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

Sponsor
Negovsky Reanimatology Research Institute (Other)
Overall Status
Withdrawn
CT.gov ID
NCT04287842
Collaborator
(none)
0
4
1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 4

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 Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
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
Actual Study Start Date :
May 1, 2015
Anticipated Primary Completion Date :
May 1, 2015
Actual Study Completion Date :
Jun 1, 2015

Arms and Interventions

Arm Intervention/Treatment
No Intervention: control

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

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
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.

Active Comparator: 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.

Drug: Desflurane
Desflurane anesthesia is introduced. This provides complete suppression of animal responses to pain, fixation, tracheal intubation and cardiac arrest.
Other Names:
  • suprane
  • Procedure: Cardiac arrest
    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.

    Active Comparator: 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.

    Drug: Sevoflurane
    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.
    Other Names:
  • Sevorane
  • Procedure: Cardiac arrest
    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.

    Outcome Measures

    Primary Outcome Measures

    1. total GSK-3b and phosphorilated (pGSK-3b) [after 15 minutes of exposition]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • breeding albino male rats weigh from 180 to 240 g
    Exclusion Criteria:
    • N/A

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Negovsky Reanimatology Research Institute

    Investigators

    • Principal Investigator: Valery Likhvantsev, MD,PhD, V. Negovskij Reanimatology Research Institute RAMS

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Negovsky Reanimatology Research Institute
    ClinicalTrials.gov Identifier:
    NCT04287842
    Other Study ID Numbers:
    • Des-2014E
    First Posted:
    Feb 27, 2020
    Last Update Posted:
    Feb 27, 2020
    Last Verified:
    Feb 1, 2020
    Keywords provided by Negovsky Reanimatology Research Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 27, 2020