Cerebral Protection by Barbiturate Anesthesia Use After Middle Cerebral John D.
Artery Occlusion
Michenfelder, MD; James H. Milde; Thoralf
Regional cerebral ischemia was produced in 18 Java monkeys by permanent middle cerebral artery (MCA) occlusion. All monkeys were thereafter paralyzed (pancuronium bromide, 0.05 mg/kg/hr) and sedated (diazepam, 0.1 mg/kg/hr) for a 48-hour period. Thirty minutes after MCA occlusion, pentobarbital sodium \s=b\
induced in nine of the monkeys (14 mg/kg) and maintained for 48 hours (7 mg/kg every two hours), with continuous supportive care. After 48 hours, all drugs were discontinued; the monkeys were observed for five days, and then killed. Seven of the control monkeys developed a cerebral infarction, three did not survive past the 48 hours of intensive care, and the other four had a notable neurologic deficit. All pentobarbital monkeys survived the seven days, but four had a cerebral infarction and two of these had a notable neurologic deficit. These differanesthesia
was
statistically significant. (Arch Neurol 33:345-350, 1976)
ences were
Accepted for publication April 9, 1975. From the departments of anesthesiology (Dr Michenfelder and Mr Milde) and neurosurgery (Dr Sundt), Mayo Clinic and Mayo Foundation, Rochester, Minn. Reprint requests to Department of Anesthesiology, Mayo Clinic, Rochester, Minn (Dr Michenfelder).
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M.
in Java
Monkeys
Sundt, Jr, MD
number of
A reported
an
investigators have
apparent cerebral
protective effect for barbiturate anes¬ thesia in experimentally induced toteal cerebral ischemia13 regional cerebral ischemia,4·5 and cerebral edema.6 These reports suggest a possible clin¬ ical indication for inducing barbitu¬
rate anesthesia in the management of acute stroke. However, much of the
data are re¬ mote from the actual clinical circum¬ stances of acute stroke. Criticisms include the possibility that the species studied was inappropriate because of differences in collateral circulation, that the technique used for producing regional ischemia was not comparable to acute stroke, that many studies examined only acute events after ischemia, and that the chronic studies did not include supportive care similar to that provided clinically. We have previously reported data indicating that dogs, cats, and gerbils may be inappropriate for studies of regional cerebral ischemia, whereas primates, having a cerebral circula¬ tion anatomically similar to man, appear to yield consistent data.5 Other
collected
experimental
studies indicate that middle cerebral artery (MCA) occlusion in primates produces an ischemie lesion resem¬ bling that in man.7 In the present study, acute stroke was produced by permanent MCA occlusion in Java monkeys followed by an extended period of intensive care. We then compared the outcome in monkeys anesthetized with pentobarbital sodi¬ um for 48 hours to that found in unanesthetized animals. MATERIALS AND METHODS
Eighteen Java monkeys of both sexes and weighing 0.8 to 1.9 kg were studied. The monkeys were studied in groups of three and were ultimately divided into two groups of nine each, distinguished by the presence or absence of pentobarbital anes¬ thesia. In all monkeys, anesthesia was initially induced and maintained with halothane (1%). Endotracheal intubation was accomplished after muscle paralysis with succinylcholine chloride (40 mg). Ventila¬
tion was controlled with a fixed-volume ventilator. A femoral artery and vein were exposed and cannulated for pressure mea¬ surements, blood samples, and drug and fluid administration. A urinary catheter and rectal thermistor were inserted and secured. The right MCA was exposed via a
transorbital
approach, using the operating microscope. In an initial six monkeys, an occlusive clip was placed across the MCA at its origination from the internal carotid artery. In two of these, clinical signs of diabetes insipidus developed within 24 hours, which considerably complicated sup¬ portive care; therefore, this entire group was discarded from the study. In the 18 monkeys retained in the study, the clip was placed across the MCA distal to the first anterior branch, which supplies an ante¬ rior-inferior portion of the frontal lobe. Diabetes insipidus did not develop in any of these. After placement of the clip, halothane
discontinued and the animals were paralyzed with pancuronium bro¬ mide, 0.05 mg/kg, and sedated with diazepam, 0.1 mg/kg, intravenously. The durai incision was sealed with oxidized cellulose and glue (alpha-cyanoacrylate) and the wound was closed. Streptomycin sulfate (100 mg) and penicillin G sodium (300,000 units) were administered intramuscularly. With completion of surgery, a 48-hour period of intensive care was initiated. The monkeys were continuously attended by two technicians under the supervision of a was
physician.
Pancuronium bromide and diazepam were continued at 0.05 mg/kg/hr and 0.1
phenylephrine hydrochloride (0.013 mg intravenously). Two monkeys (control monkey 2 and monkey 3 in the pentobar¬ bital group) developed a progressive reduc¬ tion in urinary output, which was corrected by a single dose of furosemide (1 mg). Four monkeys (two from each group) required
mg/kg/hr, respectively. Also, a solution of 5% dextrose in 0.45% saline was given to the monkeys at a rate of 5.0 mg/kg/hr.
Arterial blood pressure was monitored continuously. Mean arterial pressure, cen¬ tral venous pressure, heart rate, tempera¬ ture, and urine output were recorded every 30 minutes. Electroencephalographic and electrocardiographic recordings were tak¬ en every two hours. Blood gases and hemo¬ globin concentration were measured every four hours. Ventilation was controlled, with 40% oxygen and 60% nitrogen (humid¬ ified); it was adjusted, as necessary, according to the blood gas measurements. The extremities were wrapped and, when necessary, a heat lamp was applied. The subjects were turned every four hours. In nine of the 18 monkeys, pentobarbital anesthesia was initiated 30 minutes after MCA occlusion, with an intravenous dose of 14 mg/kg. Thereafter, pentobarbital, 7
occasional additional dose of pancu¬ ronium bromide (0.05 mg) because of spon¬ taneous movement. A variety of technical problems were encountered (partial airway obstruction, inadvertent extubation, urina¬ ry catheter obstruction, and loss of intra¬ an
route), but, to our knowledge, they were always immediately recognized and corrected without apparent detrimental effects. Body temperature was controlled with heat lamps without difficulty. Muscle paralysis was intermittently evaluated
venous
with a nerve stimulator. Fluids were administered continuously via a calibrated automatic flushing apparatus attached to the arterial line. Ventilation was adjusted to maintain a Pao2 of 100 to 200 mm Hg and a Paco2 of 33 to 37 mm Hg. The electroencephalogram was recorded every two hours from each hemisphere using parietal-frontal electrodes. After 24 hours, penicillin G benzathine (200,000 units) was
mg/kg, was given intravenously every two hours. In all other respects, the 18 monkeys were managed identically throughout the 48-hour period with the following excep¬ tions: One monkey (control monkey 4) became hypotensive after 36 hours (mean arterial pressure < 60 mm Hg) and re¬ quired intermittent doses of mephentermine sulfate (2 mg intravenously) and
given intramuscularly. After 42 hours, pentobarbital
was
dis-
Table 1.—Mean 48-Hour Values in Control Monkeys
Monkey/ Sex 1/M 2/M 3/M 4/F 5/F 6/F 7/M 8/F 9/M Mean ± SE
Buffer
Mean Arterial
Central Venous
Heart
Pressure, mm Hg
Pressure,
Beats/ min
Temper¬ ature, C
globulin, gm/dl
158 215 173 230 176 195 227 181 213 196 ±9
37.1 37.1 37.1 36.9 37.0 37.2 36.9 37.2 37.0 37.1 ± 0
9.3 14.5 11.4 10.8 10.8 13.7 8.7 9.8 9.1 10.9 ±0.7
99 113 95 74 105 114 86 99 97 98
mm
Hg
2±0
Rate,
Hemo-
w
Pa o mm
Hg
175 154 154 181 179 145 140 159 156 160 ± 5
Table 2.—Mean 48-Hour Values in Pentobarbital
Monkey/ Sex
1/M 2/F 3/M 4/M 5/M 6/F 7/F 8/F 9/F Mean ± SE
Mean Arterial
Central Venous
Heart
Pressure, mm Hg
Pressure, mm Hg
Beats/
88 90 78 91 98 111 104 100 83 94 ±3
2±0
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Rate,
min 182 208 203 218 227 139 181 198 212 196 ±9
2,
Pa CO 2, mm
Hg
33 35 37 35 33 36 36 33 33 35 ±1
pH 7.53 7.46 7.49 7.47 7.55 7.46 7.52 7.55 7.55 7.55 ± 0.01
Base, mEq/
Liter 54 53 53 51 55 51 55 55 55 53 ±1
Monkeys Buffer
Base,
Hemo-
Temper¬ ature, C
globulin, gm/dl
37.2 37.0 36.9 37.0 37.2 36.9 37.2 37.0 37.4 37.1 ± 0.1
9.7 10.3 9.7 9.0 11.2 12.2 12.2 11.7 11.2 10.8 ±0.4
Pao2,
mm
Hg
161 194 177 155 129 152 188 181 163 167 ±7
PaC02,
mm
Hg
36 34 33 36 38 33 36 34 35 35 ±1
pH 7.48 7.50 7.48 7.51 7.48 7.50 7.50 7.49 7.50 7.49 ± 0
mEq/ Liter 52 52 51
53 53 52 53 52 53 52 ±0
continued in the nine monkeys of that group. After 48 hours, all drugs and fluids were discontinued in both groups. All cath¬ eters were then removed, and when spon¬ taneous ventilation was adequate, the trachea was extubated. In three control monkeys (No. 2, 4, and 7), spontaneous respiration remained inadequate despite total reversal of the muscle relaxant, and death ensued. The remaining monkeys after partial arousal from the pentobar¬ bital or diazepam effects or both, were returned to their cages. Thereafter, neuro¬ logic deficit was graded daily by two inde¬ pendent observers and recorded for five days. On the seventh postoperative day, the monkeys were killed, the placement of the MCA clip was confirmed, and the brains were removed, fixed in a 37% formaldehyde solution, identified by a code number, and stored. After all 18 monkeys had been studied, the brains were individu¬ ally examined in sequence without knowl¬ edge of code identification. The size of each cerebral hemisphere was measured by volume displacement before sectioning into 5-mm slices. The end area of infarction
Fig
1 .—Brain from pentobarbital monkey 9. Note lack of any midline shift and the normal appearance bilaterally.
in each slice was measured with a grid; the total size of infarction was computed and then expressed as a percent of that hemis¬ phere's volume. Systemic variables tabulated in Tables 1 and 2 were compiled by calculating the mean values of the multiple measurements made in each monkey during the 48-hour period of intensive care. Statistically significant differences between the two groups were tested for by the Student t test for unpaired data (for systemic varia¬ bles, Tables 1 and 2), by the 2 test of Pearson (for survival, Table 3), and by the Wilcoxon two-sample rank test (for neuro¬ logic deficit and size of infarction, Table
3). RESULTS In terms of monitored systemic variables, the two groups were compa¬ rable and generated grand mean values that are remarkably similar (Tables 1 and 2). All of the monkeys in the pentobarbital group survived the full seven days, whereas three of the
Fig 2.—Brain from control monkey 2. Note large infarction with shift of midline struc¬
tures.
control monkeys did not survive past the 48-hour period of intensive care (Table 3). Obvious neurologic deficits were recorded in seven of the controls and only two of the pentobarbital monkeys. In two others in the pento¬ barbital group, an initial slight motor weakness (—1) was no longer evident on the day of autopsy. A similar slight deficit was initially recorded in one of the controls. Thus, in five of nine monkeys in the pentobarbital group, there was no apparent neurologic deficit at any time, as opposed to only one of nine controls. In individual monkeys, variability in the deficit (usually an improvement with time) or disagreement between the two inde¬ pendent observers accounts for the tabulated double-numbered deficits (for example: —2,-3). In all but one monkey (control monkey 5) in whom a deficit had been recorded during the five-day period of observation, an infarct was found. In the five mon¬ keys in the pentobarbital group and one control monkey in which no deficit had been recorded, there was no infarct. The size of the infarct tended to correlate with the magnitude of the deficit. Exceptions (such as control monkey 3) were accounted for by small infarcts in the internal capsule, which resulted in notable deficits. Examples of a normal brain (monkey 9 in the pentobarbital group) and of a large infarction (control monkey 2) are shown in Fig 1 and 2. The EEG recordings differed as expected in the two monkey groups. In the control monkeys, the EEG from the nonischemic hemisphere was a
predominately high frequency (18 to 24 hertz), low amplitude (5/xv to 10/xv) pattern. In the monkeys in the pento¬
barbital group, a moderate level of anesthesia was indicated in eight of the nine by a complex EEG pattern consisting of relatively low amplitude
(5µ to 10/xv), high frequency (12 to 14 Hz) activity superimposed on high amplitude (40/xv to 70/xv), low frequen¬ cy (2 to 4 Hz) activity. In one monkey (3) burst-suppression indicated a deeper level of anesthesia. The EEG from the MCA-occluded hemisphere was of little diagnostic value in those monkeys that developed only small infarctions and, even in retrospect,
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Table
After 48 Hours of Intensive Care Control
Pentobarbital Monkeys'
Monkeys
_A_
Monkey Survived 1
8
Neurologic
Yes No Yes No Yes Yes No Yes Yes
% Infarct
Deficit
r
Monkey 1
0 24
Artery Occlusion
Michenfelder, MD; James H. Milde; Thoralf
Regional cerebral ischemia was produced in 18 Java monkeys by permanent middle cerebral artery (MCA) occlusion. All monkeys were thereafter paralyzed (pancuronium bromide, 0.05 mg/kg/hr) and sedated (diazepam, 0.1 mg/kg/hr) for a 48-hour period. Thirty minutes after MCA occlusion, pentobarbital sodium \s=b\
induced in nine of the monkeys (14 mg/kg) and maintained for 48 hours (7 mg/kg every two hours), with continuous supportive care. After 48 hours, all drugs were discontinued; the monkeys were observed for five days, and then killed. Seven of the control monkeys developed a cerebral infarction, three did not survive past the 48 hours of intensive care, and the other four had a notable neurologic deficit. All pentobarbital monkeys survived the seven days, but four had a cerebral infarction and two of these had a notable neurologic deficit. These differanesthesia
was
statistically significant. (Arch Neurol 33:345-350, 1976)
ences were
Accepted for publication April 9, 1975. From the departments of anesthesiology (Dr Michenfelder and Mr Milde) and neurosurgery (Dr Sundt), Mayo Clinic and Mayo Foundation, Rochester, Minn. Reprint requests to Department of Anesthesiology, Mayo Clinic, Rochester, Minn (Dr Michenfelder).
Downloaded From: http://archneur.jamanetwork.com/ by a University of Iowa User on 06/07/2015
M.
in Java
Monkeys
Sundt, Jr, MD
number of
A reported
an
investigators have
apparent cerebral
protective effect for barbiturate anes¬ thesia in experimentally induced toteal cerebral ischemia13 regional cerebral ischemia,4·5 and cerebral edema.6 These reports suggest a possible clin¬ ical indication for inducing barbitu¬
rate anesthesia in the management of acute stroke. However, much of the
data are re¬ mote from the actual clinical circum¬ stances of acute stroke. Criticisms include the possibility that the species studied was inappropriate because of differences in collateral circulation, that the technique used for producing regional ischemia was not comparable to acute stroke, that many studies examined only acute events after ischemia, and that the chronic studies did not include supportive care similar to that provided clinically. We have previously reported data indicating that dogs, cats, and gerbils may be inappropriate for studies of regional cerebral ischemia, whereas primates, having a cerebral circula¬ tion anatomically similar to man, appear to yield consistent data.5 Other
collected
experimental
studies indicate that middle cerebral artery (MCA) occlusion in primates produces an ischemie lesion resem¬ bling that in man.7 In the present study, acute stroke was produced by permanent MCA occlusion in Java monkeys followed by an extended period of intensive care. We then compared the outcome in monkeys anesthetized with pentobarbital sodi¬ um for 48 hours to that found in unanesthetized animals. MATERIALS AND METHODS
Eighteen Java monkeys of both sexes and weighing 0.8 to 1.9 kg were studied. The monkeys were studied in groups of three and were ultimately divided into two groups of nine each, distinguished by the presence or absence of pentobarbital anes¬ thesia. In all monkeys, anesthesia was initially induced and maintained with halothane (1%). Endotracheal intubation was accomplished after muscle paralysis with succinylcholine chloride (40 mg). Ventila¬
tion was controlled with a fixed-volume ventilator. A femoral artery and vein were exposed and cannulated for pressure mea¬ surements, blood samples, and drug and fluid administration. A urinary catheter and rectal thermistor were inserted and secured. The right MCA was exposed via a
transorbital
approach, using the operating microscope. In an initial six monkeys, an occlusive clip was placed across the MCA at its origination from the internal carotid artery. In two of these, clinical signs of diabetes insipidus developed within 24 hours, which considerably complicated sup¬ portive care; therefore, this entire group was discarded from the study. In the 18 monkeys retained in the study, the clip was placed across the MCA distal to the first anterior branch, which supplies an ante¬ rior-inferior portion of the frontal lobe. Diabetes insipidus did not develop in any of these. After placement of the clip, halothane
discontinued and the animals were paralyzed with pancuronium bro¬ mide, 0.05 mg/kg, and sedated with diazepam, 0.1 mg/kg, intravenously. The durai incision was sealed with oxidized cellulose and glue (alpha-cyanoacrylate) and the wound was closed. Streptomycin sulfate (100 mg) and penicillin G sodium (300,000 units) were administered intramuscularly. With completion of surgery, a 48-hour period of intensive care was initiated. The monkeys were continuously attended by two technicians under the supervision of a was
physician.
Pancuronium bromide and diazepam were continued at 0.05 mg/kg/hr and 0.1
phenylephrine hydrochloride (0.013 mg intravenously). Two monkeys (control monkey 2 and monkey 3 in the pentobar¬ bital group) developed a progressive reduc¬ tion in urinary output, which was corrected by a single dose of furosemide (1 mg). Four monkeys (two from each group) required
mg/kg/hr, respectively. Also, a solution of 5% dextrose in 0.45% saline was given to the monkeys at a rate of 5.0 mg/kg/hr.
Arterial blood pressure was monitored continuously. Mean arterial pressure, cen¬ tral venous pressure, heart rate, tempera¬ ture, and urine output were recorded every 30 minutes. Electroencephalographic and electrocardiographic recordings were tak¬ en every two hours. Blood gases and hemo¬ globin concentration were measured every four hours. Ventilation was controlled, with 40% oxygen and 60% nitrogen (humid¬ ified); it was adjusted, as necessary, according to the blood gas measurements. The extremities were wrapped and, when necessary, a heat lamp was applied. The subjects were turned every four hours. In nine of the 18 monkeys, pentobarbital anesthesia was initiated 30 minutes after MCA occlusion, with an intravenous dose of 14 mg/kg. Thereafter, pentobarbital, 7
occasional additional dose of pancu¬ ronium bromide (0.05 mg) because of spon¬ taneous movement. A variety of technical problems were encountered (partial airway obstruction, inadvertent extubation, urina¬ ry catheter obstruction, and loss of intra¬ an
route), but, to our knowledge, they were always immediately recognized and corrected without apparent detrimental effects. Body temperature was controlled with heat lamps without difficulty. Muscle paralysis was intermittently evaluated
venous
with a nerve stimulator. Fluids were administered continuously via a calibrated automatic flushing apparatus attached to the arterial line. Ventilation was adjusted to maintain a Pao2 of 100 to 200 mm Hg and a Paco2 of 33 to 37 mm Hg. The electroencephalogram was recorded every two hours from each hemisphere using parietal-frontal electrodes. After 24 hours, penicillin G benzathine (200,000 units) was
mg/kg, was given intravenously every two hours. In all other respects, the 18 monkeys were managed identically throughout the 48-hour period with the following excep¬ tions: One monkey (control monkey 4) became hypotensive after 36 hours (mean arterial pressure < 60 mm Hg) and re¬ quired intermittent doses of mephentermine sulfate (2 mg intravenously) and
given intramuscularly. After 42 hours, pentobarbital
was
dis-
Table 1.—Mean 48-Hour Values in Control Monkeys
Monkey/ Sex 1/M 2/M 3/M 4/F 5/F 6/F 7/M 8/F 9/M Mean ± SE
Buffer
Mean Arterial
Central Venous
Heart
Pressure, mm Hg
Pressure,
Beats/ min
Temper¬ ature, C
globulin, gm/dl
158 215 173 230 176 195 227 181 213 196 ±9
37.1 37.1 37.1 36.9 37.0 37.2 36.9 37.2 37.0 37.1 ± 0
9.3 14.5 11.4 10.8 10.8 13.7 8.7 9.8 9.1 10.9 ±0.7
99 113 95 74 105 114 86 99 97 98
mm
Hg
2±0
Rate,
Hemo-
w
Pa o mm
Hg
175 154 154 181 179 145 140 159 156 160 ± 5
Table 2.—Mean 48-Hour Values in Pentobarbital
Monkey/ Sex
1/M 2/F 3/M 4/M 5/M 6/F 7/F 8/F 9/F Mean ± SE
Mean Arterial
Central Venous
Heart
Pressure, mm Hg
Pressure, mm Hg
Beats/
88 90 78 91 98 111 104 100 83 94 ±3
2±0
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Rate,
min 182 208 203 218 227 139 181 198 212 196 ±9
2,
Pa CO 2, mm
Hg
33 35 37 35 33 36 36 33 33 35 ±1
pH 7.53 7.46 7.49 7.47 7.55 7.46 7.52 7.55 7.55 7.55 ± 0.01
Base, mEq/
Liter 54 53 53 51 55 51 55 55 55 53 ±1
Monkeys Buffer
Base,
Hemo-
Temper¬ ature, C
globulin, gm/dl
37.2 37.0 36.9 37.0 37.2 36.9 37.2 37.0 37.4 37.1 ± 0.1
9.7 10.3 9.7 9.0 11.2 12.2 12.2 11.7 11.2 10.8 ±0.4
Pao2,
mm
Hg
161 194 177 155 129 152 188 181 163 167 ±7
PaC02,
mm
Hg
36 34 33 36 38 33 36 34 35 35 ±1
pH 7.48 7.50 7.48 7.51 7.48 7.50 7.50 7.49 7.50 7.49 ± 0
mEq/ Liter 52 52 51
53 53 52 53 52 53 52 ±0
continued in the nine monkeys of that group. After 48 hours, all drugs and fluids were discontinued in both groups. All cath¬ eters were then removed, and when spon¬ taneous ventilation was adequate, the trachea was extubated. In three control monkeys (No. 2, 4, and 7), spontaneous respiration remained inadequate despite total reversal of the muscle relaxant, and death ensued. The remaining monkeys after partial arousal from the pentobar¬ bital or diazepam effects or both, were returned to their cages. Thereafter, neuro¬ logic deficit was graded daily by two inde¬ pendent observers and recorded for five days. On the seventh postoperative day, the monkeys were killed, the placement of the MCA clip was confirmed, and the brains were removed, fixed in a 37% formaldehyde solution, identified by a code number, and stored. After all 18 monkeys had been studied, the brains were individu¬ ally examined in sequence without knowl¬ edge of code identification. The size of each cerebral hemisphere was measured by volume displacement before sectioning into 5-mm slices. The end area of infarction
Fig
1 .—Brain from pentobarbital monkey 9. Note lack of any midline shift and the normal appearance bilaterally.
in each slice was measured with a grid; the total size of infarction was computed and then expressed as a percent of that hemis¬ phere's volume. Systemic variables tabulated in Tables 1 and 2 were compiled by calculating the mean values of the multiple measurements made in each monkey during the 48-hour period of intensive care. Statistically significant differences between the two groups were tested for by the Student t test for unpaired data (for systemic varia¬ bles, Tables 1 and 2), by the 2 test of Pearson (for survival, Table 3), and by the Wilcoxon two-sample rank test (for neuro¬ logic deficit and size of infarction, Table
3). RESULTS In terms of monitored systemic variables, the two groups were compa¬ rable and generated grand mean values that are remarkably similar (Tables 1 and 2). All of the monkeys in the pentobarbital group survived the full seven days, whereas three of the
Fig 2.—Brain from control monkey 2. Note large infarction with shift of midline struc¬
tures.
control monkeys did not survive past the 48-hour period of intensive care (Table 3). Obvious neurologic deficits were recorded in seven of the controls and only two of the pentobarbital monkeys. In two others in the pento¬ barbital group, an initial slight motor weakness (—1) was no longer evident on the day of autopsy. A similar slight deficit was initially recorded in one of the controls. Thus, in five of nine monkeys in the pentobarbital group, there was no apparent neurologic deficit at any time, as opposed to only one of nine controls. In individual monkeys, variability in the deficit (usually an improvement with time) or disagreement between the two inde¬ pendent observers accounts for the tabulated double-numbered deficits (for example: —2,-3). In all but one monkey (control monkey 5) in whom a deficit had been recorded during the five-day period of observation, an infarct was found. In the five mon¬ keys in the pentobarbital group and one control monkey in which no deficit had been recorded, there was no infarct. The size of the infarct tended to correlate with the magnitude of the deficit. Exceptions (such as control monkey 3) were accounted for by small infarcts in the internal capsule, which resulted in notable deficits. Examples of a normal brain (monkey 9 in the pentobarbital group) and of a large infarction (control monkey 2) are shown in Fig 1 and 2. The EEG recordings differed as expected in the two monkey groups. In the control monkeys, the EEG from the nonischemic hemisphere was a
predominately high frequency (18 to 24 hertz), low amplitude (5/xv to 10/xv) pattern. In the monkeys in the pento¬
barbital group, a moderate level of anesthesia was indicated in eight of the nine by a complex EEG pattern consisting of relatively low amplitude
(5µ to 10/xv), high frequency (12 to 14 Hz) activity superimposed on high amplitude (40/xv to 70/xv), low frequen¬ cy (2 to 4 Hz) activity. In one monkey (3) burst-suppression indicated a deeper level of anesthesia. The EEG from the MCA-occluded hemisphere was of little diagnostic value in those monkeys that developed only small infarctions and, even in retrospect,
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Table
After 48 Hours of Intensive Care Control
Pentobarbital Monkeys'
Monkeys
_A_
Monkey Survived 1
8
Neurologic
Yes No Yes No Yes Yes No Yes Yes
% Infarct
Deficit
r
Monkey 1
0 24
