Effect of septic serum on vascular smooth muscle: in vitro studies using rat aortic rings.
METHODS
Septic shock in humans is characterized by hypotension, low systemic vascular resistance, and high cardiac output. We hypothesized that circulating vasodilatory substances are, in part, responsible for this low systemic vascular resistance. To investigate this possibility, we exposed isolated rat aortic rings to sera from patients with septic shock and to sera from dogs made septic by intraperitoneal implantation of infected clots. Isolated rings from rat thoracic aortas were mounted on hooks in chambers filled with modified Krebs' buffer and bubbled with 95% oxygen/5% CO2. After documentation of functional endothelium, the rings were precontracted with norepinephrine. Serum was then added and ring tension measured continuously over the next 20 mins.


RESULTS
Sera from normal humans increased ring tension by 6% (60 +/- 39 [SEM] mg tension/mg ring). Sera from nine patients with septic shock decreased tension by 30% (350 +/- 42 mg tension/mg ring; p less than .001). In response to sera from control dogs, tension increased by 16% (122 +/- 37 mg tension/mg ring). In contrast, septic dog sera caused tension to decrease by 36% (278 +/- 38 mg tension/mg ring;p less than .001). Vasodilation was unaffected when the septic patient and dog sera were dialyzed to remove molecules less than 10,000 molecular weight. Chemical deendothelialization with sodium deoxycholate also did not affect the vasodilatory response to septic patient or dog sera.


CONCLUSIONS
Septic sera can relax rat aortic smooth muscle. Dialyzing to exclude the effects of small molecules and removing the endothelium did not eliminate this vasodilatory response. These data suggest the presence in septic serum of circulating substances capable of relaxing vascular smooth muscle that may play an important role in the pathogenesis of the cardiovascular abnormalities in septic shock.
Hollenberg
S M
SM
Critical Care Medicine Department, National Institutes of Health, Bethesda, MD 20892.
Cunnion
R E
RE
Parrillo
J E
JE
D000818:Animals; D001013:Aorta, Thoracic; D004285:Dogs; D004730:Endothelium, Vascular; D006801:Humans; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000097:blood*; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000097:blood / Q000494:pharmacology*
D014665:Vasodilator Agents; D009638:Norepinephrine