity of hemorrhagic shock in this subhuman primate species.

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“…Several studies have suggested that many of the inflammatory changes resulting from traumatic injury are secondary to increased gut permeability (34,49,59), and subsequent release and recognition of gut-derived LPS due to bacterial translocation (11,16,21). This concept of physiological stress resulting in impaired gut barrier function and subsequent translocation of bacteria/endotoxin into the systemic circulation and remote organs has been termed the "gut hypothesis" (7).…”

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“…The intestine is highly sensitive to ischemia-reperfusion injury and experiences a marked reduction in blood flow during circulatory shock, due to a disproportionate constriction of the splanchnic circulation. Several studies have proposed that many of the inflammatory changes characteristic of cannulation or hemorrhagic shock are secondary to the release and recognition of gut-derived immunostimulants such as LPS, or following bacterial translocation due to increased intestinal permeability (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Nonetheless, both animal (24) and clinical (25)(26)(27) studies have failed to implicate LPS or bacterial translocation in this process.…”

“…This model structure was tantamount to a hypothesis for which there is both assenting and dissenting evidence (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). One goal of systems biology is to use mathematical modeling to address such controversies (11).…”

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“…Thus in pregnancy although there is enhanced RES activity, fibrinolytic inhibition ensures that a single dose of endotoxin will cause cortical necrosis [72], In obstructive jaundice there are other predisposing mechanisms [60]. Furthermore RES activity could be reduced in any shock on account of lowered liver perfusion [68] and also by 'endogenous endotoxinaemia' arising from the flora of ischaemic bowel [70,73], Whether the latter observation applies to man is not yet known but it seems unlikely because it has not been found in the baboon [31]. However, there is plenty of scope for the entry of endotoxin from infec tion of the mucous membranes of the respiratory and gastrointestinal tracts.…”