The effects of vasoactive drugs on intestinal functional capillary density in endotoxemic rats: intravital video-microscopy analysis.
BACKGROUND
The use of vasoactive drugs to restore arterial blood pressure in patients with septic shock remains a cornerstone of intensive care medicine. However, vasopressors can accentuate the hypoperfusion of the gut during septic shock, allowing bacterial translocation and endotoxemia. In this study, we compared the effects of different vasoactive drugs on intestinal microcirculation and tissue oxygenation, independent of the effects of fluid therapy, in a rat model of endotoxemic shock.


METHODS
Pentobarbital-anesthetized Wistar Kyoto rats were submitted to endotoxemic shock induced by Escherichia coli lipopolysaccharide (2 mg/kg IV). Arterial blood pressure was normalized by a continuous infusion of different vasoactive drugs, including epinephrine, norepinephrine, phenylephrine, dopamine, dobutamine, or a combination of dobutamine and norepinephrine. The functional capillary density (FCD) of the muscular layer of the small intestine was evaluated by intravital video-microscopy. Mesenteric venous blood gases and lactate concentrations were also analyzed.


RESULTS
FCD decreased by approximately 25% to 60% after the IV infusion of epinephrine, norepinephrine, and phenylephrine. Administration of dopamine, dobutamine, and the combination of dobutamine and norepinephrine did not induce significant alterations in gut FCD. In addition, the mesenteric venous lactate concentration increased in the presence of phenylephrine and showed a tendency to increase after the administration of epinephrine and norepinephrine, whereas there was no observable increase after the administration of dopamine, dobutamine, and the combination of dobutamine with norepinephrine.


CONCLUSIONS
This study confirms dissociation of the systemic hemodynamic and microvascular alterations in an experimental model of septic shock. Moreover, the results indicate that the use of dopamine, dobutamine, and dobutamine in combination with norepinephrine yields a protective effect on the microcirculation of the intestinal muscular layer in endotoxemic rats.
Nacul
Flavio E
FE
Laboratory of Cardiovascular Investigation, Oswaldo Cruz Institute, Fiocruz, Brazil.
Guia
Iris L
IL
Lessa
Marcos A
MA
Tibiriçá
Eduardo
E
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D019446:Endotoxemia / Q000503:physiopathology*; D004837:Epinephrine / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000503:physiopathology; D007421:Intestine, Small / Q000098:blood supply*; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D008642:Mesenteric Veins; D008833:Microcirculation / Q000187:drug effects*; D018715:Microscopy, Video; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D012772:Shock, Septic / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D002316:Cardiotonic Agents; D008070:Lipopolysaccharides; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019344:Lactic Acid; D004280:Dobutamine; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine