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 adenosine, this study explored the potential benefit of intraperitoneal or enteric adenosine on survival and inflammatory responses after volume-controlled hemorrhagic shock. Design: Prospective, randomized, and blinded. A three-phase, volume-controlled hemorrhagic shock model was used: hemorrhagic shock phase (120 mins), resuscitation 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 through the resuscitation phase, all three groups received both intraperitoneal lavage and repeated bolus injections into the ileum of vehicle (normal saline) or adenosine. In the intraperitoneal adenosine group (n = 10), adenosine solution (0.1 mM) was used for intraperitoneal lavage. In the enteric adenosine group (n = 10), adenosine (1.0 mM) was injected into the ileum. Blood cytokine concentrations and leukocyte infiltration in lungs and liver were 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 similar 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-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α concentrations nor leukocyte infiltration in the lungs and liver was different between the control and intraperitoneal adenosine 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 may not be attributable to effects of adenosine on the inflammatory response.