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Proceedings of the Anaesthetic Research Society Glasgow Meeting July 7, 1979

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Proceedings of the Anaesthetic Research Society Glasgow Meeting July 7, 1979 Br.J. Anaesth. (1979), 51-, 989P PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY GLASGOW MEETING JULY 7, 1979 EFFECT OF KETAMINE ON TRANSMISSION a 50% depression in the response to carbachol 5.46 x 10~6 1 5 IN SYMPATHETIC GANGLIA mol litre" was determined (IC50 ketamine = 8.5 x 10" 1 mol litre" , r = 0.83). Downloaded from https://academic.oup.com/bja/article/51/10/989/304330 by guest on 29 September 2021 V. MAHMOODI, A. J. BYRNE, T. E. J. HEALY AND In the concentrations used ketamine has been shown to S. Z. HUSSAIN interfere with the sympathetic final common pathway but Department of Surgery {Anaesthesia), Queen's Medical the results do not preclude a central effect at lower con- Centre, University Hospital, Clifton Boulevard, centrations. Nottingham ACKNOWLEDGEMENT An increase in arterial pressure following the injection of We gratefully acknowledge financial support from Parke ketamine is well documented and has been explained by Davis and Co. both central (Ivankovich et al., 1974) and peripheral actions (Nedergaard, 1973). The sympathetic division of REFERENCES the autonomic nervous system is the link between central Hukovic, S. (1961). Br. J. Pharmacol, 16, 188. and peripheral mechanisms for increasing arterial pressure. Ivankovich, A. D., Miletich, D. J., Reimann, C, Albrecht, It was therefore decided to investigate the effects of keta- R. F., and Zahed, B. (1974). Anesth. Analg. {Cleve.), 53, mine on this final common pathway. 924. The hypogastric nerve, hypogastric plexus and vas Nedergaard, O. A. (1973). Eur. J. Pharmacol, 23, 153. deferens of adult guineapigs were dissected (Hukovic, 1961) and mounted in Krebs' solution bubbled with oxygen 95% and carbon dioxide 5% at 32 °C. Supramaximal trans- mural (postganglionic) and nerve stimuli (preganglionic) EFFECTS OF KETAMINE ON AUTONOMIC were applied alternately and contractions of the vas deferens TRANSMISSION IN RAT ISOLATED ATRIA were measured using an isotonic transducer. The concentration of ketamine in the bath was increased A. J. BYRNE, D. R. TOMLINSON AND T. E. J. HEALY at 16-min intervals. The effect of each concentration was Department of Surgery (Anaesthesia) and Department of expressed as a percentage of the control response. For Physiology and Pharmacology, Queen's Medical Centre, comparison, the effect of hexamethonium was also studied. University Hospital, Clifton Boulevard, Nottingham Ketamine produced a dose-dependent reduction in the response to preganglionic stimulation (IC 60 2.05 x It is well recognized that ketamine stimulates the heart. 10"4 mol litre"1, r = 0.9), but did not reduce the response Adams, Parker and Mathew (1977) showed that ketamine to post-ganglionic stimulation. The response to post gan- changed the response of isolated atria to catecholamines, glionic stimulation was blocked by guanethidine 1 x but interactions between autonomic neurotransmission and 10~* mol litre"1. ketamine have not been studied in vitro. The present study The preganglionic electrodes in this study were placed was designed to investigate the effects of ketamine on the considerably proximal to the ganglionic synapse, and it response of rat atria to stimulation of the autonomic nerve was necessary therefore to confirm that ketamine was supply and to exogenous catecholamines. acting as a nicotinic blocking agent rather than as a non- Atria were removed from freshly killed Wistar rats (300- specific depressant of nerve action potentials. Experiments 450 g). Each atrium was suspended between parallel plati- were performed using the frog (Rana temporarid) rectus num wire electrodes in an organ bath containing Krebs' abdominis muscle. The muscle was mounted in frog's solution gassed with 95% O2 and 5% CO2 at 37 °C. The Ringer solution bubbled with air at 18 CC. left atrium was paced at 3 Hz by field stimulation (10-V, The contraction of the muscle in response to carbachol 2-ms pulses) to study inotropic changes. Ths right 5.46 xl0"7-1.6xl0"5 mol litre"1 was measured. The atrium was allowed to beat spontaneously and used to contractions of the preparation in the presence of carbachol study chronotropy. Noradrenergic nerves in both atria in the same concentrations with ketamine 1 x 10"4 mol were stimulated in the presence of atropine 1 x 10"6 mol litre"1 were recorded also. Ketamine caused a reversible and left atrial cholinergc nerves n the presence of pro- depression of the response to carbachol. The response of pranolol 1 x 10~e mol according to the method of Blinks the preparation to potassium chloride 3.3 x 10~2 mol litre"1 (1966). This gave graded chronotropic responses to different was unchanged by ketamine. frequencies of stimulation (2-20 Hz) from the right atrium The muscle contraction produced by carbachol 5.46 x and a single inotropic response to the pacing frequency 10~6 mol litre"1 in the presence of increasing concentra- from the left atrium. tions of ketamine was also studied. Ketamine produced a Ketamine 5 x 10~6 mol increased the maximum amplitude dose-dependent reduction in the contraction produced by of the inotropic response of the left atrium to noradrenergic carbachol. The concentration of ketamine which produced nerve stimulation (/><0.01). The duration of the response 990P BRITISH JOURNAL OF ANAESTHESIA was also markedly enhanced. In a concentration of 4x has been developed into which this ratio can be set for the 10~4 mol, ketamine caused a slight increase in resting force MGA 200 quadrupole apparatus (Centronic Limited, of contraction but a significant (P< 0.001) decrease in the Croydon); circuits to add the undesired fragmentation positive inotropy seen in response to noradrenergic nerve peaks and subtract them from the apparent, but erroneous, stimulation. reading allow the true value of the gas to be analysed. The Ketamine produced a dose-dependent slowing of the outputs of these circuits can be fed to the MGA 200 auto- right atrium. The control rate of 284 ±4 beat min"1 de- matic stability control mode (ASC) circuit providing stab- creased to 155 + 5 beat min"1 in the presence of ketamine ility of calibration of +1 % (full scale-deflection) for each 4 x 10~4 mol. This masked the effects of ketamine on the gas or vapour for more than 24 h. positive chronotropic response to noradrenergic nerve Mass spectrometers are unlikely to be of value in clinical stimulation. anaesthesia unless one instrument can be shared between Ketamine, in concentrations up to 4 x 10~4 mol, decreased several anaesthetizing locations. We have demonstrated Downloaded from https://academic.oup.com/bja/article/51/10/989/304330 by guest on 29 September 2021 the negative inotropic response to cholinergic nerve stimu- that gas can be sampled over distances of 40 m (sample lation in left atria but this effect was unrelated to the keta- flow 25 ml min"1) without serious loss of the respiratory mine concentrations used. waveform; the 90% rise time using a conventional 1-m The effects of ketamine on the responses of left atria probe was 80 ms"1 but increased to 500 ms"1 with a 40-m to exogenous noradrenaline and isoprenaline were studied. probe. The patient to mass spectrometer transit time was Potentiation of the response of the left atrium to nor- approximately 30 s. A shared facility between four opera- adrenaline by ketamine 5 x 10~6 mol was seen as a parallel ting theatres allows analysis of at least two b.p.m. for each leftward shift of the noradrenaline dose-response curve patient. (threefold increase in potency) with no increase in the maximum response. In a concentration of 2 x 10~4 mol, ketamine depressed the maximum response to noradren- 6 aline. Ketamine 5 x 10~ mol also potentiated the response MEASUREMENT OF BLOOD-GAS TENSIONS of the left atrium to isoprenaline (twofold increase in BY MASS SPECTROMETRY—THE "SUPER potency). RILEY BUBBLE" Ketamine has therefore been shown to increase the ino- tropic response both to noradrenergic nerve stimulation and to exogenous noradrenaline. This is consistent with W. W. MAPLESON, B. A. WILLIS AND R. T. CHILCOAT the hypothesis that ketamine causes a postjunctional Department of Anaesthetics, Welsh National School of sympathomimetic super-sensitivity combined with an Medicine, Cardiff increase in the available noradrenaline as a result of blockade of neuronal re-uptake which has been reported by Miletich If a small bubble of gas is equilibrated with a sample of and others (1973). blood at body temperature, the final partial pressures of gas in the bubble approximate to the initial tensions in ACKNOWLEDGEMENT the blood. This principle, with chemical analysis of the Financial assistance from Parke Davis and Co. is gratefully bubble, was used by Riley, Proemmel and Franke (1945) acknowledged. for the determination of O2 and CO2 tensions. In the present technique analysis by a respiratory mass spectro- REFERENCES meter (Centronic MGA 200) was used to determine the Adams, H. R., Parker, J. R., and Mathew, B. P. (1977). tensions of halothane and CO2 in arterial blood from dogs J. Pharmacol. Exp. Ther., 201, 171. breathing a mixture of halothane and nitrous oxide in Blinks, J. R. (1966). J. Pharmacol. Exp. Ther., 151, 221. oxygen. Miletich, D. J., Ivankovic, A. D., Albrecht, R. F., Zahed, A 5-ml all-glass syringe, modified to provide a conical B., and Ilahi, A. A. (1973). Anesthesiology., 39, 271. deadspace of about 0.2 ml and fitted with a nylon three- way tap, was flushed with the mixture which was delivered to the dog via a halothane vaporizer. The syringe was rilled with 2 ml of arterial blood and rotated in a water bath at body temperature in such a way that the bubble THE DEVELOPMENT OF THE MGA 200 MASS travelled to and fro inside the syringe for 2 min.
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