Effect of Thiopental and Ketamine on Endothelium-Dependent Relaxation Induced by Reactive Oxygen Species in Rabbit Thoracic Aorta

Choi, Mi Young; Suh, Jung Kook; Lee, Jong Won; Cho, Sang Yoon

Abstract

BACKGROUND: Reactive oxygen species (ROS) are free radicals that induce lipid peroxidation and cause tissue damage. ROS are frequently produced by ischemia and subsequent reperfusion in clinical situation and like coronary artery bypass graft surgery and transplantation. More over, some anesthetics are known to act as an antioxidants and free radical scavenger and, the aim of this study was to explore the scavenging effects of thiopental and ketamine against ROS induced by isolated rabbit thoracic aortic endothelial damage.
METHODS
Twenty white male rabbits (weighing 2.0-2.5 kg) were used. Thoracic aorta and were dissected free, cut into rings (3-4 mm), and suspended in an organ bath filled with 10 ml Krebs solution bubbled with 5% CO2 and 95% O2 at 37oC. The rings were equilibrated for 90 min and the solution changed every 15 min, and then a resting tension of 1.5 g was applied to the rings. Isometric tensions were recorded using a transducer connected to a data acqusition system (Biopac Inc. USA). Aortic rings were precontracted with norepinephrine (NE, 10-6 M), and changes in tension were measured after the cumulative administration of acetylcholine (ACh 3 x 10-7, 10-6 and 3 x 10-6 M) and nitroglycerin (NTG 10-5 M). Data are expressed as percentages of the 10-5 M NTG-induced relaxation (ACh/NTG). Percentages of ACh/NTG, before and after ROS exposure by electrolysis were noted for control and experimental groups. Aortic rings were pretreated with thiopental (3 x 10-5, 10-4 and 3 x 10-4 M, n = 9, 13, 17), ketamine (10-4 M, n = 8), catalase (1000 U/ml, n = 12), mannitol (3 x 10-4 M, n = 5) or not pretreated (free, n = 6). After 30 minutes, with the rings were exposed to ROS by electrolysis (DC 9 V, 20 mA, aortic rings 1 cm removed from the anode) in Krebs solution for 2 minutes. After electrolysis, the organ bath fluid was replaced with fresh Krebs solution, and the aortic rings were precontracted with NE and was vasorelaxation with ACh and NTG as above mentioned concentrations.
RESULTS
Endothelium-dependent vasorelaxation was induced in all concentrations of thiopental groups in a dose-dependent fashion (P <0.05 vs control value) even with ROS attack. The catalase group produced vasorelaxation after ROS attack (P <0.05 vs control value). On the other hand, no ACh-induced significant endothelium-dependent vasorelaxation after ROS exposure was observed in the ketamine and mannitol pretreated group, or in the free group (P <0.05 vs control group).
CONCLUSIONS
These findings suggest that thiopental and catalase preserve ACh induced endothelium-dependent vasorelaxation and that thiopental has a dose-dependent ROS scavenging effect like catalase.