Physiological Salt Solutions for Brain Surgery

Studies of Local pH and Pial Vessel Reactions to Buffered and Unbuffered Isotonic Solutions

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It is common experience that simple exposure of the pia-arachnoid surface of the cerebral cortex during prolonged neurosurgical procedures, such as for an exploratory craniotomy, results in the formation of adhesions between the dura and arachnoid. In certain cases there may be transitory aphasia or paresis during the first week following a simple exploratory procedure. These transitory postoperative complications are usually attributed to “edema.” This explanation has received support in the experiments of Prados, Strowger, and Feindel,15,16 who demonstrated that marked edema does develop following simple exposure of the cortex in cats and that it

It is common experience that simple exposure of the pia-arachnoid surface of the cerebral cortex during prolonged neurosurgical procedures, such as for an exploratory craniotomy, results in the formation of adhesions between the dura and arachnoid. In certain cases there may be transitory aphasia or paresis during the first week following a simple exploratory procedure. These transitory postoperative complications are usually attributed to “edema.” This explanation has received support in the experiments of Prados, Strowger, and Feindel,15,16 who demonstrated that marked edema does develop following simple exposure of the cortex in cats and that it is associated with vasodilatation and an increase in permeability of the bloodbrain barrier. They found that this reaction of the brain to exposure could be prevented, at least in part, by hormones (desoxycorticosterone, adrenal cortical extract) which tend to counteract the increase in vascular permeability.

The physical factors (temperature, mild trauma, air, light, drying, etc.) acting upon the exposed brain to produce these undesirable reactions have not received systematic study. One of these factors may be the composition of the irrigation fluid. The study of irrigation fluids for use on the exposed brain, which forms the subject of the present report, is a part of a series of investigations on the general problem of the reaction of the brain to exposure which is being carried out under the direction of Professor Wilder Penfield.

The importance of the composition of salt solutions in experimental studies of the nervous system has long been recognized.2,9,12 Studies of the in vitro metabolism of brain tissue4,7 have shown that it is sensitive to the composition of the medium in which the tissue is bathed. Much recent work has shown the dependence of the physical condition of biological materials, and the activity of many enzymes, upon the presence of various ions, often in low concentration. Little consideration has been given to the possible significance of these findings in the selection of solutions most suitable for use as irrigation fluids during operations on the brain or elsewhere or for replacing spinal fluid or filling cavities. There is little uniformity of practice among neurosurgeons with regard to the type of solution employed except that it is usually made isotonic with serum. Some use normal saline (0.85 or 0.9 per cent NaCl) while others use other “Ringer” solutions of varying composition.

Hartmann10 (see also Sachs18) has described a solution resembling spinal fluid particularly in its content of bicarbonate, but this was apparently used only for filling the ventricles of hydrocephalic infants after drainage for electrocoagulation of the choroid lexus. In spinal fluid, and in all other body fluids, the concentration of the bicarbonate ion is exceeded only by those of sodium and chloride; it constitutes about 15 per cent of the total anionic concentration. Besides serving as the main physiological buffer it is concerned in other biochemical mechanisms. Any solution that lacks this ion is therefore highly unphysiological.

In the present communication the preparation and dispensation of sterile fluids closely resembling cerebrospinal fluid are described, general methods for the study of the effects of various fluids are outlined, and studies of the reaction of the cortex to the pH of irrigating solutions are reported. Studies on the effects of different irrigation fluids on the electrical activity of the cortex, the response to cortical stimulation, the development of edema, and the formation of adhesions and other aspects of the problem are in progress.

PREPARATION OF STERILE IRRIGATION FLUIDS

The preparation of two solutions resembling spinal fluid has been worked out so that technicians would not be called upon to weigh fractions of grams, and manipulations are reduced to a minimum. The first of these, Solution A, is very similar to Locke's or Tyrode's solution. It lacks bicarbonate but is readily prepared. The second, Solution B, contains bicarbonate and is somewhat more troublesome to prepare in sterile condition. It resembles the solution designed by Hartmann10,18 but is more easily prepared in bulk and approaches the composition of spinal fluid a little more closely. In Table 1 the composition of these solutions is compared with that of cerebrospinal fluid and blood plasma.

TABLE 1

Composition of fluids mg. per 100 ml.

Blood plasmaSpinal Fluid*Solution BHartmann' SolutionSolution ARinger-LockeRinger Tyrode
AverageRange        
Chloride (as NaCl)594 726 700–750762 806 900 958 849 
Bicarbonate (as NaHCO3)193 177 182 198  10–30 10 
Phosphate (as P)4 1.5 1.2–2.11.7    1.3 
Sulfate (as S)3.4 ? ?  3.9   
Sodium316 324 301–343335 345 338 360 318 
Potassium19 13 11–1515.8 20 15.8 22 10.5 
Calcium10 5 4.5–5.55.5 5.5 5.5 8.7 7.2 
Magnesium2 3 1.0–3.50.9 4.8 2.9  2.6 
Glucose100 61 50–8080  80 (100) 100 
Freezing point−0.57 −0.57 −0.53 to −0.6−0.53‡ −0.55‡ −0.54‡ −0.58‡ −0.51‡ 
pH7.4  7.35–7.407.3± 7.3± 6.0± 7.9–8.3§ 7.4§ 

Figures given by Merritt and Fremont-Smith.13

Blood plasma contains, of course, some 7 per cent of proteins and normal spinal fluid contains a trace of protein. Both contain small amounts of urea, uric acid, amino acids, creatinine and other materials.

Calculated values.

The amount of bicarbonate present in these solutions is too low to provide appreciable buffering capacity and the pH would fall considerably in the presence of CO2.

Though the above solutions were designed with operations on the brain in mind, they should theoretically be suitable for irrigation of other organs and tissues and as perfusion fluids in experimental physiology. They differ from commonly used Ringer solutions in having a slightly lower content of calcium but the amount present is approximately equal to that in spinal fluid and to the free, ionized, calcium of serum.

Solution A. This solution is prepared according to the following simple formula and may be autoclaved. It should be autoclaved immediately after preparation.

NaCl..............................86 g.
KCl.............................. 3 g.
CaCl2·2H2O.............................. 2 g.
MgSO4·7H2O.............................. 3 g.
Dextrose..............................10 g.
Distilled water..............................10.5 liters*
This solution contains no phosphate since this ion causes precipitation of calcium and magnesium during autoclaving. Like distilled water or any unbuffered solution of neutral salts, Solution A after standing usually has a slightly acid reaction, about pH 6, due to dissolved carbon dioxide.

This solution has been adopted for all operative work in the physiological laboratories of the Montreal Neurological Institute. The same solution without glucose is used routinely in the operating rooms of this Institute. For the present, glucose is omitted since immediate autoclaving of large quantities cannot always be insured and the value of the glucose has not yet been proven.

Solution B.* Sterile preparation of this fluid requires the preparation of three separate solutions.

f1

Pyrogen-free water should, of course, be used throughout. The high salt concentration and strong alkalinity of the “stock alkaline salt solution” prevents the growth of organisms. This solution may therefore be kept for a long time provided that it is well stoppered. It should be kept in a pyrex bottle. The phenol red solution is prepared by dissolving 100 mg. phenol red (phenol sulphonephthalein) in 5 ml. 0.1 N NaOH and diluting to 100 ml. with strong sodium chloride solution, 20 g. per 100 ml.

The acid-salt solution, after gentle warming to dissolve the magnesium salt, is filtered through a sintered glass filter with gentle suction and stored in a bottle with a helmet screw cap. It cannot be autoclaved but is self-sterile. It needs to be prepared only occasionally since it is stable (if well capped) and one 300 ml. preparation is sufficient for nearly 150 liters of mixture. This solution should, at least initially, be prepared by a qualified chemist. The bottle should be stored away from surgical instruments or kept in a covered specimen jar.

The alkaline salt and glucose solutions are autoclaved in convenient quantities, usually 3 liter and 150 ml. lots respectively. Acid-salt solution is added** to the alkaline salt solution—a little more than 2 ml. of the former per liter of the latter—with thorough mixing, until the pink color is discharged. The sterile glucose solution, 50 ml. per liter, is added and the whole well agitated. The mixture should be prepared shortly before use; it should not be warmed above about 55°C. and should not be exposed in an open container for long periods.

The following facts necessitate the above method for preparation of Solution B. A bicarbonate solution cannot be sterilized by heat since the solution would become strongly alkaline as carbon dioxide is lost and the bicarbonate is converted to carbonate. Seitz filtration would not be practically feasible for routine preparation of large volumes of solution. The amount of concentrated acid added is just sufficient to convert the carbonate to bicarbonate and to produce sufficient carbonic acid, dissolved CO2, in the solution to give a nearly physiological pH. Calcium and magnesium salts would be precipitated by the carbonate solution and are therefore dissolved in the acid. The calcium chloride is readily soluble in the acid. But magnesium chloride is not very soluble and the amount of magnesium introduced in this way is not quite as high as the average amount in spinal fluid. Magnesium sulfate cannot be used since its addition to the acid solution causes precipitation of calcium sulfate. A trace of sodium sulfate could be added to the alkaline salt solution but there is no reason to believe that sulfate ion is essential. Sterile glucose solution has to be prepared separately since it becomes caramelized on autoclaving in the alkaline carbonate solution. The volume of the glucose solution approximately compensates for the loss of volume of the main solution during autoclaving.

Solution B has an initial pH of about 7.3. On standing exposed, or if heated, the solution loses carbon dioxide and becomes alkaline and calcium and magnesium carbonates precipitate. In an open dish at about 37°C, the pH rises gradually to about 7.8, the solution becomes noticeably pink, and a faint scum of precipitate forms, usually within about 2 hours. (The pink color is apparent before excessive alkalinity has developed.)

Solution B has been subjected to tests on animals and is now being used in this Institute on a trial basis as irrigation fluid in operations involving craniotomy and as replacement fluid after ventriculograms and after removal of neoplasms. Results of these trials will be reported later.

Methods for dispensing irrigation fluid for operations have been designed to avoid prolonged exposure and to maintain the fluid at a reasonably constant temperature without the danger of inadvertent overheating. In the simplest method the irrigation solution is kept in a welded stainless steel tank which stands in a serological constant temperature water bath. A 150°C. thermometer, fixed by a rubber stopper through a hole in the top of the tank, gives the temperature of the bath fluid. The tank is covered by a stainless steel lid which is left in place when the fluid is not in immediate use. (Holes may be cut in the lid large enough to hold inverted rubber bulb irrigation syringes so that the spouts dip deeply into the solution. These holes are covered by hinged lids when no bulb is in place.) The metal of the tank is extended as an “apron” round the bath in order to prevent contamination of sterile clothing by chance contact with the bath. The tank and thermometer with rubber stopper, are sterilized by autoclaving. The bath is filled to a level which will not allow overflow when the tank is in position. The water in the bath contains 2 per cent “Lyso-septol” as a safety factor and a strong dye so that if a leak should ever develop in the tank, the entry of bath fluid would be immediately detected. The apparatus now in use (Fig. 1) consists of twin tanks, made in one piece but with 2 inches space between them. This allows fresh solution to warm up on one side while the solution on the other side is being used.

Fig. 1.
Fig. 1.

Tank for holding sterile fluid in constant temperature bath.

Another apparatus,* illustrated in Fig. 2, consists of a stainless steel cylinder to contain the solution, covered with a stainless steel lid to which is attached an Aminco stainless steel heater element, the heating part of which is bent into a flat coil in such a manner that it may be lifted out with the lid. The temperature is regulated by a bimetal regulator in a stainless steel sheath inserted through a hole near the bottom of the cylinder and welded in place. The lid is cut out to allow access to the fluid but the cut out part is covered by a hinged cover whenever the fluid is not in continuous use. The whole apparatus, as far as the electric couplings, but without the bimetal thermoregulator, may be autoclaved. The thermoregulator is inserted and the couplings joined just before use. The 110 volt a.c. current in the heating element is controlled by an Aminco d.c. mercury relay. The current for the relay is supplied at 6 volt d.c. by an Aminco rectran connected to the thermoregulator.

Fig. 2.
Fig. 2.

Sterilizable apparatus for keeping sterile fluid at constant temperature, (a) Stainless steel heating element, (b) Bimetal thermoregulator. (c) Stainless steel sheath for thermoregulator.

Both of these methods are being used on a trial basis in the operating rooms of this Institute, the second apparatus being preferred. Work is in progress to simplify the second apparatus by designing a thermoregulator which may be sterilized and immersed directly in the solution.

A third apparatus for the same purpose consists of a coil of stainless steel tubing immersed in a constant temperature water bath. One end of the coil is connected by rubber tubing to a glass tube dipping into the vessel containing the solution, the other end is connected by rubber tubing to a double-valve irrigation syringe.1 The glass, steel, and rubber tubing may all be sterilized. By working the syringe, fluid is drawn through the coil and thereby warmed as it is used. The difficulty in obtaining syringes satisfactory for the purpose, and the cooling which occurs in the tube, render this method impractical for most purposes.

EXPERIMENTAL METHODS

In order to study the effects of irrigation fluids of different composition applied to the pia-arachnoid surface of the cortex under reasonably controlled conditions, a special irrigation chamber was constructed. This was a modification of the Forbes window8 which has been used for microscopic observations of pial vessels in the living animal. It consists of a dural cylinder of 13 mm. inside diameter threaded at the base so that it could be screwed tightly into a trephine opening in the skull. A disc of thin optical glass was cemented into the top in some experiments so that microscopic observations and photographs could be made of the cortical surface with dura removed. Around the rim of the top of the cylinder there were several openings to provide for continuous perfusion of fluid through the chamber, for measurements of pressure within the chamber, the insertion of glass pH electrodes, a thermocouple for local temperature measurements within the chamber, and for the insertion of electrodes for recording the electrical activity of the cortex and for its electrical stimulation. This chamber is illustrated in Fig. 3. It has proven very useful in a number of experiments in which various aspects of the reaction of the cortex to changes in surface chemical environment were to be studied.

Fig. 3.
Fig. 3.

Irrigation chamber.

The temperature of the exposed brain surface was found to be about 34°C. The irrigation fluid was admitted at about this temperature. This was achieved either by keeping the reservoir in a thermoregulated bath or by passing the fluid through coils in such a bath.

Measurements of the pH of the brain surface and of the irrigation fluid were made by means of micro glass electrodes and a silver-silver chloridesaline reference electrode similar to those described by Nims.14 The electrodes were connected to a Beckman pH meter through a switch box which allowed readings from 3 glass electrodes to be taken in rapid sequence. The wires from the glass electrodes, and the switch box, were shielded. It was necessary to ground the shielding and the water bath, while the operating table had to be carefully insulated, in order to obtain reliable and stable readings. Each glass electrode was calibrated against buffer solutions of known pH. The reference electrode was placed, in earlier experiments, against the cleaned surface of the skull of the animal; later the wick was immersed in the fluid in the irrigation chamber. The glass electrode was supported by a glass tube or light spiral wire sealed in the irrigation chamber. It was placed firmly, but not too heavily, against the cortex in the irrigation chamber to record the pH of the brain surface, or it was raised slightly in order to record the pH of the irrigation fluid. The pH of blood was determined on samples, drawn under oil, by means of a Beckman “hypodermic glass electrode” at room temperature. The value obtained was corrected for temperature according to Rosenthal17 to obtain the value at 38°.

Experiments were carried out on cats under light nembutal or dialurethane anaesthesia. In some experiments, artificial respiration was maintained.

pH EFFECTS

The pH of the Irrigation Fluid

Unbuffered solutions, such as Solution A or normal saline, usually show a pH of about 6 due to dissolved CO2. When the flow of unbuffered solution through the irrigation chamber was slowed down, the pH of the fluid usually fell further, sometimes as low as 5.5. This low pH presumably resulted from more rapid diffusion of CO2 than of base from the brain surface into the fluid. When the flow was stopped, leaving fluid static in the chamber, the pH gradually rose, reaching 6.3 to 6.8 in about 5 minutes. The pH of these solutions was never observed to reach that of the brain surface though theoretically that might be expected ultimately.

Even an appreciably alkaline, but unbuffered, salt solution (0.002 per cent added sodium carbonate, pH over 8) acquired a low pH when flowing slowly over the brain. The carbon dioxide diffusing from the brain will presumably reduce any solution to a relatively low pH unless the solution contains sufficient buffer to take care of the approximately 5 per cent carbon dioxide tension which is present at any tissue surface. For instance, a saline solution containing 0.01 M phosphate buffer at pH 7.5 changes to about pH 6.7 in the presence of 5 per cent carbon dioxide at 37°. But even with a phosphate concentration as low as 0.01 M, the phosphate causes the calcium of a balanced salt solution to precipitate on standing or warming the solution. Bicarbonate, which is the physiological buffer, is the only buffer salt that may be introduced in sufficient concentration to control the pH without rendering the fluid highly unphysiological.

A bicarbonate-containing medium, such as Solution B or spinal fluid, in equilibrium with 5 percent carbon dioxide at 38° has a pH of about 7.4. But this equilibrium is maintained only in a closed system, or if 5 per cent carbon dioxide is bubbled vigorously through the solution. Such a solution on exposure to air loses carbon dioxide and alkalinity develops. When the irrigation chamber was filled with long exposed Solution B, with a pH of 8.0 to 8.8, and the flow stopped, the pH of the fluid fell rapidly until a pH of about 7.4 was reached, and then remained constant. The rate at which this change occurred naturally depended upon the distance through which the carbon dioxide escaping from the brain surface had to diffuse into the static fluid. When the glass electrode was very close to the brain surface, the new pH was stabilized at about pH 7.4 within about 30 seconds. Records illustrating these various effects are shown in Fig. 4.

Fig. 4.
Fig. 4.

Effect of contact with the brain surface on the pH of various solutions.

Thus a properly constituted bicarbonate solution may have a pH slightly different from that of normal blood or spinal fluid, usually more alkaline, but, in contact with the brain surface, it rapidly assumes approximately the same pH as the blood. But solutions lacking bicarbonate are usually initially slightly acid, tend at first to become still more acid, and do not achieve the physiological pH within a reasonable period.

Reactions of Pial Vessels

The pial vessels were found to be very sensitive to the pH of the irrigating fluid. Whenever a fluid of pH below 7 was in the chamber, the pial vessels were markedly dilated, the whole surface appeared flushed, a network of previously invisible fine vessels became apparent, and sometimes petechial hemorrhages appeared. But when such a fluid was replaced by the bicarbonate-buffered fluid, constriction of the vessels and a blanching of the whole brain surface occurred. These changes are illustrated in the photomicrographs of Fig. 5. The extent of the vessel dilatation or constriction produced by different fluids seemed to be correlated with the pH recorded from the fluid in the chamber. Even Ringer solution containing a trace of sodium carbonate, which, as shown above, acquired a low pH in contact with the brain, produced hyperemia. Solution B produced the same, presumably normal, blood-vessel picture as human spinal fluid when either of these had been static in the chamber long enough for pH equilibrium to be reached. The reaction of the vessels to change of irrigation fluid was not instantaneous. The vessel constriction or dilatation which occurred on changing from unbuffered irrigating solution (low pH) to bicarbonate-containing solution (physiological or higher pH) or vice versa, usually took up to 30 seconds or more to become obvious.

Fig. 5.
Fig. 5.

Photomicrographs of the pial vessels of a cat brain, (a) under Solution A (unbuffered), (b), under Solution B (bicarbonate-buffered).

After long exposure of the brain the responsiveness of the vessels to change in irrigation fluid often diminished or disappeared. In these cases the vessels seemed to be in an irreversibly dilated condition; irregular dilatation or beading of vessels was often noted. We have not been able to relate this loss of responsiveness and apparent loss of vessel tone to the nature of the irrigation fluid. But we feel that dilatation and constriction of the pial vessels in response to changes in the irrigating fluid provide a useful test for the condition of the pial vessels which should help in further elucidation of factors that affect the exposed brain.

It should be pointed out that the dilatation produced by unbuffered solution is almost certainly due to low pH and not to a chemical effect of the dissolved carbon dioxide which produces the low pH. The bicarbonate-buffered medium, which produces the opposite effect, has a higher pH but at least an equal concentration of dissolved carbon dioxide and a much higher concentration of bicarbonate ion.

Observations similar to those made on cats have been made on a dog and on human subjects (with Dr. W. Penfield) during operations involving craniotomy. When the exposed brain was irrigated with Ringer solution the surface of the brain became flushed. But on turning back a flap of dura, which had protected the underlying surface from the irrigation fluid, this surface was observed to be still pale. Further, the flushing took much longer to develop under an area of thickened arachnoid. Areas of the brain lying under collections of spinal fluid remained pale and irrigation with Solution B produced in some instances a paler brain than is observed with unbuffered irrigation fluid. However, as in the animal experiments, this was not always true. Other factors may cause hyperemia during an operative procedure, besides the low pH of the usual irrigation solutions.

The pH of the Brain Surface

The pH of a given point on the brain surface varies with changes in blood pH as influenced by the respiration (Dusser de Barenne et al.5,6) It is raised briefly when the local circulation is increased as a result of increased neuronal activity and then falls (Jasper and Erickson11). The rise is presumably due to the pH of the blood being somewhat higher than that of the brain-tissue fluids. (However, none of the above authors gave values for the actual pH of the blood.) The fall in pH is presumably due to excessive production of acid metabolites during neuronal hyperactivity.

We have observed, on cats and monkeys, that the pH recorded from different points on the cortex varies appreciably. Values between 7.07 and 7.34 have been obtained during a short period when there was no obvious variation in the condition of the animal. Values of 7.0 and slightly lower have been recorded from cat, dog, and monkey cortex. At a given point, under steady conditions, the pH remains constant or shows only a slow drift. The highest values for the cortex were equal to or slightly below that of the venous blood at 38° (with one dubious exception). The pH of arterial blood is about 0.05 higher than that of venous blood, and at the temperature of the exposed cortex, 34° ±, either blood pH would perhaps be about 0.07 higher.17 The pH of the cortex surface thus tends to be appreciably lower than that of the blood supplying it.*

The variability from point to point was apparently connected with the proximity of blood vessels. Higher values were in general obtained when the electrode was on or near a large vessel. However the diameter of the electrode tips used was somewhat more than 1 mm. and the use of finer electrodes will be necessary for more precise mapping of the pH of the cortex in relation to blood vessels. A similar but more precisely observed and much more marked variation in the oxygen tension of the cortex in relation to the proximity of blood vessels has been observed by Bronk et al.3

The pH of the brain tissue, as indicated from an electrode placed on the surface of the cortex, was not appreciably affected by wide variations in the pH of the irrigating fluid. This observation is illustrated in the experiment recorded in Fig. 6, in which it is shown that even long contact with a fluid of low pH has no obvious effect on the pH of the cortex. Similar observations were made a great many times on numerous cats. This maintenance of pH is probably aided by the changes in pial circulation mentioned above though similar constancy of pH has been noted at a time when the reactivity of the pial vessels had been apparently largely lost. Presumably the main control rests in the high buffer capacity of the brain fluids and it seems as if there is some kind of barrier to the free inter-diffusion, between the tissue fluids and the irrigating fluid, of factors that affect pH. (It is perhaps relevant here to note that some time, up to 10 minutes, is often required for an electrode freshly placed on the cortex to give a steady reading. Presumably this time is required for the fluid in the concavity of the electrode tip to reach equilibrium with the brain fluids. Once placed and allowed to reach equilibrium, the electrode records changes in local pH within a few seconds.11)

Fig. 6.
Fig. 6.

Effect of pH of the irrigating fluid on the pH of the cortex. The glass electrode recording the pH of the experimental cortex was placed against the brain surface in the perfusion chamber. The electrode recording the pH of the fluid was in the same chamber but its tip was about 1 mm. above the brain. The control cortex electrode was placed against the brain surface in another chamber on the opposite side. The control chamber was filled with Solution B nearly an hour before the record was started and this solution remained there throughout so that it was presumably in equilibrium with the tissue fluids.

DISCUSSION

No obvious difference was observed in the immediate vascular reactions produced by Solution A, other Ringer-type solutions or normal saline. (A strongly hypertonic solution, 1.8 per cent sodium chloride, produced a much more pronounced reaction to the extent of petechial hemorrhages.) The marked dilatation of the superficial vascular bed of the cerebral cortex in response to the isotonic salt solutions now in current use seems to imply an irritating action of these unbuffered solutions which may play a role in the enhancement of damage caused by prolonged exposure of the cortex during neurosurgical procedures. The relative importance of the composition of the irrigation solutions in relation to other aspects of the abnormal environment in which the exposed cortex finds itself has yet to be ascertained. It is possible that control of the pH, by the use of bicarbonate, is only one of several ways in which exposure damage may be minimized through improvement in the irrigation fluid. The addition of glucose to the medium has strong support in principle but as yet its value has not been demonstrated. The presence of protein or other material exerting colloid osmotic pressure in the irrigation fluid might have value. A solution, using gelatin as the colloid, has been prepared but has received only preliminary trial. Prados, Strowger and Feindel16 reported that administration of adrenal cortical extract reduces the delayed vascular reaction to exposure of the cortex in cats. These authors noted that the extract was effective even when applied to the exposed brain. The possibilities of incorporating such a hormone in the irrigation fluid are therefore also being considered.

SUMMARY

  1. Unbuffered isotonic salt solutions in contact with the brain surface cause marked dilatation of the pial blood vessels. This hyperemia may be prevented by the use of bicarbonate buffered solutions at physiological pH or higher.

  2. Unbuffered solutions in contact with the brain surface rapidly assume a relatively low pH. A bicarbonate buffered solution may be faintly alkaline initially but, in contact with the brain surface, it rapidly assumes the physiological pH.

  3. The pH of the pia-arachnoid surface of the cortex remains essentially constant in spite of wide variations (5.3 to 8.0) in the pH of the fluid irrigating the surface in its immediate vicinity.

  4. A perfusion chamber suitable for the study of the effects of various dissolved chemical agents on the pH, electrical activity and other physiological functions of the cerebral cortex is described.

  5. Practical methods for the preparation and dispensation of two sterile solutions closely resembling spinal fluid and suitable for irrigation of the brain or other tissues, and for replacement of spinal fluid are described. One of these is a simply modified Ringer solution, the other contains bicarbonate in physiological concentration.

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Some of our neurosurgical colleagues call this “artificial spinal fluid.”

This addition is best made by means of a sterile syringe with a thin glass tube, instead of a needle, attached by rubber tubing. In view of the strong buffering capacity of the bicarbonate, exact measurement of the acid solution is not critical.

The strong pink color of the alkaline salt solution makes it unlikely that un-neutralized fluid would ever be used by mistake.

This apparatus was designed and built with the able assistance of Mr. L. Geddes.

It was interesting to observe that, on asphyxiating the animal by constriction of the trachea, the pH of the cortex fell rapidly, reaching 5.9 in 20 minutes. Blood drawn from the heart of the animal killed in this manner had a pH of 6.8. The rapid fall in pH of the brain is presumably mainly due to anaerobic glycolysis (lactic acid production) at the expense of glucose remaining in the brain.

Article Information

Aided by grants from the National Research Council of Canada.

© AANS, except where prohibited by US copyright law."

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Figures

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    Tank for holding sterile fluid in constant temperature bath.

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    Sterilizable apparatus for keeping sterile fluid at constant temperature, (a) Stainless steel heating element, (b) Bimetal thermoregulator. (c) Stainless steel sheath for thermoregulator.

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    Irrigation chamber.

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    Effect of contact with the brain surface on the pH of various solutions.

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    Photomicrographs of the pial vessels of a cat brain, (a) under Solution A (unbuffered), (b), under Solution B (bicarbonate-buffered).

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    Effect of pH of the irrigating fluid on the pH of the cortex. The glass electrode recording the pH of the experimental cortex was placed against the brain surface in the perfusion chamber. The electrode recording the pH of the fluid was in the same chamber but its tip was about 1 mm. above the brain. The control cortex electrode was placed against the brain surface in another chamber on the opposite side. The control chamber was filled with Solution B nearly an hour before the record was started and this solution remained there throughout so that it was presumably in equilibrium with the tissue fluids.

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