A pharmacological composition for induction of a reversible torpor-like state and hypothermia in rats
| Autor: | Irina S. Fadeeva, Anatoly L. Kovtun, Olga V. Glushkova, Nadezhda M. Zakharova, Maxim O. Khrenov, V. P. Kutyshenko, Dmitry A. Prokhorov, Yury S. Tarahovsky, Natalia P. Komelina |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Hibernation Male medicine.medical_specialty Serotonin Reserpine Xenon Respiratory rate Torpor Ischemia Hypothermia 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Open field Body Temperature 03 medical and health sciences Magnesium Sulfate 0302 clinical medicine Oxygen Consumption Respiratory Rate Heart Rate Phenothiazines Internal medicine Heart rate medicine Animals Sorbitol Ivabradine General Pharmacology Toxicology and Pharmaceutics Rats Wistar Phospholipids Chemistry Brain General Medicine medicine.disease Propranolol Drug vehicle Rats Drug Combinations 030104 developmental biology Endocrinology Diphenhydramine Propylthiouracil Injections Intravenous medicine.symptom |
| Zdroj: | Life sciences. 219 |
| ISSN: | 1879-0631 |
| Popis: | Aims To initiate a state of artificial torpor we suggested a pharmacological multi-targeting strategy for simulation of the physiological pattern of natural hibernation including a significant reduction in heart rate, respiratory rate, body temperature and oxygen consumption as well as a decline in brain activity known as torpor. Materials and methods We have developed a composition which initiates a pharmacologically induced torpor-like state (PITS-composition), made up of eight therapeutic agents, inert gas xenon and lipid emulsion served as a drug vehicle. Key findings After a single intravenous injection to rats, PITS-composition causes a rapid decline in heart rate followed by a steady decrease in body temperature from about 38.5 °C to 31.5 °C, at ambient temperature of 22 °C–23 °C. The hypothermic state may continue on average for 16–17 h with the subsequent spontaneous return of heart rate and body temperature to the initial values. In the open field test at torpor the motility, rearing and grooming were suppressed but 4–8 days later they were restored. Significance Suspended animation states, including natural hibernation or pharmacologically induced synthetic torpor are of special attention of medicine, since it may improve survival rate after cardiac arrest, brain hemorrhage and ischemia, and during long-term space traveling. The suggested here multi-targeting strategy made possible to develop the pharmacological composition able, after a single intravenous injection, to initiate long, stable and reversible hypothermia and torpor at room temperature. After the torpor, animals were able to spontaneously restore both physiological parameters, and behavioral reactions. |
| Databáze: | OpenAIRE |
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