Effect of Drug
Conditions
Keywords
nitric oxide, erythrocyte, propofol, thiopental
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.
Detailed description
Male patients aged 18-45 years with 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) who applied to the anaesthesiology and reanimation clinic outpatient clinic for preoperative preparation were planned to be included in the study. Women, patients with ASA class \>1, patients with known thiopental/propofol allergy and patients outside the age range of 18-45 years were excluded from the study. Venous blood samples will be taken from the patients included in the study and incubated with thiopental and 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.All patients included in the study will be informed and their written and verbal consent will be obtained.
Interventions
DRUGPropofol
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.
DRUGThiopental
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.
Sponsors
Melike Cengiz
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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)
Exclusion criteria
* Women patients * ASA class \>1 * Patients with known thiopental/propofol allergy * Patients outside the age range of 18-45 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The effects of thiopental and propofol on erythrocyte NO synthase activity and erythrocyte-mediated NO release. | 120 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The effects of thiopental and propofol on erythrocyte haemorheology | 120 days | 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. |
Countries
Turkey (Türkiye)
Outcome results
None listed