I am writing a review paper describing the history (through the present
day) of experiments designed to provide artificial support for maintaining
normal brain activity following total circulatory or respiratory collapse.
The ultimate goal of such research is to preserve normal brain function
across lengthly periods (weeks/months) of cardiac or respiratory arrest.
There is a very substantial scientific literature (a brief chronology of
which is provided below) describing an increasingly successfull series of
experiments where animal brains have been supported by artificial methods
after complete circulatory and respiratory failure.
If you are aware of any additional literature which should be included in
this review or if you have comments regarding the appropriateness of this
technology for current laboratory / distant future human clinical therapy
please reply with an email note to annala at neuro.usc.edu.
1812 -- Legallois put forth the original idea for resuscitating decapitated
heads through the use of blood transfusion.
1836 -- Cooper showed in rabbits that compression of the carotid and vertebral
arteries leads to death of an animal; such deaths can be prevented if
the circulation of oxygenated blood to the brain is rapidly restored.
1857 -- Brown-Sequard decapitated a dog, waited ten minutes, attached four
rubber tubes to the arterial trunks of the head, and injected blood
containing oxygen by means of a syringe. Two or three minutes later
voluntary movements of the eyes and muscles of the muzzle resumed.
After cessation of oxygenated blood transfusion movements stopped.
1887 -- Laborde made what appears to be first recorded attempt to revive the
heads of executed criminals by connecting the carotid artery of the
severed human head to the carotid artery of a large dog. According
to Laborde's account, in isolated experiments a partial restoration
of brain function was attained.
1912 -- Heymans maintained life in an isolated dog's head by connecting the
carotid artery and jugular vein of the severed head to the carotid
artery and jugular vein of another dog. Partial functioning in the
severed head was maintained for a few hours.
1928 -- Bryukhonenko and Cechulin showed life could be maintained in the
severed head of a dog by connecting the carotid artery and jugular
vein to an artificial circulation machine.
Chute-AL, Smyth-DH. Metabolism of the isolated perfused cat's brain. Quart
J Exp Physiol 29:379-394 (1939).
Geiger-A, Magnes-J. The isolation of the cerebral circulation and the
perfusion of the brain in the living cat. Am J Physiol 149:517-536 (1947).
*Geiger-A. Correlation of brain metabolism and function by use of a brain
perfusion method in situ. Physiol Rev 38:1-20 (1958).
Geiger-A. Technique of brain perfusion in situ. Methods Med Res 9:248-254
Demikhov-VP. Transplantation of the Head. "Experimental Transplantation of
Vital Organs". Consultants Bureau, New York (1962).
*Meder-R, Massopust-LC-Jr, White-RJ, Verdura-J, Albin-MS. Isolated brain
perfusion--electromechanical system requirements. Proc 16th Ann Conf Eng
Med Biol 5:28-29 (1963).
*White-RJ, Albin-MS, Verdura-J. Isolation of the monkey brain: in vitro
preparation and maintenance. Science 141:1060 (1963).
*Gilboe-DD, Cotanch-WW, Glover--MB. Extracorporeal perfusion of the isolated
head of a dog. Nature 202:399-400 (1964).
Sano-K, Terao-H, Hayakawa-I, Kamano-S, Saito-I. Experimental transplantation
of the head: two-headed dogs. Neurol Medicochir (Tokoyo) 6:35-38 (1964).
*White-RJ, Albin-MS, Verdura-J. Preservation of viability in the isolated
monkey brain utilizing a mechanical extracorporeal circulation. Nature
(Lond) 202:1082-1083 (1964).
*Gilboe-DD, Cotanch-WW, Glover-MB. Isolation and mechanical maintenance of
the dog brain. Nature (Lond.) 206:94-96 (1965).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Brain transplantation: prolonged
survival of brain after carotid-jugular interposition. Science 150:779 (1965).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Transplantation of the isolated
canine brain. Physiologist 8:304 (1965).
Suda-I, Kito-K, Adachi-C. Viability of long term frozen cat brain in vitro.
Nature 212:268 (1966).
*White-RJ, Albin-MS, Locke-GE. Vascular preparation of the isolated canine
brain. Anatomical Record 154:441 (1966).
*White-RJ, Albin-MS, Locke-GE. Whole brain preservation near 0 degrees C.
Cryobiology 2:315 (1966).
*White-RJ, Albin-MS, Verdura-J, Locke-GE. Prolonged whole brain refrigeration
with electrical and metabolic recovery. Nature 209:1320 (1966).
*Allweis-C, Abeles-M, Magnes-J. Perfusion of cat brain with simplified blood
after filtration through glass wool. Amer J Physiol 213:83-86 (1967).
Andjus-RK, Suhara-S, Sloviter-HA. An isolated, perfused rat brain preparation,
its spontaneous and stimulated activity. J Appl Physiol 22:1033-1039 (1967).
*Sloviter-HA, Kamimoto-T. Erythrocyte substitute for perfusion of brain.
Nature (lond) 216:458-460 (1967).
Taslitz-N, Acosta-Rua-G, White-RJ, Albin-MS. The rat brain as an isolated
organ preparation. Anat Rec 157:332 (1967).
White-RJ, Albin-MS, Verdura-J, Locke-GE. The isolated monkey brain: operative
preparation and design of support systems. J Neurosurg 27:216-225 (1967).
*White-RJ, Albin-MS, Locke-GE, Davidson-E. Preparation and metabolic
performance of the transplanted brain. Surgical Forum 18:463 (1967).
White-RJ, Albin-S, Yashon-D, Austin-J, Austin-P, Taslitz-N. Mechanical
circulatory support of the failing brain. Trans Amer Soc Artif Int Organ
*White-RJ, Albin-MS. Mechanical circulatory support of the isolated brain.
"Organ perfusion and preservation." (Norman-JC, Folkman-J, Hardison-WG,
Rudolf-LE, Veith-FJ eds). Appleton-Century Crofts, NY. (1968).
White-RJ. "Experimental transplantation of the brain." Human Transplantation
(Rapaport-FT, Dausset-J eds). pp 692-709 (1968).
Thompson-AM, Robertson-RC, Bauer-TA. A rat head-perfusion technique developed
for the study of brain uptake of materials. J Appl Physiol 24:407-411 (1968).
*White-RJ, Albin-MS, Yashon-D. Neuropathological investigation of the
transplanted canine brain. Transplant Proceed 1:259 (1969).
*Clark-LC, Kaplan-S, Becattini-F, Benzing-G. Perfusion of whole animals with
perfluorinated liquid emulsions using the Clark bubble-defoam heart-lung
machine. Fed Proc Am Soc Exp Biol 29:1764-1770 (1970).
Taslitz-N, White-RJ, Wolin-LR, Yashon-D. Adequacy of single carotid
perfusion of the brain. Anatomical Record 166:388 (1970).
*White-RJ, Albin-MS, Yashon-D, Verdura-J, Austin-JC, Austin-PE-Jr, Demian-YK.
Autoregulation in the isolated brain during profound hypothermia and
hypercarbia. Brain and Blood Flow (Ross-RW ed). Pitman, London. pp.209 (1970).
Horst-WD, Jester-J. The use of isolated perfused rat brain in a study of
14-C-L-Dopa metabolism. Life Sci 10(I):685-689 (1971).
*Jahnchen-E, Krieglstein-J. Die aufnahme von promazin, chlorpromazin und
deren desmethylmetaboliten in das isoliert perfundierte rattenhirn. Naunyn-
Schmiedebergs Arch Pharmak 268:300-309 (1971).
Mukherji-B, Turinsky-J, Sloviter-HA. Effects of perfusion without glucose
on amino acids and glycogen of isolated rat brain. J Neurochem 18:1783-1785
Sloviter-HA, Yamada-H. Absence of direct action of insulin on metabolism
of the isolated perfused rat brain. J Neurochem 18:1269-1274 (1971).
White-RJ, Wolin-LR, Massopust-LC, Taslitz-N, Verdura-J. Primate cephalic
transplantation: neurogenic separation, vascular association. Transplantation
Proceedings 3:602-604 (1971).
Vasan-NS, Abraham-J, Bachhawat-BK. Sulphate metabolism in acute EAE rats
using isolated brain perfusion technique. J Neurochem 18:59-66 (1971).
*Zimmer-R, Lang-R, Oberdoister-G. Post-ischaemic reactive hyperaemia of the
isolated perfused brain of dog. Pflugers Arch Ges Physiol 328:332-343 (1971).
Fleck-WV, Krieglstein-J, Urban-W. Zwei apparaturen zur perfusion des
isolierten rattenhirns. Arzneim-Forsch 22:1225-1230 (1972).
Ghosh-AK, Mukherji-B, Slovitar-HA. Metabolism of isolated rat brain perfused
with glucose or mannose as substrate. J Neurochem 19:1279-1285 (1972).
Krieglstein-G, Krieglstein-J, Stock-R. Suitability of the isolated perfused
rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedeberg's
Arch Pharmacol 275:124-134 (1972).
Krieglstein-G, Krieglstein-J, Urban-W. Long survival time of an isolated
perfused rat brain (Short Communication). J Neurochem 19:885-886 (1972).
Stock-R, Krieglstein-G, Krieglstein-J. Studies on energy metabolism of an
isolated perfused rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 274:R112
Zivin-JA, Snarr-JF. A stable preparation for rat brain perfusion: effect of
flow rate on glucose uptake. J Appl Physiol 32:658-663 (1972).
Zivin-JA, Snarr-JF. Glucose and D(-)-3-hydroxybutyrate uptake by isolated
perfused rat brain. J Appl Physiol 32:664-668 (1972).
Fleck-W, Krieglstein-J, Reichmann-M. A two-circuit apparatus for the
perfusion of the isolated rat brain. Naunyn-Schmiedeberg's Arch Pharmacol
Gruner-J, Krieglstein-J, Rieger-H. Comparison of the effects of chloral
hydrate and trichloroethanol on the EEG of the isolated perfused rat brain.
Naunyn-Schmiedeberg's Arch Pharmacol 277:333-348 (1973).
Krieglstein-J, Stock-R. Comparative study of the effects of chloral hydrate
and trichloroethanol on cerebral metabolism. Naunyn-Schmiedeberg's Arch
Pharmacol 277:323-332 (1973).
Krieglstein-J, Stock-R, Rieger-H. Influence of therapeutic and toxic doses of
neuroleptics and antidepressants on energy metabolism of the isolated perfused
rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 279:243-254 (1973).
Krieglstein-J, Stock-R. The isolated perfused rat brain as a model for
studying drugs acting on the CNS. Psychopharmacologia 35:169-177 (1974).
White-RJ. Hypothermic preservation and transplantation of brain.
Resuscitation 4:197 (1975).
Woods-HF, Graham-CW, Green-AR, Youdim-MBH, Grahame-Smith-DG, Highes-JT. Some
histological and metabolic properties of an isolated perfused rat brain
preparation with special reference to monoamine metabolism. Neuroscience
Woods-HF, Youdim-MBH. The isolated perfused rat brain preparation--a
critical assessment. Essays Neurochem Neuropharmacol 3:49-69 (1978).
Dirks-B, Krieglstein-J, Lind-HH, Rieger-H, Schutz-H. Fluorocarbon perfusion
medium applied to the isolated rat brain. J Pharm Methods 4:95-108 (1980).
*Llinas-R, Yarom-Y, Sugimori-M. Isolated mammalian brain in vitro: new
technique for analysis of electrical activity of neuronal circuit function.
Fed Proc 40(8)-2240-2245 (1981).
Shapovalov-AI, Shiriaev-BI, Tamarova-ZA. "A study of neuronal activity of
mammalian superfused or intra-arterially perfused CNS preparations."
Electrophysiology of isolated mammalian CNS preparations (Kerkut-GA, Wheal-HV
eds). pp 367-394 (1981).