Effect of nitric oxide on capillary hemodynamics and cell injury in the pancreas during Pseudomonas pneumonia-induced sepsis.
Sepsis-induced nitric oxide (NO) overproduction has been implicated in a redistribution of flow from the pancreas making it vulnerable to ischemic injury in septic shock. To test this hypothesis in a remote injury model of normotensive sepsis, we induced Pseudomonas pneumonia in the rat and used intravital video microscopy (IVVM) of the pancreas to measure functional capillary density, capillary hemodynamics [red blood cell (RBC) velocity, lineal density, and supply rate], and lethal cellular damage (propidium iodine staining) at 6 and 24 h after the induction of pneumonia. With pneumonia, plasma nitrite/nitrate [NO2(-)/NO3(-)(NOx(-))] levels were doubled by 21 h (P < 0.05). To assess the effect of NO overproduction on microvascular perfusion, N6-(1-iminoethyl)-L-lysine (L-NIL) was administered to maintain NOx(-) levels at baseline. Pneumonia did cause a decrease in RBC velocity of 23% by 6 h, but by 24 h RBC velocity and supply rate had increased relative to sham by 22 and 38%, respectively (P < 0.05). L-NIL treatment demonstrated that this increase was due to NO overproduction. With pneumonia, there was no change in functional capillary density and only modest increases in cellular damage. We conclude that, in this normotensive pneumonia model of sepsis, NO overproduction was protective of microvascular perfusion in the pancreas.
Tribl
Barbara
B
Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Canada. barbara.tribl@akh-wien.ac.at
Bateman
Ryon M
RM
Milkovich
Stephanie
S
Sibbald
William J
WJ
Ellis
Christopher G
CG
D000818:Animals; D002196:Capillaries / Q000473:pathology / Q000503:physiopathology; D004396:Coloring Agents; D006439:Hemodynamics; D008297:Male; D008856:Microscopy, Fluorescence; D009569:Nitric Oxide / Q000097:blood*; D010179:Pancreas / Q000098:blood supply*; D018410:Pneumonia, Bacterial / Q000473:pathology* / Q000503:physiopathology*; D011419:Propidium; D011552:Pseudomonas Infections; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling
D004396:Coloring Agents; D009569:Nitric Oxide; D011419:Propidium