Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury.
Supplemental L-arginine during cardioplegic arrest and reperfusion avoids regional postischemic injury.
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DOI：
10.1016/s0022-5223(95)70226-1
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发表时间：
1995-08
期刊：
影响因子：
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通讯作者：
Hiroki Sato;Zhi-Qing Zhao;D. Mcgee;Mark W. Williams;J. Hammon;Jakob Vinten-Johansen
中科院分区：
文献类型：
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作者：
Hiroki Sato;Zhi-Qing Zhao;D. Mcgee;Mark W. Williams;J. Hammon;Jakob Vinten-Johansen
未增强的低温停搏液不能预防缺血后局部或全身缺血心脏的内皮和收缩功能障碍。本研究验证了补充血液心脏停搏液和再灌注一氧化氮前体L-精氨酸将通过L-精氨酸-一氧化氮途径保护内皮功能，减少梗死面积和逆转心脏停搏后局部收缩功能障碍的假设。在23只麻醉的狗中，结扎冠状动脉左前降支90分钟，之后建立全旁路手术“血运重建”。在10只狗中，给予未补充的多剂量低温血液心脏停搏液，共60分钟的心脏停搏。在8只狗，L-精氨酸静脉注射（每分钟4毫克/公斤）和血液心脏停搏液（10毫摩尔）在逮捕期间。在5只狗中，在心脏停搏液和再灌注期间，使用一氧化氮合成阻断剂N ω-硝基-L-精氨酸（1 mmol）阻断L-精氨酸-一氧化氮通路。与心脏停搏液相比，L-精氨酸可显著降低心肌梗死面积（氯化三苯基四氮唑）（28.2% ± 4.1% vs 40.5% ± 3.5%），而N ω-硝基-L-精氨酸可逆转心肌梗死面积（氯化三苯基四氮唑）（68.9% ± 3.0%）（p < 0.05）。缺血后局部节段功（毫米汞柱/毫米）（声测法），L-精氨酸（92 ± 15）明显优于心脏停搏液（28 ± 3）和N ω-硝基-L-精氨酸（26 ± 6）。与含血心脏停搏液（1.10 ± 0.11）相比，L-精氨酸组（0.46 ± 0.06）节段舒张刚度显著降低，而N ω-硝基-L-精氨酸组（2.70 ± 0.43）节段舒张刚度显著升高。在缺血-再灌注的冠状动脉左前降支血管环中，含血停搏液组对内皮型一氧化氮的刺激剂乙酰胆碱的最大舒张反应被抑制（77% ± 4%），而L-精氨酸可显著逆转（92% ± 3%）。所有组的平滑肌功能均未受影响。我们的结论是，心脏停搏液补充L-精氨酸减少梗死面积，保留缺血后的收缩和舒张区域功能，并通过L-精氨酸-一氧化氮途径防止动脉内皮功能障碍。（J THORAC CARDIOVASC SURG 1995;110：302-14）
Unenhanced hypothermic cardioplegia does not prevent postischemic endothelial and contractile dysfunction in hearts subjected to antecedent regional or global ischemia. This study tested the hypothesis that supplementing blood cardioplegic solution and reperfusion with the nitric oxide precursor l-arginine would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction by the L-arginine-nitric oxide pathway. In 23 anesthetized dogs, the left anterior descending coronary artery was ligated for 90 minutes, after which total bypass was established for surgical “revascularization.” In 10 dogs, unsupplemented multidose hypothermic blood cardioplegic solution was administered for a total of 60 minutes of cardioplegic arrest. In eight dogs, L-arginine was given intravenously (4 mg/kg per minute) and in blood cardioplegic solution (10 mmol) during arrest. In five dogs, the nitric oxide synthesis blocker N ω-nitro-L-arginine (1 mmol) was used to block the L-arginine–nitric oxide pathway during cardioplegia and reperfusion. Infarct size (triphenyltetrazolium chloride) as percent of the area at risk was significantly reduced by L-arginine compared with blood cardioplegic solution (28.2% ± 4.1% versus 40.5% ± 3.5%) and was reversed by N ω-nitro-L-arginine to 68.9% ± 3.0% (p < 0.05). Postischemic regional segmental work in millimeters of mercury per millimeter (sonomicrometry) was significantly better with l-arginine (92 ± 15) versus blood cardioplegic solution (28 ± 3) and N ω-nitro-L-arginine (26 ± 6). Segmental diastolic stiffness was significantly lower with L-arginine (0.46 ± 0.06) compared with blood cardioplegic solution (1.10 ± 0.11) and was significantly greater with N ω-nitro-l-arginine (2.70 ± 0.43). In ischemic-reperfused left anterior descending coronary arterial vascular rings, maximum relaxation response to acetylcholine, the stimulator of endothelial nitric oxide, was depressed in the blood cardioplegic solution group (77% ± 4%) and was significantly reversed by L-arginine (92% ± 3%). Smooth muscle function was unaffected in all groups. We conclude that cardioplegic solution supplemented with L-arginine reduces infarct size, preserves postischemic systolic and diastolic regional function, and prevents arterial endothelial dysfunction via the L-arginine–nitric oxide pathway. (J THORAC CARDIOVASC SURG 1995;110:302-14)