Dopexamine reverses colonic but not gastric mucosal perfusion defects in lethal endotoxin shock.
BACKGROUND
Whilst dopexamine appears to increase overall splanchnic blood flow in postoperative and septic patients, the effects on gastric mucosal perfusion are controversial and based on concomitantly increasing mucosal to arterial PCO(2) gradients (PdCO(2)). We hypothesized that dopexamine alters splanchnic blood flow distribution and metabolism during experimental endotoxin shock and modifies the inflammatory response induced by endotoxin.


METHODS
In an experiment with anaesthetized normovolaemic, normoventilated pigs, 21 animals were randomized into: (i). subacute lethal endotoxin shock for 14 h (n=7 at baseline); (ii). endotoxin shock with dopexamine infusion (aiming to exceed baseline cardiac output, n=7); or (iii). controls (n=7). Regional blood flow and metabolism were monitored.


RESULTS
Endotoxin produced a hypodynamic phase followed by a normo/hyperdynamic, hypotensive phase. Despite increasing systemic blood flow in response to dopexamine, proportional splanchnic blood flow decreased during the hypodynamic phase. Dopexamine gradually decreased fractional coeliac trunk flow, while fractional superior mesenteric arterial flow increased. Dopexamine induced early arterial hyperlactataemia and augmented the gastric PdCO(2) gradient while colonic luminal lactate release and colonic PdCO(2) gradient were reversed. Dopexamine did not modify the inflammatory response as evaluated by arterial IL-1beta and IL-6 concentrations.


CONCLUSIONS
Dopexamine protects colonic, but not gastric mucosal epithelium in experimental endotoxin shock. This may be related to redistribution of blood flow within the splanchnic circulation.
Tenhunen
J J
JJ
Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland. tenhji@anes.upmc.edu
Martikainen
T J
TJ
Uusaro
A
A
Ruokonen
E
E
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects; D003106:Colon / Q000098:blood supply*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019446:Endotoxemia / Q000503:physiopathology; D004731:Endotoxins; D005753:Gastric Mucosa / Q000098:blood supply; D007413:Intestinal Mucosa / Q000098:blood supply; D019344:Lactic Acid / Q000097:blood; D010313:Partial Pressure; D012039:Regional Blood Flow / Q000187:drug effects; D012769:Shock / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D014665:Vasodilator Agents; D002245:Carbon Dioxide; D019344:Lactic Acid; C046318:dopexamine; D004298:Dopamine