ATP PRECURSOR DEPLETION AND POSTISCHEMIC MYOCARDIAL RECOVERY

被引:16
作者
BOLLING, SF
BOVE, EL
GALLAGHER, KP
机构
[1] UNIV MICHIGAN,SCH MED,DEPT SURG,THORAC SURG SECT,THORAC SURG RES LAB,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109
关键词
D O I
10.1016/0022-4804(91)90053-O
中图分类号
R61 [外科手术学];
学科分类号
摘要
Although cardioplegia reduces myocardial metabolism during ischemia, adenosine triphosphate (ATP) depletion occurs, which may contribute to poor functional recovery after reperfusion. Augmenting myocardial adenosine during ischemia is successful in improving ATP repletion and myocardial recovery following ischemia. If adenosine is an important determinant of ischemic tolerance, then depletion or elimination of myocardial adenosine should lead to poor functional and metabolic recovery after ischemia. To test this hypothesis, isolated, perfused rabbit hearts were subjected to 120 min of 34°C ischemia. Hearts received St. Thomas cardioplegia alone or cardioplegia containing 200 μM adenosine, or cardioplegia containing 15, 5, 2.5, or 0.025 μg/ml adenosine deaminase (ADA), which catalyzes the breakdown of adenosine to inosine, making adenosine unavailable as an ATP precursor. Functional recovery was determined and myocardial nucleotide levels were measured before, during, and after ischemia. Following ischemia and reperfusion, control hearts recovered to 51 ± 3% of preischemic developed pressure (DP). There was significantly better recovery in adenosine-augmented hearts (68 ± 7%), while ADA hearts had significantly worse recovery. Hearts treated with 0.025 μg/ml ADA recovered to only 29 ± 5% of DP and higher dose ADA hearts failed to demonstrate any recovery of systolic function. Furthermore, adenosine enhanced metabolic recovery, whereas ADA resulted in greatly depleted ATP and precursor reserves. Postischemic developed pressure closely paralleled the availability of myocardial adenosine, consistent with the hypothesis that myocardial adenosine levels at end ischemia and early reperfusion are important determinants of functional recovery after global ischemia. © 1991.
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页码:629 / 633
页数:5
相关论文
共 15 条
  • [1] ADENOSINE DEAMINASE FROM HUMAN ERYTHROCYTES - PURIFICATION AND EFFECTS OF ADENOSINE-ANALOGS
    AGARWAL, RP
    SAGAR, SM
    PARKS, RE
    [J]. BIOCHEMICAL PHARMACOLOGY, 1975, 24 (06) : 693 - 701
  • [2] TIGHT-BINDING INHIBITORS .4. INHIBITION OF ADENOSINE DEAMINASES BY VARIOUS INHIBITORS
    AGARWAL, RP
    SPECTOR, T
    PARKS, RE
    [J]. BIOCHEMICAL PHARMACOLOGY, 1977, 26 (05) : 359 - 367
  • [3] ROLE OF ADENOSINE IN CORONARY VASODILATION DURING EXERCISE
    BACHE, RJ
    DAI, XZ
    SCHWARTZ, JS
    HOMANS, DC
    [J]. CIRCULATION RESEARCH, 1988, 62 (04) : 846 - 853
  • [4] BOLLING SF, 1990, J THORAC CARDIOV SUR, V99, P469
  • [5] ENHANCED MYOCARDIAL PROTECTION WITH ADENOSINE
    BOLLING, SF
    BIES, LE
    GALLAGHER, KP
    BOVE, EL
    [J]. ANNALS OF THORACIC SURGERY, 1989, 47 (06) : 809 - 815
  • [6] TIGHT-BINDING INHIBITORS .2. NON-STEADY STATE NATURE OF INHIBITION OF MILK XANTHINE-OXIDASE BY ALLOPURINOL AND ALLOXANTHINE AND OF HUMAN ERYTHROCYTIC ADENOSINE DEAMINASE BY COFORMYCIN
    CHA, S
    AGARWAL, RP
    PARKS, RE
    [J]. BIOCHEMICAL PHARMACOLOGY, 1975, 24 (23) : 2187 - 2197
  • [7] ELY SW, 1985, J THORAC CARDIOV SUR, V90, P549
  • [8] HUMPHREY SM, 1982, J THORAC CARDIOV SUR, V84, P16
  • [9] KROLL K, 1989, CIRC RES, V6, P1147
  • [10] PROCTOR KG, 1985, CIRC RES, V59, P474