Hudspeth D A, Williams M W, Zhao Z Q, Sato H, Nakanishi K, McGee D S, Hammon J W, Vinten-Johansen J, Van Wylen D G
Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1096.
Ann Thorac Surg. 1994 Sep;58(3):719-27. doi: 10.1016/0003-4975(94)90733-1.
This study tests the hypothesis that the adenosine deaminase inhibitor pentostatin (2-deoxycoformycin), when given before ischemia or during infusions of blood cardioplegia, augments interstitial adenosine levels and prevents postcardioplegia dysfunction in hearts with antecedent ischemia. Twenty-one anesthetized dogs were placed on cardiopulmonary bypass, and the hearts were made globally ischemic for 30 minutes. Dogs received blood cardioplegia with no pentostatin (BCP group, n = 6), pretreatment pentostatin (0.2 mg/kg) infused 5 minutes before global ischemia (PS-PTx group, n = 7), or pentostatin included only in the blood cardioplegia without pretreatment (PS-BCP group, n = 8). Microdialysate myocardial adenosine levels (an index of interstitial fluid levels) increased only modestly in the BCP group (from 0.55 +/- 0.13 microM to 2.64 +/- 0.50 microM) and the PS-BCP group (from 0.55 +/- 0.18 microM to 1.08 +/- 0.48 microM) during normothermic ischemia, but interstitial adenosine levels were not augmented further during cardioplegic arrest in either group. In contrast, the adenosine level in the PS-PTx group was significantly (p < 0.05) augmented during global ischemia (from 0.50 +/- 0.13 microM to 63.16 +/- 28.08 microM) and cardioplegia infusion (to 15.26 microM +/- 5.61 microM). Relative to baseline, postischemic left ventricular performance (end-systolic pressure-volume relation) was depressed in both the BCP (from 5.5 +/- 1.2 mm Hg/mL to 3.8 +/- 0.4 mm Hg/mL) and PS-BCP groups (from 7.1 +/- 0.9 mm Hg/mL to 3.8 +/- 0.7 mm Hg/mL). In contrast, PS-PTx restored postischemic performance (from 6.2 +/- 0.5 mm Hg/mL to 7.5 +/- 0.9 mm Hg/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
腺苷脱氨酶抑制剂喷司他丁（2-脱氧助间型霉素）在缺血前或血液停搏液输注期间给药，可提高心肌间质腺苷水平，并预防既往有缺血情况的心脏在心脏停搏后出现功能障碍。21只麻醉犬接受体外循环，心脏整体缺血30分钟。犬分为三组：未接受喷司他丁的血液停搏液组（BCP组，n = 6）；在整体缺血前5分钟输注喷司他丁（0.2 mg/kg）进行预处理的组（PS-PTx组，n = 7）；仅在血液停搏液中加入喷司他丁而未进行预处理的组（PS-BCP组，n = 8）。在常温缺血期间，BCP组（从0.55±0.13 μM升至2.64±0.50 μM）和PS-BCP组（从0.55±0.18 μM升至1.08±0.48 μM）的微透析心肌腺苷水平（反映间质液水平的指标）仅适度升高，但两组在心脏停搏期间间质腺苷水平均未进一步升高。相比之下，PS-PTx组在整体缺血期间（从0.50±0.13 μM升至63.16±28.08 μM）和停搏液输注期间（升至15.26 μM±5.61 μM）腺苷水平显著升高（p < 0.05）。相对于基线，BCP组（从5.5±1.2 mmHg/mL降至3.8±0.4 mmHg/mL）和PS-BCP组（从7.1±0.9 mmHg/mL降至3.8±0.7 mmHg/mL）缺血后左心室功能（收缩末期压力-容积关系）均降低。相比之下，PS-PTx组恢复了缺血后功能（从6.2±0.5 mmHg/mL升至7.5±0.9 mmHg/mL）。（摘要截选至250词）
