Intraperitoneal, but not enteric, adenosine administration improves survival after volume-controlled hemorrhagic shock in rats

Objective: To circumvent the potential adverse systemic side effects of ade nosine, this study explored the potential benefit of intraperitoneal or ent eric adenosine on survival and inflammatory responses after volume-controll ed hemorrhagic shock. Design: Prospective, randomized, and blinded. A three-phase, volume-control led hemorrhagic shock model was used: hemorrhagic shock phase (120 mins), r esuscitation phase (60 mins), and observation phase (72 hrs), Three groups were compared: controls, intraperitoneal adenosine, and enteric adenosine. Setting: Animal research facility. Subjects: Male Sprague-Dawley rats. Interventions, Starting at 20 mins of hemorrhagic shock and continuing thro ugh the resuscitation phase, all three groups received both intraperitoneal lavage and repeated bolus injections into the ileum of vehicle (normal sal ine) or adenosine. In the intraperitoneal adenosine group (n = 10), adenosi ne solution (0.1 mM) was used for intraperitoneal lavage. In the enteric ad enosine group (n = 10), adenosine (1.0 mM) was injected into the ileum. Blo od cytokine concentrations and leukocyte infiltration in lungs and liver we re studied in 12 separate rats (control and intraperitoneal adenosine, n = 6 each) with the same hemorrhagic shock model at resuscitation time 1 hr or 4 hrs. Measurements and Main Results: Mean arterial pressure and heart rate were s imilar between the three groups during hemorrhagic shock and resuscitation. Potassium, lactate, and blood urea nitrogen concentrations were lower and arterial pH was higher in the intraperitoneal and enteric adenosine groups compared with the control group (both p < .05). Survival time to 72 hrs was longer in the intraperitoneal adenosine group than in the control group (p < .05). Neither plasma interleukin-1 beta interleukin-6, interleukin-10, a nd tumor necrosis factor-a concentrations nor leukocyte infiltration in the lungs and liver was different between the control and intraperitoneal aden osine groups. Conclusions: The administration of adenosine via the intraperitoneal route improves survival time after severe volume-controlled hemorrhagic shock in rats without worsening hypotension or bradycardia. This beneficial effect m ay not be attributable to effects of adenosine on the inflammatory response .