Department of Biochemistry, Medical University of Gdansk, Gdańsk, Poland; Department of Physiology, Medical University of Gdansk, Gdańsk, Poland.
Institute of Applied Radiation Chemistry, Technical University of Lodz, Łódź, Poland.
Pharmacol Rep. 2018 Apr;70(2):378-384. doi: 10.1016/j.pharep.2017.09.011. Epub 2017 Oct 13.
Pyruvate improves contractility of normal, hypoxic, and post-ischemic myocardium. However, sodium overload is a major problem with its therapeutic application if sodium pyruvate is used. Development of alternative forms such as N-1-methylnicotinamide (MNA) pyruvate may help to overcome this problem. The aim of the study was to investigate the effect of MNA pyruvate in a murine model of cardiac ischemia.
Seven month old male ApoELDLr mice that develop myocardial infarction when exposed to hypoxic stress, were used in this study. Hypoxia (8% O2 in inspired air) was maintained for 8min and was followed by reoxygenation (21% O2 in inspired air). Four groups of mice were treated 10min before the hypoxic event by intravenous injection of MNA, MNA pyruvate, sodium pyruvate, and saline as control. The myocardial ischemia and damage was recorded by ECG. Four hours following the hypoxic episode serum troponin T and creatine kinase activity were measured.
Significant hypernatremia was found in the sodium pyruvate group. During hypoxia, control and MNA group developed profound STU depressions on ECG while no changes were observed in MNA pyruvate and sodium pyruvate group. Creatine kinase activity and troponin T content in the mice plasma were significantly higher in the control and MNA group as compared to the MNA pyruvate and sodium pyruvate group.
This study demonstrated that administration of MNA pyruvate prior to a hypoxia-induced cardiac event was cardioprotective. This intervention did not cause hypernatremia in contrast to sodium pyruvate.
丙酮酸可改善正常、缺氧和缺血后心肌的收缩性。然而，如果使用丙酮酸钠，其治疗应用中的钠超负荷是一个主要问题。开发替代形式，如 N-1-甲基烟酰胺（MNA）丙酮酸，可能有助于克服这个问题。本研究的目的是研究 MNA 丙酮酸在心肌缺血的小鼠模型中的作用。
本研究使用了一种在暴露于缺氧应激时会发展为心肌梗死的 7 月龄雄性 ApoELDLr 小鼠。缺氧（吸入空气中 8%的 O2）持续 8 分钟，随后再复氧（吸入空气中 21%的 O2）。四组小鼠在缺氧事件前 10 分钟通过静脉注射 MNA、MNA 丙酮酸、丙酮酸钠和生理盐水作为对照进行治疗。通过心电图记录心肌缺血和损伤。缺氧发作后 4 小时测量血清肌钙蛋白 T 和肌酸激酶活性。
在丙酮酸钠组发现明显的高钠血症。在缺氧期间，对照组和 MNA 组的心电图上出现明显的 STU 压低，而 MNA 丙酮酸组和丙酮酸钠组则没有观察到变化。与 MNA 丙酮酸组和丙酮酸钠组相比，对照组和 MNA 组的小鼠血浆肌酸激酶活性和肌钙蛋白 T 含量明显升高。
本研究表明，在缺氧诱导的心脏事件前给予 MNA 丙酮酸可起到心脏保护作用。与丙酮酸钠不同，这种干预不会导致高钠血症。
