Academic Journal
Ubiquitous protective effects of cyclosporine A in preventing cardiac arrest-induced multiple organ failure
| العنوان: | Ubiquitous protective effects of cyclosporine A in preventing cardiac arrest-induced multiple organ failure |
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| المؤلفون: | Cour, Martin, Abrial, M., Jahandiez, V., Loufouat, J., Belaidi, E., Gharib, A., Varennes, A., Monneret, G., Thibault, H., Ovize, Michel, Argaud, Laurent |
| المساهمون: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-10-IBHU-0004,OPeRa,Organ ProtEction and ReplAcement(2010) |
| المصدر: | J Appl Physiol (1985) ; https://hal.science/hal-01859551 ; J Appl Physiol (1985), 2014, 117 (8), pp.930-6. ⟨10.1152/japplphysiol.00495.2014⟩ |
| بيانات النشر: | HAL CCSD |
| سنة النشر: | 2014 |
| المجموعة: | HAL Lyon 1 (University Claude Bernard Lyon 1) |
| مصطلحات موضوعية: | Animals, Rabbits, Cardiotonic Agents/*pharmacology, Cell Respiration/drug effects, Cyclosporine/*pharmacology, Heart Arrest/*physiopathology, Hemodynamics/drug effects, Mitochondria/drug effects/pathology, Mitochondrial Membrane Transport Proteins/metabolism, Multiple Organ Failure/physiopathology/*prevention & control, Myocardial Reperfusion Injury/drug therapy/physiopathology, Oxidative Phosphorylation/drug effects, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Opening of the mitochondrial permeability transition pore (mPTP) appears to be a pivotal event in myocardial ischemia-reperfusion (I/R) injury. Resuscitated cardiac arrest (CA) leads to the post-CA syndrome that encompasses, not only myocardial dysfunction, but also brain injury, failure of other organs (kidney, liver, or lung), and systemic response to I/R. We aimed to determine whether cyclosporine A (CsA) might prevent multiple organ failure following CA through a ubiquitous mPTP inhibition in each distant vital organ. Anesthetized New Zealand White rabbits were subjected to 15 min of CA and 120 min of reperfusion. At the onset of resuscitation, the rabbits received CsA, its non-immunosuppressive derivative NIM811, or vehicle (controls). Survival, hemodynamics, brain damage, organ injuries, and systemic I/R response were analyzed. Fresh mitochondria were isolated from the brain, heart, kidney, liver, and lung to assess both oxidative phosphorylation and permeability transition. CsA analogs significantly improved short-term survival and prevented multiple organ failure, including brain damage and myocardial dysfunction (P \textless 0.05 vs. controls). Susceptibility of mPTP opening was significantly increased in heart, brain, kidney, and liver mitochondria isolated from controls, while mitochondrial respiration was impaired (P \textless 0.05 vs. sham). CsA analogs prevented these mitochondrial dysfunctions (P \textless 0.05 vs. controls). These results suggest that CsA and NIM811 can prevent the post-CA syndrome through a ubiquitous mitochondrial protective effect at the level of each major distant organ. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | hal-01859551; https://hal.science/hal-01859551 |
| DOI: | 10.1152/japplphysiol.00495.2014 |
| الاتاحة: | https://hal.science/hal-01859551 https://doi.org/10.1152/japplphysiol.00495.2014 |
| رقم الانضمام: | edsbas.3C9FFC73 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1152/japplphysiol.00495.2014 |
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