Augmenting intracellular adenosine improves myocardial recovery.
The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. Isolated adult rabbit hearts were subjected to 120 minutes of mildly hypothermic ischemia (34 degrees C) with modified St. Thomas' Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution or by inhibiting adenosine degradation with 2-deoxycoformycin, a noncompetitive inhibitor of adenosine deaminase. Four groups of hearts were studied: (1) control (n = 23)--cardioplegia alone; (2) adenosine group (n = 10)--adenosine 200 mumol/L added to the cardioplegic solution; (3) 2-deoxycoformycin group (n = 8)--2-deoxycoformycin 1 mumol/L added to the cardioplegic solution; and (4) a combined adenosine/deoxycoformycin group (n = 10). Recovery of developed pressure 45 minutes after reperfusion in the control group averaged only 38% +/- 4% of baseline values. Significantly better recovery was evident in the adenosine (66% +/- 7%), deoxycoformycin (59% +/- 2%), and adenosine/deoxycoformycin (75% +/- 2%) groups. The slope of the relationship between end-diastolic pressure and volume was used as an index of diastolic stiffness. The slope averaged 85 +/- 2 mm Hg/ml in the control group 45 minutes after reperfusion, significantly higher than that in the adenosine (31 +/- 6), deoxycoformycin (75 +/- 5), and adenosine/deoxycoformycin (58 +/- 5) groups; this suggests better diastolic function in the adenosine-augmented groups. During ischemia, adenosine levels were significantly elevated in the adenosine-augmented groups, whereas adenosine triphosphate decreased equally in all four groups, which indicates that augmenting myocardial adenosine had no effect on depletion of adenosine triphosphate during ischemia. After reperfusion, adenosine triphosphate levels were depressed in the control group but increased in the other groups above baseline values, which suggests that improvement in functional recovery was due to accelerated repletion of adenine nucleotide stores in the adenosine-augmented groups.
Bolling
S F
SF
Thoracic Surgery Research Laboratory, University of Michigan Medical School, Ann Arbor.
Bies
L E
LE
Bove
E L
EL
Gallagher
K P
KP
D000241:Adenosine / Q000008:administration & dosage / Q000032:analysis / Q000494:pharmacology*; D058892:Adenosine Deaminase Inhibitors; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001794:Blood Pressure; D002314:Cardioplegic Solutions / Q000008:administration & dosage; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004338:Drug Combinations; D006321:Heart / Q000502:physiology; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000032:analysis*; D015649:Pentostatin / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits
D058892:Adenosine Deaminase Inhibitors; D002314:Cardioplegic Solutions; D004338:Drug Combinations; D015649:Pentostatin; D000255:Adenosine Triphosphate; D000241:Adenosine