Morita K, Ihnken K, Buckberg G D, Young H H
Department of Surgery, University of California, Los Angeles School of Medicine 90024-1741, USA.
J Thorac Cardiovasc Surg. 1995 Oct;110(4 Pt 2):1221-7. doi: 10.1016/s0022-5223(95)70008-0.
Coenzyme Q10 (CoQ10) is a natural mitochondrial respiratory chain constituent with antioxidant properties. This study tests the hypothesis that CoQ10 administered before the onset of reoxygenation on cardiopulmonary bypass, can reduce oxygen-mediated myocardial injury and avoid myocardial dysfunction after cardiopulmonary bypass. The antioxidant properties of CoQ10 were confirmed by an in vitro study in which normal myocardial homogenates were incubated with the oxidant, t-butylhydroperoxide. Fifteen immature piglets (< 3 weeks old) were placed on 60 minutes of cardiopulmonary bypass. Five piglets underwent cardiopulmonary bypass without hypoxemia (oxygen tension about 400 mm Hg). Ten others became hypoxemic on cardiopulmonary bypass for 30 minutes by lowering oxygen tension to approximately 25 mm Hg, followed by reoxygenation at oxygen tension about 400 mm Hg for 30 minutes. In five piglets, CoQ10 (45 mg/kg) was added to the cardiopulmonary bypass circuit 15 minutes before reoxygenation, and five others were not treated (no treatment). Myocardial function after cardiopulmonary bypass was evaluated from end-systolic elastance (conductance catheter), oxidant damage (lipid peroxidation) was assessed by measuring conjugated diene levels in coronary sinus blood, and antioxidant reserve capacity was determined by measuring malondialdehyde in myocardium after cardiopulmonary bypass incubated in the oxidant, t-butylhydroperoxide. Cardiopulmonary bypass without hypoxemia caused no oxidant damage and allowed complete functional recovery. Reoxygenated hearts (no treatment) showed a progressive increase in conjugated diene levels in coronary sinus blood after reoxygenation (2.3 +/- 0.6 A233 nm/0.5 ml plasma at 30 minutes after reoxygenation) and reduced antioxidant reserve capacity (malondialdehyde: 1219 +/- 157 nmol/g protein at 4.0 mmol/L t-butylhydroperoxide), resulting in severe postbypass dysfunction (percent end-systolic elastance = 38 +/- 6). Conversely, CoQ10 treatment avoided the increase in conjugated diene levels (2.1 +/- 0.6 vs 1.1 +/- 0.3, p < 0.05 vs no treatment), retained normal antioxidant reserve (896 +/- 76 nmol/g protein, p < 0.05 vs no treatment), and allowed nearly complete recovery of function (94% +/- 7%, p < 0.05 vs no treatment). We conclude that reoxygenation of the hypoxemic immature heart on cardiopulmonary bypass causes oxygen-mediated myocardial injury, which can be limited by CoQ10 treatment before reoxygenation. These findings imply that coenzyme Q10 can be used to surgical advantage in cyanotic patients, because therapeutic blood levels can be achieved by preoperative oral administration of this approved drug.
辅酶Q10（CoQ10）是一种具有抗氧化特性的天然线粒体呼吸链成分。本研究检验了这样一个假设：在心肺转流复氧开始前给予CoQ10，可减少氧介导的心肌损伤，并避免心肺转流后的心肌功能障碍。通过一项体外研究证实了CoQ10的抗氧化特性，该研究将正常心肌匀浆与氧化剂叔丁基过氧化氢一起孵育。15只未成熟仔猪（<3周龄）接受60分钟的心肺转流。5只仔猪在无低氧血症（氧分压约400mmHg）的情况下进行心肺转流。另外10只仔猪在心肺转流过程中通过将氧分压降至约25mmHg持续30分钟而出现低氧血症，随后在氧分压约400mmHg下复氧30分钟。在5只仔猪中，在复氧前15分钟将CoQ10（45mg/kg）添加到心肺转流回路中，另外5只未接受治疗（未治疗组）。通过收缩末期弹性（导管）评估心肺转流后的心肌功能，通过测量冠状窦血中的共轭二烯水平评估氧化损伤（脂质过氧化），并通过测量在氧化剂叔丁基过氧化氢中孵育的心肺转流后心肌中的丙二醛来确定抗氧化储备能力。无低氧血症的心肺转流未造成氧化损伤，并允许功能完全恢复。复氧的心脏（未治疗组）在复氧后冠状窦血中的共轭二烯水平逐渐升高（复氧后30分钟为2.3±0.6 A233nm/0.5ml血浆），抗氧化储备能力降低（丙二醛：在4.0mmol/L叔丁基过氧化氢时为1219±157nmol/g蛋白），导致严重的转流后功能障碍（收缩末期弹性百分比=38±6）。相反，CoQ10治疗避免了共轭二烯水平的升高（2.1±0.6对1.1±0.3，与未治疗组相比p<0.05），保留了正常的抗氧化储备（896±76nmol/g蛋白，与未治疗组相比p<0.05），并允许功能几乎完全恢复（94%±7%，与未治疗组相比p<0.05）。我们得出结论，心肺转流时低氧未成熟心脏的复氧会导致氧介导的心肌损伤，而在复氧前进行CoQ10治疗可限制这种损伤。这些发现表明，辅酶Q10可用于紫绀型患者的手术治疗，因为术前口服这种已获批准的药物可达到治疗血药浓度。
