The Effects of Propofol and Thiopental on Nitric Oxide Production and Release in Erythrocytes

NCT06485388 | Completed

• 1 other identifier: Akdeniz U. Faculty
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Hypotension is frequently encountered during the use of these commonly used intravenous anaesthetic agents (thiopental and propofol). This is thought to be a consequence of their effects on the sympathetic nervous system, myocardial contractility or vascular tone. However, propofol causes a greater fall in systemic arterial blood pressure than any other drug used for induction of anaesthesia. Propofol causes profound vasodilation, whereas its myocardial depressant effect is not clear. The vasodilatation occurs in both arterial and venous systems. The decrease in systemic arterial blood pressure after thiopental induction is mainly due to peripheral vasodilatation caused by depression of the medullary vasomotor centre and inhibition of the sympathetic nervous system. However, how this peripheral vasodilator effect occurs after both drugs and which mediators accompany it have not yet been fully elucidated. In previous studies, it has been emphasised that systemic vasodilation may be related with increased formation of nitric oxide (NO), a small gaseous and lipophilic molecule which plays an important role in the regulation of vascular homeostasis and haemoregulation. It is important to elucidate the mechanisms that may mediate thiopental- and propofol-mediated vasodilatation in future studies in order to help the methods and treatments that can be developed to prevent hypotension caused by these drugs, which are widely used in clinical practice. Therefore, the aim of this study was to investigate the effects of thiopental and profol on erythrocyte NO synthase activity and erythrocyte-mediated NO release.

Conditions

Effect of Drug

Keywords

nitric oxide; erythrocyte; propofol; thiopental

Outcome Measures

Primary Outcomes (1)

• The effects of thiopental and propofol on erythrocyte NO synthase activity and erythrocyte-mediated NO release.

  Blood samples will be taken from healthy human volunteers aged 25-45 years. Measurements will be performed using the fluorescent NO probe 4-amino-5-methylamino-20,70-difluorofluorescein diacetate. Propofol and thiopental will be added to the suspensions at doses of 100, 250, 500 and 1000 µM and incubated for 30 minutes. We will repeate these experiments in the presence of L-NAME, a non-specific nitric oxide synthase inhibitor. The nitrite/nitrate concentration will be measured in the supernatant of the erythrocyte suspensions after centrifugation.Intracellular calcium measurements will also be made during propofol and thiopental experiments. Fluo-4 calcium dye will be added to the medium and flow cytometric measurements will be repeated.

  120 days

Secondary Outcomes (1)

• The effects of thiopental and propofol on erythrocyte haemorheology

  120 days

Study Arms (2)

Thiopental

ACTIVE COMPARATOR

Venous blood samples will be taken from the patients included in the study and incubated with thiopental (dose: 100, 250, 500 and 1000µM) after appropriate procedures in the laboratory environment. . After incubation, all resuspensions will be subjected to flow cytometric analysis to evaluate erythrocyte NO synthase activity and erythrocyte-mediated NO release.

Drug: Thiopental

Propofol

ACTIVE COMPARATOR

Venous blood samples will be taken from the patients included in the study and incubated with propofol (dose: 100, 250, 500 and 1000µM) after appropriate procedures in the laboratory environment. . After incubation, all resuspensions will be subjected to flow cytometric analysis to evaluate erythrocyte NO synthase activity and erythrocyte-mediated NO release.

Drug: Propofol

Interventions

Propofol DRUG

Venous blood samples will be taken from the patients included in the study and incubated with propofol (dose: 100, 250, 500 and 1000µM) after appropriate procedures in the laboratory environment. . After incubation, all resuspensions will be subjected to flow cytometric analysis to evaluate erythrocyte NO synthase activity and erythrocyte-mediated NO release.

Propofol

Thiopental DRUG

Venous blood samples will be taken from the patients included in the study and incubated with thiopental (dose: 100, 250, 500 and 1000µM) after appropriate procedures in the laboratory environment. . After incubation, all resuspensions will be subjected to flow cytometric analysis to evaluate erythrocyte NO synthase activity and erythrocyte-mediated NO release.

Thiopental

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male patients
• Aged 18-45 years
• ASA (American Society of Anaesthesiologists) class I (normal, healthy person without any disease or systemic problem other than surgical pathology that does not cause a systemic disorder)

You may not qualify if:

• Women patients
• ASA class \>1
• Patients with known thiopental/propofol allergy
• Patients outside the age range of 18-45 years

Sponsors & Collaborators

• Melike Cengiz: lead

Study Sites (1)

Akdeniz University School of Medicine, Department of Anesthesiology and Intensive Care, Turkey

Antalya, Turkey (Türkiye)

Location

MeSH Terms

Interventions

Propofol; Thiopental

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Thiobarbiturates; Barbiturates; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Ulku Arslan Yildiz, MD

  Akdeniz University School of Medicine, Department of Anesthesiology and Intensive Care, Turkey

  PRINCIPAL INVESTIGATOR

• Pinar Ulker, PhD

  Akdeniz University School of Medicine, Department of Physiology

  PRINCIPAL INVESTIGATOR

• Ahmet Yildirim

  Akdeniz University School of Medicine, Department of Physiology

  PRINCIPAL INVESTIGATOR

• Ayse Gulbin Arici, Professor

  Akdeniz University School of Medicine, Department of Anesthesiology and Reanimation, Turkey

  PRINCIPAL INVESTIGATOR

• Murat Yilmaz, Professor

  Akdeniz University School of Medicine, Department of Anesthesiology and Intensive Care, Turkey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD,Professor Doctor

Study Record Dates

• First Submitted: March 17, 2024
• First Posted: July 3, 2024
• Study Start: March 1, 2024
• Primary Completion: July 1, 2024
• Study Completion: July 7, 2024
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)