Effect of adenosine deaminase inhibitors on the heart's functional and biochemical recovery from ischemia: a study utilizing the isolated rat heart adapted to 31P nuclear magnetic resonance.
The concept of limiting irreversible damage due to ischemic arrest by inhibiting nucleoside breakdown was tested in the isolated perfused rat heart. Functional recovery measurements were combined with continuous high-energy phosphate measurements by means of 31P nuclear magnetic resonance (NMR) and with nucleoside release measurements in the reperfusion period. The adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and 2'-deoxycoformycin (DCF) were given 5 min before ischemia and for the first 5 min of reperfusion. These treated groups were compared with a control, untreated group. These were further compared with a group of hearts arrested with potassium and to a group combining potassium arrest and EHNA. It was found that all treated groups recovered mechanical function significantly better than the untreated group. DCF, K+, and K+ + EHNA slowed ATP decline and resulted in better ATP recovery than untreated or EHNA-treated, and all treatments decreased nucleoside base release. Intracellular pH fell equally in all groups and recovered to preischemic values. Thus, these adenosine deaminase inhibitors improve functional recovery following ischemia, although this improvement was not well correlated with purine losses observed during reperfusion.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology; D003327:Coronary Disease / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D058892:Adenosine Deaminase Inhibitors; D003070:Coformycin; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; D000255:Adenosine Triphosphate; D009700:Nucleoside Deaminases; D000225:Adenine; D011188:Potassium