Bolling S F, Bies L E, Bove E L, Gallagher K P
Thoracic Surgery Research Laboratory, University of Michigan Medical School, Ann Arbor.
J Thorac Cardiovasc Surg. 1990 Mar;99(3):469-74.
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.
本研究的目的是确定在全心缺血期间增加心肌腺苷水平是否能改善再灌注后的功能恢复。将成年兔离体心脏用改良的圣托马斯医院心脏停搏液进行心肌保护，使其经历120分钟的轻度低温缺血（34摄氏度）。在缺血期间，通过在心脏停搏液中提供外源性腺苷或用2-脱氧助间型霉素（一种腺苷脱氨酶的非竞争性抑制剂）抑制腺苷降解来增加心肌腺苷水平。研究了四组心脏：（1）对照组（n = 23）——仅使用心脏停搏液；（2）腺苷组（n = 10）——在心脏停搏液中加入200 μmol/L腺苷；（3）2-脱氧助间型霉素组（n = 8）——在心脏停搏液中加入1 μmol/L 2-脱氧助间型霉素；（4）腺苷/2-脱氧助间型霉素联合组（n = 10）。对照组再灌注45分钟后左心室发展压的恢复平均仅为基线值的38%±4%。腺苷组（66%±7%）、2-脱氧助间型霉素组（59%±2%）和腺苷/2-脱氧助间型霉素联合组（75%±2%）的恢复明显更好。舒张末期压力与容积之间关系的斜率用作舒张期僵硬度的指标。再灌注45分钟后，对照组的斜率平均为85±2 mmHg/ml，显著高于腺苷组（31±6）、2-脱氧助间型霉素组（75±5）和腺苷/2-脱氧助间型霉素联合组（58±5）；这表明腺苷增加组的舒张功能更好。在缺血期间，腺苷增加组的腺苷水平显著升高，而所有四组的三磷酸腺苷均同等程度降低，这表明增加心肌腺苷对缺血期间三磷酸腺苷的消耗没有影响。再灌注后，对照组的三磷酸腺苷水平降低，而其他组高于基线值，这表明功能恢复的改善是由于腺苷增加组中腺嘌呤核苷酸储备的加速补充。
