Journal of the neurological Sciences. 1975,26:319-333

319

~ ElsevierScientificPublishing Company, Amsterdam Printedin The Netherlands

Changes of Epidural Pressures after Experimental Occlusion of One Middle Cerebral Artery in Cats

TORU HAYAKAWA AND ARTHUR G. WALTZ

Cerebrovascular Clinical Research Center, Department of Neurology, University o/Minnesota, Minneapolis, Minn. 55455 (U.S.A.).

(Received 2 April, 1975)

INTRODUCTION Acute occlusion of a major cerebral artery in animals can cause cerebral edema (Teraura, Meyer, Sakamoto, Hashi, Marx, Sterman-Marinchesu and Shinmaru 1972, Bartko, Reulen, Koch and Schtirmann 1972; Harrison, Brownbill, Lewis and Ross Russell 1973; O'Brien, Waltz and Jordan 1974), and in humans swelling of the brain may be the chief cause of death early after the onset of cerebral ischemia (Shaw, Alvord and Berry 1959; Ng and Nimmannitya 1970). However, there have been few studies of the relationships between intracranial pressure (ICP), ischemic cerebral edema, cerebral swelling, and cerebral infarction (McQueen, Jelsma, Bacci and Pereira 1970; Halsey and Capra 1972; Brock, Beck, Markakis and Dietz 1972; Dorsch and Symon 1972; O'Brien and Waltz 1973b). Previous investigations in animals have emphasized changes that occur early after the onset of ischemia; the course of the development and resolution of swelling of the brain, its relationship to the neurologic deficits and the sizes of the infarcts caused by acute cerebral ischemia, and the effects of different anesthetic agents have not been determined. Therefore, we have measured epidural pressures (EDP) in cats up to 7 days after occlusion of one middle cerebral artery (MCA), using either a barbiturate or a volatile anesthetic agent (halothane) for the surgical procedure. This investigation was supported in part by Research Grant NS-3364 from the National Institutes of Health, Public Health Service. Address for reprints: Arthur G. Waltz, M.D., Chairman, Department of Neurology, Pacific Medical Center, P.O. Box 7999, San Francisco, Calif. 94120, U.S.A.

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polyethylene tube

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METHODS

Construction of EDP devices A silicone rubber membrane (medical grade Silasdc sheeting]t 0.05 mm thick was attached to a shallow metal cylinder containing a conical depression 6 mm in diameter and 1.5 mm deep with a capacity of approximately 16 #1 (Fig. 1). The membrane was attached to the cylinder with silicone rubber adhesive (Silastic type A) in such a way that the membrane was free of wrinkles but not stretched or taut. The adhesive was applied thickly, to protect the edges of the membrane during and after implantation in the skull of an experimental animal. The chamber of the EDP device was continuous with a thin metal tube, 0.6 mm inner diameter and 8.5 mm long, which was connected to a pressure-insensitive polyethylene tube 1.2 mm inner diameter. Implantation of EDP devices EDP devices were implanted in the skulls of 29 unselected adult cats anesthetized with phencyclidine hydrochloride, 1 mg/kg injected intramuscularly, and sodium pentobarbital, 25 mg/kg injected intraperitoneaUy. Through scalp incisions, hiparietal burr holes were made with an air drill; after hemostasis and cleaning of the exposed dura, one sterilized device was placed in each burr hole, with the membrane just touching the dura. Oxidized cellulose was placed around the rims of the burr holes as a vehicle for the application of contact adhesive (Eastman 910), so that the adhesive did not reach the membranes. A quick-setting epoxy cement was used over the small and the EDP devices to reinforce the fixation, The scalp incisions were closed around the polyethylene tubes. Boiled, bubble-free water was used to fill the chambers of the EDP devices and the polyethylene tubes before implantation. Before and between measurements of EDP, the end of each tube was sealed by heating, and a plastic cap was attached to the scalp to prevent accidental damage or dislodgement. Measurement of EDP For measurement of EDP the cats were tranquillized, when necessary, with phen-

CHANGES OF EPIDURAL PRESSURES

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cyclidine hydrochloride, 1 mg/kg injected intramuscularly. Measurements were delayed until 30 to 60 min after an injection to avoid any possible influence on ICP, although this dose of phencyclidine does not produce increases of cerebral blood flow (Reivich, Kassel and Sano 1974) (unpublished observations from our laboratory using 133Xe in squirrel monkeys). The end of the polyethylene tube attached to an EDP device was cut open and connected to 2 three-way stopcocks and a calibrated isovolumetric strain gauge recording on a polygraph (Fig. 2). One of the stopcocks was connected to a calibrated microliter syringe and a reservoir of bubble-free water; the other was connected to a large syringe. The chamber of the EDP device was evacuated by withdrawing the plunger of the large syringe and closing the stopcock. The chamber was then filled from the calibrated syringe with a known amount of water, and the stopcocks were adjusted so that the pressure in the system was recorded by the strain gauge. Although the error of a microliter syringe is, at maximum, from 0.1 to 0.3/A (less than 3 % of the amount injected), several injections and observations were made for each measurement of E D P to insure accuracy.

microliter ~ syringe~11 reserv°ir"-,~ 4 ~ ~ "~ ,~, ~

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, ~ ~,pressure device brain ~_~ Fig. 2. Schematic diagram of system used for standardization of E D P devices.

Determination of sensitivity and reliability o] EDP devices The sensitivity and the reliability of measurements made with the EDP devices were determined in two ways. In vitro measurements were made in a rigid plastic box, at different pressures and with different amounts of water used to fill the chambers of the devices. Ten devices were tested both before and after 2 weeks of implantation in the skulls of cats. The values for pressure obtained with the devices were compared to values obtained with a water-filled manometer attached to the box. In vivo measurements of EDP were made daily for 2 weeks after implantation of 14 devices in 7 cats, with different amounts of water used to fill the chambers. In 3 of these cats the E D P values obtained on the last day of observation were compared to values for cerebrospinal fluid (CSF) pressure recorded from a needle placed in the cisterna magna.

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Standardization of EDP devices beJore MCA occlusion or manipulation Twenty-two cats were tranquillized with phencyclidine hydrochtoride, 1 mg/kg injected intramuscularly, 4 to 7 days after implantation of E D P devices. In our laboratory the resting values for CSF pressure recorded from the cisternae magnae of the 3 tranquillized cats that had E D P devices implanted was approximately 5 mm Hg. Therefore, the volume of boiled water required to produce a recorded value for E D P of 5 mm Hg was determined for each device by evacuating the system and refilling it from the microliter syringe. For subsequent measurements the same amount of water was instilled into the chamber of the device. Cisternal punctures were not done for calibration in each cat because of the danger of damage to the medulla. Values for E D P were expressed in absolute terms, although the actual E D P was unknown because of standardization to the reference value of 5 mm Hg. MCA occlusion or manipulation After standardization of the E D P devices, 11 cats were anesthetized with sodium pentobarbital, 25 m g / k g injected intraperitoneally. The other 11 cats were anesthetized with halothane, administered through an endotracheal tube in a concentration of 1 - 2 % of the inspired gas mixture (which otherwise consisted of air with oxygen added to increase the concentration of oxygen to approximately 35%). Respirations were spontaneous; no mechanical assistance was used. The origin of the left MCA of each cat was exposed through the orbit by enlargement of the optic foramen, without additional craniectomy (O'Brien and Waltz 1973a). After careful dissection from the arachnoid, the MCA was held free from the brain with a bipolar coagulating forceps. In 10 cats of each group given one type of anesthesia the MCA was coagulated at its origin. The l l t h cat of each group had a sham operation: the MCA was grasped with the forceps but not occluded. The enlarged optic foramen was closed with a silicone rubber membrane (Silastic 500-3), and sealed with oxidized cellulose and contact adhesive (Eastman 910). In this way changes of ICP could develop inside an intact cranium without leakage of CSF. Measurements after MCA occlusion or manipulation E D P was first measured 24 hr after MCA occlusion or sham operation, and subsequently at intervals of 12, 24, or 48 hr up to 7 days (the longer intervals were used at later times after arterial occlusion or manipulation). Each cat also was examined at regular intervals for the presence of neurologic deficits, manifested by weakness of a limb, forced devi,ation of the head, circling, or defective placing or stepping reactions (Lee, Mastri, Waltz and Loewenson 1974). Food and water were made available but no fluids were given parenterally. Cats that survived 7 days after MCA occlusion or a sham operation were killed after the final measurements of EDP, by the intravenous injection of a saturated solution of potassium chloride. The brains were removed from all cats, including those that died before 7 days and those that did not have MCA occlusion or mani-

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pulation. Each brain was inspected grossly, particularly for evidence of swelling, tentorial herniation, or inflammation related to" the implantation of the E D P devices. The brains were then fixed in 10% formalin and sectioned coronally at 3 levels: at the tips of the temporal lobes; between the optic chiasm and the infundibulum; and at the posterior mammillary bodies. After embedding in paraffin, histologic sections were made and stained with hematoxylin and eosin for gross and microscopic examination to determine the size or absence of an infarct. RESULTS

Sensitivity and reliability of EDP devices The values for pressure recorded with the E D P devices varied in vitro and in vivo with the amount of water used to fill the chambers of the devices, as in a preliminary study (O'Brien and Waltz 1973b). However, when the devices were filled in vitro with the amount of water required to give the correct reading at a pressure of 5 m m Hg in the rigid plastic box, the values recorded with the devices at higher pressures were virtually the same as those recorded with the manometer, indicating good linearity of response. For example, at 10.0 m m Hg the mean value for measurements with 8 devices was 9.7, with a standard error of 0.14; at 20 m m Hg the mean was 19.8 and the standard error 0.17; at 30 m m Hg the mean was 29.6 and the standard error 0.12; and at 40 m m Hg the mean was 39.7 and the standard error 0.12. Moreover, there was little variability among different observations made with a single device at a given pressure; the greatest difference between any 2 observations was 1.8 m m Hg, but most differences were less than 1.0. The differences between the values recorded in vitro with 10 devices before and after 2 weeks of implantation were minimal. The greatest difference recorded for a single device was 0.5 m m Hg, at a pressure of 40 m m Hg. In the 7 cats in which E D P devices were implanted but no additional surgical +50

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procedures were done, recorded EDP values varied for the first 3 days after implantation (Fig. 3). However, from the fourth day to the end of the observation period of 2 weeks daily fluctuations of EDP values were negligible. The greatest change from one day to another after the fourth day was 1.5 mm Hg. Not all these devices were standardized to 5 mm Hg; thus, results were expressed as deviations from the value recorded at day 5 (Fig. 3). In 3 cats without MCA manipulation and with relatively normal CSF pressures, . changes of ICP produced by arterial pulsation, respiration, abdominal compression and CO~ inhalation were recorded as well by the EDP devices as by needles placed in the cisterna magna (Fig. 4) (O'Brien and Waltz 1973b).

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Inflammatory changes were apparent in the dura underlying the EDP devices in most cats; the inflammation usually was minimal, and less than that produced by latex membranes (O'Brien and Waltz 1973b). Inflammatory changes were noted over the underlying cortex only very rarely, and had no apparent relationship to changes of EDP.

Effects of sham operations In the 2 cats with sham operations, the greatest increase of EDP was 0.3 mm Hg, recorded 2 days after MCA manipulation in the cat receiving pentobarbital for anesthesia, and the greatest decrease was 1.5 mm Hg, recorded at 7 days in the cat receiving halothane. No neurologic deficits developed in either cat, other than transient lethargy related to the anesthesia and the surgical procedures, and no areas of infarction were observed on gross or microscopic examination of the coronal sections of the brains.

325

CHANGES OF EPIDURAL PRESSURES

EJJects of M C A occlusion and anesthetic agents Three cats died within 24 hr of M C A occlusion, without recovering consciousness. No E D P measurements were made after occlusion in these cats; however, inspection of the brains revealed massive swelling and transtentorial herniation, particularly on the side of M C A occlusion, indicative of an increase of ICP and the development of a gradient of pressure from the side of occlusion to the opposite side. Two of these cats were anesthetized with halothane and one with pentobarbital. In 3 cats, little or no change of E D P was recorded after M C A occlusion (cats 15, 16 and 17, Table 1), and no E D P gradients were noted. However, all 3 of these cats had severe neurologic deficits and persistent lethargy, and 2 of them died after 2 days of occlusion. There was no transtentorial herniation, and the infarcts were confined to the basal ganglia and internal capsules of the hemispheres with occluded arteries, without extension to the cortex. One of the cats that died the second day after occlusion received pentobarbital for anesthesia; the other 2 cats received halothane.

TABLE 1 EDP

(ram Hg)

IN 17 CATS THAT SURVIVED AT LEAST 2 4 r m AFTER M C A OF DECREASING MAXIMUM EDP

Cat

Maximum EDP, side o/ occlusion

Corresponding EDP, s i d e opposite occlusion

Difference

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

47.7 43.6 41.5 39.6 37.6 25.5 20.8 17.5 17.2 16.8 16.4 14.4 13.9 10.6 6.4 5.2 4.4

33.5 38.6 28.5 27.6 31.8 23.5 13.8 17.9 16.6 14.6 15.0 14.2 11.0 11.3 6.5 5.0 4.8

14.2 5.0 13.0 12.0 5.8 2.0 7.0 --0.4 0.6 2.2 1.4 0.2 2.9 --0.7 --0.1 + 0.2 --0.4

OCCLUSION, LISTED IN ORDER

Time o/ Survival maximum EDP (hr) time (days) 24 24 24 36 24 36 24 48 60 48 48 24 24 36 36 24 24

1 1 1 7 7 7 1 7 7 7 7 7 7 7 2 7 2

Anesthesia pentobarbital pentobarbital pentobarbital pentobarbital halothane pentobarbita! pentobarbital pentobarbital halothane pentobarbital halothane halothane halothane halothane halothane halothane pentobarbital

Marked increases of EDP, to values greater than 20 mm Hg, were recorded from 7 cats after M C A occlusion (cats 1 through 7, Table 1). In these cats, side-to-side gradients of E D P were noted at the time of maximum EDP, 24 - 36 hr after occlusion (Table 1; Fig. 5). Four of these died after 7 days of occlusion, with massive swelling of the brain, transtentorial herniation, and large infarcts involving extensive areas of the cerebral cortex as well as the basal ganglia and internal capsules of the hemispheres with occluded arteries. The 3 cats that survived until the end of the observation period had somewhat smaller infarcts, with involvement of

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T. HAYAKAWA~ A. G. W A L T Z

o/\.--°

63 tad

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....

t

Days After Occlusion

Fig. 5. EDP recorded from cat 4, showing marked increases after MCA occlusion.

cerebral cortex only in the ectosylvian regions. However, these 3 cats all had severe neurologic deficits, with little or no improvement of function during the period of observation. Only 1 of these 7 cats received halothane for anesthesia. In 7 cats, moderate increases of EDP, from 10 to 18 mm Hg, were recorded after MCA occlusion (Table 1). Maximal values were recorded 24 - 36 hr after occlusion in 3 of these, and at 48 - 60 hr in the other 4. Gradients of E D P were not remarkable. Neurologic deficits varied from minimal head deviation and circling to severe weakness of the limbs opposite occluded arteries, and generally became less during the period of observation. Each of these cats survived the entire 7 days, at which time 4 cats had no apparent neurologic deficits. Infarcts involved cortex in 3 cats, in the ectosylvian regions only; the infarcts in the other 4 cats were confined to the basal ganglia and internal capsules. Five of these cats received halothane for anesthesia, including the 3 with infarcts involving cortex. In all cats with recorded increases of E D P after MCA occlusion, whether marked or moderate, EDP gradually decreased toward normal during the latter part of the period of observation (Fig. 5). E D P gradients likewise lessened during this time. Five to 7 days after occlusion E D P values were close to those recorded before occlusion and no gradients were noted. Cats anesthetized with pentobarbital generally recovered consciousness later than those anesthetized with halothane, and remained lethargic considerably longer. Only 4 of the 10 cats anesthetized with pentobarbital survived for 7 days after MCA occlusion, while 7 of the 10 cats anesthetized with halothane survived the entire observation period. However, there were no apparent differences between the groups in sizes of infarcts. As noted, a greater number of cats anesthetized with pentobarbital had marked increases of EDP, and a greater number of cats anesthetized with halothane had moderate increases of EDP. The mean of the maximal values for E D P recorded from the side of an occluded MCA in 9 cats anesthetized with pentobarbital was 28.6 mm Hg, with a standard error of 4.99; the mean for 8 cats anesthetized with halothane was 15.2 mm Hg, with a standard error of 3.56. This difference was significant at a level of P < 0.05.

CHANGES OF EPIDURAL PRESSURES

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DISCUSSION

Methods for measurement of ICP

Each technique for measurement of ICP developed over the past several years has one or more undesirable characteristics. Hoppenstein (1965) described a hydrodynamic balloon that could be inserted in the epidural or subarachnoid spaces; however, the pressures recorded with such devices depend on the volume of fluid used to fill their chambers (O'Brien and Waltz 1973b). Thus, for each device that we have used we have instilled the same volume of fluid in the chamber of the device for measurements of EDP. Schettini, McKay, Majors, Mahig and Nevis (1971) and Schettini and Walsh (1974) have shown that many different intracranial pressures can be recorded. Among these are CSF pressure from the subarachnoid space or ventricles, and the reactive pressure exerted by the surface of the brain when compressed. Pressures recorded epidurally may include either of these. For accurate epidural measurement of any intracranial pressure, the sensing device must come into complete coplanar approximation with the outer surface of the dura, and the periphery of the device must be rigid to prevent "tenting" (Schettini et al. 1971). Otherwise, the adherence of the dura to the skull or inflammation around the implanted device may cause a reactive pressure to be recorded (Coroneos, McDowall, Gibson, Pickerodt and Keaney 1973). Our device, with a rigid periphery and a smooth membrane that is not taut, provides reasonable coplanar approximation to the dura. Even under the best of circumstances, however, the relatively dense dura may cause distortion of pressures transmitted from an intradural to an extradural location. The implantation of a device for measurement of ICP may cause changes within the cranial cavity that themselves will influence the recorded ICP (Edvinsson, Nielsen, Owman and West 1971). In the present study care was taken to avoid damage to the brain during implantation; nonetheless, there was considerable variability of the EDP values recorded for the first 3 days after implantation. For this reason, MCA occlusion or sham operations were done only 4 days or more after implantation. Recognition and correction of base-line shift is a major problem for long-term measurement of ICP (Numoto, Wallman and Donaghy 1973; Gobiet, Bock, Liesegang and Grote 1974). By always filling the chamber of a given device with the same volume of water and referring the recorded EDP to a standard pressure of 5 mm Hg, we have provided for automatic correction of base-line shift. The reference value of 5 mm Hg is a reasonable value for the "normal" CSF pressure of cats, and the EDP values recorded subsequently may be used for comparison with values reported by others. When using fluid-filled systems for measurement of ICP it is important that the fluid be completely incompressible. Incompressibility requires the removal of all gases from the fluid and the absence of any leaks in the system. Gases can be removed from water by boiling; unfortunately, tiny leaks cannot be prevented, particularly at relatively high pressures. Therefore, evacuation and re-instillation

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of water into the chambers of the EDP devices was done'before each determination, and several determinations were made for each measurement. Other important factors must be considered if EDP devices are to be used. The devices must be fixed firmly in the skull. The pressure-transmitting membranes must be smooth but not stiff or taut; otherwise, distortion may occur during transmission. The devices must cause no or minimal tissue reaction. Our devices appear to be satisfactory in these respects. Moreover, construction is relatively simple and inexpensive, and calibration is simple and accurate. The major disadvantages are that relative, not absolute, EDP values are obtained; and that the EDP pressures that are recorded may not be those of the CSF but of the brain compressed against the dura. EJJects of M C A occlusion

Previous studies by others (McQueen et al. 1970; Halsey and Capra 1972; Brock et al. 1972; Dorsch and Symon 1972) have differed from the present study with respect to the model used for producing acute cerebral ischemia, the duration of the measurements of ICP, and other technical features. For example, in the present study the cranium was intact after an MCA was occluded; the enlarged optic foramen through which the MCA was approached was completely sealed to prevent leakage of CSF. A preliminary report (O'Brien and Waltz 1973b) indicated that changes of EDP after MCA occlusion may be marked but transient, and that sideto-side gradients can be detected. No previous study has related the amplitude and duration of changes of ICP after acute experimental cerebral ischemia to the neurologic deficits and the characteristics of the resulting infarcts. As in studies of humans with strokes (Christensen, Brodersen, Olesen and Paulson 1973), values for ICP after MCA occlusion in cats are variable. In 3 cats of the present study without marked changes of EDP but with severe neurologic deficits, the infarcts were in the internal capsules and basal ganglia, and presumably not of sufficient size to cause enough swelling to produce intracranial hypertension. In other cats with severe neurologic deficits, larger infarcts resulted in massive swelling of the brain, marked EDP increases, and transtentorial herniation. The most favorable outcome of MCA occlusion was associated with moderate EDP increases: all 7 cats survived with slight or no neurologic deficits. The reasons for the variability of the neurologic deficits, the sizes of the infarcts, and the extent of swelling are unknown; presumably, variations of the anatomy of the cerebral vasculature, and thus of blood flow to ischemic regions through collateral channels, are important, as are ischemic changes in the microvasculature (Waltz and Sundt 1967), post-ischemic reactive hyperemia (Yamaguchi, Waltz and Okazaki 1971), and increases of water content (O'Brien et al. 1974). In the present study, 9 of 20 cats with MCA occlusion died before the end of the observation period of 7 days. Seven of these probably died from massive swelling of the brain with transtentorial herniation, evident at inspection. This frequency of transtentorial herniation is considerably greater than in studies of humans with strokes (Shaw et al. 1959; Ng and Nimmannitya 1970), perhaps because the cat has a tentorium of bone rather than of a more flexible fibrous tissue.

CHANGES OF EPIDURAL PRESSURES

329

The time course of EDP increases caused by MCA occlusion in the present study was similar to that of increases of the water content of ischemic and infarcted cerebral tissue in cats (O'Brien et al. 1974) as well as to that of swelling of infarcted brain in humans with severe ischemic strokes (Shaw et al. 1959; Ng and Nimmannitya 1970). Moreover, EDP increases were related directly to the extent of swelling of the brain, and in turn to the sizes of the ischemic cerebral infarcts. However, in certain cats with moderately large infarcts involving cortex, there were only moderate EDP changes, while in other cats with similar infarcts EDP changes were marked. In these cats the infarcted tissue may have contained an increased proportion of water yet not have been swollen to an increased volume (Beks and Kerckhoffs 1971). Alternatively, the pressure of a focal expanding process may have been dissipated by the structural components of cerebral tissue or compensated for by changes of intracranial blood or CSF volume (Langfitt, Weinstein, Kassel and Gagliardi 1964; Langfitt, Weinstein, Kassell and Simeone 1964; Goodman, Becker and Seelig 1972; LSfgren and Zwetnow 1973; Johnston, Rowan, Har,r~er and Jennett 1973). Focal increases of tissue pressure, however, could have affected local tissue perfusion (Frei, Wallenfang, P611, Reulen, Schubert and Brock 1973). Side-to-side E D P gradients

No pressure gradients can exist in CSF that communicates freely (Ommaya and Hekmatpanah 1972). Although supratentorial-to-infratentorial gradients may be measured in the presence of transtentorial herniation (Goodman et al. 1972; Johnston and Rowan 1974), it seems unlikely that side-to-side gradients of EDP could develop because of blockage of the circulation of CSF (O'Brien and Waltz 1973b; Johnston and Rowan 1974), even when there is displacement of midline structures. However, if infarcted and ischemic tissue swells so that CSF is displaced and the cerebral surface touches the dura under an epidurally implanied pressure device, the pressure of the brain will be measured. A cerebral surface that is in contact with CSF must have the same pressure as the CSF; but if the brain swells, displaces CSF, and becomes pressed against the dura and the epidural device, the pressure that is recorded as EDP will be a reactive pressure from compression ofthe brain. This reactive pressure will be higher than that of the CSF, and may be quite variable from region to region of brain because of differences of supporting structures, blood volume, edema, and other factors (Schettini et al." 1971; Schettini and Walsh 1974). When EDP pressures are relatively low and no gradients can be measured after MCA occlusion, it is likely that CSF pressure is being recorded; when EDP pressures are relatively high (20 mm Hg of more) and gradients are demonstrated, it is likely that the pressure of compressed cerebral tissue is being recorded. Changes of EDP after MCA occlusion probably develop in 6 stages (Fig 6): (1) before focal swelling of the brain occurs there is no change of tissue pressure or EDP; (2) focal cerebral ischemia causes a focal increase o.f water content and swelling of the brain with an increase of regional tissue pressure and a gradient to surrounding tissue (Reulen and Kreysch 1973); (3) the focal swelling and increased

330

T. HAYAKAWA, A. G. WALTZ

/

i

Fig. 6. Stages in the development of changes of EDP after MCA occlusion. A before focal swelling of brain. No change of tissue pressure or EDP; B: focal swelling of brain causes increase of regional tissue pressure but no change of EDP; C: further swelling of brain causes increase of CSF pressure reflected in EDP. No side-to-side EDP gradients exist; D: CSF is displaced by expanding brain and EDP on side of occlusion reflects pressure of brain; E: additional swelling causes increasingly greater EDP reflecting pressure of compressed brain. Side-to-side EDP gradients develop. EDP opposite occluded artery may reflect CSF pressure or pressure of brain; F: pressure gradients cause subfalcial and transtentorial herniation of cerebral tissue.

tissue pressure surpass the resistance of structural components and/or exceed the capacity of compensation by changes of blood and CSF volume, resulting in an increase of CSF pressure and EDP; (4) the expanding brain displaces CSF from the overlying subarachnoid space and the surface of the brain touches the dura; (5) additional swelling of the brain causes the recording of an increasingly higher EDP value which is greater than that recorded from the opposite side; the pressure recorded over the opposite hemisphere may be either that of CSF or the compressed brain; (6) pressure gradients cause subfalcial and transtentoriat herniation of cerebral tissue. Because the changes of EDP are related to the severity and size of the infarct and to the swelling of the brain, measurements of EDP may be useful for studies of the treatment of cerebral edema in experimental models of acute cerebral ischemia.

Effects of anesthesia In contrast to reports of others using different experimental models or species (Yatsu, Diamond, Graziano and Lindquist 1972; Smith, Hoff, Nielsen and Larson 1974), there was no evidence in the present study for a protective effect of barbi-

CHANGES OF EPIDURAL PRESSURES

331

turates against acute focal cerebral ischemia and infarction. In the group of cats anesthetized with pentobarbital, there were more deaths, a greater frequency of transtentorial herniation, and greater increases of EDP (indicative of greater swelling of the brain). Under optimal circumstances, anesthesia with pentobarbital may result in a lower CSF pressure than anesthesia with halothane (Ishii 1966; McDowall, Barker and Jennett 1966; Jennett, McDowall and Barker 1967; Zattoni and Siani 1972; Adams, Gronert, Sundt and Michenfelder 1972; Shapiro, Wyte and Loeser 1974; Smith et al. 1974). However, if respiration is spontaneous and mechanical assistance is not used, respiratory depression with increases of arterial carbon dioxide tension may cause secondary changes of intracranial blood volume and intracranial pressure that supersede the effects of anesthesia with barbiturates. Moreover, in the present study the cats anesthetized with halothane recovered more quickly from anesthesia than those anesthetized with pentobarbital; atelectasis, pneumonitis, and other pulmonary factors may also have contributed to the generally worse situation encountered by us with pentobarbital anesthesia. The oxygen added to the mixture of gases used for vaporizing the halothane probably had little or no effect (Regli, Yamaguchi and Waltz 1970). Adequate and appropriate respiratory care may be more important than suppression of cerebral metabolism or induced decreases of intracranial blood volume for the care of humans with acute ischemic strokes. ACKNOWLEDGEMENTS

Technical advice and statistical analyses were provided by Margaret Jordan. Technical assistance was provided by Carlos Verdeja, Terry Hansen, and Richard Abrohams. SUMMARY

Epidural pressures (EDP) were measured in 29 cats. Twenty cats had the left middle cerebral artery (MCA) occluded; pentobarbital was used for anesthesia for 10 of these, and halothane was used for the other 10. Two cats had sham operations: the MCA was manipulated but not occluded. Seven cats were used for testing the reliability of the EDP devices. EDP was measured successfully and was directly related to the swelling of the brain and to the size of the cerebral infarct resulting from MCA occlusion. Side-to-side pressure gradients were demonstrated in 7 cats with marked increases of EDP after occlusion; in these cats, E D P may have reflected the pressure of compressed cerebral tissue rather than the pressure of cerebrospinal fluid. Cats anesthetized with pentobarbital had greater increases of EDP and died before the end of the period of observation more frequently than cats anesthetized with halothane, probably because of respiratory depression and slower recovery with pentobarbital. Measurements of EDP may be useful for studies of the treatment of cerebral edema in experimental models of acute cerebral ischemia.

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T. HAYAKAWA, A. G. WAH'Z REFERENCES

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