Reoxygenation Injury in Hypoxemic Immature Hearts

低氧未成熟心脏的复氧损伤

• 批准号: 12671331
• 负责人: MORITA Kiyozo
• 金额: $ 2.11万
• 依托单位: JIKEI UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671331/
• 关键词: reoxygenation injury; cyanosis; antioxidant; immature heart; cardiopulmomary bypass; endosystolic elastance; lipidperoxidation; complex heart anomaly; 抗活性酸素; 抗酸素ストレス耐性

A series of in vivo experiments using hypoxemic immature piglets was performed to test the hypotheses that uncontrolled reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass (CPB) with the conventional high pO2 pmduces a reoxygenation injury that a) is mediated by oxidants derived myocardial lipidperoxidation , and b) is avoidable by controlling pO2 at CPB and additives to the CPB prime (Controlled Reoxygenation).Immature piglets (<3 weeks old) were placed on 120 minutes of cardiopulmonary bypass, and 5 piglets served as biochemical control without CPB (biochemical Control Group). Five piglets underwent CPB without hypoxemia (CPB control). Twenty eight others were made hypoxic on CPB for 60 minutes by lowering p02 to 20-30mmHg, followed by reoxygenation for 60 minutes at pO2-400mmHg (Hyperoxic REOX Group) or pO2100mmHg (Normoxemic REOX Group). Others were allocated to the treatment groups in which following additives were administered to the CPB: deferoxamine ( … More 50mg/kg total dose); the NO-synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME, 4mg/kg); L-arginine (20 mg/kg); antioxidants (MPG Catalase Coenzyme Q10); Glutamate/ Asparatate (13mMol).Post CPB myocardial function was evaluated from endsystolic elastance (Ees, conductance catheter) and Starling curv analysis. Myocardial conjugated diene (CD) production, ( a marker of lipidperoxidation) creatine phosphokinase (CPK) leakage were assessed as biochemical markers of injury, and antioxidant reserve capacity determined by measuring malondialdehyde (MDA) in post CPB myocardium incubated in the oxidant, t-butyl hydroperoxide(t-BHP).CPB without hypoxia caused no oxidant or functional damage. Conversely, reoxygenation (Hyperoxic) raised myocardial conjugated dienes and CPK production, reduced antioxidant reserve capacity, and produced severe postbypass dysfunction. In contrast, deferoxamine, inhibition of NO production by L-NAME, reduction of antioxidants by MPG catalase, coenzyme Q10 equally avoided conjugated dienes production and CPK release, retaine normal antioxidant reserve, and functional recovery was significantly improved in all Rx groups.We conclude that reoxygenation of the hypoxemic immature heart by initiating the conventional hyperoxic CPB causes oxidant damage characterized by lipid peroxidation and reduced antioxidants, leading to functional depression surgical reoxygenation injury of myocardium . These detrimental effects can be reduced by starting CPB at the physiological pO2 or addition of anti-oxidants agents to the CPB. Less

采用低氧血症的未成熟仔猪进行了一系列体内实验，以检验以下假设：在常规高pO 2条件下启动心肺转流（CPB）时，紫绀未成熟心脏的不受控制的复氧可导致复氧损伤，a）由氧化剂引起的心肌脂质过氧化介导，和B）可通过控制CP B的pO 2和CP B预充的添加剂来避免将未成熟的小猪（<3周龄）置于120分钟的心肺转流中，5只小猪用作没有CPB的生化对照（生化对照组）。5头仔猪接受CPB，无低氧血症（CPB对照）。另28例在体外循环中先将氧分压降至20- 30 mmHg，再于氧分压为2100 mmHg或400 mmHg时复氧60分钟。其他人被分配到治疗组，在这些治疗组中，向CPB中给予以下添加剂：去铁胺（ ...更多信息 50 mg/kg总剂量）; NO合成酶抑制剂N -硝基-L-精氨酸甲酯（L-NAME，4 mg/kg）、L-精氨酸（20 mg/kg）、抗氧化剂（MPG过氧化氢酶辅酶Q10）、谷氨酸/天冬氨酸（13 mMol）。以心肌共轭二烯（CD）的产生、肌酸磷酸激酶（CPK）的漏出作为心肌损伤的生化指标，以丙二醛（MDA）的含量测定心肌的抗氧化储备能力。相反，复氧（高氧）提高心肌共轭二烯和CPK的生产，降低抗氧化储备能力，并产生严重的旁路术后功能障碍。相反，去铁胺、L-NAME抑制NO生成、MPG过氧化氢酶还原抗氧化剂、辅酶Q10同样避免了共轭二烯的生成和CPK的释放，保留了正常的抗氧化剂储备，我们得出结论，通过启动常规高氧CPB对低氧血症的未成熟心脏进行再氧合可引起以脂质过氧化为特征的氧化损伤，抗氧化剂，导致功能性抑郁症手术心肌复氧损伤。通过在生理pO 2下启动CPB或向CPB中添加抗氧化剂，可以减少这些有害影响。少