INTERMITTENT AORTIC CROSS-CLAMPING PREVENTS CUMULATIVE ADENOSINE-TRIPHOSPHATE DEPLETION, VENTRICULAR-FIBRILLATION, AND DYSFUNCTION (STUNNING) - IS IT PRECONDITIONING
INTERMITTENT AORTIC CROSS-CLAMPING PREVENTS CUMULATIVE ADENOSINE-TRIPHOSPHATE DEPLETION, VENTRICULAR-FIBRILLATION, AND DYSFUNCTION (STUNNING) - IS IT PRECONDITIONING
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DOI：
10.1016/s0022-5223(95)70228-8
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发表时间：
1995-08-01
影响因子：
6
通讯作者：
WECHSLER, AS
中科院分区：
文献类型：
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作者：
ABDELFATTAH, AS;DING, M;WECHSLER, AS
本研究旨在确定间歇性热主动脉钳夹是否会引起累积性心肌顿抑，或者在体内犬模型中首次缺血发作后心肌是否会进行预处理。使用选择性核苷转运抑制剂对硝基苄基硫代肌苷 (NBMPR) 和特异性腺苷脱氨酶抑制剂 erythro-9-[2-羟基-3-壬基]腺嘌呤 (EHNA) 评估三磷酸腺苷分解代谢和随后的嘌呤释放对再灌注介导的缺血后心室功能障碍和心律失常的作用。三十二只麻醉狗通过声测法监测左心室收缩力（关闭旁路）。在体外循环期间，在缺血前用盐水溶液（对照组，n = 8）或EHNA（100μmol/L）和NBMPR（25μmol/L）（EHNA/NBMPR组，n = 8）对狗进行治疗。心脏经历 60 分钟的整体缺血和 120 分钟的再灌注 (n = 16) 或 6 次 10 分钟的整体缺血和 10 分钟的再灌注，然后进行 60 分钟的再灌注 (n = 16)。对照组中 60 分钟的持续缺血导致三磷酸腺苷损失 80%，并诱导再灌注介导的心室颤动和严重的左心室功能障碍。 EHNA/NBMPR 治疗增强了缺血期间的心肌腺苷捕获，减弱了心室颤动，并增强了左心室功能恢复，尽管三磷酸腺苷有类似的消耗（80% 损失）。在间歇性缺血实验中，第一次10分钟的缺血和再灌注在对照组和药物治疗组中均引起显着的三磷酸腺苷耗竭、心室颤动和左心室顿抑。首次缺血发作后，对照组心室颤动的患病率高于药物治疗组（p < 0.05）。在 EHNA/NBMPR 治疗组中，缺血 10 分钟后，腺苷是心肌中积累的主要核苷（与对照组相比，p < 0.05）。随后的缺血发作阻止了心室颤动，并且没有引起两组中累积的左心室顿抑。 EHNA/NBMPR 治疗组在间歇性缺血后左心室功能完全恢复，但对照组仍处于震惊状态。与持续缺血不同，间歇性缺血和再灌注保留了心肌三磷酸腺苷、有限的嘌呤释放，并防止心室颤动和累积性击晕。这些结果表明，间歇性缺血和再灌注增强了内源性保护机制或“预处理”机制。核苷捕获改善了持续或重复缺血后的功能恢复。结论是，三磷酸腺苷的保存或核苷转运的阻断可能在激活内源性心肌保护机制中发挥重要作用，该机制是针对随后的缺血应激的“先决条件”。
This study was designed to determine whether intermittent warm aortic crossclamping induces cumulative myocardial stunning or if the myocardium becomes preconditioned after the first episode of ischemia in canine models in vivo. The role of adenosine triphosphate catabolism and subsequent release of purines on reperfusion-mediated postischemic ventricular dysfunction and arrhythmias was assessed with the use of selective inhibitors of nucleoside transport, p-nitrobenzylthioinosine (NBMPR), and a specific adenosine deaminase inhibitor, erythro-9- [2-hydroxy-3-nonyl] adenine (EHNA). Thirty two anesthetized dogs were instrumented to monitor left ventricular contractility, off bypass, by sonomicrometry. During cardiopulmonary bypass dogs were treated before ischemia with either saline solution (control group, n = 8) or EHNA (100 mu mol/L) and NBMPR (25 mu mol/L) (EHNA/NBMPR group, n = 8). Hearts were subjected to either 60 minutes of global ischemia and 120 minutes of reperfusion (n = 16) or 6 episodes of 10 minutes of global ischemia and 10 minutes of reperfusion, followed by 60 minutes of reperfusion (n = 16). Sixty minutes of sustained ischemia resulted in 80% loss of adenosine triphosphate and induced reperfusion-mediated ventricular fibrillation and severe left ventricular dysfunction in the control group. EHNA/NBMPR treatment augmented myocardial adenosine trapping during ischemia, attenuated ventricular fibrillation, and enhanced left ventricular functional recovery, despite similar depletion of adenosine triphosphate (80% loss). In the intermittent ischemia experiment, the first episode of 10 minutes of ischemia and reperfusion caused significant adenosine triphosphate depletion, ventricular fibrillation, and left ventricular stunning in both control and drug-treated groups. The prevalence of ventricular fibrillation was greater in the control group than in the drug-treated group after the first episode of ischemia (p < 0.05). Adenosine was the major nucleoside accumulated in the myocardium at the end of 10 minutes of ischemia in the EHNA/NBMPR-treated group (p < 0.05 versus control). Subsequent episodes of ischemia prevented ventricular fibrillation and did not cause cumulative left ventricular stunning in either group. Left ventricular function fully recovered in the EHNA/NBMPR-treated group after intermittent ischemia, but remained stunned in the control group. Unlike sustained ischemia, intermittent ischemia and reperfusion preserved myocardial adenosine triphosphate, limited purine release, and prevented ventricular fibrillation and cumulative stunning. These results suggest that intermittent ischemia and reperfusion augmented the endogenous protective mechanism or mechanisms of ''preconditioning.'' Nucleoside trapping improved functional recovery after sustained or repetitive ischemia. It is concluded that adenosine triphosphate preservation or blockade of nucleoside transport may play an important role in the activation of endogenous myocardial protective mechanisms that ''precondition'' against subsequent ischemic stress.