INTERSTITIAL ATP LEVEL AND DEGRADATION IN CONTROL AND POSTMYOCARDIAL INFARCTED RATS

With the aim of estimating interstitial levels and the breakdown proce ss of ATP, cardiac microdialysis was performed in the left ventricular wall of in situ control and postinfarcted as well as of isolated, Lan gendorff-perfused rat hearts. With the use of a bioluminescence techni que for dialysate ATP measurement, the baseline interstitial fluid ATP concentration in in situ hearts was estimated to be 38 +/- 8 nM. Regi onal ischemia induced an early peak increase in interstitial fluid ATP to 373 +/- 73 nM that correlates with the maximal incidence of ventri cular arrhythmias. During continuous infusion of individual adenine nu cleotides (50 mu M ATP, ADP, or AMP), the dialysate samples were analy zed for adenine nucleotides, nucleosides, and bases using HPLC with ul traviolet detection. The patterns of catabolites were consistent with the major pathway of metabolism, that is, sequential dephosphorylation catalyzed by a chain of separate ecto-nucleotidases. In in situ posti nfarcted hearts as well as in perfused hearts, a reduced catabolism ra te of extracellular adenine nucleotides was observed. In conclusion, i n in situ rat hearts, ATP can be released in substantial amounts in th e interstitium where it readily undergoes enzymatic degradation. Depho sphorylation occurs sequentially and faster in in situ control hearts than in in situ postinfarcted or in perfused hearts.