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Updated: Aug 28, 2025
Author Spotlight: A Unique Mouse Model of Asphyxia-Induced Cardiac Arrest
Published on: April 14, 2023
Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats
Peng Wang1,2, Ying Li1,3, Baihui Yan1,4
1Multidisciplinary Neuroprotection Laboratories, Center of Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
Introduction 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-PyP5+, Mn(III) ortho meso-tetrakis (N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE, BMX-001), in both mouse and rat models of CA. Methods 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. Results 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 (p < 0.05) but not hippocampus neuronal death (23% MnBuOE vs. 34% vehicle group, p = 0.49). In rats, they had a better body-weight recovery and increased rotarod latency after MnBuOE treatment when compared to vehicle group (p < 0.01 vs. vehicle). MnBuOE-treated rats had a low percentage of hippocampus neuronal death (39% MnBuOE vs. 49% vehicle group, p = 0.21) and less tubular injury (p < 0.05) relative to vehicle group. Conclusions 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.
Insights
Manganese porphyrin MnBuOE improves survival and neurological function after cardiac arrest (CA) in animal models. This superoxide dismutase mimic reduces brain and kidney injury, showing therapeutic potential for CA patients.
Area of Science:
- Biomedical Science
- Neuroscience
- Pharmacology
Background:
- Cardiac arrest (CA) and subsequent resuscitation cause global cerebral ischemia and reperfusion injury, leading to significant neurological deficits and mortality.
- Manganese porphyrins, acting as superoxide dismutase mimics, have demonstrated efficacy in mitigating ischemic damage in various organs.
- MnTnBuOE-2-PyP5+ (MnBuOE) is a third-generation lipophilic manganese porphyrin evaluated for its neuroprotective and organ-protective effects.
Purpose of the Study:
- To evaluate the efficacy of MnBuOE in improving outcomes following cardiac arrest and resuscitation in preclinical mouse and rat models.
- To assess MnBuOE's impact on survival rates, neurological function, and organ injury, specifically neuronal death and kidney tubular injury.
- To determine the therapeutic potential of MnBuOE as a treatment for post-cardiac arrest syndrome.
Main Methods:
- Forty-eight animals (mice and rats) were subjected to 8 minutes of cardiac arrest and resuscitated.
- MnBuOE or vehicle was administered immediately post-resuscitation, followed by daily subcutaneous injections.
- Outcomes including body weight, spontaneous activity, neurological deficits, rotarod performance, neuronal death, and kidney tubular injury were assessed by blinded investigators.
Main Results:
- MnBuOE treatment significantly reduced mortality in mice by 50% compared to vehicle controls.
- Mice and rats treated with MnBuOE showed significant improvements in body weight recovery, spontaneous activity, neurological function, and rotarod performance.
- MnBuOE reduced cortical neuronal death and kidney tubular injury in mice and rats (p < 0.05), but did not significantly decrease hippocampal neuronal death.
Conclusions:
- MnBuOE demonstrates significant therapeutic potential by improving survival and functional recovery after cardiac arrest in both mouse and rat models.
- The compound effectively mitigates brain and kidney injury, contributing to improved overall animal well-being post-cardiac arrest.
- Further evaluation in female animals and those with comorbidities is recommended before advancing MnBuOE to clinical trials for cardiac arrest patients.
