Endotoxin has an indirect vasodilatory effect on isolated human skeletal muscle arterioles.
BACKGROUND
Septic shock and its effects are a major cause of mortality in the intensive care environment. The exact effect and mechanism of endotoxin has yet to be fully described. With a better understanding of this process, better clinical tools could be developed to treat these patients.


OBJECTIVE
Endotoxin has no direct effect on human skeletal muscle microvasculature and requires the release of an endothelial-derived factor to produce the vasodilation seen in gram-negative sepsis.


METHODS
Benchtop research using an isolated arteriole model with controlled exposure to endotoxin.


METHODS
University medical center.


METHODS
First-order arterioles (approximately 150- micro m diameter) were isolated from human cremasteric muscles and pressurized to physiologic levels before exposure to an endotoxin-rich effluent with and without an upstream conduit vessel (superficial epigastric vein). The vasodilatory effect was measured with videomicroscopy and compared with control samples.


METHODS
Mean vessel diameter and percentage of loss in tone.


RESULTS
When compared with controls, the isolated arteriole had no significant response when exposed to endotoxin alone (3.5% change in basal tone). When the endotoxin was allowed to pass over an upstream conduit vessel, the arteriole showed marked dilation (14.2% loss of basal tone).


CONCLUSIONS
This study demonstrates that endotoxin has no direct vasodilatory effect on human skeletal muscle arterioles, but it is the release of an endothelial factor from the upstream conduit vessels that produces the loss of tone in the microvasculature. Further research is ongoing to characterize the factors involved (nuclear factor-kappaB, tumor necrosis factor alpha, and interleuklin 6) for possible clinical intervention (antioxidants, cyclosporine, and nitric oxdide synthase inhibitors).
Campbell
Matthew
M
Department of Surgery, Eastern Virginia Medical School, Norfolk, USA.
Britt
L D
LD
D001160:Arterioles / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology*; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D018482:Muscle, Skeletal / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001427:Bacterial Toxins; D004731:Endotoxins; D014665:Vasodilator Agents; C027952:salmonella toxin