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

Phase 4

Withdrawn

• Conditions: Heart Arrest
• Interventions: Drug: Desflurane; Drug: Sevoflurane; Procedure: Cardiac arrest

• Registration Number: NCT04287842
• Lead Sponsor: Negovsky Reanimatology Research Institute

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-01-21
• Study Start: 2015-05
• Primary Completion: 2015-05
• Study Completion: 2015-06
• Status Verified: 2020-02
• Study First Submitted QC: 2020-02-25
• Last Update Submitted: 2020-02-25
• Study First Posted: 2020-02-27
• Last Update Posted: 2020-02-27

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

• breeding albino male rats weigh from 180 to 240 g

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Exclusion Criteria

• N/A

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
desflurane	Cardiac arrest	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.
training ischemia	Cardiac arrest	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.
sevoflurane	Cardiac arrest	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.
desflurane	Desflurane	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.
sevoflurane	Sevoflurane	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.

Primary Outcome Measures

Name	Time	Method
total GSK-3b and phosphorilated (pGSK-3b)	after 15 minutes of exposition