Bolling S F, Bove E L, Gallagher K P
Department of Surgery (Section of Thoracic Surgery), University of Michigan Medical School, Ann Arbor 48109.
J Surg Res. 1991 Jun;50(6):629-33. doi: 10.1016/0022-4804(91)90053-o.
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 degrees C ischemia. Hearts received St. Thomas cardioplegia alone or cardioplegia containing 200 microM adenosine, or cardioplegia containing 15, 5, 2.5, or 0.025 micrograms/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 microgram/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.
尽管心脏停搏液可在缺血期间降低心肌代谢，但仍会发生三磷酸腺苷（ATP）耗竭，这可能导致再灌注后功能恢复不佳。在缺血期间增加心肌腺苷可成功改善缺血后ATP补充及心肌恢复。如果腺苷是缺血耐受的重要决定因素，那么心肌腺苷的耗竭或消除应导致缺血后功能和代谢恢复不良。为验证这一假设，将离体灌注兔心置于34℃缺血120分钟。心脏分别接受单纯圣托马斯心脏停搏液、含200微摩尔腺苷的心脏停搏液、含15、5、2.5或0.025微克/毫升腺苷脱氨酶（ADA）的心脏停搏液，后者可催化腺苷分解为肌苷，使腺苷无法作为ATP前体。在缺血前、缺血期间及缺血后测定心脏功能恢复情况并测量心肌核苷酸水平。缺血及再灌注后，对照心脏恢复至缺血前舒张末压（DP）的51±3%。腺苷增强组心脏恢复情况明显更好（68±7%），而ADA组心脏恢复情况明显更差。用0.025微克/毫升ADA处理的心脏仅恢复至DP的29±5%，更高剂量ADA组心脏未能显示任何收缩功能恢复。此外，腺苷可促进代谢恢复，而ADA导致ATP及前体储备大量耗竭。缺血后舒张末压与心肌腺苷的可利用性密切相关，这与以下假设一致：缺血末期及早期再灌注时的心肌腺苷水平是全心缺血后功能恢复的重要决定因素。
