The Effects of Propofol and Thiopental on Nitric Oxide Production and Release in Erythrocytes
NCT Number: NCT06485388
Status: COMPLETED
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Effect of Drug
Interventions: DRUG: Propofol|DRUG: Thiopental
Sponsor: Melike Cengiz
Sex: MALE
Age: ADULT
Enrollment: 12
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (PARTICIPANT)|Primary Purpose: OTHER
Start Date: 2024-03-01
Completion Date: 2024-07-07
Locations: Akdeniz University School of Medicine, Department of Anesthesiology and Intensive Care, Turkey, Antalya, Turkey

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.

Primary Outcome Measures: 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 Outcome Measures: The effects of thiopental and propofol on erythrocyte haemorheology, The effects of thiopental and propofol on erythrocyte haemorheology. Blood samples will be taken from healthy male volunteers and leucocytes will be extracted. The RBC deformability will be measured as an elongation index (EI) for various liquid shear stresses by laser diffraction analysis using an ectacytometer (LORRCA, RR Mechatronics, Hoorn, The Netherlands).RBC aggregation will be assessed using the same echacytometer. Aggregation will be determined by placing 1 ml of blood in the space between the cup and bob. The sample will then be sheared at a speed of 800 1/s for 10 seconds to disperse pre-existing aggregates. After 10 seconds, the shear will be abruptly reduced to zero and the level of laser light reflected from the sample will be digitally recorded for 120 seconds., 120 days