Interstitial ATP level and degradation in control and postmyocardial infarcted rats.
With the aim of estimating interstitial levels and the breakdown process of ATP, cardiac microdialysis was performed in the left ventricular wall of in situ control and postinfarcted as well as of isolated, Langendorff-perfused rat hearts. With the use of a bioluminescence technique for dialysate ATP measurement, the baseline interstitial fluid ATP concentration in in situ hearts was estimated to be 38 +/- 8 nM. Regional ischemia induced an early peak increase in interstitial fluid ATP to 373 +/- 73 nM that correlates with the maximal incidence of ventricular arrhythmias. During continuous infusion of individual adenine nucleotides (50 microM ATP, ADP, or AMP), the dialysate samples were analyzed for adenine nucleotides, nucleosides, and bases using HPLC with ultraviolet 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 postinfarcted hearts as well as in perfused hearts, a reduced catabolism rate of extracellular adenine nucleotides was observed. In conclusion, in in situ rat hearts, ATP can be released in substantial amounts in the interstitium where it readily undergoes enzymatic degradation. Dephosphorylation occurs sequentially and faster in in situ control hearts than in in situ postinfarcted or in perfused hearts.
Kuzmin
A I
AI
Institute of Experimental Cardiology, National Cardiology Research Center, Moscow 121 552, Russia.
Lakomkin
V L
VL
Kapelko
V I
VI
Vassort
G
G
D000241:Adenosine / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D019271:Hypoxanthine / Q000378:metabolism; D066298:In Vitro Techniques; D007288:Inosine / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D019820:Xanthine / Q000378:metabolism
D019820:Xanthine; D019271:Hypoxanthine; D000249:Adenosine Monophosphate; D007288:Inosine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine