Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts.
It has been proposed that administration of adenine nucleotide precursors might accelerate replenishment of myocardial ATP and "free" ADP, thus improving recovery of depressed contractility of postischemic hearts. To test this hypothesis, Langendorff-perfused rabbit hearts were subjected to 20 min of global ischemia and reperfused for 2 h with normal perfusate (n = 8) or perfusate containing 100 mumol/l of the ATP precursors adenosine (n = 8) or 5-amino-4-imidazolecarboxamide riboside (AICAriboside; n = 8). After reperfusion, developed pressure in untreated hearts averaged 70-80% of base line, whereas ATP content was reduced to approximately 70% of preischemic values. AICAriboside administration did not increase tissue ATP levels or contractility. However, in every heart that received adenosine during reperfusion, ATP content increased from a mean value of 65 +/- 4% of base line to 84 +/- 5% at the end of reperfusion (P less than 0.001). Free ADP also increased in adenosine-treated hearts from 40 to 50% of base line at the beginning of reperfusion, to normal levels by 60 min. However, no improvement in contractility was observed in the hearts that received adenosine. These results support the hypothesis that decreased availability of nucleotide precursors is responsible for depressed ATP levels in postischemic hearts; however, reduced ATP and free ADP levels may not be directly responsible for the depressed function of stunned myocardium.
Ambrosio
G
G
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Jacobus
W E
WE
Mitchell
M C
MC
Litt
M R
MR
Becker
L C
LC
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology*
D007093:Imidazoles; D010710:Phosphates; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; C031143:AICA ribonucleotide