Disparate effects of preconditioning and MLA on 5'-NT and adenosine levels during coronary occlusion.
Ischemic preconditioning has been proposed to protect the heart against infarction by increasing 5'-nucleotidase (5'-NT) activities and augmenting adenosine levels during sustained coronary artery occlusion. To test this theory, anesthetized dogs received four 5-min episodes of preconditioning ischemia, pretreatment with the pharmacological "preconditioning mimetic" monophosphoryl lipid A (MLA, 35 micrograms/kg i.v.) or no intervention before coronary artery ligation. At 20 min into occlusion (the crucial time at which myocyte death begins in this model), myocardial samples were obtained for measurement (by high-performance liquid chromatography) of ectosolic and cytosolic 5'-NT activity and adenosine levels. Preconditioning and MLA pretreatment limit infarct size in the canine model by 75 and 50%, respectively. However, only MLA augmented 5'-NT activity [i.e., cytosolic 5'-NT in the ischemic subendocardium was 26 +/- 1, 39 +/- 7, and 26 +/- 6 nmol. mg protein-1. min-1 in preconditioned, MLA, and control groups (P < 0.05), respectively]. Moreover, adenosine levels (in nmol/mg protein) were increased with MLA treatment (2.30 +/- 0.44) but attenuated in preconditioned dogs (1.11 +/- 0.23; P < 0.05) versus controls (1.87 +/- 0.29). Thus 5'-NT and adenosine levels need not be increased beyond control values during sustained occlusion to elicit cardioprotection.
Przyklenk
K
K
Heart Institute, Good Samaritan Hospital, Los Angeles, California, USA.
Hata
K
K
Zhao
L
L
Kloner
R A
RA
Elliott
G T
GT
D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D004734:Energy Metabolism; D019157:Ischemic Preconditioning, Myocardial; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism
D008050:Lipid A; D010710:Phosphates; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; D000241:Adenosine; C048436:monophosphoryl lipid A