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Cerebral CO2 Reactivity and Autoregulation in Patients Undergoing Microanastomosis. David Zinke, M.D., William Hayward, BSc, Neil Poll, MSC, and George Austin, M.D., From the Section of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, California. Typewritten manuscript with several handwritten notes, 3 pg

Zinke, David

Hayward, William

Poll, Neil

Austin, George

Loma Linda University 
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Cerebral CO2 Reactivity and Autoregulation in Patients 
Undergoing Microanastomosis 
David Zinke 
William Hayward 
Neil Poll 
George Austin 
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Zinke, David; Hayward, William; Poll, Neil; and Austin, George, "Cerebral CO2 Reactivity and Autoregulation 
in Patients Undergoing Microanastomosis" (1000). The Dr. George M. Austin Neurology Research 
Collection. 42. 
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CEREBRAL CO2 REACTIVITY AND AUTOREGULATIO:i IN PATIENTS UNDERGOING MICROANAST0>10SIS 
David Zinke, MD, William Haywc,1rd> 8Sc, Neil Poll, MSC, and Geoi·ge Austin, MD 
Patients \·1ere referred to the corqJlra-1 blood flm·1 lab vrith angiographic 
evidence of a high internal carotid artery or middle cerebral artery stenqsis 
or occlusion. All patients had experienced -frequen.t transie;it 'ischemic attacks 
(TIA's) or a minor stroke and have s~~sequently und~rgone a superficial tempo- . 
ra l to middle cerebral artery anastomosis~ . < 
· • A · 133 _· - \ . . 
-. - --- A -i2 rumrf;e I \! Xenon....... cerebra l hl.ooo flm·1 gray (CBFq) \•Jas done on all -- \ -- . 
p_gig.o.ts as described by ,hustin (l). This was \done b,,x ·starting· an I. V. in a 
convenient atmEiD, and~ mci of Xenon133 dissolved in .4 cc of.normal saline - . 
. injected as a bolus,. . The gamma activity \·tas then counted in the expired air 
1and also over eight .regional areas of the cerebral hemispheres. A two-component 
. . . 
1system was ,:1ssumed with a fast (gr-ay) component lasting up to eight minutes 
· and a slow (\'/hite matter plus extra cerebral) component continuing thereafter • . . 
The Fick equation \·1ith time varying arterial concentrations was assumed to 
hold for both compartments. A PDPll digital computer is· then used to solve 
,t~ese equations. The patients were then asked to inhale a mixture of 7% co2 
,. 
and room air. A. 12-minute CBFg me_asurement \·:as then repeated. The Paco2 \'las 
monitored, as well as a continuous capnog-ram of the end-expired air using a 
. Beckman CO2 analyzer, employing an infra-red technique. CO2 reactivity was 
tested in nine controls. Their resting CBFg \·tas 6~2 and after CO2 in-
halation, 88.8 ~ 15.2 cc/lOOgm/min with a t.Paco2 of 10.3mm Hg~ giving a percent · 
CO2 reactivity of 2.73 ! 1.54 (~;CBF.g/mm Hg CO2). He then defined depres sed 
~~~~ • O 5 cl e ri _yecl from I val u es ) . Au to-
regulation was then tested on nine controls with a resting CBFg of 74 ! 8cc/100gm/min 
From the Sect ion of r leuros urgcry, Lon121 Linda University School of Medicine, · 
Loma Lind,1, California. 
l 
/ 
( Jhei r blood pressure was then elevated by an average ot l Ymm Hg using a con-
tinuous Neo-synephrine drip \·lith a change in CBFg of 3.4 ! 2cc/100gm/min. 
----D~utoregul a ti on ,-,as therufefined as a change in CBFg greater than .71%/rmn 
change io m~n arterial pressure (CBFg change_ of two standard deviations from 
.co;1trol values). Intact CO2 reactivity \•:as demonstrated in 19 of 23 (83%) 
patients. The resting CBFg \•ias 48.7 ~ 1L7cc/100gm/min and after CO2 inhalationi. . 
66.5:: 15.2 \·rith a ti.Paco2 of 9.7mm Hg giving a percent CO2 reactivity of 3.7 :: _ 
1.37. Four of the nineteen had depressed autoregulation and an additional 
three experienced -preoperative strokes; in four patients \•dth depressed CO2 
reactivity:, t\-10 also had depressed autoregulation and one ·had a preoperative 
. . 
. . 
stroke. In comparison> dysautoregulation occurred in 35 of 65 patients., with 
. . 
_. the h_ighest incidencei. 10/14 (71%):, in internal carotid artery stenosis., and _ 
the lowest> 3/12 {25%), · in middle cerebral artery stenosis. · Minor strokes 
were noted preoperat1vely in 19/35 (54%) \·tith dysautoregulation and 4/30 {13%} 
with autoregulation intact. The postoperat1ve reduction of TIA's was 82% in-
dysautoregulation patients compared to 92% with autoregulation intact • 
. Autoregulation refers to the ability of the brain to maintain a constant 
profusion CBF over a ·,·ride range of pressures, i.e. 70-170mm Hg· MABP. The main 
controlling features being myogenic effected by Jntraluminal pressure or rapidly 
acting neuronal influences (sympathetic nervous system) or extracellular 
fluid pH( 2, 3, 4)_ In addition, CBF is responsive to variations in Paco2 with 
a wide and even more sensitive c~ange in the CBF. The CBF varies almost 
linearly with a range of values Pa{ o2 30-80mm Hg. The best explanation of __ _ _ 
this is that the intravascular co~· diffuses iapidly to extravascular and causes 
changes in pll \·tith acidosis or hypercarbia causing smooth muscle relaxation 
and increase in cerebral blood flo~ and alkalosis or hypocarbia causing smooth 
·• ·-- -- ~· -~:-•· .,. 
muscle constriction and a reduct-ion in cerebral blood flo·.-1. CO2 reactivity 
2 
I'...:,... V • r . • ." ,..,, •I . ., .., ~ 
, . ~ . " , .. -· . . ~ 
... ~ 
.,.. 
, may a·1 so be mecnatea tnrouyr, 11eur ·u11d I Lflctll~t:::> \ ::>_y1 , 1~1 -u .11:.. ..... '--J ......... .,,, ...... ~ --··· 
. (4 5 6 7 8) . l ( :v I~ r •1.,:.~ C, ·~~11.0'" .. , nucle1 reflexes , , , ' . -o ,, · ~--- ~ -- r,c,c;~. c~ 
Gotoh and others have postulated a dual control of the cerebral circula~ 
tion ~ith autoregulation op~rating on larg~r arteries with raore dense sympathetic 
innervation and a muscula r: )._~)Y-~r, \1 hile carbon dio;ddc or the chemical control 
~-~- b-L-
of blood flow involves smaller arteries Hith coarse or oo innervation andP.-e ~-
-. (9) 
muscular layer • 
Autoregulation and CO2 reactivity probably involve different sizes of 
cerebral vessels. Cerebral dysautoregulation is more common than d-epressed 
co2 reactivity in str_oke type patients · and is probably more fundamental in the 
pathogenesis of stroke and TIA's. This may be the result of reduced intra-
luminal pressure of larger cerebral arteries (greater than 50 microns}. 
REFERENCES 
1. Austin G~ Laffin D, Rauhe S, et al: Intravenous isotope injection method 
of cerebral blood flow measurements: Accuracy and reproducibility. Proc 
of the International Symposium of Cerebral Circulation and Metabolism. 
Philadelphia, 1973 
1• 
2. Symon L, Held K, Dorsch NHC: On the myogenic nature of autoregulatory 
mechanism in the cerebral circulation. In Cerebral Blood Flow ~nd Intra-
cranial Pressures. Proc 5th Int Symposium, Roma-Siena 1971, Part 1. 
Europ Neural 6:11-19, 1971/1972 
3. Gotch F, Ebihara SI, ·Toyota M, et al: Role of aut.omic nervous system in 
autoregulation of humari cerebral evaluation. Europ Neural 6:203-207, 1972 
4. James IM, Miller RA, Purves MJ: Observations on the extrinsic neural con-
trol of cerebral blood flow in the baboon. Circa Res 25:77-93, 1969 
5. Harper AM, Glass HI : Effects of alterations in the arterial carbon di-
oxide tension on the blood flow through the cerebral cortex and normal 
and low arterial pressure. J Neural, Neurosurg, Psychiat 28:449-452, 1965 
6. Reivich M: Arterial PC02 and cerebral neurodynamics, Am J Physiol 206(1): 
25-35, 1964 
7. Lassen NA: Brain extracellular pH: The main factor controlling blood 
flow. Scand J Cli~ Lab Invest 22:247-251, 1965 
8. Shalit MN, Reinmuth OM, Shimoiyo S, et a] : Carbon dioxide and cerebral 
circulation control. The intravascular effect. Arih Neural 17:337-341, 1967 
9 . . Gotoh F, Muramatsu F, Fukuuchi Y, et al: Dual control of cerebral circu-
lation: Separate sites of act"ion in vascular tree in autoregulation und 
chemical control. In Bi~ai~_C_i_r:-culation and __ f·lc_ta~_q_lJ...~i- Langfitt TH, 
McHenry LC, Reivick M, et al (Eels). SpringcrVerlag, NY, 1975 


English

Cerebral CO2 Reactivity and Autoregulation in Patients Undergoing Microanastomosis

Some Descriptive Concepts of Conscious Man. George Austin and William Hayward. Section of Neurosurgery, Loma Linda University, Loma Linda, California, No date, manuscript, 3 pg

Loma Linda University 
TheScholarsRepository@LLU: Digital 
Archive of Research, Scholarship & 
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The Dr. George M. Austin Neurology Research 
Collection Special Collections and Archives 
1000 
Some Descriptive Concepts of Conscious Man 
George Austin 
Section of Neurosurgery, Loma Linda University 
William Hayward 
Section of Neurosurgery, Loma Linda University 
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Recommended Citation 
Austin, George and Hayward, William, "Some Descriptive Concepts of Conscious Man" (1000). The Dr. 
George M. Austin Neurology Research Collection. 50. 
https://scholarsrepository.llu.edu/george-austin-collection/50 
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"SOHE DESCRIPTIVE CONCEPTS OF CONSCIOUS MAN" 
George Austin & William Hayward 
Section of Neurosurgery 
Loma Linda University 
Loma Linda, California 
Current interest in developing improved cybernetic models of conscious 
man prompts us to inquire more deeply into the interlocking anatomic, physio-
logic, and philosophic implications which must be considered. It is no longer 
profitable nor useful to refute certain questions as to whether qualitative 
. values of thought such as joy, envy, sadness, etc. can be quantitated, nor to 
deny the critical nature of inductive thought and ideational thinking as 
important in distinguishing the mentation of conscious man from that of our 
more sophisticated models. 
-· 
Conscious man in the normal range is aware of knowing multiple percep-
tion~ at any instant. This is in contradistinction to the a~tomatisms of 
psychomptor seizures, types of daydreaming, and sleepwalking in which percep-
tion occurs but for which there is no demonstrable recall. It is assumed 
that speech is an observable form of behavior, that perception by affirmative 
vocalization presupposes knowledge of an event, and that descriptive comnuni-
cation of, and awareness of knowing an event are different exclusive aspects 
of the same thing. We can then approximate a function·of the general level of 
knowing by discriminative testing and other language probings, based on the 
additional formulation that there should exist no sensory dysphasia and that 
human speech ,is man's most sensitive form of language. This presupposes that 
the level of awareness of knowing at a given time is proportional to the 
connnunicated description of the external world. Such an approach permits us 
• 
, to conveniently grade depressed conscious man into testable levels of con-
fusion~ stupor, and coma for purposes of clinical evaluation. To some extent 
,,. 
.... . 
-2-
the;,,e may be further related to brain anatomy and physiology as observed and 
studied under pathologic conditions. We have measured certain experimentally 
observed features of man's brain function which may serve as guideposts in 
developing hypotheses and future brain models: 
a. From head injury patients with uncomplicated concussions we observe 
·- that, associate~ with the transient loss of consciousness, there 
follows a limited period (varying from days to seconds) of 
gradually decaying retrograde and post-traumatic amnesia, demon-
strated by the patient's communicating to us inability to recall 
just prior and just aftef events. This implies that the recall or 
memory mechanisms are more sensitive than the filing of percep-
tions. 
b. Total surgical removal of the nondominant hemisphere (approximately 
1/3 of total brain mass) under local anesthesia evokes no change 
in the patient's conscious state during or following the opera-
tion. Further, there is no chan~e in the patient's intellectual 
function as measured by the usual psychological testing. Removal 
of the terminal 6 cm. of either temporal lobe, frontal lobe, or 
, occipital lobe fails to alter the patient's communicated descrip-
tion of general awareness, although it may affect specific percep-
.. 
tions (visual or auditory). 
c. Interruption, by chemical leucotomy bilaterally, of the frontal 
ideational cortex connections to the thalamus (medialis dorsalis 
nucleus) shows a significant depression of all modalities of 
intensity discrimination including time perception. 
d. Electrical stimulation of the thalamus (ventralis lateralis nucleus) 
during stereotatic surgery can produce complete mutism for periods 
up to two minutes, but, as shown by appropriate verbal testing, 
this does not block the patient's filing and recall of information 
r 
I 
-3-
received during this period of mutism. 
The effects of diffusely and progressively eradicating brain function, 
i.e. total cerebral blood flow reduced to less than 60 percent of normal, or 
generalized cerebral edema, or diffuse hyponatremia, etc., gradually induce 
confusion, stupor, and coma in that order. (Confusion being arbitrarily 
described as a state of responsiveness in which there is a prolonged latency 
in response to verbal stimulation, and where the communicated response shows 
inaccuracy and poor orientation; stupor being a condition in which the patient 
either tends to fall asleep or is in a sleep-like condition from which he may 
be aroused by appropriate stimulus; coma, a sleep-like condition in which the 
patient cannot be stimulated to respond for communication, no matter how 
strongly the stimuli are applied.) Studies on time perception during condi-
tions of stupor show a consistent underestimation during the emergence from a 
prolonged stupor such as that encountered in long-term experimental cave 
dwellers. This is opposite to the time perception of patients with Parkinson's 
disease who experience an overestimation and exaggerated time sense. 
The gross nonlinearities and the stabilities of multiple levels of 
discrimination, which we find when experimentally testing intensity discrimi-
nation ability in patients, suggest that in a systems analysis model of the 
problem of perception in man, one should consider nonlinear systems capable 
of multiple levels of both amplitude and frequency stability in an N-dimen-
sional attribute or perception space. It further suggests that this exists in 
at least an (N+l) awareness space~ 
, I ,i 
', .... •- .; _,.. 


Some Descriptive Concepts of Conscious Man

A manuscript outline of possible inherited disorders presumably created by Dr. Austin. No date

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The Dr. George M. Austin Neurology Research 
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Inherited Disorders 
George Austin 
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Austin, George, "Inherited Disorders" (1000). The Dr. George M. Austin Neurology Research Collection. 43. 
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.-
,. 
INHERITED DISORDERS 
I. Single gene human defects: 
1. 
2. 
3. 
Autosomal dominant inheritance: in general the following 
rules apply: 
a. Every Affected person has at least one cjffect.eJ 
parent. 
An Offect~ person marrying a normal individual has only~n. 
ave!'~'i) equal number of ,f f ected and normal children. 
~ 41h 
Normal children of an ~ff ectf-tk parent have normal 
children and grandchildren. 
4. Males and females are equally likely to betiffected. 
5. The trait can appear in every generation. 
6. Heterozygotes are ~ffected. 
Variat4on!in these rules are as follows! OneA~alled expressivity at '§ER '\ 
and A penetrance: the effects of a single gene defect may be 
influenced both by the individual's environment and by thousands of 
other genes that may alter the phenotypic expression of a genii-' 
~~aaei"'{l. A typical example of this is Waardenbur~syndrome in 
which the patient has a white forelock, deafness, abnormal iris and 
some hearing loss. However, the individual may have none of these 
', 
because the dominant gene has been modified. The situation in 
which the expressivity is close to nil is called the lack of 
penetrance or forme fruste of the__,,disease. 
2. Pleotropy (meaning many forms): 
In this condition a single genetic defect may produce multiple 
anomalies. For example, there may be an abnormality of connective 
tissue with various structures involved such as Marfan's syndrome 
with multiple bone anomalies, hyperextensible fingers and toes and 
excessive elasticity of the skin. 
3 . Mutations 
These arrive spontaneously from time to time. About 80% will have 
no family history· and, therefore, would be expected to represent a 
fresh mutation. In general the unaffected parents are not at 
increased risk of having additional effected offspring. 
4. Phenocopies 
In this situation (very rare), an individual appears with a 
syndrome. The syndrome appears to be due to a non-genetic 
phenomena or at least to a different genotype. 
5. Sex limited inherence 
This is a trait that appears in only one sex and there is sex 
limited. Males are almost always sex effected, usually because of 
X-linked inheritance. Examples of this are premature baldness. 
6. Homozygous dominant genotype 
This can occur in the offspring of two individuals who are 
heterozygous or homozygous for the same dominant gene. The 
availability of gene markers were Huntington's disease has shown 
that there are no phenotypic differences between heterozygotes and 
homozygotes for this dominant condition. A homozygote would have 
100% of the offspring effected. 
AUTOSOMAL RECESSIVE INHERITANCE 
The following rules apply: 
1. If an effected person is born to normal parents, both parents 
are heterozygotes, and on the average one-quarter of their 
offspring will be effected. One half will be heterozygotes 
and one-quarter will be normal. 
2. If effected siblings come from a consanguineous marriage, 
there is good evidence of recessive inheritance. 
3. If an effected person and a normal genotype marry, all of 
their children will be phenotypically normal heterozygotes. 
4. If an effected person and a heterozygote marry, on the average 
one-half of the children will be effected and one-half will be 
heterozygotes. 
5. If two effected people marry, all of their children will be 
effected. 
6. Males and females are equally likely to be effected. 
' 
7. Heterozygotes are phenotypically normal but carriers of the 
trait. 
II. MULTI-FACTORIAL INHERITANCE 
This is a condition where close relatives tend to resemble each 
other with respect to a number of quantitative or measurable 
characteristics such as height, weight, size and shape of nose and 
other facial features, blood pressure and intelligence. Most of 
the time the variations in population result from a number of genes 
and environmental factors acting together to determine the final 
result. A large number of relatively common congenital anomalies 
and diseases that are fairly familial do not fit the expectations 
for mendelian inheritance and most likely these conditions result 
from multi-factorial inheritance of a continuously distributed 
variable. In these situations the effected patient has a liability 
or predisposition to the condition representing the sum of genetic 
and environmental influences (possibly intracranial aneurysms). 
This concept explains the relatively high risk of the trait in the 
first degree relatives, i.e., children and siblings who share 50% 
of their genes and the much lower risk to the more distant 
relatives who are lucky to inherit only a few of the high liability 
genes. Other examples of multi-factorial inheritance with similar 
risks for siblings and offspring of effected individuals are 
congenital vascular anomalies, idiopathic epilepsy, congenital 
megacolon and cases of cleft lip and many forms of cancer. At 
present attention is being focused on a group of common disorders 
with multi-factorial cause such as arteriosclerotic heart disease, 
diabetes mellitus, cancer and arthritis. Genetically determined 
predisposing factors and biochemical and molecular phenomena are 
being used to identify individuals at increased risk who would be 
most likely to benefit from preventive measures such as the use of 
drugs, special diets, changes in lifestyle and changes in 
occupation. We can, therefore, say that phenotypically similar 
conditions can be due to different mutations, non-genetic factors 
or combinations of both. Therefore, to determine the risk to 
future offspring, a physician must take a very thorough family 
history including an??? possible environmental 
\ 
('1 


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Cerebral CO2 Reactivity and Autoregulation in Patients Undergoing Microanastomosis

Some Descriptive Concepts of Conscious Man

Inherited Disorders

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