Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats
<i>Introduction</i> Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissu...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2079-7737/11/7/957 |
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| author | Peng Wang Ying Li Baihui Yan Zhong Yang Litao Li Zhipeng Cao Xuan Li Ines Batinic-Haberle Ivan Spasojevic David S. Warner Huaxin Sheng |
| author_facet | Peng Wang Ying Li Baihui Yan Zhong Yang Litao Li Zhipeng Cao Xuan Li Ines Batinic-Haberle Ivan Spasojevic David S. Warner Huaxin Sheng |
| author_sort | Peng Wang |
| collection | DOAJ |
| description | <i>Introduction</i> Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Mn(III) <i>ortho meso-</i>tetrakis (<i>N</i>-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. <i>Methods</i> Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. <i>Results</i> Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (<i>p</i> < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, <i>p</i> = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (<i>p</i> < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, <i>p</i> = 0.21) and less tubular injury (<i>p</i> < 0.05) relative to vehicle group. <i>Conclusions</i> We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials. |
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| spelling | doaj.art-d4801eb592674fea9a873bfe3ebe760a2023-12-01T21:54:08ZengMDPI AGBiology2079-77372022-06-0111795710.3390/biology11070957Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and RatsPeng Wang0Ying Li1Baihui Yan2Zhong Yang3Litao Li4Zhipeng Cao5Xuan Li6Ines Batinic-Haberle7Ivan Spasojevic8David S. Warner9Huaxin Sheng10Multidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USADepartment of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USADepartment of Medicine, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USAMultidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA<i>Introduction</i> Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain, kidney, and other tissues. This study evaluates the efficacy of a third generation lipophilic Mn porphyrin, MnTnBuOE-2-PyP<sup>5+</sup>, Mn(III) <i>ortho meso-</i>tetrakis (<i>N</i>-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. <i>Methods</i> Forty-eight animals were subjected to 8 min of CA and resuscitated subsequently by chest compression and epinephrine infusion. Vehicle or MnBuOE was given immediately after resuscitation followed by daily subcutaneous injections. Body weight, spontaneous activity, neurologic deficits, rotarod performance, and neuronal death were assessed. Kidney tubular injury was assessed in CA mice. Data were collected by the investigators who were blinded to the treatment groups. <i>Results</i> Vehicle mice had a mortality of 20%, which was reduced by 50% by MnBuOE. All CA mice had body weight loss, spontaneous activity decline, neurologic deficits, and decreased rotarod performance that were significantly improved at three days post MnBuOE daily treatment. MnBuOE treatment reduced cortical neuronal death and kidney tubular injury in mice (<i>p</i> < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, <i>p</i> = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (<i>p</i> < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, <i>p</i> = 0.21) and less tubular injury (<i>p</i> < 0.05) relative to vehicle group. <i>Conclusions</i> We demonstrated the ability of MnBuOE to improve post-CA survival, as well as functional outcomes in both mice and rats, which jointly account for the improvement not only of brain function but also of the overall wellbeing of the animals. While MnBuOE bears therapeutic potential for treating CA patients, the females and the animals with comorbidities must be further evaluated before advancing toward clinical trials.https://www.mdpi.com/2079-7737/11/7/957cardiac arrestfunctional deficitmanganese porphyrinBMX-001ischemia/reperfusionoutcome |
| spellingShingle | Peng Wang Ying Li Baihui Yan Zhong Yang Litao Li Zhipeng Cao Xuan Li Ines Batinic-Haberle Ivan Spasojevic David S. Warner Huaxin Sheng Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats Biology cardiac arrest functional deficit manganese porphyrin BMX-001 ischemia/reperfusion outcome |
| title | Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats |
| title_full | Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats |
| title_fullStr | Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats |
| title_full_unstemmed | Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats |
| title_short | Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats |
| title_sort | manganese porphyrin promotes post cardiac arrest recovery in mice and rats |
| topic | cardiac arrest functional deficit manganese porphyrin BMX-001 ischemia/reperfusion outcome |
| url | https://www.mdpi.com/2079-7737/11/7/957 |
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