Division of Cardiothoracic Surgery, Department of Surgery, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0068, USA.
J Thorac Cardiovasc Surg. 2012 Jul;144(1):250-5. doi: 10.1016/j.jtcvs.2011.10.095. Epub 2012 Feb 11.
To determine the role of the p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 (es-ENT1) in postmyocardial infarction reperfusion injury-mediated ventricular fibrillation and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine and p-nitrobenzylthioinosine to inhibit both adenosine deamination and transport in a canine model of off pump acute myocardial infarction.
Anesthetized adult dogs (n = 37), instrumented to monitor the percentage of systolic segmental shortening and wall thickening using sonomicrometry, underwent 90 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Myocardial coronary blood flow, adenosine triphosphate pool, infarct size, and the incident of ventricular fibrillation and cardioversion were also measured. The dogs received an intravenous infusion of the vehicle (control) or 100 μM of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 μM p-nitrobenzylthioinosine before ischemia (preconditioning group) or just before reperfusion (postconditioning group).
In the control group, adenosine triphosphate depletion was associated with the accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the pre- and postconditioning groups during ischemia and remained detectable during reperfusion. In both groups, recovery of systolic segmental shortening and wall thickening and a reduction in the incidence of ventricular fibrillation (P < .05 vs the control group) coincided with retention of myocardial nucleosides. The infarct size in the 3 groups was not significantly different, independent of myocardial blood flow during ischemia.
Preconditioning or postconditioning with erythro-9 (2-hydroxy-3-nonyl)-adenine/p-nitrobenzylthioinosine significantly reduced the incidence of ventricular fibrillation and cardioversion and attenuated regional contractile dysfunction mediated by postmyocardial infarction reperfusion injury. It is concluded that p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 played a major role in these events.
确定对硝基苄基硫代肌苷敏感的平衡核苷转运蛋白 1（es-ENT1）在心肌梗死后再灌注损伤介导的心室颤动和区域性功能障碍中的作用。我们使用赤式-9（2-羟基-3-壬基）-腺嘌呤和对硝基苄基硫代肌苷抑制脱氨酶和运输在非体外循环急性心肌梗死犬模型中。
麻醉成年犬（n=37），使用超声心动描记术监测收缩节段缩短和壁增厚的百分比，进行左前降支冠状动脉闭塞 90 分钟和再灌注 120 分钟。还测量了心肌冠状血流、三磷酸腺苷池、梗死面积以及心室颤动和电复律的发生。犬在缺血前（预处理组）或再灌注前（后处理组）接受载体（对照）或 100μM 赤式-9（2-羟基-3-壬基）-腺嘌呤和 25μM 对硝基苄基硫代肌苷的静脉输注。
在对照组中，三磷酸腺苷耗竭与缺血过程中肌苷的积累多于腺苷有关，并且在再灌注过程中被冲洗掉。在缺血期间，心肌腺苷和肌苷是预处理和后处理组中的主要核苷，并且在再灌注期间仍然可检测到。在两组中，收缩节段缩短和壁增厚的恢复以及心室颤动的发生率降低（P<0.05 与对照组相比）与保留心肌核苷同时发生。三组的梗死面积无明显差异，与缺血期间的心肌血流无关。
用赤式-9（2-羟基-3-壬基）-腺嘌呤/对硝基苄基硫代肌苷预处理或后处理可显著降低心肌梗死后再灌注损伤介导的心室颤动和电复律的发生率，并减轻区域性收缩功能障碍。结论是对硝基苄基硫代肌苷敏感的平衡核苷转运蛋白 1在这些事件中起主要作用。
