PATTERN OF AMP DEGRADATION IN ISCHEMIC RABBIT LUNG-TISSUE

Because adenine nucleotide catabolites may be important during postisc hemic lung reperfusion, we examined the pathway of adenosine monophosp hate (AMP) degradation in ischemic lung tissue. Once the pattern of de gradation is known, pharmacological interventions can be considered, o ffering new methods of reducing lung reperfusion injury. For this purp ose we used the isolated rabbit lung. Rabbit lungs were flushed in sit u with a modified Krebs Henseleit solution (60 ml/kg). The lungs were removed and stored deflated immersed in saline solution at 37 degrees C. At regular times, biopsies were taken, and adenine nucleotides, nuc leosides, and bases were measured in these biopsies using high perform ance liquid chromatography (HPLC). During lung ischemia, a very signif icant increase of inosine monophosphate (IMP) was found Adenosine leve ls on the other hand did not increase. Hypoxanthine was the major end catabolite of ischemic lung tissue (constituting 92% of the nucleoside and purine base fraction at 4 hours ischemia). To further determine t he pathway of AMP degradation, 400 mM of the adenosine deaminase inhib itor erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA) was added to the lung flush solution. During ischemia, adenosine triphosphate (ATP) breakdo wn was unaltered but adenosine became the major catabolite (2.8 rimes the concentration of hypoxanthine al 4 hours ischemia). These data sug gest that: 1) in rabbit lung tissue, dephosphorlation of AMP to adenos ine is more important than deamination to IMP; 2) hypoxanthine is the major end catabolite of ischemic lung tissue. By inhibiting the enzyme deaminase, reduced hypoxanthine levels and increased adenosine levels were obtained Pharmacological interventions are now available to inte rfere with the formation of adenine nucleosides and bases in ischemic lung tissue. The importance of adenine nucleotide catabolites to posti schemic lung reperfusion injury is discussed.