Vision is as necessary an element in scientific achievement as is the carefully controlled experiment.-Ernest Gellhorn, 1953 SOME OF TIIE NEUROENDOCRINE SUBSTANCES that play a prominent role in the central nervous system are found in the peripheral circulation. Their exact functions are not entirely clear, but it appears evident that alterations in their concentration in the circulating blood are associated with profound overt mental and physical changes, TM as well as possibly initiating sudden serious disturbances of pulmonary ventilation, myocardial contractility, microcireulatory homeostasis, gastrointestinal and renal function, and carbohydrate metabolism. ~-9 These in turn may lead to the development of a shock-like state and death. The purpose of this study was to make a precise systematic inquh T into the effects of general anaesthetics as administered in clinical practice on the circulating blood level of four biogenic amines and to attempt to interrelate these with any changes that might appear in the mean arterial blood pressure, urine output , haematocrit, blood water, blood sugar, serum potassium, serum inorganic phosphorus, pyruvate, lactate, oxygen tension, acid-base balance, and serum transaminases (SGOT and SGPT). MATERIALS ANn METHODS Serial crossover tests were carried out in four consecutive sets of experiments in 10 to 15 trained, large (20 to 30 kg.) male dogs. Each animal received a general anaesthetic at one-to two-week intervals without prior administration of premedicant drugs or antisialogogues. After an overnight fast, a dog was weighed, then an intravenous infusion of 0.9 per cent saline was started in a forepaw vein after drawing a blood sample for estimation of blood sugar, serum potassium, serum inorganic phosphorus, SCOT, SGPT, whole blood histamine, and serotonin and plasma catecholamines (epinephrine and norepinephrine). Anaesthesia was then induced with 20 mg./kg, thiopenta] (2.S$ solution), and the dog was intubated with a large cuffed tube that was attached to a gas machine which delivered NsO ~ O~ (except with cyclopropane, when N20 was not used). A gas flow was used sufllcient to provide a minute ventilation of 350 to 400 ml./kg.

MUN)3ELEER AND DECASTRO reduced an analgesic a~d sedatwe state for surgmal procedures, without using balblturates or volatile a~aesthetm agents, whmh they called neuroleptanalgesla They employed a comb!#atlon of drugs developed by Janssen m Belgmm to* aecomphsh this state and many anaesthetists are now usmg thas techmque m Europe 1-~ Of the numerous new analgesm and sedatwe ~lrugs recently developed by Janssen, the combination of droperldol (R4749, dehydrobenzpendol, Inapsine| and fentanyl (R4263, phentanyl, Subhmase| an a 50 lk mxxture has been found ' I to provide the most satisfactory anaesthetm eondatmns an both ammals and m man, without causing sermus pl~ysmlogmal disturbances that cannot be controlled effectwely 7 s The pharmaeologma| propertms of these two drugs are summarized m Table I

There is a circumstance attending accidental injury which does not belong to disease, namely, that the injury done has, in all cases, a tendency to produce both the disposition and means of cure.-John Hunter, 1861IN A PBEVIOUSLY HEALTHY I~EBSON, physical injury is said to initiate a series of metabolic and endocrine processes which are associated with recovery and normal convalescence. 1 Many years ago, it was shown that simple haemorrhage alone may also initiate metabolic changes which are simply reflected by an increased concentration of nitrogen in the urine; and recently Moore has reported on his comprehensive studies of this subject. 2 Cannon recognized the concept of a neuroendocrine response to stress and described an increase in the activity of the sympathetic nervous system and in the output of epinephrine-like substances. In our time, Hans Selye attempted to find a single explanation for the endocrine and metabolic response to stress and postulated that increased adrenocortical activity initiated and controlled the total body response to stress, s Numerous studies have been done to determine the haemodynamic effects of the stress caused by haemorrhage with and without the overlying effect of general anaesthesia. ~-9 Only in the past few years have studies been reported on the effect of this combination on the reftexogenic areas, 1O.lZ the liver and anaerobic metabolism, 12,1s the heart, 14 the spinal cord and reticular activating system, 1B the respiratory system, ~s-~s and the neuroendocrine system. ~9 It appears as ff general anaesthesia by itself with thiepental, diethyl ether, and cyclepropane might produce a stress response, but this is not easily shown by measurement of corfieosteroids in the blood. 2~ This report deals with a continuation of our systematic study of some neuroendocrine and metabolic effects of general anaesthesia ~ with particular reference to the influence of graded severe haemorrhage. MAI~L~S AND METHO~Serial crossover tests were carried out on 10 trained male dogs each weighing 25 to 30 kg. Every animal received a general anaesthetic ten times, one every two to three weeks in rotation, with the anaesthetics ~or maintenance as shown in Table I.

No abstract

Trm EXPERIMENTS ltEPORTED here were designed to reveal some biochemical effects which might be produced by the repeated inhalation of Forane by dogs and monkeys, and to compare its influence on the cardiac irritability of dogs with that of other halogenated anaesthetics. METHODS Biochemical Effects in DogsTwo groups of five mature, pedigreed, female beagles were used, having a mean body weight of 10.6 kg. Each of the dogs in one of these groups had an open liver biopsy taken, under thiopentone anaesthesia, a month before the experiment. These received 3 hours of anaesthesia a day on five consecutive days. The other group of beagles was anaesthetized for 4 hours a day on alternate days, up to a total of 16 hours.After food had been withheld for 12 hours, anaesthesia was induced by mask inhalation of <4 per eent Forane in oxygen, and the dogs were intubated. No premedication or muscle relaxant drugs were used. The animals were then eonneeted to a non-rebreathing system, using Fink valves, and maintained under surgical anaesthesia with spontaneous respiration for the appropriate periods by the administration of between 1.0 and 1.5 per cent Forane in oxygen. Fluotec vapourisers were used which had been recalibrated by gas chromatography. Arterial and venous blood samples were drawn immediately after induction and just before termination of anaesthesia, and these were analysed by standard techniques for the variables listed in Tables I and II. No intravenous fluids were given. The blood chemistry results were studied for evidence of changes occurring during a single day's anaesthesia, those seen between the 'start' samples on the first day and the 'start' samples on the last day, and the effects of serial removal of blood. 1,2After the last anaesthetic, those dogs that received 3 hours of anaesthesia on five successive days were sacrificed by intravenous injection of a barbiturate, and tissue specimens of liver, kidney, pancreas, small bowel, spleen, lungs, and heart were taken for gross and microscopic examination.