CHANGES IN ADENINE-NUCLEOTIDES DURING HEMORRHAGIC-SHOCK AND REPERFUSION

Certain tissues are known to be susceptible to shock-induced damage: l iver, small bowel mucosa, and small bowel wall. This study was done to assess the changes in adenine nucleotides induced by hemorrhagic shoc k. Male Sprague-Dawley rats (n = 21; 300-350 g) were anesthetized with sodium pentobarbital (50 mg/kg, ip) and mechanically ventilated. The external jugular vein and common carotid artery were cannulated. Lapar otomy was done. Hemorrhagic shock was induced by withdrawing blood int o a heparinized syringe until a mean arterial blood pressure of 40 mm Hg was obtained and was maintained for 30 min by continued withdrawals . Shed blood was then reinfused through the venous catheter. No additi onal fluid was administered. The animals were observed for another 60 min. Throughout the procedure, biopsies were taken of liver and small bowel. The small bowel biopsies were separated into mucosal and wall f ractions. Nucleotides were extracted. ATP, ADP, AMP, adenosine, inosin e, xanthine, and hypoxanthine were measured with gradient HPLC. Cellul ar ATP concentrations decreased significantly during shock (P < 0.05). Liver ATP dropped from 8.93 +/- 0.55 to 2.91 +/- 0.16 mu mol/g dry ti ssue (mean +/- SEM) (33%), small bowel mucosal ATP from 9.40 +/- 1.04 to 3.26 +/- 0.21 (35%), and small bowel wall ATP from 5.47 +/- 0.36 to 2.74 +/- 0.18 (50%). The nucleotide response to shock in small bowel mucosa was closer to that of liver than to that of small bowel wall. A fter reperfusion, ATP levels were partially restored in liver, small b owel mucosa, and small bowel wall, but not to preshock values. All of the metabolites (adenosine, inosine, hypoxanthine, and xanthine) incre ased during shock (P < 0.05), and did not return to preshock levels af ter reperfusion. The abnormalities in ATP and its metabolites, and the ir persistence after reperfusion, suggest a possible mechanism for the production of postshock damage. (C) 1996 Academic Press