thiopental and Hemolysis

Propofol has free radical scavenging properties similar to those of recognized phenol-based antioxidants. We have examined these properties in an in vitro model of radical-induced cellular injury, comparing its activity with that of thiopentone (which has also been shown to have radical scavenging activity). Haemolysis of human erythrocytes was induced using the azo compound 2,2'-azo-bis(2-amidinopropane) dihydrochloride (ABAP). This was achieved by incubating a 10% suspension of erythrocytes with ABAP 100 mmol litre-1 at 37 degrees C. For propofol, at concentrations of 12.5, 25 and 50 mumol litre-1, the times to achieve 50% haemolysis were mean 126 (SEM 7) min (95% confidence interval 108-144 min), 150 (8) (129-170) min and 182 (12) (160-180) min, respectively (Intralipid control 107 (7) (90-125) min, ANOVA P < 0.0001). For thiopentone, at concentrations of 62.5, 125 and 250 mumol litre-1, the values were 117 (2) (112-121) min, 126 (3) (119-133) min and 138 (2) (132-144) min, respectively (saline control 109 (2) (104-113) min, ANOVA P < 0.0001). Spectroscopic analysis in the visible and ultraviolet spectra demonstrated a steady increase in the proportion of methaemoglobin during haemolysis, with the highest concentrations in the propofol-containing flasks. The formation of methaemoglobin was preceded by the generation of ferrylhaemoglobin (a Fe4+ haemoglobin species). Further experiments examining oxidation of purified methaemoglobin to ferrylhaemoglobin by hydrogen peroxide suggested that propofol, but not Intralipid or thiopentone, reduced ferrylhaemoglobin back to the met- state, and thereby explained the higher concentrations of methaemoglobin in the propofol-containing erythrocyte suspensions. We conclude that propofol is a more potent free radical scavenger in this model of oxidant stress than thiopentone, and that reduction of high oxidation states of haemoglobin may contribute to such activity.

Topics: Adult; Anesthetics, Intravenous; Cell Culture Techniques; Erythrocytes; Female; Free Radical Scavengers; Hemoglobins; Hemolysis; Humans; Male; Oxidation-Reduction; Oxidative Stress; Propofol; Spectrophotometry; Thiopental

An investigation was performed to compare the cerebral protective properties of etomidate, isoflurane, and thiopental. In separate groups of spontaneously hypertensive rats, etomidate, isoflurane, or thiopental was administered to achieve and maintain burst-suppression of the electroencephalogram (3-5 bursts/min) for the duration of the experiment. A fourth group received 1.2 minimal alveolar concentration halothane. All groups underwent 3 hours of middle cerebral artery occlusion and then 2 hours of reperfusion. Thereafter, the animals were killed and the volume of injured brain was determined by staining with 2,3,5-triphenyltetrazolium. Physiological parameters did not differ among the four groups during the investigation, with the exception that hemolysis occurred in the etomidate group (free hemoglobin levels, approximately 0.4 g.dl-1). The volume of injured brain in the thiopental group (56 +/- 10 mm3) was significantly smaller than that in the halothane control group (99 +/- 13 mm3). The volumes of injured brain in the etomidate and isoflurane groups (145 +/- 11 mm3 and 139 +/- 14 mm3, respectively) were significantly larger than those in the control and thiopental groups. We speculate that the apparently detrimental effect of etomidate may be the result of the binding of nitric oxide of cerebral endothelial origin by the iron component of free hemoglobin. Intracranial pressure was not recorded, and in the isoflurane group, there may have been adverse effects on cerebral perfusion pressure associated with vasodilation caused by high concentrations of isoflurane. The results are consistent with a protective effect by barbiturates.

Topics: Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Brain; Brain Damage, Chronic; Brain Ischemia; Dose-Response Relationship, Drug; Etomidate; Halothane; Hemolysis; Isoflurane; Male; Rats; Rats, Inbred SHR; Regional Blood Flow; Thiopental

Topics: Acetylcholine; Amobarbital; Amphetamine; Atropine; Barbiturates; Bemegride; Cell Membrane; Chlorpromazine; Epinephrine; Erythrocytes; Hemolysis; Hexobarbital; Norepinephrine; Osmotic Fragility; Pentobarbital; Phentolamine; Physostigmine; Scopolamine; Thiopental

Topics: Crystallization; Hemolysis; Hexobarbital; Humans; Injections, Intra-Arterial; Methohexital; Solutions; Thiopental; Thrombosis

Topics: Adult; Anemia, Hemolytic; Australia; Blood Chemical Analysis; Blood Platelet Disorders; Chlorpromazine; Diuresis; Eclampsia; Female; Fetal Death; Fetal Heart; Heart Rate; Hemoglobinuria; Hemolysis; Humans; Mannitol; Pregnancy; Pregnancy Complications, Hematologic; Promethazine; Seizures; Thiopental; Urinary Catheterization