Heart and Vascular Institute, Hershey, PA, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, College of Medicine, Pennsylvania State University, 500 University Drive, H041, Hershey, PA, 17033, USA.
Cardiovasc Toxicol. 2018 Oct;18(5):436-449. doi: 10.1007/s12012-018-9454-2.
This study was aimed at determining the efficacy of epinephrine, followed by chest compressions, in producing a return of spontaneous circulation (ROSC) during cyanide (CN)- or hydrogen sulfide (HS)-induced toxic cardiac pulseless electrical activity (PEA) in the rat. Thirty-nine anesthetized rats were exposed to either intravenous KCN (n = 27) or HS solutions (n = 12), at a rate that led to a PEA within less than 10 min. In the group intoxicated by CN, 20 rats were mechanically ventilated and received either epinephrine (0.1 mg/kg i.v. n = 10) followed by chest compressions or saline (n = 10, "control CN") when in PEA. PEA was defined as a systolic pressure below 20 mmHg and a pulse pressure of less than 5 mmHg for 1 min. In addition, seven spontaneously breathing rats were also exposed to the same CN protocol, but infusion was stopped when a central apnea occurred; then, as soon as a PEA occurred, epinephrine (0.1 mg/kg IV) was administered while providing manual chest compressions and mechanical ventilation (CPR). Finally, 12 rats were intoxicated with HS, while mechanically ventilated, and received either saline (n = 6, "control HS") or epinephrine (n = 6) with CPR when in PEA. None of the control-intoxicated animals resuscitated (10 rats in the control CN group and 6 in the control HS group). In contrast, all the animals intoxicated with CN or HS that received epinephrine followed by chest compressions, returned to effective circulation. In addition, half of the spontaneously breathing CN-intoxicated animals that achieved ROSC after epinephrine resumed spontaneous breathing. In all the animals achieving ROSC, blood pressure, cardiac output, peripheral blood flow and [Formula: see text]O returned toward baseline, but remained lower than the pre-intoxication levels (p < 0.01) with a persistent lactic acidosis. Epinephrine, along with CPR maneuvers, was highly effective in resuscitating rodents intoxicated with CN or HS. Since epinephrine is readily available in any ambulance, its place as an important countermeasure against mitochondrial poisons should be advocated. It remains critical to determine whether the systematic administration of epinephrine to any victims found hypotensive following CN or HS intoxication could prevent PEA, decrease post-ischemic brain injury and increase the efficacy of current antidotes by improving the circulatory status.
这项研究旨在确定肾上腺素在氰化物（CN）或硫化氢（HS）引起的中毒性心脏无脉电活动（PEA）大鼠中产生自主循环恢复（ROSC）的效果，方法是在麻醉大鼠中静脉内给予 KCN（n = 27）或 HS 溶液（n = 12），以在不到 10 分钟内导致 PEA。在被 CN 中毒的组中，20 只大鼠接受机械通气，并在 PEA 时接受肾上腺素（0.1 mg/kg 静脉内 n = 10）或生理盐水（n = 10，“对照 CN”）。PEA 定义为收缩压低于 20mmHg 和脉搏压低于 5mmHg 持续 1 分钟。此外，七只自主呼吸的大鼠也暴露于相同的 CN 方案中，但当发生中心性呼吸暂停时停止输注；然后，一旦发生 PEA，就给予肾上腺素（0.1mg/kg 静脉内），同时提供手动胸部按压和机械通气（CPR）。最后，12 只大鼠被 HS 中毒，同时接受机械通气，并在 PEA 时接受生理盐水（n = 6，“对照 HS”）或肾上腺素（n = 6）加 CPR。没有对照中毒的动物复苏（对照 CN 组中的 10 只大鼠和对照 HS 组中的 6 只大鼠）。相比之下，接受肾上腺素后进行胸部按压的所有 CN 或 HS 中毒的动物均恢复了有效循环。此外，接受肾上腺素后恢复自主呼吸的半自主呼吸 CN 中毒动物中有一半恢复了 ROSC。在所有达到 ROSC 的动物中，血压、心输出量、外周血流量和 [Formula: see text]O 恢复到基线水平，但仍低于中毒前水平（p < 0.01），并伴有持续的乳酸酸中毒。肾上腺素与 CPR 操作一起，在复苏 CN 或 HS 中毒的啮齿动物方面非常有效。由于肾上腺素在任何救护车上都很容易获得，因此应该提倡将其作为对抗线粒体毒物的重要对策。仍然需要确定是否可以通过改善循环状态，对任何发现中毒性低血压的 CN 或 HS 中毒患者进行全身性肾上腺素治疗，以防止 PEA、减少缺血后脑损伤并提高现有解毒剂的效果。
