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The Journal of Thoracic and Cardiovascular Surgery, Vol 92, 488-501, Copyright © 1986 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
ER Rosenkranz, F Okamoto, GD Buckberg, J Vinten-Johansen, BS Allen, J Leaf, H Bugyi, H Young and RJ Barnard
This study tests the hypotheses that postischemic adenosine triphosphate
levels are unreliable predictors of functional recovery, myocardial
adenosine triphosphate concentration of less than 2 mumol/gm does not
indicate irreversible damage, mitochondrial adenosine triphosphate
generating capacity can be nearly normal despite low levels of tissue
adenosine triphosphate and the failure to replenish adenosine triphosphate
after ischemia is due to depletion of the adenosine nucleotide pool, which
can be replenished partially by exogenous precursors (e.g.,
5-amino-4-imidazolecarboxamide ribotide [AICAR]). Myocardial adenosine
triphosphate was depleted to less than 2 mumol/gm by either global ischemia
(37 degrees C aortic clamping) or regional ischemia (acute coronary
occlusion). Reperfusion was either with normal blood or with
substrate-enriched blood cardioplegic solution during total vented bypass.
Tissue adenosine triphosphate content and mitochondrial adenosine
triphosphate generating capacity were measured, and functional recovery was
determined by right heart bypass function curves or regional segmental
shortening (ultrasonic crystals). Hearts undergoing 15 minutes of global
ischemia and normal blood reperfusion had impaired functional recovery
(stroke work index = 58 +/- 5%; p less than 0.05 of control) despite
adenosine triphosphate concentration greater than 2 mumol/gm. Transmural
mitochondrial State 3 respiration averaged 83% of control values despite
adenosine triphosphate levels of 1 mumol/gm in hearts undergoing 45 minutes
of 37 degrees C global ischemia and 2 additional hours of aortic clamping
with multidose glutamate-enriched blood cardioplegia. AICAR increased
adenosine triphosphate to 2 mumol/gm (p less than 0.05), but functional
recovery was nearly complete (stroke work index = 94 +/- 2% of control) and
was comparable with and without AICAR. Hearts undergoing 4 hours of
regional ischemia recovered 31 +/- 5% systolic shortening after controlled
reperfusion despite tissue adenosine triphosphate less than 0.5 mmol/gm
(15% of control), and they retained 63% adenosine triphosphate generating
capacity. Postischemic adenosine triphosphate levels correlate poorly with
functional recovery, and adenosine triphosphate levels less than 2 mumol/gm
do not indicate irreversible ischemic injury. Low postischemic levels may
be repleted partially by adenine nucleotide precursor supplementation
(AICAR).(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Biochemical studies: failure of tissue adenosine triphosphate levels to predict recovery of contractile function after controlled reperfusion
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