Impact if Desflurane Preconditioning on the Content of the Phospho-GSK-3b in the Rat's Neurons in the Model of I/R

Study Overview
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Brief Summary
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Endpoint implementation of reactions initiated by ischemia is the mitochondrial transition pore permeability. Mitochondria pores opening results in a release of factors triggering apoptosis primarily the cytochrome С Inhibition of the pores opening protects ischemic damage of the cells. The key enzyme regulating the mitochondrial permeability transition pore is GSK-3b: the phosphorylation of the enzyme inactivates the enzyme and prevents pore opening. Aim of studi is to determine content of the phosphorylatcd GS K-3b in neurons of rat brain in the model of total tschemia/reperfusion.

Detailed Description
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Endpoint implementation of reactions initiated by ischemia is the mitochondrial transition pore permeability. Mitochondria pores opening results in a release of factors triggering apoptosis. primarily the cytochrome С Inhibition of the pores opening protects ischemic damage of the cells. The key enzyme regulating the mitochondrial permeability transition pore is glycogen synthase-kinase 3b (GSK-3b): the phosphorylation of the enzyme inactivates the enzyme and prevents pore opening. We have shown in previous study that preconditioning with sevoflurane increases the content of the phosphorylated form of 6SK-3b and protects the mitochondria of neurons in rats brain during ischemia/reperfusion. Aim of studi is to determine content of the phosphorylated GS K-3b in neurons of rat brain in the model of total ischemia/reperfusion influenced by: 1 MAC desflurane vs control group; 1 MAC desflurane vs 1 MAC sevoflurane and 1 MAC desflurane vs training ischemia.

Official Title
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Neuroprotective Effect of Desflurane in the Experimental Study: the Impact if Desflurane Preconditioning on the Content of the Phosphorylated Form of GSK-3b in the Neurons of the Rat's Brain in the Model of Ischemia/Reperfusion

Conditions
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Heart Arrest

Intervention / Treatment
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* Drug: Desflurane
* Drug: Sevoflurane
* Procedure: Cardiac arrest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: breeding albino male rats weigh from 180 to 240 g Exclusion Criteria: N/A
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>Induction of anesthesia: Chloralhydrat intraperitoneal 300 mg/kg. This provides complete suppression of animal responses to pain, fixation, tracheal intubation. After fixation of the animal in the supine position trachea is intubated and mechanic ventlation with air using an animal respirator is performed. | |
| Experimental: training ischemia<br>Induction of anesthesia: Chloralhydrat intraperitoneal 300 mg/kg. Comparison of a total GSK-3 and phosphorytated (Ser9) GSK-3beta (pGSK3b) in brain tissuesupracardiac bundle of vessels by means of a special hook after cardiac arrest and absence of ventilation lasts 10 min. | Procedure: Cardiac arrest<br>* Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min.<br>|
| Active Comparator: desflurane<br>Intervention. Drug: Desflurane. Desflurane 8 vol% anesthesia is introduced. This provides complete suppression of animal responses to pain, fixation, tracheal intubation and cardiac arrest. After fixation of the animal in the supine position trachea is intubated and mechanic ventlation with air using an animal respirator is performed. Surgery: Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min. | Drug: Desflurane<br>* Desflurane anesthesia is introduced. This provides complete suppression of animal responses to pain, fixation, tracheal intubation and cardiac arrest.<br>* Other names: suprane;Procedure: Cardiac arrest<br>* Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min.<br>|
| Active Comparator: sevoflurane<br>Sevoflurane anesthesia is introduced. This provides complete suppression of animal responses to pain, fixation, tracheal intubation and cardiac arrest. After fixation of the animal in the supine position trachea is intubated and mechanic ventlation with air using an animal respirator is performed. Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min. | Drug: Sevoflurane<br>* Desflurane anesthesia is introduced. This provides complete suppression of animal responses to pain, fixation, tracheal intubation and cardiac arrest. After fixation of the animal in the supine position trachea is intubated and mechanic ventlation with air using an animal respirator is performed. Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min.<br>* Other names: Sevorane;Procedure: Cardiac arrest<br>* Cardiac arrest is induced by intrathoracic clamping of the supracardiac bundle of vessels by means of a special hook. Period of cardiac arrest and absence of ventilation lasts 10 min. The animal is then resuscitated by means of chest compressions and mechanichal ventilation with air. Cardiac activity and systemic blood circulation recovers within 1 min; spontaneous respiration will be resumed after a period of 4-6 min.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| total GSK-3b and phosphorilated (pGSK-3b) |  | after 15 minutes of exposition | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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desflurane, preconditioning