Evidence that adenosine contributes to maintenance of hepatosplanchnic blood flow during peritoneal sepsis in rats.
Sepsis induced derangements in hepatosplanchnic perfusion can contribute to organ damage and death. Adenosine, a common and potent metabolic vasodilator, has not been evaluated as a mechanism for maintenance of blood flow during sepsis. We tested the hypothesis that adenosine receptor blockade would cause a decrease in hepatosplanchnic blood flow during intraperitoneal (i.p.) sepsis in the rat. Rats (250-350 g) were catheterized for hemodynamic and blood flow measurements with tracer microspheres. Sepsis was induced with an i.p. injection of cecal material (150 mg/kg in D5W; 5 mL/kg), and baseline measurements were taken 24 h later. Animals then received either the adenosine receptor antagonist 8-PTH (10 mM, 1.5 mL/kg), its vehicle (1.5 mL/kg) or normal saline (1.5 mL/kg), intravenously, and measurements were repeated 1 and 10 min later. There was a significant increase in hepatosplanchnic portal resistance in septic animals given 8-PTH, with no change in mean arterial blood pressure (MAP) or heart rate. Regionally, there was a significant decrease in gastric, small intestinal, cecal, and pancreatic blood flow when compared with vehicle. Adenosine receptor blockade caused a significant reduction in hepatosplanchnic blood flow during sepsis, suggesting that maintenance of splanchnic blood flow during sepsis involves receptor mediated adenosine actions.
Motew
S J
SJ
Department of Surgery, University of Illinois College of Medicine at Chicago 60612, USA.
Mourelatos
M G
MG
Miller
R N
RN
Ferguson
J L
JL
Law
W R
WR
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives*
D058915:Purinergic P1 Receptor Antagonists; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine