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The Journal of Thoracic and Cardiovascular Surgery, Vol 103, 73-77, Copyright © 1992 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
SF Bolling, DA Olszanski, EL Bove and KF Childs
Depletion of adenosine triphosphate precursors, such as myocardial
adenosine, during global ischemia results in poor postischemic adenosine
triphosphate repletion and functional recovery. Neonatal hearts may be more
resistant to this deleterious effect of ischemia, because they are
characterized by low 5'-nucleotidase activity, which may result in higher
sustained endogenous myocardial adenosine triphosphate precursor levels
during ischemia. Adult hearts, however, have high levels of 5'-nucleotidase
activity leading to depleted precursors during ischemia and poor
postischemic functional recovery. Augmenting myocardial adenosine
exogenously during ischemia in adult hearts has a beneficial effect on
recovery. The present study tested if preservation of nucleotide
precursors, better adenosine triphosphate repletion, and enhanced
postischemic myocardial recovery in adult hearts could be achieved with a
"neonatal" strategy. Therefore 5'- nucleotidase inhibitors were
administered to isolated, perfused adult rabbit hearts subjected to 120
minutes of ischemia (at 34 degrees C) to determine if this improved
functional recovery. Hearts received St. Thomas' Hospital cardioplegic
solution (control hearts) or cardioplegic solution containing
5'-nucleotidase inhibitors: pentoxifylline, thioinosine,
[s-(p-nitrophenyl)-4-thioinosine], or thioinosine's dimethyl sulfoxide
vehicle alone. After ischemia and reperfusion, recovery of systolic
function, diastolic function, and myocardial oxygen consumption was
significantly better with 5'-nucleotidase inhibition. No changes in
coronary flow were noted. We speculate and are pursuing the theory that the
mechanism of 5'-nucleotidase inhibition's favorable action is due to
preventing the catabolism, transport, and loss of nucleotide precursors
during ischemia, maintaining adenosine triphosphate precursor availability.
ARTICLES
Enhanced myocardial protection during global ischemia with 5'- nucleotidase inhibitors
Thoracic Surgery Research Laboratory, University of Michigan Medical School, Ann Arbor.
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