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 μg/kg iv) 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.