Lee S H, Doliba N, Osbakken M, Oz M, Mancini D
Division of Circulatory Physiology, Columbia Presbyterian Medical Center, New York, NY 10032, USA.
J Thorac Cardiovasc Surg. 1998 Aug;116(2):344-9. doi: 10.1016/s0022-5223(98)70136-9.
Mitochondrial abnormalities have been described in cardiac tissue of patients with heart failure. These changes may result from chronic hypoxia. Our goal was to determine whether mitochondrial functional capacity can be improved in patients with heart failure by means of long-term left ventricular assist device therapy, which improves myocardial oxygen supply by decreasing myocardial work.
Mitochondria were isolated from myocardial tissue obtained from 13 patients with heart failure without a left ventricular assist device (HF group) and seven patients with heart failure treated with a left ventricular assist device (LVAD-HF group). Mitochondrial respiratory rates (State 2, State 3, and State 4) were measured by means of polarographic techniques with reduced nicotinamide adenine dinucleotide-dependent (pyruvate/malate, alpha-ketoglutarate, glutamate) and -independent (succinate) substrates. The respiratory control index of Chance (State 3/State 4) and Lardy (State 3/State 2) and phosphorus to oxygen ratios were determined.
The respiratory control index of Chance was higher in LVAD-HF than in HF when using NADH-dependent substrates pyruvate/malate and alpha-ketoglutarate (pyruvate/malate HF: 4.9 +/- 1.0; LVAD-HF: 6.5 +/- 1.5; alpha-ketoglutarate HF: 8.5 +/- 2.4; LVAD-HF: 11.8 +/- 2.9; both p = 0.04). Similarly, the respiratory control index of Lardy was greater in the LVAD-HF than the HF group when alpha-ketoglutarate and glutamate were used as substrates (alpha-ketoglutarate HF: 7.8 +/- 1.7; LVAD-HF: 9.9 +/- 1.5; glutamate HF: 7.6 +/- 2.2; LVAD-HF: 10.7 +/- 2.1; both p = 0.04). The phosphorus to oxygen ratio was comparable for both groups using all substrates. No change in mitochondrial respiration was observed after left ventricular assist device therapy with the NADH-independent substrate, succinate.
Cardiomyocyte mitochondrial function is improved by long-term therapy with a left ventricular assist device. This improvement suggests that cardiomyocyte metabolic dysfunction in heart failure may be reversed with left ventricular assist device support.
心力衰竭患者心脏组织中已发现线粒体异常。这些变化可能源于慢性缺氧。我们的目标是确定长期左心室辅助装置治疗能否改善心力衰竭患者的线粒体功能能力，该治疗通过减少心肌做功来改善心肌氧供。
从13例未使用左心室辅助装置的心力衰竭患者（心力衰竭组）和7例接受左心室辅助装置治疗的心力衰竭患者（左心室辅助装置 - 心力衰竭组）获取的心肌组织中分离出线粒体。采用极谱技术，使用依赖于烟酰胺腺嘌呤二核苷酸还原型（丙酮酸/苹果酸、α - 酮戊二酸、谷氨酸）和不依赖于烟酰胺腺嘌呤二核苷酸还原型（琥珀酸）的底物，测量线粒体呼吸速率（状态2、状态3和状态4）。测定钱斯呼吸控制指数（状态3/状态4）和拉迪呼吸控制指数（状态3/状态2）以及磷氧比。
当使用依赖于烟酰胺腺嘌呤二核苷酸的底物丙酮酸/苹果酸和α - 酮戊二酸时，左心室辅助装置 - 心力衰竭组的钱斯呼吸控制指数高于心力衰竭组（丙酮酸/苹果酸 心力衰竭组：4.9±1.0；左心室辅助装置 - 心力衰竭组：6.5±1.5；α - 酮戊二酸 心力衰竭组：8.5±2.4；左心室辅助装置 - 心力衰竭组：11.8±2.9；两者p = 0.04）。同样，当使用α - 酮戊二酸和谷氨酸作为底物时，左心室辅助装置 - 心力衰竭组的拉迪呼吸控制指数大于心力衰竭组（α - 酮戊二酸 心力衰竭组：7.8±1.7；左心室辅助装置 - 心力衰竭组：9.9±1.5；谷氨酸 心力衰竭组：7.6±2.2；左心室辅助装置 - 心力衰竭组：10.7±2.1；两者p = 0.04）。两组使用所有底物时的磷氧比相当。使用不依赖于烟酰胺腺嘌呤二核苷酸的底物琥珀酸进行左心室辅助装置治疗后，未观察到线粒体呼吸的变化。
长期左心室辅助装置治疗可改善心肌细胞线粒体功能。这一改善表明，心力衰竭时心肌细胞代谢功能障碍可能通过左心室辅助装置支持得到逆转。
