Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat.
OBJECTIVE
To test the effects of dobutamine and dopexamine on hepatic portal and sinusoidal blood flow in a model of normodynamic endotoxemia.


METHODS
Randomized, controlled trial.


METHODS
Experimental laboratory.


METHODS
Male Wistar rats (250-350 g).


METHODS
A total of 40 male Wistar rats were randomized into four groups: a control group, which only received Ringer's solution; an endotoxin group, which received a continuous infusion of 2 mg/kg body weight (bw)/hr of endotoxin; a dobutamine group, which received endotoxin and a continuous infusion of dobutamine (3 microg/kg bw/min); and a dopexamine group, which received endotoxin and dopexamine (2 microg/kg bw/min). The experimental period was 120 min.


RESULTS
Mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) were detected. Portal blood flow was measured using an ultrasonic flow probe positioned around the portal vein, and sinusoidal blood flow was detected in the left liver lobe using intravital microscopy. All detected variables remained stable in the control group. In the endotoxin group, HR increased significantly and MAP decreased significantly from 111 +/- 10 mm Hg to 95 +/- 8 mm Hg at 120 mins, whereas CO remained unchanged. Both in the dobutamine and the dopexamine group HR increased and MAP decreased more than in the endotoxin group. CO increased in both groups significantly. Portal blood flow (23 +/- 4 mL/min to 16 +/- 3 mL/min) and sinusoidal blood flow (38.6 +/- 2.5 to 22.8 +/- 1.2 10(3) microm(3)/sec) decreased significantly in the endotoxin group. In the dobutamine and the dopexamine group portal and sinusoidal blood flow remained at baseline values.


CONCLUSIONS
In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow. These preservations of hepatic blood flow during endotoxemia could portend beneficial effects but need to be studied further.
Secchi
A
A
Department of Anaesthesiology, University of Heidelberg, Heidelberg, Germany.
Ortanderl
J M
JM
Schmidt
W
W
Walther
A
A
Gebhard
M M
MM
Martin
E
E
Schmidt
H
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004280:Dobutamine / Q000494:pharmacology / Q000627:therapeutic use*; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D016903:Drug Monitoring; D019446:Endotoxemia / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; C046318:dopexamine; D004280:Dobutamine; D004298:Dopamine