Enflurane (Ethrane, compound 347) in man *
Enflurane (2 chloro-1, 1,2-trifluoroethyl difluoro methyl ether) (CHFrOCFrCHFC1) is a halogenated liquid developed by Ross Terrell with the trade name Ethrane1’2. Enflurane has a pleasant, non-irritating smell, is volatile, colourless, non-flammable, stable with soda-lime, and unaffected by metals, light, moisture, heat and oxygen. It is non-explosive in anaesthetic concentrations when mixed with oxygen, air or nitrous oxide. Table 1 shows its physical and chemical characteristics. Virtue et al. 3 confirmed the anaesthetic properties of enflurane in dogs. They found that the agent was incompatible with the use of adrenaline and discovered some evidence of neuromuscular excitation under deep anaesthesia. McDowell and his colleagues4 also used enflurane on dogs. They produced some cardiac and respiratory depression and reported that it
The Effect of Ēthrane on Cardiac Muscle Mechanics
The inotropic effect of Ēthrane on the intrinsic contractile stale of the cat papillary heart muscle was studied in terms of mechanics of contraction. Negative inotropic responses to Ēthrane were compared with those of methoxyflurane and halothane. Ēthrane caused dose-dependent decreases in maximal velocity (Vmax), peak force (Fm), power, and work during isotonic contraction, and was less depressant than halothane and methoxyflurane. A greater concentration of Ēthranc (11 mg/100 ml) was required to produce the same degree of depression (50 per cent) in myocardial power as either methoxyflurane (4 mg/100 ml) or halothane (3 mg/100 ml). Similarly, a 50 per cent reduction in Vmax required a higher concentration of Ēthrane (233 per cent more than halothane and 18 per cent more than methoxyflurane). Therefore, Ēthrane was less depressant to myocardial contractility than methoxyflurane or halothane. Probable mechanisms and significance of the change in the active state resulting from anesthetics are discussed.
New method for analysis of enzymatic reactions: Thermolysin-catalyzed synthesis of aspartame precursor
Aspartame is an artificial sweetener which is 200 times sweeter than sucrose. A precursor of aspartame, N-(benzyloxycarbonyl)-l-aspartyl-l-phenylalanine methyl ester (Z-APM) was synthesized and hydrolyzed with thermolysin in an aqueous monophasic system. Graphical plotting methods and/or nonlinear regression have been used to analyze enzymatic reactions because of the nonlinearity of enzymatic rate equations. There are, however, problems: the former require accurate measurement of the initial reaction rate and the latter gives no analytical information. The authors proposed a method to solve the nonlinear enzymatic rate equations with respect to the concentration of a product with the Taylor expansion, especially for the reversible Theorell-Chance mechanism (Murakami, Y., Hirata, M., and Hirata, A., J. Ferment. Bioeng., 82, 246–252, 1996). This solution, however, is complex for practical use. In this paper, a simpler solution to explain the thermolysin-catalyzed synthesis of Z-APM is obtained. New methods to determine the kinetic parameters, especially for the reversible Theorell-Chance mechanism, based on the approximated solution are proposed. The results calculated using the obtained kinetic parameters can satisfactorily explain the experimental results, which demonstrates the effectiveness of the proposed analysis. We must know the relation between the concentrations of substrates and a product, and accurately evaluate of the result obtained using Taylor expansion when we determine the kinetic parameters using our newly developed methods. The methods to determine the kinetic parameters of the reversible Theorell-Chance mechanism described in this paper is, however, expected to be applied to general enzymatic reactions.