No abstract

The effects of halothane, isoflurane, and enflurane on ionic currents induced by bath application of gamma-amino-butyric acid (GABA) were studied with the rat dorsal root ganglion neurons maintained in primary culture. The whole-cell patch clamp technique was used to record the current. In normal neurons before exposure to anesthetics, GABA at low concentrations (1-3 x 10(-6) M) induced a small sustained inward current. At higher concentrations (3 x 10(-5) M-1 x 10(-3) M), GABA induced a large inward current, which decayed to a steady-state level (desensitization). Halothane (0.86 mM), isoflurane (0.96 mM), and enflurane (1.89 mM), each equivalent to the respective 2 minimum alveolar concentration (MAC) units, augmented the sustained current evoked by 3 x 10(-6) M GABA to 330-350% of control and the peak current evoked by 3 x 10(-5) M of GABA to 136-145% of control. The decay phase of the current was accelerated by the anesthetics, the time for the current to decline to 70% of the peak being reduced to 23-39% of control. In contrast, the densitized steady-state current evoked by high concentrations of GABA was decreased by anesthetics. In conclusion, general anesthetics exert a dual effect on the GABA receptor channel complex: to potentiate the nondesensitized (both peak and sustained) current and to suppress the desensitized steady-state current. The potentiation of the GABA receptor channel response may be a primary action of anesthetics leading to surgical anesthesia.

No abstract

Anaesthesia with ether, halothane, methoxyflurane (Penthrane) and Ohio 347 (Ethrane) increased the energy stores in mouse brain as much as 1.7-fold above the control values. The greatest increases were observed in glucose and glycogen. Glucose-6-P was increased in some cases and UDP glucose was consistently lower in the anaesthetized animals. Hypothermia in conjunction with anaesthesia modified some of the observed changes. Hypothermia alone was associated with an increase in P-creatine and glucose and a decrease in UDPglucose in the brain.The cerebral metabolic rate was depressed by all the anaesthetic agents to about 50 per cent of the control value. When the body temperature was lowered to 25", the cerebral metabolic rate fell to 73 per cent of the control rate. A temperature coefficient of 1.035 was calculated as the fractional change/degree between 25" and 34".ANAESTHESIA affects the levels of glucose and rclated metabolites in the brain. Levels of glucose and the ratio of glucose in brain to that in blood increase after anaesthesia with chloroform, ether and phenobarbital (MAYMAN, GATFIELD and BRECKENRIDGE, 1964). In addition, both phenobarbital and ether produce consistent increases in the content of glycogen in brain, together with increased levels of glucose-6-P and decreased levels of UDPglucose (NELSON, SCHULZ, PASSONNEAU and LOWRY, 1968). These observed changes occur over a period of 5-8 h after which a new steady state is reached.The increased levels of glycogen are of particular interest because of the relatively slow increase in comparison to increases of glucose and related metabolites. Although the glycogen level in brain is comparatively lower than in other tissues, it normally comprises at least one-quarter of the total energy reserve of brain. In addition, cerebral glycogen appears to be uniquely affected in many diverse situations. Increases in levels of cerebral glycogen have been observed in association with certain metabolic diseases (TOURTELLOTTE et al., 1966) and after induced trauma (K~IVANEK, 1958; GUTH and WATSON, 1968). Increases have also been observed after the administration of such varied agents as the convulsants, methionine sulphoximine (FOLBERGROVA, PAS-SONNEAU, LOWRY and SCHULZ, 1969) and pentylenetetrazole (PALLADIN, 1954) ; reserpine (ALBRECHT, 1957; GEY, RUTISHAUSER and PLETSCHER, 1965); sympathomimetic agents (PALLADIN, 1954); and anaesthetics, including barbiturates (VACCARI, MALAGUTI and FREGNI, 1951 ; ESTLER and HEIM, 1960) and ether (ESTLER and HEIM,

Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done.