ON THE CARDIOVASCULAR EFFECT OF PROPRANOLOL DURING HALOTHANE ANAESTHESIA EN NORMOVOLAEMIC AND HYPOVOLAEMIC DOGS

Brit. J. Anaesth. (1970), 42, 272

ON THE CARDIOVASCULAR EFFECT OF PROPRANOLOL DURING HALOTHANE ANAESTHESIA EN NORMOVOLAEMIC AND HYPOVOLAEMIC DOGS BY K. H. W E I S AND H. D. BRACKEBUSCH SUMMARY

Propranolol* (Black et al., 1964, 1965) which inhibits exclusively the beta receptors postulated by Ahlquist (1948), whereby the action of catecholamines on the heart is reduced or completely abolished, may be considered a suitable agent for the treatment of catecholamine-induced cardiac arrhythmias (Payne and Senfield, 1964; Somani and Lum, 1965; Hellewell and Potts, 1965; Frey and Kaergard-Nielson, 1966; Iwatsuki et al., 1966; Johnstone, 1966; Lucchesi et al., 1966). Among current anaesthetics, it is in particular cyclopropane (Presel et al., 1960; Katz, 1965) and halothane which easily lead to cardiac arrhythmias, as both increase the cardiac sensitivity to adrenaline (Hall and Norris, 1958; Millar, Gilbert and Brindle, 1958; Johnstone and Nisbet, 1961; Katz, 1965).

Halothane (Raventos, 1956; Bloodwell et al., 1961; Morrow and Morrow, 1961; Lindgren, Westermark and Wahlin, 1965; Black, 1965; Price and Price, 1966; Hellewell and Potts, 1966) as well as propranolol (Iwatsuki et al., 1966; Nakano and Kusakari, 1966; Kabela and Mendez, 1966) show a marked intrinsic effect on the heart and cardiovascular system: both slow the heart rate and reduce the cardiac output and arterial pressure. Gander and associates (1966a) put weight on the fact that in animal experiments the circulatory parameters measured change in the direction of cardiac insufficiency after beta blockade (dp/dt decreases strongly and the enddiastolic ventricular volume rises). It may be K. H. W E I S , Prof.Dr.med.; H. D . BRACKEBUSCH, Dr.ing.;

• Propranolol = 1 isopropyl-amino-S-Cl-naphtyloxy)2-propranolol hydrochloride=Dociton. The required amounts of the test substance were kindly provided by Rhein-Pharma, Arzneimittel GmbH, Heidelberg.

from the Abteilung fur Anaesthesiologic der UniversitSt and the Experirnentell-chirurgische Abteilung of the Chirurgische UniversitfitsHinik, WUrzburg, West Germany.

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The circulatory effects of propranolol during halothane anaesthesia were investigated in fifteen dogs, in eight of which a moderate hypovolaemia was produced. Mean aortic pressure and flow, stroke volume, cardiac performance, and time of presssure rise showing infusion of adrenaline were measured or derived. The investigation led to the following findings: (1) The circulatory responses were similar in normo- and hypovolaemic animals. The ability of the latter to maintain an adequate cardiac output was markedly restricted. (2) Halothane significantly reduced flow, pressure, cardiac performance in both groups, and heart rate in the normovolaemic group. There was a nonsignificant decrease of heart rate in the hypovolaemic group and of stroke volume in both groups. (3) Propranolol significantly prolonged the time of pressure rise, slowed down and stabilized the heart rate and reduced the flow. The fall of stroke volume was significant in the normovolaemic group and the fall of cardiac performance was significant in the hypovolaemic group only. There was no significant change of pressure. (4) Adrenaline significantly increased pressure and cardiac performance after beta blockade but caused non-significant changes in other parameters except stroke volume in the hypovolaemic group. Two hypovolaemic animals had an irreversible asystole. It is emDhasized that, particularly in hypovolaemia and under propranolol during halothane anaesthesia, reliance on estimation of the arterial pressure may lead to completely false conclusions.

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CARDIOVASCULAR EFFECT OF PROPRANOLOL

METHODS

The tests were carried out in fifteen healthy mongrel dogs of either sex, weighing between 12 and 23 kg (mean 17.9 kg, SE 0.9 kg). There were two groups of seven and eight animals, each of which was subjected to the same conditions with the following exception. In the animals of Group 2, with continuous control of the mean arterial pressure measured in the ascending aorta, hypovolaemia was produced by withdrawal of blood sufficient to achieve a mean arterial pressure of 79 (mean; SE 2.5) mm Hg. The surgical preparation was carefully performed so that after stabilization only a negligible loss of blood occurred, which was compensated by an intravenous infusion of dextran (6 per cent, 30 ml/ hour). All the test animals received the same anaesthesia. After induction with thiopentone 10 mg/kg intravenously, a mixture of nitrous oxide (3 L/min) and oxygen (1.5 l./min) was inhaled; muscular relaxation was obtained by repeated single injections of suxamethonium and after endotracheal intubation ventilation was controlled by means of a mechanical ventilator (Pulmomat; Drager). Ventilation was monitored by means of an infra-red carbon dioxide analyzer (Uras-M; Hartmann & Braun). The expired carbon dioxide concentration was maintained between 3 and 4 vol. per cent. Halothane was administered through a Vapor

(Drager) and maintained over the whole experimental period. In order to measure flow and pressure in the ascending aorta the latter was exposed after splitting die sternum. The flow was measured electromagnetically (Medicon flowmeter); the pressure was measured widi a Statham element through a catheter introduced into the carotid artery. Additionally, the pressure in the femoral artery was controlled. The accuracy of measurement of flow and blood pressure was ±5 per cent. The femoral vein was cannulated for administration of injections. The measured values, flow and pressure of the ascending aorta and the femoral artery pressure, were continuously recorded by a magnetic tape recorder (MAS 24; Telefunken). Figure 1 shows an oscillogram of the parameters formed by flow and pressure. At the same time the mean values of the pressures and of the aortic flow were recorded by a direct writer (Hellige) for the purpose of direct control of the course of the test. In order to change the circulatory parameters during the effect of halothane, adrenaline was infused before and after propranolol injection. The well-known cardiac arrhythmias induced by adrenaline will not be especially mentioned. The course of the test was divided into seven sections. The initial values (I) were recorded after stabilization of flow and pressure following preparation. The time required for preparation was about 45 minutes and stable conditions followed 125rnmHg

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thus expected, during halothane anaesthesia and simultaneous beta blockade, that the summating effect of these two agents will reduce the ability of the heart to maintain an adequate cardiac output more than the administration of either substance alone. Anaesthesia is often required for surgery in patients showing varying degrees of reduction in circulating blood volume. It is highly desirable to know whether propranolol can be used with safety in such cases. So far no clinical reports and only few reports of animal investigations have been published concerning the use of propranolol with halothane (Iwatsuki et al., 1966; Craythome and Huffington, 1966). The following investigation was undertaken to study the response of the cardiovascular system of normo- and hypovolaemic dogs during halothane anaesthesia and induced beta-blockade.

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RESULTS

Mean aortic pressure (fig. 2). Inhalation of halothane significandy lowered die pressure, and adrenaline infusion significandy raised the pressure, in bodi groups. After recovery from die adrenaline effect the mean pressure fell

significandy, approaching die previous levels. A slight fall in pressure followed the injection of propranolol but this was not statistically significant. The second adrenaline infusion caused again a significant pressure rise which, however, in comparison widi die precedent adrenaline effect amounted to 73 per cent only in the first and 68 per cent in the second group. Heart rate (fig. 3). Halodiane caused a significant reduction in pulse rate in die first group. The decrease in die second group, however, was not significant. In neither group did adrenaline lead to significant alterations. Propranolol caused a significant slowing of pulse rate in botii groups. No significant alteration of pulse rate was noted during the second adrenaline infusion. Mean aortic flow (fig. 4). Halodiane significandy reduced die flow in bodi groups. In both groups adrenaline effected an increase of die flow, but this increase was significant only for die second group. Propranolol significandy reduced die flow in both groups. The second adrenaline infusion did not lead to a significant change. Stroke volume (fig. 5). Halothane inhalation was followed by an insignificant decrease in mean values in bodi groups. Adrenaline caused a significant increase of the stroke volume. It is statistically established diat propranolol decreased die stroke volume of die first but not of the second group. Only in die latter group did die second infusion of adrenaline cause significant increase in stroke volume. Cardiac performance (fig. 6). Halothane caused a significant decrease in bodi groups. Adrenaline raised die performance significandy in bodi groups. Propranolol reduced this value which, however, was significant only for die second group. The second adrenaline infusion again signicandy increased the cardiac performance in both groups. Time of pressure rise (fig. 7). The mean time of pressure rise during die first infusion of adrenaline was, in die first group 1.5 min (SE 0.25) and in die second group 1.85 min (SE 0.39).

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between 15 and 30 minutes after preparation. The test animals then received 1.5 vol. per cent halothane (II). The new steady state of the circulation parameters was achieved after at least 15 minutes. In section HI adrenaline (2.5 ^g/kg/min) was infused for a 5-minute period (infusion pump; Braun). After the disappearance of the adrenaline effect, which lasted between 4 and 6 minutes (IV), propranolol (V) (0.5 mg/kg) was injected over a period of 2 minutes. In section VI die adrenaline infusion already described was repeated, and in the final section (VH), the disappearance of the adrenaline effect (length of time about 5 minutes) was awaited. Each experiment ran for about 2 hours. For the evaluation of the experimental results the mean pressure, mean flow, heart rate, stroke volume and mean cardiac performance were ascertained in each of die seven stages. The cardiac performance was derived from die product of mean flow and mean pressure. This simplified relation did not take into consideration die part of die so-called alternating current cardiac performance and dius led to smaller values (approx. 10-20 per cent) (Wetterer and Kenner, 1968). The values which had not been measured (stroke volume, cardiac performance) were calculated with die aid of an analog computer (RAT 700; Telefunken). Furthermore, die time of pressure rise during adrenaline infusion before and after propranolol administration was estimated. This is die time during which pressure rises from 10 to 90 per cent of die final value. The statistical significance of die results was ascertained by comparison of die paired difference of mean values between succeeding periods using Student's t test. Changes were held to be significant when P<0.05. As it is impossible to decide die significance of change in mean values by inspection of die figures, the probability values have been included in die figures.

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STARTING VALUE

BRITISH JOURNAL OF ANAESTHESIA

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DISCUSSION

The initial values for both groups of animals differed considerably. In the ascending aorta of the hypovolaemic animals the mean pressure was 57 per cent, the flow 44 per cent, and the cardiac performance 25 per cent, of the values of the control animals; there was no difference in the heart rate. It was the purpose of the present experiment to avoid haemorrhagic shock because it was not intended that the capability of the cardiovascular compensatory mechanisms should be markedly restricted. Zeig, Buckley and Macy (1968) indicated that even during blockade of the vegetative nervous system the cardiac reserves are sufficient to compensate for blood loss of a degree which does not lead to a shock. To gauge the extent of the blood withdrawal, the adjustment of the mean aortic pressure proved to be a reliable parameter; referred to the pressure value under halothane anaesthesia it could be shown that this level was maintained also after disappearance of the effect of the second adrenaline infusion. Larger volume changes, e.g. by influx of extracellular fluid, may thus be excluded. Halothane. In the hypovolaemic animals halothane in a concentration of 1.5 vol. per cent reduced the blood pressure to 63 per cent, the aortic flow to 81 per cent and the cardiac performance to 45 per cent of the initial values. Significant changes in heart rate and stroke volume could not be demonstrated. The wide range of heart rates indicates the different reactions of the individual animal

In both groups, however, the important result is a statistically significant reduction of the mean

aortic flow. In all normovolaemic animals the parameters, except the stroke volume, showed a marked decrease. If the control group had been larger then the decrease in stroke volume might have achieved significance (see fig. 5). The observed changes are characteristic of halothane (Severinghaus and Cullen, 1958; Morrow and Morrow, 1961; Bloodwell et aL, 1961; Gander et aL, 1966b; Price and Price, 1966; Smith and Corbascio, 1966; Shinozaki, Mazuzan and Abajian, 1968). Adrenaline. In order to produce a cardiovascular stress during halothane anaesthesia, adrenaline was infused. In both groups the blood pressure was elevated, reaching 118 and 116 per cent of the starting values. The aortic How, stroke volume and cardiac performance increased in both groups. For the aortic flow in the normovolaemic animals, however, the probability was only 90 per cent, which may be related to the small number of tests. The heart rate did not change. Ventricular extrasystoles in the phase of pressure rise were occasionally observed. Propranolol. In contrast to the observations made by Sharma (1967), propranolol did not significantly decrease the blood pressure, which was already considerably reduced by halothane. Nevertheless, the somewhat lower mean values point to changes of that kind (Iwatsuki et al., 1966). The effect on the pulse rate was evident. It always decreased significantly and remained almost unchanged during the rest of the test period. The aortic flow, stroke volume and cardiac performance decreased in both groups but the decrease in stroke volume did not achieve significance in Group 2, nor did the decrease in cardiac performance in Group 1. Similar changes were reported by Iwatsuki and co-workers (1966) during 1 per cent halothane anaesthesia. Craythome and Huffington (1966) observed a significant decrease of the blood pressure, heart rate, stroke volume and cardiac output when propranolol was administered during cydoproprane anaesthesia; under halothane anaesthesia, however, only a reduced heart rate was noted. Considering the absolute values, the importance of the present findings becomes evident. In the

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The mean value was prolonged during the second adrenaline infusion after propranolol was given in the first group to 2.46 min (SE 025), and in the second group to 2.9 min (SE 0.48). An important result was that in two of the hypovolaemic animals after propranolol, infusion of adrenaline led to cardiac arrest in asystole; in neither animal could the heart be restarted. In one normovolaemic animal asystole occurred in the same circumstances but the heart action was restored by cardiac massage. Asystole was diagnosed by e.c.g. and direct inspection.

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CARDIOVASCULAR EFFECT OF PROPRANOLOL

of the same kind, but distinctly restricted in extent in the hypovolaemic animals. Propranolol caused an additional restriction of the regulatory range by its beta blocking effect, A special feature relating to clinical use is the fact that the most easily accessible circulatory parameter, namely the arterial blood pressure, provides the least information because it remains alterable in spite of the beta blockade and may thus lead to misinterpretation. The decisive parameters which are not easily measurable clinically, namely the aortic flow and stroke volume, decrease in a threatening way. So much the more, therefore, should further decrease in blood pressure be considered a most alarming sign. The indication for the administration of propranolol in clinical practice is usually to abolish cardiac arrhythmia. According to the present results from animal experiments, similar reactions in humans cannot be excluded. Propranolol should, therefore, be used with caution, especially in patients with deficient blood volume. ACKNOWLEDGEMENT

The authors gratefully acknowledge the technical assistance of Mr. Walter Kiesewetter. REFERENCES

Ahlquist, R. P. (1948). A study of the adrenotropic receptors. Amer. J. Physiol., 60, 60. Arbula, A., and Thai, A. P. (1966). The hemodynamic effects of alpha- and beta-adrenergic blockade. Surgery, 60, 60. Bloodwell, R. D., Brown, R. C , Christenson, G. R,, Goldberg, L. I., and Morrow, A. G. (1961). The effect of Fluothane on myocardial contractile force in man. Anesth. Analg. Curr. Res., 40, 352. Black, G. W. (1965). A review of the pharmacology of halothane. Brit. J. Anaesth., 37, 688. Black, J. W., Crowther, A. F., Shanks, R. G., Smith, L. H., and Domhorst, A. C. (1964). A new adrenergic beta-receptor antagonist Lancet, 1, 1080. Duncan, W. A. M., and Shanks, R. G. (1965). Comparison of some properties of pronethalol and propranolol. Brit. J. Pharmacol., 25, 577. Craythorne, N. W. B., and Huffington, P. E. (1966). Effects of propranolol on the cardiovascular response of cyclopropane and halothane. Anesthesiology, 27, 580. Frey, H. H., and Kaergaard-Niebon, C (1966). Study on the effect of a 0-fldrenolytic agent upon thiobarbiturate-arrhythmia in the dog. Arch. int. Pharmacodyn., 162, 93. Gander, M., Veragut, t)., Kohler, R., and Lflthy, E. (1966a). Cardiac haemodynamics under /3-receptor blockade in dogs. Cardiologica (.Basel), 49, SuppL VI, 17.

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hypovolaemic animals the aortic flow after propranolol was 0.68 l./min. This represents 56 per cent of the initial value of 1.22 l./min, but only 25 per cent of the initial value of 2.74 l./min in the control group, where the flow itself was reduced by 43 per cent to 1.19 l./min. This indicates the extreme condition of the circulation before further adrenaline infusion. Compared with the effects of the first adrenaline infusion the pressure alone changed significantly in the nonnovolaemic animals. Heart rate, aortic flow and stroke volume did not change significantly although there was a significant elevation in cardiac performance. In the hypovolaemic animals there were significant changes in pressure, stroke volume and cardiac performance, but not in heart rate or aortic flow in the six survivors. The rise in mean aortic pressure showed a pronounced delay in both groups. This demonstrates that after the administration of propranolol the effect of adrenaline infusion occurs more slowly. A pronounced effect as found by Shanks (1966) could not be observed. In order to interpret the findings in the hypovolaemic animals after beta blockade the loss of two animals under the second adrenaline infusion must be noted. Asystole suddenly occurred in these two animals initiated, viewed retrospectively, by a continuous decrease of the mean aortic pressure. At the extremely low values then obtaining for aortic flow and stroke volume, the animals were obviously unable to maintain adequate coronary perfusion. Neither immediate cardiac massage nor additional adrenaline was successful in restoring spontaneous cardiac activity. Lennartz, Greeff and Heeg (1966) demonstrated that despite the reduction of maximal rate of rise of left ventricular pressure (dp/dt) caused by halothane, the response to isoproterenol (Moran, 1963) indicated that the sensitivity of the beta receptors was unchanged. Thus, the negative inotropic effect of halothane is not due to beta blockade. The combination of halothane and propranolol receives its critical importance in that both substances, although through different mechanisms, have a negative inotropic effect. On the whole, the experiments comparing hypovolaemic and nonnovolaemic animals under halothane anaesthesia showed that the ability to maintain an adequate cardiac output was indeed

278

Severinghaus, J. W., and Cullen, S. C. (1958). Depression of myocardium and body oxygen consumption with Fluothane. Anesthesiology, 19, 165. Shanks, R. G. (1966). The effect of propranolol on the cardiovascular responses to isoprenaline, adrenaline and noradrenaline in the anaesthetized dog. Brit. J. Pharmacol, 26, 322. Sharma, P. L. (1967). Effect of propranolol on arterial hypotension induced by halothane in the dog under nitrous oxide anaesthesia. Brit. J. Anaesth., 39, 215. Shinozaki, T., Mazuzan, J. E. jr., and Abajian, J. jr. (1968). Halothane and the heart. Brit. 7. Anaesth., 40,79. Smith, N. T., and Corbascio, A. N. (1966). The cardiovascular effects of nitrous oxide during halothane anesthesia in the dog. Anesthesiology, 27, 560. Somani, p., and Lum, B. K. B. (1965). The antiarrhythmic actions of beta adrenergic blocking agents. J. Pharmacol exp. Ther., 147, 194. Wetterer, E., and Kenner, Th. (1968). Dynarmk des Arterienpulses. Berlin: Springer. Zeig, N. J., Buckley, N. M., and Macy, J. (1968). Effects of acute hemorrhage after adrenergic blockade in splenectomized dogs. Amer. J. Physiol, 214, 33. L'EFFET CARDIOVASCULAIRE DE PROPANOLOL DURANT L'ANESTHESIE A L'HALOTHANE CHEZ DES CHIENS NORMOVOLEMIQUES ET HYPOVOLEMIQUES SOMMAIRE

Les effets d'halothane sur la circulation ont etc etudies chez quinze chiens, dont huit ou une hypovolemk avait eti produite. La pression et le flux aortiques moyens, le volume pulsatile, la performance du coeur et le moment de Paugmentation de la pression sous infusion d'adrenaline ont iti mesures ou calcules. L'investigation a donn£ les resultats suivants: (1) Les reactions circulatoires furent similaires chez les animaux normovolemiques et hypovolemiques. On nota chez ces derniers une restriction marquee de la capacity de maintenir un d^bit cardiaque adequat- (2) L'halothane retluisit significativement lc flux, la pression et la performance cardiaque dans les deux groupes, et la frequence cardiaque dans le groupe nonnovolemique. II y eut une restriction non-significative de la frequence du coeur dans le groupe hypovolcmique et du volume pulsatile dans les deux groupes. (3) Propanolol retarda significativement le moment de Paugmentation de la pression, recluisit et stabilisa la frequence cardiaque et diminua le flux. La reduction du volume pulsatile fut significative dans le groupe normovolemique et la diminution de la performance du coeur ne fut significative
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Gander, M., Veragut, U. P., Liithy, E., and Hegglin, R. (1966b). Hemodynamic effects of halothane in the closed chest dog. Helv. med. Acta, 33, 351. Hall, K. D., and Norris, F. H. jr. (1958). Fluothane sensitisation of the dog heart to the action of epinephrine. Anesthesiology, 19, 631. Hellewell, J., and Potts, N. W. (1965). Propranolol and ventricular arrhythmias with halothane. Anaesthesia, 20, 269. (1966). Propranolol during controlled hypotension. Brit. J. Anaesth., 38, 794. Iwatsuki, K., Yusa, T., Yasuda, J., Hashimoto, Y., Takahashi, K., and Iwatsuki, N. (1966). Effect of propranolol on cardiac arrhythmias induced by adrenaline under halothane anesthesia. J. exp. Med., 88, 263. Johnstone, M. (1966). Propranolol (Inderal) during halotbane anaesthesia. Brit. J. Anaesth., 38, 516. Nisbet, H. I. A. (1961). Ventricular arrhythmias during halothane anaesthesia. Brit. J. Anaesth, 33, 9. Kabela, E., and Mendez, R. (1966). Action of propranolol on the atriovcntricular node and its response to adrenaline and isoprenaline. Brit. J. Pharmacol, 26, 473. Katz, R. L. (1965). Effects of alpha- and beta-adrenergic blocking agents on cyclopropane-catecholamine cardiac arrhythmias. Anesthesiology, 26, 289. Lennartz, H., Greeff, K., and Heeg, E. (1966). Einflufl verschiedener Narkotika auf den intrakardialen Druckanstieg (dp/dt) nach Blockade der /3-Rezeptoren. Verh, dtsch. Ges. Kreisl. Forsch., 32, 296. Lindgren, P., Westermark, L., and Wiihlin, A. (1965). Blood circulation in skeletal muscles under halothane anaesthesia in the cat. Acta anaesth. scand., 9, 83. Lucchesi, B. R., Whithsitt, L. S., and Brown, N. L. (1966). Propranolol (Inderal) in experimentallyinduced cardiac arrhythmias. Canad. J. Physiol. and Pharmacol., 44, 543. Millar, R. A., Gilbert, R. G. B., and Brindle, G. F. (1958). Ventricular arrhythmias during anaesthesia with halothane. Anaesthesia, 13, 164. Moran, N. C. (1963). Adrenergic receptors within the cardiovascular system. Circulation, 28, 987. Morrow, D. H., and Morrow, A. G. (1961). The effects of halothane on myocardial contractile force and vascular resistance: direct observations made in patients during cardiopulmonary bypass. Anesthesiology, 22, 537. Nakano, J., and Kusakari, T. (1966). Effects of beta adrenergic blockade on the cardiovascular dynamics. Amer. J. Physiol., 210, 833. Payne, J. P., and SenfieW, R. M. (1964). Pronethalol in treatment of ventricular arrhythmias during anaesthesia. Brit. med. J., 1, 603. Presel, P. E., MacCaunell, K. L., and Nickerson, M. (1960). Cardiac arrhythmias induced by minimal doses of epinephrine in cyclopropane-anesthetized dogs. Circulat. Res., 8, 948. Price, H. L., and Price, M. L. (1966). Has halothane a predominant circulatory action? Anesthesiology, 27, 764. Raventos, J. (1956). The action of Fluothane: a new volatile anaesthetic. Brit. J. Pharmacol., 11, 394.

BRITISH JOURNAL OF ANAESTHESIA

CARDIOVASCULAR EFFECT OF PROPRANOLOL OBER DEN KARDIOVASKULAREN EFFEKT VON PROPANOLOL WAHREND DER HALOTHAN-NARKOSE BEI NORMOVOLAMISCHEN UND HYPOVOLAMISCHEN HUNDEN ZUSAMMENFASSUNG

stung; in der normovolamischen Gruppe wurde auch die Herzfrequrnz herabgesetzt. Es kam zu einer nicht signiiikanten Verminderung der Herzfrequenz in der hypovolamischen Gruppe und des Schlagvolumens in beiden Gruppen. (3) Signifikant wurde durch Propanolol die Zeit des Druckanstiegs verlangert, die Herzfrequenz verlangsamt und stabilisiert und die Stromung reduziert. Ein signifikanter Abfall des Schlagvolumens wurde in der normovolamischen Gruppe, ein Absinken der Herzleistung nur in der hypovolamischen Gruppe beobachteL Es kam zu keiner signifikanten Veranderung des Drucks. (4) Adrenahn erhohte nach der Beta-Rezeptoren-Blockade Druck und Herzleistung signifikant, bewirkte aber nur nicht signifikante VerSnderungen der andercn Parameter auOer bei dem Schlagvolumen in der hypovolamischen Gruppe. Bei zwei hypovolamischen Tieren kam es zu einer irreversiblen Asystolie. (5) Es wird nachdriickh'ch betont, dafi besonders bei Hypovolamie und unter Propanololwirkung ein zu starkes Vertrauen auf die Bestimmung des arteriellen Drucks wahrend der Halothan-Narkose moglicherweise zu vollkommen falschen Schliissen fiihren kann.

EDITORIAL continued from page 271 there are difficulties in defining the need for the desirable water content of moist inspired gas in various clinical situations. At present the evidence is inadequate or anecdotal, and the technological achievements of the nebulizer manufacturers may outstrip our clinical knowledge, to the extent that harmful effects on the lungs may be caused inadvertently. The recognition of factors predisposing to an excess of bronchial mucus are fairly well known, and although measurements of the viscosity of this non-Newtonian fluid have recently been reported we are still unable to quantitate its

mass and topographical distribution. Until this can be done the control of humidification therapy must remain empirical. Meanwhile it may be wise to consider very carefully the indications for raising the water content of inspired gas above that of saturation and whether humidification of anaesthetic gases during prolonged anaesthesia would benefit patients, especially those with secretional difficulties. More information is required concerning the effects on lung mechanics and gas exchange in normal man of breathing dry air for prolonged periods.

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Die Wirkungen von Propanolol auf den Kreislauf wahrend einer Halothan-Narkose wurden an fiinfzehn Hunden untersucht; bei acht Hunden war eine maflige Hypovolamie erzeugt worden. Mittlerer Aortendruck und Stromung, Schlagvolumen, Herzleistung und Zeit des nach Adrenalin-Infusion eintretendcn Blutdruckanstiegs wurden gemessen oder abgeleitet. Die Untersuchung fiihrte zu folgenden Befunden: (1) Die Kreislaufreaktionen waren bei normo- und hypovolamischen Versiichstieren gleich. Die Fahigkeit zur Aufrechterhaltung eines ausreichenden Herzschlagvolumens war bei den letzteren deutlich eingeschrankt. (2) Halothan bewirkte in beiden Gruppen eine signifikante Reduzierung von Stromung, Druck und Herzlei-

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