Effect of dopexamine on intestinal tissue concentrations of high-energy phosphates and intestinal release of purine compounds in endotoxemic rats.
OBJECTIVE
To determine the effect of dopexamine, a synthetic catecholamine ligand for dopaminergic and beta2-adrenergic receptors, on intestinal release of adenosine 5'-triphosphate (ATP) degradation products and on intestinal tissue concentrations of high-energy phosphates during endotoxemia.


METHODS
Randomized, controlled trial.


METHODS
Experimental laboratory.


METHODS
Twenty-one male Wistar rats.


METHODS
Rats given endotoxin (Escherichia coli lipopolysaccharide [LPS]; 1.5 mg/kg i.v. over 60 mins) were treated with a continuous infusion of dopexamine (DPX; 2.5 microg/kg/min, n = 7, group LPS + DPX) or 0.9% saline (n = 7, group LPS) during a study period of 120 mins. Animals in the control group (n = 7) received a volume-equivalent infusion of 0.9% saline without endotoxin.


RESULTS
In all groups, arterial and portal venous concentrations of adenosine, hypoxanthine, and uric acid were measured at baseline and at 60 and 120 mins after the endotoxin challenge, and we calculated the portal venous/arterial concentration differences as an indicator of the intestinal release of the purine compounds. Furthermore, at the end of the study, the intestinal tissue concentrations of the high-energy phosphates ATP, adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), creatine phosphate, and adenosine were determined, and we calculated the adenine nucleotide pool, the ATP/ADP and AMP/adenosine ratios, and the adenylate energy charge of the intestinal tissue. Endotoxemia decreases intestinal tissue ATP, ADP, AMP, and creatine phosphate concentrations, increases tissue adenosine content, and increases the release of hypoxanthine and uric acid from the intestinal tract. Dopexamine attenuates the endotoxin-induced decrease of the intestinal tissue adenine nucleotide pool, the AMP/adenosine ratio, and the release of the ATP-degradation products hypoxanthine and uric acid from the intestinal tract.


CONCLUSIONS
Normotensive endotoxemia is associated with a deterioration of the intestinal energy balance and an increased release of ATP degradation products, indicating intestinal tissue ischemia. Furthermore, these results suggest the beneficial effects of dopexamine on pathophysiologic alterations of the intestinal energy metabolism during endotoxemia.
Schmidt
H
H
Department of Anesthesiology, University of Heidelberg, Germany.
Weigand
M A
MA
Schmidt
W
W
Plaschke
K
K
Martin
E
E
Bardenheuer
H J
HJ
D000241:Adenosine / Q000378:metabolism*; D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019446:Endotoxemia / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D010725:Phosphocreatine / Q000378:metabolism*; D011687:Purines / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D011687:Purines; D010725:Phosphocreatine; C046318:dopexamine; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; D004298:Dopamine