Nitrite therapy is neuroprotective and safe in cardiac arrest survivors.
Nitrite therapy is neuroprotective and safe in cardiac arrest survivors.
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DOI：
10.1016/j.niox.2012.03.007
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Perez-Pinzon MA
中科院分区：
文献类型：
--
作者：
Dezfulian C;Alekseyenko A;Dave KR;Raval AP;Do R;Kim F;Perez-Pinzon MA
心脏骤停在初始复苏后导致显著的死亡率，这在大多数情况下是由于缺血再灌注诱导的脑损伤和较小程度的心肌功能障碍。亚硝酸盐先前已被证明可以保护局灶性脑和心脏缺血的动物模型免受再灌注损伤。亚硝酸盐治疗后，小鼠心脏骤停改善22小时生存，通过改善心肌收缩力。这些改善伴随着短暂的线粒体抑制，减少了对心脏的氧化损伤。基于亚硝酸盐也可以防止缺血性脑损伤的初步证据，我们试图在大鼠窒息心脏骤停模型中验证这一假设，并延长存活时间（7 d）。心脏骤停导致海马CA 1迟发性神经元死亡，其特征在于在这个和其他心脏骤停模型。亚硝酸盐治疗没有改变停搏后血流动力学，但确实导致CA 1神经元存活率显著增加（75%）。这与治疗后不久的β-亚硝酸盐和S-亚硝基硫醇水平增加有关，但与cGMP无关。线粒体功能复苏后1小时的趋势改善亚硝酸盐治疗。基于有希望的临床前数据，第一次在人类心脏骤停幸存者中进行亚硝酸盐输注的I期试验已经进行。我们目前的初步数据显示，低剂量亚硝酸盐输注不会导致低血压或引起高铁血红蛋白血症。因此，亚硝酸盐似乎是安全和有效的临床翻译作为一个有前途的治疗心脏骤停介导的心脏和脑损伤。
Cardiac arrest results in significant mortality after initial resuscitation due in most cases to ischemiareperfusion induced brain injury and to a lesser degree myocardial dysfunction. Nitrite has previously been shown to protect against reperfusion injury in animal models of focal cerebral and heart ischemia. Nitrite therapy after murine cardiac arrest improved 22 h survival through improvements in myocardial contractility. These improvements accompanied transient mitochondrial inhibition which reduced oxidative injury to the heart. Based on preliminary evidence that nitrite may also protect against ischemic brain injury, we sought to test this hypothesis in a rat model of asphyxia cardiac arrest with prolonged survival (7 d). Cardiac arrest resulted in hippocampal CA1 delayed neuronal death well characterized in this and other cardiac arrest models. Nitrite therapy did not alter post-arrest hemodynamics but did result in significant (75%) increases in CA1 neuron survival. This was associated with increases in hippo-campal nitrite and S-nitrosothiol levels but not cGMP shortly after therapy. Mitochondrial function 1 h after resuscitation trended towards improvement with nitrite therapy. Based on promising preclinical data, the first ever phase I trial of nitrite infusions in human cardiac arrest survivors has been undertaken. We present preliminary data showing low dose nitrite infusion did not result in hypotension or cause methemoglobinemia. Nitrite thus appears safe and effective for clinical translation as a promising therapy against cardiac arrest mediated heart and brain injury.
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影响因子：
37.8
作者：
Dezfulian C;Shiva S;Alekseyenko A;Pendyal A;Beiser DG;Munasinghe JP;Anderson SA;Chesley CF;Vanden Hoek TL;Gladwin MT
通讯作者：
Gladwin MT
影响因子：
82.9
作者：
Hunter, CJ;Dejam, A;Gladwin, MT
通讯作者：
Gladwin, MT
影响因子：
37.8
作者：
Dejam, Andre;Hunter, Christian J.;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.
影响因子：
37.8
作者：
Gonzalez, Felix M.;Shiva, Sruti;Arai, Andrew E.
通讯作者：
Arai, Andrew E.
影响因子：
12.7
作者：
HORN, M;SCHLOTE, W
通讯作者：
SCHLOTE, W