Br.J. Anaesth. (1979), 51-, 989P

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY GLASGOW MEETING JULY 7, 1979 EFFECT OF KETAMINE ON TRANSMISSION IN SYMPATHETIC GANGLIA V. MAHMOODI, A. J. BYRNE, T. E. J. HEALY AND S. Z. HUSSAIN

ACKNOWLEDGEMENT

An increase in arterial pressure following the injection of ketamine is well documented and has been explained by both central (Ivankovich et al., 1974) and peripheral actions (Nedergaard, 1973). The sympathetic division of the autonomic nervous system is the link between central and peripheral mechanisms for increasing arterial pressure. It was therefore decided to investigate the effects of ketamine on this final common pathway. The hypogastric nerve, hypogastric plexus and vas 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 transmural (postganglionic) and nerve stimuli (preganglionic) were applied alternately and contractions of the vas deferens were measured using an isotonic transducer. The concentration of ketamine in the bath was increased at 16-min intervals. The effect of each concentration was expressed as a percentage of the control response. For comparison, the effect of hexamethonium was also studied. Ketamine produced a dose-dependent reduction in the response to preganglionic stimulation (IC 60 2.05 x 10"4 mol litre"1, r = 0.9), but did not reduce the response to post-ganglionic stimulation. The response to post ganglionic stimulation was blocked by guanethidine 1 x 10~* mol litre"1. The preganglionic electrodes in this study were placed considerably proximal to the ganglionic synapse, and it was necessary therefore to confirm that ketamine was acting as a nicotinic blocking agent rather than as a nonspecific depressant of nerve action potentials. Experiments were performed using the frog (Rana temporarid) rectus abdominis muscle. The muscle was mounted in frog's Ringer solution bubbled with air at 18 CC. The contraction of the muscle in response to carbachol 5.46 xl0" 7 -1.6xl0" 5 mol litre"1 was measured. The contractions of the preparation in the presence of carbachol in the same concentrations with ketamine 1 x 10"4 mol litre" 1 were recorded also. Ketamine caused a reversible depression of the response to carbachol. The response of the preparation to potassium chloride 3.3 x 10~2 mol litre"1 was unchanged by ketamine. The muscle contraction produced by carbachol 5.46 x 10~6 mol litre" 1 in the presence of increasing concentrations of ketamine was also studied. Ketamine produced a dose-dependent reduction in the contraction produced by carbachol. The concentration of ketamine which produced

We gratefully acknowledge financial support from Parke Davis and Co. REFERENCES

Hukovic, S. (1961). Br. J. Pharmacol, 16, 188. Ivankovich, A. D., Miletich, D. J., Reimann, C , Albrecht, R. F., and Zahed, B. (1974). Anesth. Analg. {Cleve.), 53, 924. Nedergaard, O. A. (1973). Eur. J. Pharmacol, 23, 153.

EFFECTS OF KETAMINE ON AUTONOMIC TRANSMISSION IN RAT ISOLATED ATRIA A. J. BYRNE, D. R. TOMLINSON AND T. E. J. HEALY

Department of Surgery (Anaesthesia) and Department of Physiology and Pharmacology, Queen's Medical Centre, University Hospital, Clifton Boulevard, Nottingham It is well recognized that ketamine stimulates the heart. Adams, Parker and Mathew (1977) showed that ketamine changed the response of isolated atria to catecholamines, but interactions between autonomic neurotransmission and ketamine have not been studied in vitro. The present study was designed to investigate the effects of ketamine on the response of rat atria to stimulation of the autonomic nerve supply and to exogenous catecholamines. Atria were removed from freshly killed Wistar rats (300450 g). Each atrium was suspended between parallel platinum wire electrodes in an organ bath containing Krebs' solution gassed with 95% O2 and 5% CO 2 at 37 °C. The left atrium was paced at 3 Hz by field stimulation (10-V, 2-ms pulses) to study inotropic changes. Ths right atrium was allowed to beat spontaneously and used to study chronotropy. Noradrenergic nerves in both atria were stimulated in the presence of atropine 1 x 10"6 mol and left atrial cholinergc nerves n the presence of propranolol 1 x 10~e mol according to the method of Blinks (1966). This gave graded chronotropic responses to different frequencies of stimulation (2-20 Hz) from the right atrium and a single inotropic response to the pacing frequency from the left atrium. Ketamine 5 x 10~6 mol increased the maximum amplitude of the inotropic response of the left atrium to noradrenergic nerve stimulation (/>100 73.4 ±3.1 in the dose-response curve between the nettle- and liverMethohexitone 46.4 + 2.6 27.8 + 3.7 fed groups appeared to result from a competitive reaction Thiopentone 79.0 ±3.9 42.7 ±5.8 but non-competitive factors seemed to be present for the Propanidid 42.7 + 3.3 intralipid group. 58.2 ±2.4 In Group 3 experiments the differences in response to Ketamine >100 >100 Nitrous oxide >100 >100 the membrane probe were more pronounced. has isomers including A16-alphaxalone and 3/J-hydroxyalphaxalone which, although differing only slightly in structure3 are completely "non-anaesthetic". If a nonanaesthetic isomer of alphaxalone protected against HPNS, this would be further positive evidence of separate receptors for anaesthetics and pressure, and preliminary results support this. It is probable however that these receptors are linked, since preliminary screening of a range of non-anaesthetic anticonvulsants in mice have not indicated that this type of drug will be of any value in treating pressure-induced convulsions. In view of all these data, it seems likely that there is some interaction between the separate sites for anaesthesia and pressure.

Halsey, M. J., Wardley-Smith, Bridget, and Green, C. J. (1978). Br.J. Anaesth., 50, 1091.

THE INFLUENCE OF DIET ON THE SUSCEPTIBILITY OF XENOPUS LAEVIS TADPOLES TO THIOPENTONE AND A MEMBRANE PROBE M. E. HAW Department of Anaesthesia, Leeds General Infirmary, Leeds

Burns, C. P., Luttenegger, D. G., Wei, Shiao Ping, L., and Spector, A. A. (1977). Lipids, 12, 747. Miller, K. W., and Pang, Kam-Yee Y. (1976). Nature (Lond.), 263, 253. Van Deenan, L. K. M., De Grier, J., and Demel, R. A. (1972). Biochem. Soc. Symp., 33, 377.

THE EFFECT OF HALOTHANE AND ENFLURANE ON SPECIFIC AIRWAYS CONDUCTANCE IN MAN J. R. LEHANE, C. JORDAN AND J. G. JONES

Anaesthetics can selectively perturb lipid bilayer mem- Division of Anaesthesia, Clinical Research Centre, Watford branes (Miller and Pang, 1976). The physical nature of a Road, Harrow, Middlesex membrane may be modified by altering the nature of its phospholipid molecules (Van Deenan, De Grier and Riigheimer, Himmler and Greiner (1974) reported that Demel, 1972). In addition, there is evidence that the enflurane increased airways resistance (Raw) whereas Roily nature of the fatty acids in the phospholipids of the mem- and Malcolm-Thomas (1975) found that both enflurane brane bilayer may be altered by the media or food which and halothane caused a reduction in Ravi. Changes in lung is available to the cells or animals concerned (Burns et al., volume during anaesthesia profoundly affect .Raw (Lehane, 1977). Jordan and Jones, 1979). However, neither Riigheimer and Xenopus laevis tadpoles were produced from wild-caught, colleagues nor Roily and Malcolm-Thomas allowed for the laboratory-reared toads, following induced mating and effects of changes in lung volume and this omission may spawning. Separate groups were fed on diets of: (1) liver account for the differences in their results. powder; (2) nettle powder; or (3) aminosol and intralipid. We have used the forced airflow oscillation method The tadpoles were reared for 3 weeks at 22 °C and then (Lehane, Jordan and Jones, 1979) to determine airflow numerous experiments were performed. resistance over a range of lung volumes during anaesthesia. Group 1 experiments compared tadpoles reared on The resulting hyperbolic plot of resistance against lung nettle powder and liver powder. Equal numbers of both volume can be redrawn after correcting for the asymptote groups of tadpoles were placed in 200 ml of free-standing to yield a linear plot of conductance against volume. The water and 1 nag of thiopentone dissolved in 0.5 ml of water slope of this line, the specific airways conductance (sGaw),

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REFERENCES REFERENCE

PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY

only at a very late stage from radiological evidence of pulmonary oedema when the pulmonary artery wedge and plasma colloid osmotic pressures are normal. We have developed a simple technique to obtain an index of AEM permeability in animals (Jones et al., 1978) and we now report a development of this technique for use in man. An aerosol of the hydrophilic molecule 88m Tc DTPA (mol. wt 452 dalton) in saline was generated using a disposable "Acorn" nebulizer and a settling bag to remove particles greater than 2.0 \aa in size (Taplin and Chopra, 1978). Male staff volunteered to be subjects for the study. After breathing the aerosol for 3 min, the disappearance rate of the isotope from the lung was derived using two scintillation detectors, one over the rib cage and the other over the thigh. The latter was used to correct for the increasing activity of 98m Tc DTPA extracted from the lung into the circulation. The two curves were analysed to produce a mono-exponential lung clearance curve. Seven subjects who were non-smokers had a mean lung clearance !Tj of 72.4 + 7.4 min (SEM), whereas 11 cigarette smokers had a mean clearance Th of 27.0 ± 6.2 min (SEM) (P < 0.001). We have also studied three patients (non-smokers). Two with pulmonary oedema following myocardial infarction had 7"j of 88 min and 49 min, and one with permeability pulmonary oedema from systemic lupus had a Tj of 32 min. These results indicate that AEM permeability is increased in symptomless cigarette smokers but it is not known how this effect is mediated. Because of relatively low molecular weights of 88m Tc DTPA the test provides a sensitive index of early alveolar epithelial damage. In non-smokers a rapid clearance may suggest the presence of a pathological process predisposing to pulmonary oedema, but the addition to the test of a measurement of the clearance of a second marker of larger molecular weight would improve its value in predicting the development of permeability pulmonary oedema in smokers and non-smokers.

REFERENCES

REFERENCES

Lehane, J. R., Jordan, C , and Jones, J. G. (1979). Br. J. Anaesth., 51, 65P. Roily, G., and Malcolm-Thomas, B. (1975). Acta Anaesthesiol. Belg., 26, (Suppl.) 43. Riigheimer, E., Himmler, J., and Greiner, K. (1974). Prakt. Anasth., 9, 87.

Jones, J. G., Berry, M., Hulands, G. H., and Crawley, J. C. W. (1978). Am. Rev. Respir. Dis., 118, 1007. Taplin, G. V., and Chopra, S. K. (1978). Progr. Nuclear Med., 5, 119.

A NEW METHOD FOR MEASURING ALVEOLAR EPITHELIAL MEMBRANE PERMEABILITY IN MAN J. G. JONES, B. D. MTNTY, G. H. HULANDS, J. C. W. CRAWLEY AND N. VEALL

Divisions of Anaesthesia and Radioisotopes, Clinical Research Centre, Northwick Park Hospital, Harrow, Middlesex An increase in permeability of the alveolar epithelial membrane (AEM) is believed to be initiated by a large variety of processes associated with the development of the adult respiratory distress syndrome. There is no suitable method available for the early diagnosis of an increase in permeability of the AEM in man. The diagnosis can be made

FRESH GAS AND VENTILATORY REQUIREMENTS DURING CONTROLLED VENTILATION WITH T-PIECE SYSTEMS C. M. CONWAY Westminster Hospital School, London Measurements during controlled ventilation of gas composition within the corrugated tubing of both conventional and coaxial D systems have shown considerable longitudinal mixing of fresh and expired gas along the system. If a uniform mix of these gases is assumed and if carbon dioxide output (KcOj) and VD/VT are assumed to be constant, the prevailing CO 2 will be a function of fresh gas flow, [VF], minute ventilation, Vn, and the character of the inspiratory waveform. Based on these assumptions, theoretical analyses have been performed using square, sinusoidal, exponential and

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is independent of changes in lung volume. Changes in sGaw therefore reflect changes in bronchomotor tone. We have measured the change in sGaw when halothane 1.3% or enflurane 2.5% was added during light nitrous oxide anaesthesia. Patients were allocated randomly into two groups of 10, one group receiving halothane, the other enflurane. All patients were non-smokers. Premedication was with oral diazepam 15 mg/70 kg. Following thiopentone and pancuronium, anaesthesia was maintained with 70% nitrous oxide and ventilation adjusted to give a PE'CO, of 5 kPa. During this period of light nitrous oxide anaesthesia at least three measurements of sGaw were made. Halothane or enflurane was added to the inspired gas mixture and further measurements of sGaw were obtained 3, 8, 15 and 25 min later. End-tidal concentrations of these agents were measured continuously using a mass spectrometer. At 15 min the range of end-tidal concentrations of both agents was 0.76-0.93 MAC. Measurements of sGaw during light nitrous oxide anaesthesia showed a skewed distribution which was normalized by taking logarithms. This permitted the application of the paired t test. Following addition of halothane, sGaw increased significantly in each of five patients (P