Insufficient cardiorespiratory response to exercise secondary to central nervous system lesions – what is anoxic encephalopathy

Acta medica scandinavica. Vol. 180, fasc. 1, 1966

From the first department of medicine (head: pentti I. Halonen, M. D.), university of

Helsinki, helsinki, finland

Insufficient cardiorespiratory response to exercise

Secondary to central nervous system lesions



The growing interest in neurocardio-

Vascular problems, especially concern-

Ing the role of the higher cardio-

Regulatory centers, is reflected in two

Recent symposia (1, 11). The participa-

Tion of medullary and supramedullary

Regions in cardiac control has been

Illustrated in animal experiments, but

The clinical counterparts of the cardiac

Effects of experimental brain lesions are

Limited mainly to the sub-endocardial

what is anoxic encephalopathy

Changes evoked by intracranial bleedings

(7, 17). On the other hand, the circula-

Tory effects of spinal cord lesions (1 3) ,

Diabetic neuropathy (14) and carotid

Sinus hypersensitivity (1 5 ) are well


In 1964 we reported a patient whose

Heart rate in sinus rhythm could not be

Raised over a limit of 120/min. By phys-

Ical exercise of pharmacological agents

(4). This patient had years ago had

Encephalitis and showed neurological

Sequelae at the time of the study. Pres-

Sure and flow measurements revealed

That the limited heart-rate response to

Submitted for publication december 23, 1965.

Exercise was compensated by a 100 %

Increase in the stroke volume. The pe-

Ripheral vascular bed reacted normally

what is anoxic encephalopathy

On exercise and in postural blood-pres-

Sure tests.

The present report describes the sec-

Ond patient so far encountered with a

Similar heart-rate restriction in sinus

Rhythm combined with normal peripheral

Vasomotion and neurological signs sug-

Gestive of a central origin of the syn-


Case report

The patient was a 46-year-old farmer who

Entered the hospital june 3, 1965 for cardio-

Logical investigations. The history revealed

A head trauma with a brief period of uncon-

Sciousness in childhood. As long as he could

Remember his mouth had been drawn out

Of shape, but he had no engrams of a febrile

Illness in connection with the facial paresis.

He had been hearing poorly since the age

Of 20. Bad hearing was frequent among his

what is anoxic encephalopathy


Starting from time of the world war I1

He had been distressed by vague dizziness in



Connection with muscular exertion. This

Symtom was sometimes accompanied by a

Fit of cramps. He had noticed no gross pulse-

Rate alterations during these attacks. On

June 8, 1964 when going to micturate at

Night he suddenly lost consciousness, exam-

Inations in a municipal hospital revealed

Supraventricular tachycardia of 150lmin.

Combined with a left bundle-branch block

And some ventricular extrasystoles in the

ECG. The subsequent electrocardiograms

Showed a normal sinus rhythm of 60-

80/min., normal a-v conduction and the left

Bundle-branch block. Leucocytes were up to

10,300 per mms but the serum transaminases

what is anoxic encephalopathy

Remained normal. He was treated as having

A myocardial infarction and made full re-

Covery. After this event he had suffered also

From chest pain in connection with physical

Exertion. Coronary dilators and digitalis

Were prescribed and an oral diuretic was

Added later.

In october 1964 he was admitted to

Another municipal hospital because of con-

Tinued exertional angina, a feeling of pres-

Sure in the neck and brief periods of uncon-

Sciousness. Epilepsy was suspected and the

Treatment was changed accordingly. This

Resulted in worsening of his cardiac symp-

Toms, and the medication with digitalis,

Diuretics and coronary dilators was re-


General and neurological findings. The patient

Was of average build.What is anoxic encephalopathy there was a paresis

Of the left facial nerve. Nothing abnormal

Was found in the pupils, deep tendon and

Abdominal reflexes. The babinski sign was

Negative on both sides. No rales were

Audible in the lungs and the liver was in the

Costal margin. No ankle edema. Blood pres-

Sure was 150/90 supine and the pulse rate

Regular at 72/min. The postural blood-pres-

Sure and pulse reactions were tested several

Times, with normal findings. The right radial

Pulse disappeared when the right arm was

Raised over the head level. Simultaneously a

Weak systolic murmur became audible on the

Right side of the neck. A grade II/VI systolic

Ejection type murmur with no diagnostic

Characteristics was audible in the third and

Fourth left intercostal space near the sternal

what is anoxic encephalopathy

Border. The second sound in the pulmonary

Area was split. The eye-grounds showed

Changes of grade I1 of keith and wagener.

The ECG revealed sinus rhythm with nor-

Mal a-v conduction, total left bundle-

Branch block and no signs of the previous

Dubious myocardial infarction. Long tracings

Revealed occasional atrial ectopic beats.

Chest X-ray showed no pulmonary pathol-

Ogy and a heart of 435 ml/M2 BSA with

A slight left ventricular prominence. X-ray

Films from the skull were normal and the in-

Tervertebral foramens of the cervical spine

Were not narrowed. Vital capacity and

Forced expiratory volume were 85 yo, maxi-

Mal breathing capacity and expiratory peak

Flow 90 yo and 100 % respectively.

In a detailed neurological examination at

what is anoxic encephalopathy

The department of neurology, an insuffi-

Cient eye convergency was found in addition

To the facial paresis of central origin. The

Electroencephalogram was not diagnostic.

The ophthalmodynamometric tracings re-

Vealed symmetrical and normal systolic and

Diastolic pressures. An audiogram was con-

Sistent with otosclerosis.

Laboratory data showed a normal’ BSR, no

Anemia, a normal amount and differentiation

Of leucocytes, normal serum cholesterol and

PBI, normal serum creatinine, no sugar,

Protein or formed elements in the urine,

Normal blood sugar, normal serum electro-

Lytes and negative blood wasserman tests,

Normal acid-base balance at rest and during

Moderate exercise, normal 24-hour excre-

Tions of catecholamines and vanillin mandel-

what is anoxic encephalopathy

Ic acid, normal antistreptolysin and anti-

Staphylolysin titers, and negative rheuma-

Toid factor, LE-cell and toxoplasma dye tests.

The cerebrospinal fluid was under normal

Pressure with no cells, normal protein con-

Centration and negative wasserman test.

Paper electrophoresis and immunophoresis

Of the serum proteins were normal.

Cardiological investigations. An aortography

Showed normal right-sided subclavian, caro-


Tid and vertebral arteries. The left carotid

Artery was also normal but there was a long

Relative occlusion of the subclavian artery

Just after the bifurcation of the internal

Mammarian artery (fig. L), the left vertebral

Artery rising from this occlusion and being

what is anoxic encephalopathy

Filled slowly in the cephalad direction. There

Were no signs of a retrograde filling of the

Subclavian artery via the vertebral artery.

The exercise tolerance was tested by an

Electrically braked ergometer (elema-scho-

Nander), the patient pedalling in the sitting

Position. The ECG was continuously moni-

Tored through bipolar electrodes attached to

The chest. The resting heart rate of 76/min.

Was increased to 93/min. During the 211,

Minutes period he was able to pedal a load

Of 300 kpm/min. (fig. 2), after which he

Lost consciousness and fell from the bicycle.

He recovered rapidly on resting supine, and

The test was repeated with a similar sequence

Of events. Later on exercise testing was per-

Formed in the supine position together with

what is anoxic encephalopathy

Measurements of pressure-flow relationships

(table I). The cardiac output was measured

By the fick principle, expired air being

Collected into douglas bags. The patient

Tolerated the first load of 200 kpm/min. For

Five minutes, at the end of which a fit of

Cramps occurred and the respiration became

Discontinuous. A period of 10 minutes was

Fig. 1. An aortography showing the delayed

Filling of the left vertebral artery rising from the

Occlusion in the left subclavian artery marked

By the arrow.

Kpm/min., which the patient tolerated for

3 minutes with similar symptoms. Expired

Air was collected between 3-5 minutes dur-

Ing the first load and between 1-3 minutes

During the second load. No signs of dyspnea

Were evident during the exercise periods.What is anoxic encephalopathy

As is evident from the table I, the patient

Was unable to increase the heart rate over a

Limit of 9 I/min. Further, the respiratory min-

Ute volume was not increased by the second

Allowed before the second load of 400 load over that achieved already at the lower

Fig. 2. A: the heart rate in sinus rhythm of 76/min. When the patient was sitting on the ergometer.

B: the heart rate in sinus rhythm of 93/min. When the patient was pedalling a load of 300 kpm/min.


TABLE I. Respiratory and circulatory data at rest and during two successive exercise periods

Rest, legs 200 400

On the pedals (kpm /min) (kpmlmin)

Respiratory minute volume, l/min

Oxygen uptake, ml/min

Oxygen content, vol. Yo

Pulmonary arterial blood

what is anoxic encephalopathy

Brachial arterial blood

Cardiac output, 1 /min

Heart rate, beats/min

Stroke volume, ml

Brachial arterial pressure, mm hg

Total peripheral resistance, dyn. Sec. Cm-5
















I59/85: 122




71 1








Exercise level, and the cardiac output was

Essentially the same during the loads in

Spite of a 100 yo difference in the mechanical

Work. The reaction of the peripheral vascu-

Lar bed was commensurate with the change

In the total blood flow, and no blood-pres-

Sure drop occurred.

An intravenous injection of atropine in a

Dose of 1.0 mg raised the heart rate from

65/min. To 90/min. In one minute with no

Further rise during the following 5 minutes.What is anoxic encephalopathy

Subcutaneous epinephrine in a dose of

0.05 microg. Raised the heart rate by 12



In considering this case there hardly

Is any doubt that generalized athero-

Sclerosis including the coronary arteries

Was the primary disease. The convulsive

Response to muscular exertion evidently

Originated via cerebral hypoxia due to

Handicapped vertebral circulation. This

Response is, however, not the essence of

The findings which demonstrated that

Cerebral pathology can distinctly modify

The cardiopulmonary response to exer-


The respiratory regulation was ex-

Actly the clinical image of the findings

In the hypothalamically injured dogs of

Smith (16). Since the maximal breath-

Ing capacity obtained by voluntary ven-

what is anoxic encephalopathy

Tilation was normal, the innervation of

The ventilatory muscles must have been

Intact. The fact that no further increase

Occurred in the ventilatory volume on

Increasing the mechanical work, even

In the face of the short duration of the

Exercise, speaks for a disarranged func-

Tion of the higher integrating centers.

This is also evidence in favor of a cen-

Tral origin for the hyperpnea of exer-

Cise in general, and especially a t low

Levels of stress when no abnormalities

Exist in the blood chemistry (10).

The attempt to block the vagal ac-

Tivity did not accelerate the heart more

Than muscular exercise; nor was the

Heart rate a t rest low and concordant

With vagal preponderance. A centrally

Originated infrequent discharge through

what is anoxic encephalopathy

The sympathetic nervous system seems

To be the most relevant explanation.


The blockage of the terminal sympa-

Thetic neurones by guanethidine does

Not result in the hemodynamic picture

Present in this patient (6, 18) because

Accompanying peripheral effects inter-

Fere. On the other hand complete car-

Diac denervation results in a limited

Heart-rate response to exercise with

Enhanced stroke volumes (2). The

Stroke-volume response to exercise in

The patient was of the magnitude ob-

Served at exercise levels entailing a

More than 6-fold increase in oxygen up-

Take ( 5 ) , and was thus out of proportion

To the external load. The absence of a

Further rise in the stroke volume might

what is anoxic encephalopathy

Be due to intrinsic myocardial disease

Evoked by coronary atherosclerosis, but

In the light of the findings of rosen (1 2)

And manning et al. (8) a centrally in-

Duced decrement in the myocardial con-

Tractile force may also be implicated.

In the lack of metabolic data no ex-

Planation can be offered as to how the

Patient managed the three minutes of

The heavier exercise with an unaltered

Cardiac output and oxygen consump-

Tion. Already the first A-V oxygen dif-

Ference was abnormally large in pro-

Portion to the oxygen uptake and near

The maximum found in normal subjects

During supine leg exercise (3, 5). Since

No further widening of the A-V oxygen

Difference occurred during the second

Load, an oxygen debt must have been

what is anoxic encephalopathy

Developed despite the curious absence

Of dyspnea. While the heart rate, cardiac

Output and respiratory response were not

Gradable, the neurological signs ap-

Peared faster during the second load

Reflecting an earlier appearance of cere-

Bral hypoxia.

The heart rate has been shown to be

Fixed in exercise in patients with tabes

Dorsalis (13), and in idiopathic postu-

Ral hypotension as can be judged from

The pressure tracings of marshall et al.

(9). Both these disease states are char-

Acterised by postural blood-pressure re-

Actions. The present case and the one

Previously reported (4) show that the

Heart in sinus rhythm may respond with

Poor acceleration to muscular exercise

In patients with intact peripheral vaso-

what is anoxic encephalopathy

Motion. The evidence that this mis-

Management can issue from supraspinal

Central-nervous-system lesions of both

Inflammatory and ischemic origin advo-

Cates an objective exercise testing of

Patients with a history of exercise in-

Tolerance combined with central neuro-

Logical signs.


An exceptional case is reported with

The following hemodynamic and respira-

Tory findings: the heart rate in sinus

Rhythm could n.Ot be raised over about

90 beatslmin. By muscular exercise, in-

Travenous atropine or subcutaneous epi-

Nephrine; the maximal minute ventila-

Tion increased only to 30 l/min. In phys-

Ical exercise; the A-V oxygen differ-

Ence was abnormally large during light

Exercise and no graded increase occurred

what is anoxic encephalopathy

In heart rate, cardiac output and oxygen

Uptake during heavier exercise. A fit

Of cramps, brief periods of unconscious-

Ness and irregular breathing occui red

During muscular exercise. No postural

Blood pressure decline was demonstrable

And the peripheral vascular bed reacted

Normally on effort.


The patient had a facial paresis of

Central origin, and aortography revealed

An inadequate vertebral circulation due

To occlusion in the left subclavian ar-

Tery. In the light of the evidence gained

From animal experimentation, the most

Probable mechanism evoking the ab-

Normal exercise circulation and respira-

Tion was a disintegrating function of the

Supraspinal centers.



what is anoxic encephalopathy

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2. DONALD, D. E. SHEPHERD, J. T. : sustained

Capacity for exercise in dogs after complete

Cardiac denervation. Amer. J. Cardiol. 14:

853, 1964.


G. WADE, 0. L.: the effect of exercise

On the cardiac output and circulatory dynam-

Ics of normal subjects. Clin. Sci. 14: 37,



Abnormal circulatory responses to exercise

As sequelae to encephalitis. Acta med. Scand.

176: 763, 1964.

5. FRICK, M. H. SOMER, T.: base-line effects

On response of stroke volume to leg exercise

In the supine position. J. Appl. Physiol. 19:

639, 1964.


WALD, E.: the effects of autonomic nervous

what is anoxic encephalopathy

System inhibition on the circulatory response

To muscular exercise. J. Clin. Invest. 41:

1981, 1962.


Subendocardial and E.C.G. Changes in intra-

Cranial bleeding. Brit. Med. J. I : 1479, 1964.


M. De V.: central inhibition of tonic

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Physiol. 205: 1221, 1963.


HERD, J. T.: blood pressure during supine

Exercise in idiopathic orthostatic hypotension.

Circulation 24: 76, 1961.

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To exercise. Pediatrics 32. Suppl. 4 : 680,


11. RANDALL, W. C.: nervous control of the

Heart. Williams wilkins, baltimore 1965.What is anoxic encephalopathy

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Oblongata stimulation in the cat. Acta phy-

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13. SHARPEY-SCHAFER, E. P.: circulatory re-

I flexes in chronic disease of the afferent ner-

Vous system. J. Physiol. (lond.) 134: 1, 1956.


Absent circulatory reflexes in diabetic neuri-

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16. SMITH, 0. A.: in: discussion after the paper

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