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Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents
Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct th...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253071/ https://www.ncbi.nlm.nih.gov/pubmed/37296668 http://dx.doi.org/10.3390/cells12111548 |
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author | Choudhary, Rishabh C. Shoaib, Muhammad Hayashida, Kei Yin, Tai Miyara, Santiago J. d’Abramo, Cristina Heuser, William G. Shinozaki, Koichiro Kim, Nancy Takegawa, Ryosuke Nishikimi, Mitsuaki Li, Timmy Owens, Casey Molmenti, Ernesto P. He, Mingzhu Vanpatten, Sonya Al-Abed, Yousef Kim, Junhwan Becker, Lance B. |
author_facet | Choudhary, Rishabh C. Shoaib, Muhammad Hayashida, Kei Yin, Tai Miyara, Santiago J. d’Abramo, Cristina Heuser, William G. Shinozaki, Koichiro Kim, Nancy Takegawa, Ryosuke Nishikimi, Mitsuaki Li, Timmy Owens, Casey Molmenti, Ernesto P. He, Mingzhu Vanpatten, Sonya Al-Abed, Yousef Kim, Junhwan Becker, Lance B. |
author_sort | Choudhary, Rishabh C. |
collection | PubMed |
description | Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest. |
format | Online Article Text |
id | pubmed-10253071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102530712023-06-10 Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents Choudhary, Rishabh C. Shoaib, Muhammad Hayashida, Kei Yin, Tai Miyara, Santiago J. d’Abramo, Cristina Heuser, William G. Shinozaki, Koichiro Kim, Nancy Takegawa, Ryosuke Nishikimi, Mitsuaki Li, Timmy Owens, Casey Molmenti, Ernesto P. He, Mingzhu Vanpatten, Sonya Al-Abed, Yousef Kim, Junhwan Becker, Lance B. Cells Article Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest. MDPI 2023-06-05 /pmc/articles/PMC10253071/ /pubmed/37296668 http://dx.doi.org/10.3390/cells12111548 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Choudhary, Rishabh C. Shoaib, Muhammad Hayashida, Kei Yin, Tai Miyara, Santiago J. d’Abramo, Cristina Heuser, William G. Shinozaki, Koichiro Kim, Nancy Takegawa, Ryosuke Nishikimi, Mitsuaki Li, Timmy Owens, Casey Molmenti, Ernesto P. He, Mingzhu Vanpatten, Sonya Al-Abed, Yousef Kim, Junhwan Becker, Lance B. Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title | Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title_full | Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title_fullStr | Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title_full_unstemmed | Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title_short | Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents |
title_sort | multi-drug cocktail therapy improves survival and neurological function after asphyxial cardiac arrest in rodents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253071/ https://www.ncbi.nlm.nih.gov/pubmed/37296668 http://dx.doi.org/10.3390/cells12111548 |
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