Restoration of Middle Cerebral Artery Flow in Experimental Infarction

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At the present time a patient with an acute middle cerebral artery occlusion represents an unanswered challenge for effective treatment. Conservative management has done little to alter the size of the resulting cerebral infarctions and the magnitude of related neurological deficits. Although occasional young persons withstand this catastrophe,1 these patients generally do poorly, and the survivors can hardly be called therapeutic successes.6

The purpose of this work was to determine what benefits and hazards might be anticipated if flow through an occluded middle cerebral artery could be restored. Possible protective measures of hemodilution were investigated,

At the present time a patient with an acute middle cerebral artery occlusion represents an unanswered challenge for effective treatment. Conservative management has done little to alter the size of the resulting cerebral infarctions and the magnitude of related neurological deficits. Although occasional young persons withstand this catastrophe,1 these patients generally do poorly, and the survivors can hardly be called therapeutic successes.6

The purpose of this work was to determine what benefits and hazards might be anticipated if flow through an occluded middle cerebral artery could be restored. Possible protective measures of hemodilution were investigated, and particular attention directed to the problem of hemorrhagic cerebral infarction. Information of this nature is of utmost importance in determining the feasibility of middle cerebral artery surgery. The isolated but dramatic reported results serve to stimulate further studies and investigation so that such procedures can be undertaken more often and with reasonable hope of success.3,8

This study is based on experimental procedures in 100 squirrel monkeys and 35 cats. The squirrel monkey was used in the studies of massive cerebral infarction, the cat in those of smaller lesions. The necessity for two models was determined by previous studies and concurrent clinical experience emphasizing the difference between the two sizes of infarction.10,12,14

Materials and Methods Massive Cerebral Infarction (Monkeys)

The monkey used was the squirrel monkey (Saimiri sciureus), average weight 75 kg. The animals were anesthetized with 0.25 ml of sodium pentobarbital (Nembutal 50 mg/ml) injected into the intrapleural space with a ⅝ in. No. 25 hypodermic needle. The animals were utilized as acute or chronic preparations.

Acute Preparations

Tracheostomies were performed with the electrosurgical unit. The monkey was then placed in a Waltz headholder. A unilateral scalp flap was reflected with the electrosurgical unit. The origin of the right middle cerebral artery was exposed by the retro-orbital extradural approach under the operating microscope. Details of this approach have been described previously.2,13 The dura over the hemispheres was then excised under microscopic guidance and the cortex overlaid with a transparent sheet of plastic (Saran Wrap). The camera assembly, described previously, was then focused on a localized area of cortex.16 Mean systemic blood pressures were measured throughout the experiment by a Tycos manometer attached to a bubble trap in turn attached to a siliconized polyethylene catheter inserted into the exposed femoral artery. The animals were maintained at normotensive or hypertensive levels depending upon the type of experiment. The mean blood pressure ranged between levels of 80 and 120 mm Hg in the normotensive groups and between 120 and 160 mm Hg in the group treated with vasopressors. In no animal prepaartions did blood loss exceed 5 cc.

A miniature Mayfield clip was next applied, under microscopic control, to the previously exposed middle cerebral artery. The middle cerebral artery was occluded for 3 hours during which time cortical changes were recorded photographically. At the end of 3 hours the spring clip was removed from the middle cerebral artery and the major circulation reestablished. Photographic records were continued for another hour.

Twenty such animals were operated on, studied, and photographed. These animals were separated into three groups. The control group of 10 animals had no treatment during the 3 hours of middle cerebral artery occlusion. A second group of five animals received a combination of low-molecular-weight dextran and salt-poor human serum albumin in a dosage equal to that administered to the chronic animals treated with hemodilution (see below). In the third group of five animals, the systemic blood pressure was artificially elevated by the intermittent intravenous administration of metaraminol (aramine) in an average dosage of .025 mg/kg every ½ to 1 hour. The frequency of administration was governed by the animal's particular response to vasopressor and measured mean blood pressure.

Chronic Preparations

The animals were intubated with a small polyethylene tube and placed in an atraumatic headholder. A linear scalp incision was made with the cutting current of the Bovie electrosurgical unit. A small frontotemporal craniectomy was extended down the sphenoid wing. The middle cerebral artery was then approached under the operating microscope through a small dural incision overlying the optic nerve, an approach referred to and referenced above The middle cerebral artery was occluded with a miniaturized Mayfield clip. This period of occlusion varied from 3 hours to permanent, depending upon the group classification of the animal. If the clip was removed, the wound was closed after its removal. If the clip was permanently applied, the wound was closed immediately. Maximum blood loss varied between 3 and 5 cc and no animals became hypotensive.

Animals were divided into the following groups (Table 1):

  1. Control group of 10 animals. Middle cerebral artery was permanently occluded.

  2. Control group of 10 animals, with hemodilution treatment. Middle cerebral artery was permanently occluded. The animals received 6 cc (1.5 gm)/kg of 25% salt-poor serum albumin plus 12 cc/kg of 10% low-molecular-wright dextran, the two agents being mixed and administered over a 1-hour period with the treatment starting 1 hour after occlusion of the artery.

  3. Group of 10 animals with 6 hours of arterial occlusion and no treatment.

  4. Group of 10 animals with 6 hours of arterial occlusion plus hemodilution treatment. Dilution accomplished as in item 2 above.

  5. Group of 10 animals with 3 hours of arterial occlusion and no treatment.

  6. Group of 20 animals with 3 hours of arterial occlusion plus hemodilution treatment. Dilution accomplished as in items 2 and 4.

  7. Group of 10 animals with 3 hours of arterial occlusion plus hemodilution by albumin alone. The animals were given 4 cc (1 gm)/kg of 25% concentrated salt-poor human serum albumin over a 1-hour period with treatment starting 1 hour after occlusion of artery.

TABLE 1

Chronic squirrel monkey cerebral infarctions

GroupNo. of AnimalsSurvivorsDeathsMortality & Morbidity (%)
No. of AnimalsClinical StateAutopsy FindingsNo. of AnimalsClinical StateAv. Time to DieAutopsy Findings   
MCA, permanently occluded,severelargestuporoussevere90 mortality
no dilution101hemiplegicinfarct9hemiplegic24–26 hrsedema10 morbidity
MCA, permanently occluded,stuporoussevere
dilution with Alb. &10010hemiplegic24–30 hrsedema100 mortality
LMWD
MCA, temporarily occludedstuporoussevere
6 hrs, no dilution10010hemiplegic24–30 hrsedema100 mortality
MCA, temporarily occluded1 hemiplegicinfarctstuporoussevere60 mortality
6 hrs, dilution with Alb.1043 no deficitno infarct6hemiplegic18–24 hrsedema10 morbidity
& LMWD
MCA, temporarily occludedstuporoussevere40 mortality
3 hrs, no dilution106no deficitno infarct4hemiplegic18–24 hrsedema 0 morbidity
MCA, temporarily occludedhemiplegicsevere30 mortality
3 hrs, dilution with Alb.107no deficitno infarct3coma4 hrsedema 0 morbidity
alone
MCA, temporarily occludedstuporoussevere80 mortality
3 hrs, dilution with Alb.204no deficitno infarct16hemiplegic10–18 hrsedema 0 morbidity
& LMWD

MCA = middle cerebral artery

Alb. = 25% salt poor human serum albumin

LMWD = low molecular weight dextran—10%—(Rheomacrodex)—supplied by Pharmacia Co.

Each animal was observed daily and the clinical course reported. In case of death from the lesion, the brains were removed and fixed. Survivors were allowed to live at least 7 days, then killed, and the brain fixed. All brains were subjected to microscopic evaluation.

Materials and Methods Small Areas of Cerebral Infarction (Cats)

Chronic animals were prepared in an identical manner to that previously reported.13 The middle cerebral artery was permanently occluded by a retro-orbital extradural approach; the wound was then promptly closed. The 16 members of the originally reported group of control animals were used as part of the control group in this report.13 Nine additional control animals were operated on to extend the chronic group of animals with permanent middle cerebral artery occlusion to 25 animals.

In 10 animals, the middle cerebral artery was temporarily occluded for 6 hours, the clip removed, and then the wound closed. No animals in this group received dilution or any treatment other than supportive care.

The animals with temporary occlusion and the control animals with permanent occlusion were followed for 7 days, then killed, and the brains fixed. Selected brains were subjected to microscopic evaluation. The volumes of cerebral infarction were measured in each animal in a manner previously described.13

Results of Studies on Monkeys

This species tolerated the anesthesia and the surgery well. In acute animals it was not necessary to supplement the anesthesia. In the chronic preparations the animal commonly reacted from anesthesia so that it was possible to determine and observe his clinical deterioration from the increasing cerebral edema.

Acute Preparations: Cortical Flow Observations

The microcirculatory changes following occlusion of the middle cerebral artery were essentially those that have been described previously (Fig. 1 AD). These included: darkening of venous blood in the areas of ischemia, venous sludging in areas of reduced flow, development of small foci of cortical pallor, the gradual coalescence of these areas of cortical pallor, arterial spasm in areas of cortical pallor, edema in areas of ischemia, occasional venous platelet thrombi, and the transformation of dark venous blood to bright red blood in selected areas. These changes took place over the 3-hour period during which the middle cerebral artery was occluded. The animals remained normotensive throughout the acute experiment.

Fig. 1 A.
Fig. 1 A.

Monkey parietal cortex prior to occlusion of middle cerebral artery. Slight pallor from light reflex is artifact.

Fig. 1 B.
Fig. 1 B.

Cerebral cortex 30 minutes following MCA occlusion. Pallor is developing in cortex; veins become darker (poorly shown in this slide).

Fig. 1 C.
Fig. 1 C.

Cerebral cortex 1 hour following occlusion. Pallor is progressing; venous sludging present.

Fig. 1 D.
Fig. 1 D.

Cerebral cortex 3 hours following occlusion. Arterial spasm present in areas of pallor; venous sludging more marked.

In the five animals in which dilution was employed using low-molecular-weight dextran and serum albumin, the same changes in the cortex were observed to take place, although perhaps there was some delay in the development of the pallor and spasm. Certainly by the end of the 3-hour occlusion there was no obvious difference between the control group and the group treated with dilution.

In the five animals in which the blood pressure was maintained at slightly elevated levels using metaraminol (aramine) intermittently intravenously, there was no significant change from the control group maintained at normotensive levels. The animals tended to develop a tachyphylaxis so that it became increasingly difficult to keep the animal's mean blood pressure in the neighborhood of 140 to 160 mm Hg.

Following restitution of blood flow to the areas of ischemia, all animals in the acute preparations showed evidence of reconstituted blood flow (Fig. 1 E and F).

Fig. 1 E.
Fig. 1 E.

Cerebral cortex 5 minutes following removal of occluding slip. Cortex is recolorizing, spasm reversing.

Fig. 1 F.
Fig. 1 F.

Cerebral cortex 30 minutes following removal of occluding clip. Veins are redder; entire cortex has background hyperemia. (Luxury perfusion syndrome of Lassen.)

The earliest change was a complete transformation of dark venous blood to bright red blood in all areas of ischemia. This occurred within a few minutes following removal of the clip. Next there was a gradual recolorization of the cortex along with the simultaneous decrease in the degree of venous sludging. Thereafter, the major arteries resumed their normal caliber, and this progressed in a step-wise fashion throughout the areas of ischemia and followed in each instance the recolorization of the underlying cortex. Finally, there was the stage of reactive hyperemia in which the cortex took on a reddish hue. In conjunction with this change in the cortical color, small vessels could be observed in the cortex which were not apparent early in the experiment prior to occlusion of the middle cerebral artery. Observations were continued for 1 hour following restitution of blood flow. Near the end of this period, there was often evidence of cerebral edema with the cortex overlapping to a minor degree the sharp margins of the resected dura around the edge of the craniectomy.

Chronic Preparations: Neurological Status and Gross Pathology

The results of the chronic experiments are summarized in Table 1. It should be noted that since “morbidity” represented complete and profound hemiplegia, one must add these to the mortality figures in summarizing the poor results. The combined mortality and morbidity figure was relatively favorable in only two groups. The group subjected to middle cerebral artery occlusion for 3 hours without dilution treatment had a combined figure of 40% while the animals subjected to middle cerebral artery occlusion for 3 hours with albumin treatment had a combined figure of 30%. The combined figure was 100% in three groups and 70% and 80% in the two others.

The histological changes were studied by light microscopy, and will be described separately in a future communication.4 The early demise of these animals along with the vast amount of edema associated with the areas of ischemia prevented a gross delineation of the areas of infarction, and therefore, in contrast to the cats, volumetric measurements were not possible.

Figures 2 through 8 show representative gross specimens from these groups.

Fig. 2.
Fig. 2.

Infarction followed permanent MCA occlusion, no treatment: The animal died 24 hours after surgery, after having awakened from anesthesia. The degree of edema was typical of this group of animals.

Fig. 3.
Fig. 3.

Infarction following permanent MCA occlusion with hemodilution. Following occlusion of the vessel the animal was treated by hemodilution with albumin and low molecular weight dextran. The degree of edema was typical in this group of animals. The animal died 16 hours after surgery, after having awakened from anesthesia.

Fig. 4.
Fig. 4.

Infarction following 6 hours of MCA occlusion, no treatment. Small areas of hemorrhage in this specimen were uncommon in the group as a whole. The large amount of edema was typical of the group. This animal died 20 hours after surgery, after having awakened from anesthesia.

Fig. 5.
Fig. 5.

Infarction following 6 hours of MCA occlusion with hemodilution. During period of occlusion the animal was treated with hemodilution using albumin and low molecular weight dextran. The degree of edema shown is typical for this group. The animal died 3 days following surgery and had a severe hemiplegia before death.

Fig. 6.
Fig. 6.

No infarction 3 hours after MCA occlusion, with no hemodilution. The animal was killed 1 week after surgery; he had no paresis at the time of death.

Fig. 7.
Fig. 7.

No infarction 3 hours after MCA occlusion; hemodilution with albumin alone. The animal had no paresis at the time of death and was killed 1 week after surgery.

Fig. 8.
Fig. 8.

Infarction following 3 hours of MCA occlusion and hemodilution with albumin and low molecular weight dextran. This degree of edema was typical for this group. The animal died 16 hours after surgery.

Results of Studies on Cats

The results of the experiments in the cat are summarized in Table 2. The cat has a smaller cerebral infarction from middle cerebral artery occlusion than does the monkey, and accordingly in the control group the mortality was only 13%. However, invariably the animal did develop a cerebral infarction from occlusion of the vessel so that the combined mortality and morbidity was 100%. The average volume of infarction in this group as computed by the average end area method described in detail previously13 was 3.73 cc.

TABLE 2

Chronic cerebral infarctions in the cat

GroupNo. of AnimalsSurvivorsDeathsMortality & Morbidity (%)
No. of AnimalsClinical StateAutopsy FindingsNo. of AnimalsClinical StateAv. Time to DieAutopsy Findings   
Permanentstuporinfarct14 mortality
MCA occlusion2522hemiparesisinfarct3hemiparesis3 days& edema86 morbidity
6 hr. MCAneurologicallynormal or smallsevere10 mortality
occlusion109negativeinfarct1stupor12 hrsedema 0 morbidity

The group of animals in which the middle cerebral artery was temporarily occluded for 6 hours had a 10% mortality and no morbidity. However, some of the animals that appeared to be neurologically negative clinically did have a small infarction found at autopsy. The size of this infarction in the survivors never exceeded 0.5 cc in size. This group appears to be statistically different from the control group.

Figure 9 shows representative gross specimens from these animals.

Fig. 9.
Fig. 9.

The brain on the left shows a typical cerebral infarction in a cat with permanent middle cerebral artery occlusion. The brain on the right shows a typical absence of infarction following 6 hours of occlusion of this vessel.

Discussion

It appears from this work that anatomical cerebral infarction (as distinct from physiological paralysis) does not develop immediately following occlusion of a major vessel. The period between occlusion of the vessel and development of the anatomical infarction varied in the two species. In previous studies it has been shown that the nature of response to occlusion of the middle cerebral artery was the same in the cat and monkey but that the changes were more rapid in their development in the monkey, and more severe in their appearance.12 It is therefore assumed that these differences in response are primarily related to the degree of ischemia and that the severe ischemia in the squirrel monkey results in a potentially massive cerebral infarction whereas the moderate ischemia in the cat results in a smaller infarction. Cortical flow studies have confirmed the differences in the degree of ischemia in these two species following middle cerebral artery occlusion.17 Accordingly, in the discussion below, reference will be made to a massive infarction and a moderate infarction, and attention will not be directed to possible basic differences in behavior related to the species studied. No information is available that indicates there is a species variability in this response to injury other than that related to the degree of ischemia.

Harvey and Rasmussen5 performed similar studies on Rhesus monkeys (Macaca mulatta). They found that at least 50 minutes of middle cerebral artery occlusion was required to produce infarcts of sizes comparable to those produced by permanent occlusion of this vessel. This work was carefully performed on Rhesus monkeys, but the individual groups of animals were small. It was done before the availability of the operating microscope, and the dura was opened in an intradural approach to the vessel. Therefore, it is difficult to make comparisons between the two studies. It should be noted, however, that in their study the two animals that had middle cerebral artery occlusion for 50 minutes had hemorrhagic infarctions. We used an extradural approach and left the dura over the hemispheres undisturbed; the incidence of hemorrhagic infarction was obviously less.

Due to the differences in the extent of the surgical exposures for the acute and chronic preparations, it was not possible for us to use the same animal both as an acute and chronic model of cerebral infarction. Therefore, observations were made in a large number of acute and chronic animals and correlated and extrapolated to arrive at the following conclusions.

Massive Cerebral Infarction

This size cerebral infarction might be represented clinically by an acute middle cerebral artery occlusion with no collateral blood flow demonstrable by arteriography. Various techniques of hemodilution in this experimental work did very little to alter the final result. It might be stated, parenthetically, this has been our concurrent clinical experience.10 Furthermore, techniques of hemodilution did little to provide protection between the time of occlusion and restitution of blood flow.

Artificial elevation of the blood pressure in the acute experiments did not appear encouraging and so were not correlated with further chronic studies. Recent studies by Waltz15 indicate little promise for treatment by means of elevating the pressure above what is normotensive for the animal. This is not to imply that an adequate perfusion pressure is not necessary. It is now common knowledge that hypotension will cause a failure in collateral circulation.9,15

It was encouraging that even with this severe degree of ischemia a number of monkeys tolerated middle cerebral artery occlusion for 3 hours without the development of an infarction. Of course in these survivors the amount of edema present 24 and 48 hours following occlusion of the vessel is unknown, but was probably less than that present in the group which died. It was felt that severe edema was the chief cause of mortality in both the animals without restored blood flow and the animals with restored blood flow.

Moderate Cerebral Infarction

This degree of ischemia might be represented clinically by an acute middle cerebral artery occlusion with collateral flow demonstrable by arteriography. These patients, in contrast to those without demonstrable collateral flow, might be considered for surgical intervention even hours following occlusion of the middle cerebral artery. Experimentally, middle cerebral artery occlusion in the cat was tolerated for 6 hours without the uniform development of a cerebral infarction. Restoration of blood flow in this group definitely altered the final result, supporting clinical reports.3,8

Techniques of hemodilution were not studied in this group because they have been reported previously.14 Although these techniques of hemodilution showed initial promise in modifying the size of infarction in the work previously reported, it should be noted that hemodilution in the previous series was instituted prior to middle cerebral artery occlusion. This, of course, is not the common clinical situation and would have had application only to selected emergencies encountered at the operating table.

Problems of Reconstituted Flow

Edema seems to be the major limiting factor in the restoration of cerebral blood flow. Edema was the chief cause of mortality in all animals studied, and it was present whether or not blood flow was reconstituted. In the acute animals it could be seen to develop and was present in its early stages 3 hours after the middle cerebral artery had been occluded. Restoration of blood flow did not decrease the edema in the acute animals if it was already in its early development. In fact, it appeared that the edema was more severe following the restitution of flow in some cases. This can be correlated with the results in the chronic animals; those that died following only 3 hours or middle cerebral occlusion died on the average approximately 6 hours sooner than did the group in which flow was not restored or in which occlusion had persisted for a longer period of time, 6 hours. It also is of some interest that the only cat that died following restitution of blood flow died of massive cerebral edema within 6 hours following the time of restored blood flow, or approximately one-fourth the time any cat in the chronic control group took to die from edema.

The animals that did not die following restoration of blood flow were possibly more resistant to the formation of edema. The edema from ischemia and the edema from reactive hyperemia might be of different origins, explaining to some extent the differences in individual response to restored flow.

This work has shed little light on the actual nature of this edema, its mechanism or means of control. Figure 1 F demonstrates reactive hyperemia in the area of cortex following restitution of blood flow, and could be termed the “luxury perfusion syndrome of Lassen.”7 It could very well be the result of a failure in the autoregulatory mechanism of the cerebral tissues in the areas of previous ischemia. Whatever its cause, it represents a potent hazard, and one which apparently increases if one attempts hemodilution as a protective measure. Table 1 shows that when the middle cerebral artery was occluded for only 3 hours, the animals receiving no treatment or albumin alone did better than those treated with more vigorous techniques of hemodilution.

To our surprise, few of the infarctions had significant areas of hemorrhage and none of the infarctions could be described as frankly hemorrhagic. Therefore, although this report is only significant to this problem in a negative sense, it does imply that the actual cause of a hemorrhagic cerebral infarction must be more complicated than the mere restitution of blood flow to an area of severe ischemia. We have seen clinical restitution of blood flow in a middle cerebral artery result in a hemorrhagic cerebral infarction.11

Protective Measures

It appears from this work that some techniques and methods must be developed for the preservation of cerebral tissue and control of edema during the period of a severe ischemia. Hemodilution offers little encouragement as a final or partial solution unless the problem of edema can be resolved.

One is forced to conclude that, when dealing with cerebral infarctions of large volume as represented by those in the monkeys, hemodilution is not beneficial and indeed may be harmful. This is undoubtedly related to the alterations in the blood-brain barrier that occur in areas of ischemia.Hemodilution, if instituted promptly after the onset of ischemia, seems to be effective in smaller areas of cerebral infarctions in which there may not be maximal damage to this barrier.14 However, considerations in addition to the microcirculatory patterns and blood viscosity are of greater importance in the larger cerebral infarctions.

Fruitful lines of investigation might be directed toward the search for a toxic factor liberated from areas of ischemia because of a slow and gradual failure of collateral circulation. An instantaneous failure would be expected were this purely a problem of hemodynamics. In a previous report, evidence was presented that serotonin or a serotonin-like factor might be responsible for the spontaneous spread and self-perpetuation of a cerebral infarction.2

Clinical Correlation

Following the conclusion of the previously described experimental studies, we had the opportunity to operate on two elderly patients with acutely occluded middle cerebral arteries.

In one of these, occlusive embolus was believed to have originated in an ulcerated plaque at the bifurcation of the carotid artery. In the other patient the source of the embolism was never determined but it was felt to be cardiac. Both of these vessels were operated on under the operating microscope, and the arteriotomy was repaired using 7-0 arterial silk suture. Considerable experience had been obtained in the laboratory suturing small vessels under the operating microscope so that the task at surgery was certainly not difficult. Temporary occlusion of the middle cerebral artery and its branches was achieved by using miniaturized Mayfield clips of the size used to occlude the middle cerebral arteries in the experimental animals. Both of these patients were operated on because they showed evidence in the later films of the arteriograms of collateral blood flow, and it was felt that restoration of blood flow was possible and could be beneficial even hours after the occlusion in these patients.

In one of these patients there was definite clinical improvement immediately following the surgery, but the patient later died of pulmonary complications before postoperative arteriograms could be performed. She was, however, feeding herself following surgery and making a good neurological recovery.

In the second case, illustrated in Fig. 10, there was a complete right hemiplegia and aphasia prior to surgery. Following surgery the patient had return of function in the right leg, but none in the right arm. The aphasia, however, cleared gradually so that by 4 weeks after surgery the patient had virtually no expressive or receptive speech impairment. It was calculated that this vessel had been occluded at least 12 hours when it was opened at surgery.

Fig. 10.
Fig. 10.

Left: Preoperative arteriogram on a patient with an acute middle cerebral artery occlusion. Later films in the arterial sequence demonstrated collateral filling of the region of the middle cerebral artery. Right: Postoperative arteriogram in same patient. The time interval between vessel occlusion and operative opening was 12 hours. The patient was improved postoperatively.

Both of these cases were encouraging because although the time of occlusion was 8 hours in the first case and 12 hours in the second, restoration of blood flow was accomplished without the production of a hemorrhagic infarction. Also both patients were improved clinically following the restoration of flow, although both patients remained hemiparetic.

The clinical experience in these two cases correlates well with the experimental studies reported above.

Experience obtained in the laboratory with the operating microscope and microsuture techniques facilitates the surgery. Although we still prefer the clip-graft for aneurysms, in this particular type of surgery with a normal arterial wall and the means of controlling hemorrhage, microsuture seems to be preferable because the length of the arteriotomy can be better controlled and can include bifurcation sites when necessary.

Summary

An alteration in the final size of a cerebral infarction was achieved by the restitution of cerebral blood flow in the squirrel monkey following 3 hours of middle cerebral artery occlusion and in the cat following 6 hours of middle cerebral artery occlusion. Restoration of flow prevented an infarct in some animals; in other animals the cerebral edema continued to progress and led to death.

It appears that anatomical cerebral infarction is distinct from physiological paralysis and does not develop immediately following occlusion of a major vessel but rather develops over a matter of hours. The clinical application of these observations may be important to the surgeon considering major surgery for occlusive vascular disease in a patient with a neurological deficit.

Restitution of blood flow in the acute preparations of cerebral ischemia resulted in a reactive hyperemia which was documented photographically.

The chief cause of mortality in the chronic animals was cerebral edema. This was true of animals with temporary or with permanent occlusion of the middle cerebral artery. This edema limits the usefulness of hemodilution as a treatment in large cerebral infarctions.

Two successful human middle cerebral artery embolectomies have been described for correlation with the experimental work.

References

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    NofzingerJ. D.SundtT. M.MurphyF. Clinical studies in the use of hemodilution for cerebral ischemia. (In preparation)NofzingerSundtMurphy

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    SundtT. M.Jr.NofzingerJ. D. Clip-grafts for aneurysm and small vessel surgery. Part 1. Repair of segmental defects with clip-grafts; laboratory studies and clinical correlations. Part 2. Clinical application of clip-grafts to aneurysms; technical considerations. J. Neurosurg.196727:477489.SundtJr.NofzingerJ. Neurosurg.27:477–489.

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    SundtT. M.Jr.WaltzA. G. Hemodilution and anticoagulation. Effects on the neurovascular and microcirculation of the cerebral cortex after arterial occlusion. 196717:230238.SundtJr.Waltz17:230–238.

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    SundtT. M.Jr.WaltzA. G. Experimental cerebral infarction: retro-orbital, extradural approach for occluding the middle cerebral artery. Proc. Staff Meet. Mayo Clin.196641:159168.SundtJr.WaltzProc. Staff Meet. Mayo Clin.41:159–168.

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    SundtT. M.Jr.WaltzA. G.SayreG. P. Experimental cerebral infarction: modification by treatment with hemodiluting, hemoconcentrating, and dehydrating agents. J. Neurosurg.196726:4656.SundtSayreJ. Neurosurg.26:46–56.

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This work was supported by U.S. Public Health Service Grants NB-06822 and NB-06826.

Article Information

New address: Section of Neurosurgery, Mayo Clinic, Rochester, Minnesota 55901.

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

Headings

Figures

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    Monkey parietal cortex prior to occlusion of middle cerebral artery. Slight pallor from light reflex is artifact.

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    Cerebral cortex 30 minutes following MCA occlusion. Pallor is developing in cortex; veins become darker (poorly shown in this slide).

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    Cerebral cortex 1 hour following occlusion. Pallor is progressing; venous sludging present.

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    Cerebral cortex 3 hours following occlusion. Arterial spasm present in areas of pallor; venous sludging more marked.

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    Cerebral cortex 5 minutes following removal of occluding slip. Cortex is recolorizing, spasm reversing.

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    Cerebral cortex 30 minutes following removal of occluding clip. Veins are redder; entire cortex has background hyperemia. (Luxury perfusion syndrome of Lassen.)

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    Infarction followed permanent MCA occlusion, no treatment: The animal died 24 hours after surgery, after having awakened from anesthesia. The degree of edema was typical of this group of animals.

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    Infarction following permanent MCA occlusion with hemodilution. Following occlusion of the vessel the animal was treated by hemodilution with albumin and low molecular weight dextran. The degree of edema was typical in this group of animals. The animal died 16 hours after surgery, after having awakened from anesthesia.

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    Infarction following 6 hours of MCA occlusion, no treatment. Small areas of hemorrhage in this specimen were uncommon in the group as a whole. The large amount of edema was typical of the group. This animal died 20 hours after surgery, after having awakened from anesthesia.

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    Infarction following 6 hours of MCA occlusion with hemodilution. During period of occlusion the animal was treated with hemodilution using albumin and low molecular weight dextran. The degree of edema shown is typical for this group. The animal died 3 days following surgery and had a severe hemiplegia before death.

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    No infarction 3 hours after MCA occlusion, with no hemodilution. The animal was killed 1 week after surgery; he had no paresis at the time of death.

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    No infarction 3 hours after MCA occlusion; hemodilution with albumin alone. The animal had no paresis at the time of death and was killed 1 week after surgery.

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    Infarction following 3 hours of MCA occlusion and hemodilution with albumin and low molecular weight dextran. This degree of edema was typical for this group. The animal died 16 hours after surgery.

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    The brain on the left shows a typical cerebral infarction in a cat with permanent middle cerebral artery occlusion. The brain on the right shows a typical absence of infarction following 6 hours of occlusion of this vessel.

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    Left: Preoperative arteriogram on a patient with an acute middle cerebral artery occlusion. Later films in the arterial sequence demonstrated collateral filling of the region of the middle cerebral artery. Right: Postoperative arteriogram in same patient. The time interval between vessel occlusion and operative opening was 12 hours. The patient was improved postoperatively.

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