Sharma Arti B, Barlow Matthew A, Yang Shao-Hua, Simpkins James W, Mallet Robert T
Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA.
Resuscitation. 2008 Jan;76(1):108-19. doi: 10.1016/j.resuscitation.2007.04.028. Epub 2007 Jul 6.
Cerebral oxidative stress and metabolic dysfunction impede neurological recovery from cardiac arrest-resuscitation. Pyruvate, a potent antioxidant and energy-yielding fuel, has been shown to protect against oxidant- and ischemia-induced neuronal damage. This study tested whether acute pyruvate treatment during cardiopulmonary resuscitation can prevent neurological dysfunction and cerebral injury following cardiac arrest.
Anesthetized, open-chest mongrel dogs underwent 5 min cardiac arrest, 5 min open-chest cardiac compression (OCCC), defibrillation and 3-day recovery. Pyruvate (n=9) or NaCl volume control (n=8) were given (0.125 mmol kg(-1) min(-1) i.v.) throughout OCCC and the first 55 min recovery. Sham dogs (n=6) underwent surgery and recovery without cardiac arrest-resuscitation.
Neurological deficit score (NDS), evaluated at 2-day recovery, was sharply increased in NaCl-treated dogs (10.3+/-3.5) versus shams (1.2+/-0.4), but pyruvate treatment mitigated neurological deficit (NDS=3.3+/-1.2; P<0.05 versus NaCl). Brain samples were taken for histological examination and evaluation of inflammation and cell death at 3-day recovery. Loss of pyramidal neurons in the hippocampal CA1 subregion was greater in the NaCl controls than in pyruvate-treated dogs (11.7+/-2.3% versus 4.3+/-1.2%; P<0.05). Cardiac arrest increased caspase-3 activity, matrix metalloproteinase activity, and DNA fragmentation in the CA1 subregion; pyruvate prevented caspase-3 activation and DNA fragmentation, and suppressed matrix metalloproteinase activity.
Intravenous pyruvate therapy during cardiopulmonary resuscitation prevents initial oxidative stress and neuronal injury and enhances neurological recovery from cardiac arrest.
脑氧化应激和代谢功能障碍会阻碍心脏骤停复苏后的神经功能恢复。丙酮酸是一种有效的抗氧化剂和产生能量的燃料,已被证明可保护神经元免受氧化剂和缺血诱导的损伤。本研究测试了心肺复苏期间急性丙酮酸治疗是否能预防心脏骤停后的神经功能障碍和脑损伤。
麻醉的开胸杂种犬经历5分钟心脏骤停、5分钟开胸心脏按压(OCCC)、除颤和3天恢复。在整个OCCC期间和恢复的前55分钟给予丙酮酸(n = 9)或NaCl容量对照(n = 8)(0.125 mmol kg⁻¹ min⁻¹静脉注射)。假手术犬(n = 6)接受手术和恢复,未经历心脏骤停复苏。
在恢复2天时评估的神经功能缺损评分(NDS),NaCl治疗组犬(10.3±3.5)与假手术组(1.2±0.4)相比急剧增加,但丙酮酸治疗减轻了神经功能缺损(NDS = 3.3±1.2;与NaCl组相比P<0.05)。在恢复3天时采集脑样本进行组织学检查以及炎症和细胞死亡评估。NaCl对照组海马CA1亚区锥体细胞的损失比丙酮酸治疗组犬更大(11.7±2.3%对4.3±1.2%;P<0.05)。心脏骤停增加了CA1亚区的半胱天冬酶-3活性、基质金属蛋白酶活性和DNA片段化;丙酮酸可防止半胱天冬酶-3激活和DNA片段化,并抑制基质金属蛋白酶活性。
心肺复苏期间静脉注射丙酮酸治疗可预防初始氧化应激和神经元损伤,并增强心脏骤停后的神经功能恢复。