title: Myocardial stunning and preconditioning: age, species, and model related differences: role of AMP-5'-nucleotidase in myocardial injury and protection.
abstract: Mechanisms of myocardial stunning include myocardial adenosine triphosphate (ATP) depletion, catecholamine release, and oxygen free radical formation. Although the latter is the most widely supported mechanism, levels of 5'-nucleotidase (directs AMP dephosphorylation) are inversely related to functional recovery following ischemia and may also have a role in ischemic injury. Previous studies reveal that 5'-nucleotidase levels increase with age and also vary with species. An inhibitor of this enzyme (alpha, beta methylene adenosine 5'-diphosphate) was effective in maintaining AMP levels in vitro but was ineffective in dogs due to limited permeability. Observed species-specific differences in recovery from myocardial stunning may be related to differences in AMP accumulation and subsequent metabolism. Species showing improved recovery from stunning may accumulate AMP as a result of feedback inhibition of 5'-nucleotidase. Using a model of extreme experimentally-induced ischemia, we found that adenosine treatment allowed full recovery of ventricular function within 30 minutes, probably by entrapping ATP catabolites. Similarly, enhancement of adenosine production by N-diarylalkylpeprazine derivatives has also been shown to be cardioprotective in the setting of global normothermic ischemia. Novel strategies for pharmacological intervention in the ATP catabolic pathway should use animal models involving species that are tolerant to myocardial stunning.
authors: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0532.
authors: A S
authors: AS
authors: Abd-Elfattah
authors: M
authors: M
authors: Ding
authors: A S
authors: AS
authors: Wechsler
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology* / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D004285:Dogs; D009200:Myocardial Contraction / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000503:physiopathology / Q000517:prevention & control; D011817:Rabbits; D051381:Rats; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D015720:5'-Nucleotidase