Influence of amrinone on intestinal villus blood flow during endotoxemia.
OBJECTIVE
The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase (PDE) inhibitor amrinone on mucosal villus blood flow in a normotensive model of endotoxemia.


METHODS
Twenty-four anesthetized and ventilated rats underwent laparotomy, and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with amrinone pretreatment (40 microg/kg/min, start 30 minutes before LPS infusion) (amrinone group), or infusion of equivalent volumes of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles = VE) were measured 30 minutes before and at 0, 60, and 120 minutes after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and VE.


RESULTS
In this normotensive endotoxemia model, MAP remained stable in the control and the LPS group but significantly decreased in the amrinone group.The endotoxin-induced decrease of V(E) and D(A) of central arterioles of mucosal villi could be attenuated and prevented, respectively. Thus, the endotoxin-induced decrease of mucosal villus blood flow was diminished but not fully restored by amrinone infusion.


CONCLUSIONS
Our results indicate that amrinone during an early stage of sepsis is of limited value. It attenuates mucosal hypoperfusion but contributes to systemic hypotension.
Schmidt
W
W
Department of Anesthesiology, University of Heidelberg, Germany.
Tinelli
M
M
Secchi
A
A
Gebhard
M M
MM
Martin
E
E
Schmidt
H
H
D000676:Amrinone / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D019446:Endotoxemia / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D010726:Phosphodiesterase Inhibitors; D000676:Amrinone