고지순화(高地馴化)가 흰쥐의 운동능력에 미치는 영향

Abstract

[한글]

EFFECT OF HIGH ALTITUDE ACCLIMATIZATION ON THE WORK CAPACITY OF THE RAT

Yong Kook Choi

Department of Physiology, Yonsei University College of Medicine, Seoul, Korea

(Directed by Drs. P.H. Lee and S.K. Hong)

The work capacity of a living organism is mainly determined by the capacity to

supply oxygen to working muscles. The capacity to supply oxygen to the muscle is in

turn determined by the alveolar ventilation, the oxygen diffusing capacity, the

oxygen saturation capacity of the blood, the capillary density of the muscle and

the cardiac output. It has been known for many years that a prolonged exposure to a

low oxygen or a high altitude environment results in a series of adaptive changes

which are characterized by increases in the ventilatory function as well as in the

erythrocyte count and the oxygen diffusing capacity. since the increase in the

erythrocyte count and the oxygen diffusing capacity would invariably enhance the

oxygen saturation capacity of the circulating blood, it is theoretically possible

that a high altitude acclimatization could result in a considerable improvement of

the work capacity. On the other hand, an increase in the erythrocyte count as a

result of high altitude acclimatization would increase the viscosity of the

circulating blood and, consequently, the blood flow to the working muscle would be

reduced because of an increased resistance. In other words, it is also

theoretically possible that a high altitude acclimatization could reduce the work

capacity.

In view of these two contradictory theoretical possibilities, this investigation

was undertaken to delineate the net effect of two opposing forces in determining

the work capacity of high altitude-acclimatized rats.

A total of 160 albino rats, weighing approximately 200gm, were divided into two

groups, the experimental and the control. The experimental animals were exposed 8

hours a day and 5 days a week to a simulated altitude of 18,000 feet for a period

of 7 weeks. The rats were subjected to 12,000 feet on the first day of exposure and

then gradually brought to 18,000 feet in the course of subsequent 4 days, in order

to avoid any serious effects that the animals might experience from the sudden

exposure to high altitude.

A daily exercise load was given from the middle of the third week of exposure on

a motor-driven drum revolving at a rate of 15 meters per minute. The rats were made

to run daily for a period of 10 minutes until the end of the 5th week, 15 minutes

during the 6th week and 20 minutes during the 7th week. a day. Experimental animals

were given the running exercise at an altitude of 18,000 feet while the control at

the ground level. For the determination of the work capacity, the rats were forced

to run on the drum until exhaustion and the endurance time was recorded. At the

point of exhaustion, a blood sample was obtained by a puncture of the left

ventricle and analyzed it for oxygen, carbon dioxide, pH and lactic acid.

The animals were then sacrificed and various organs were removed for weighing; a

femur was also removed for electrolytes determination. Histopathological

examinations of various organs were also made. Twenty-four hour urine samples were

also collected during the entire experimental period and their electrolyte

concentrations were measured.

The erythrocyte count increased progressively during the period of high altitude

exposure, and thus it increased by 50% after 3 weeks and leveled off at this level

the reafter. The hematocrit ratio increased from the pre-exposure level of 38% to

50% after 3 weeks. The hemoglobin concentrations increased from the pre-exposure

level of 11.3±0.36 gm% to 17.1±0.4 gm% at the end of the 7th week.

The daily urinary excretion of Na**+ and K**+ increased after 4 weeks of high

altitude exposure, amounting to 2.5 fold increase for Na**+ and 4 fold increase for

K**+ through out the rest of the experimental period. Moreover, the daily excretion

of Cl**_ was nearly doubled in the experimental group after 4 weeks of exposure.

These findings indicate that a characteristic respiratory alkalosis develops fully

after 4 weeks of intermittent high altitude exposure as empolyed in this

investigation. In other words, as a result of hyperventilation, the Na**+

reabsorption would be reduced while the Na**+-K**+ exchange mechanism would be

enhanced, resulting in an increased excretion of both Na**+ and K**+. On the other

hand, a greater elimination of HCO^^5**- in the form of CO^^2 would increase the

plasma concentration of Cl**-, and hence its excretion would also be increased.

The average endurance time on treadmill running was approximately 5 hours at the

onset of the experiment. However, at the end of the experimental period, it

increased to 7 hours and 46 minutes in the control group and to 10 hours and 35

minutes in the experimental group, the difference being highly significant

(P<0.02). Moreover, when the endurance time was evaluated as a function of the

hematocrit ratio, it was found that the endurance time increased linearly until the

hematocrit ratio increased to 55%. However, there was no further increase in the

endurance time beyond 5% of the hematocrit ratio.

The arterial oxygen content at the point of complete exhaustion increased from

the pre-exposure level of 13.9 to 23.6 vols % at the end of the experimental

period. On the other hand, the arterial carbon dioxide content at the point of

complete exhaustion did not vary significantly during the experimental period. The

arterial blood pH at the point of exhaustion at the end of experimental period was

significantly lower in the experimental group as compared to the control. It was

also of interest to note that the concentration of lactic acid in the arterial

blood at the point of exhaustion became lower toward the end of the experimental

period in both groups. However, there was no statistical difference between the two

groups in the concentration of lactic acid at a given period of experiment.

Among various organs removed, the spleen alone showed a significant reduction in

the weight in both groups toward the end of the experimental period. Otehr organs

showed little change, although the weight of the heart and the adrenal glands were

somewhat increased toward the end of the experimental period in the

altitude-acclimatized group. Moreover, there was a sign of cardiac hypertrophy in

the experimental group. The bone Na content was reduced in both groups during the

experimental period, while the bone K content In creased progressively during the

experimental period in both groups, the magnitude of increase being

significantly greater in the experimental group than in the control.

It appears from these results that the work capacity of the rat shows a

remarkable improvement after a high altitude acclimatization. On the basis of blood

gas analysis, one can easily see that this improvement in the work capacity is not

due to the improvement in the anaerobic work capacity. The fact that the work

capacity is linearly proportional to the hematocrit ratio until it reaches 55%

indicates that an increase in the oxygen saturation capacity is the main

determinant of the work capacity. However, it is also evident that, when the

hematocrit ratio is greater than 55%, the work capacity does not increase any

further, possibly because of an increased blood viscosity.

[영문]

The work capacity of a living organism is mainly determined by the capacity to supply oxygen to working muscles. The capacity to supply oxygen to the muscle is in turn determined by the alveolar ventilation, the oxygen diffusing capacity, the oxygen saturation capacity of the blood, the capillary density of the muscle and

the cardiac output. It has been known for many years that a prolonged exposure to a low oxygen or a high altitude environment results in a series of adaptive changes which are characterized by increases in the ventilatory function as well as in the

erythrocyte count and the oxygen diffusing capacity. since the increase in the erythrocyte count and the oxygen diffusing capacity would invariably enhance the oxygen saturation capacity of the circulating blood, it is theoretically possible

that a high altitude acclimatization could result in a considerable improvement of the work capacity. On the other hand, an increase in the erythrocyte count as a result of high altitude acclimatization would increase the viscosity of the circulating blood and, consequently, the blood flow to the working muscle would be reduced because of an increased resistance. In other words, it is also theoretically possible that a high altitude acclimatization could reduce the work capacity.

In view of these two contradictory theoretical possibilities, this investigation was undertaken to delineate the net effect of two opposing forces in determining the work capacity of high altitude-acclimatized rats.

A total of 160 albino rats, weighing approximately 200gm, were divided into two groups, the experimental and the control. The experimental animals were exposed 8 hours a day and 5 days a week to a simulated altitude of 18,000 feet for a period of 7 weeks. The rats were subjected to 12,000 feet on the first day of exposure and then gradually brought to 18,000 feet in the course of subsequent 4 days, in order to avoid any serious effects that the animals might experience from the sudden exposure to high altitude.

A daily exercise load was given from the middle of the third week of exposure on a motor-driven drum revolving at a rate of 15 meters per minute. The rats were made to run daily for a period of 10 minutes until the end of the 5th week, 15 minutes

during the 6th week and 20 minutes during the 7th week. a day. Experimental animals

were given the running exercise at an altitude of 18,000 feet while the control at the ground level. For the determination of the work capacity, the rats were forced to run on the drum until exhaustion and the endurance time was recorded. At the point of exhaustion, a blood sample was obtained by a puncture of the left

ventricle and analyzed it for oxygen, carbon dioxide, pH and lactic acid.

The animals were then sacrificed and various organs were removed for weighing; a femur was also removed for electrolytes determination. Histopathological examinations of various organs were also made. Twenty-four hour urine samples were also collected during the entire experimental period and their electrolyte concentrations were measured.

The erythrocyte count increased progressively during the period of high altitude exposure, and thus it increased by 50% after 3 weeks and leveled off at this level the reafter. The hematocrit ratio increased from the pre-exposure level of 38% to 50% after 3 weeks. The hemoglobin concentrations increased from the pre-exposure level of 11.3±0.36 gm% to 17.1±0.4 gm% at the end of the 7th week.

The daily urinary excretion of Na**+ and K**+ increased after 4 weeks of high altitude exposure, amounting to 2.5 fold increase for Na**+ and 4 fold increase for K**+ through out the rest of the experimental period. Moreover, the daily excretion of Cl**_ was nearly doubled in the experimental group after 4 weeks of exposure.

These findings indicate that a characteristic respiratory alkalosis develops fully after 4 weeks of intermittent high altitude exposure as empolyed in this investigation. In other words, as a result of hyperventilation, the Na**+ reabsorption would be reduced while the Na**+-K**+ exchange mechanism would be

enhanced, resulting in an increased excretion of both Na**+ and K**+. On the other hand, a greater elimination of HCO^^5**- in the form of CO^^2 would increase the plasma concentration of Cl**-, and hence its excretion would also be increased.

The average endurance time on treadmill running was approximately 5 hours at the onset of the experiment. However, at the end of the experimental period, it increased to 7 hours and 46 minutes in the control group and to 10 hours and 35 minutes in the experimental group, the difference being highly significant

(P<0.02). Moreover, when the endurance time was evaluated as a function of the hematocrit ratio, it was found that the endurance time increased linearly until the hematocrit ratio increased to 55%. However, there was no further increase in the endurance time beyond 5% of the hematocrit ratio.

The arterial oxygen content at the point of complete exhaustion increased from the pre-exposure level of 13.9 to 23.6 vols % at the end of the experimental period. On the other hand, the arterial carbon dioxide content at the point of complete exhaustion did not vary significantly during the experimental period. The arterial blood pH at the point of exhaustion at the end of experimental period was significantly lower in the experimental group as compared to the control. It was also of interest to note that the concentration of lactic acid in the arterial blood at the point of exhaustion became lower toward the end of the experimental period in both groups. However, there was no statistical difference between the two groups in the concentration of lactic acid at a given period of experiment.

Among various organs removed, the spleen alone showed a significant reduction in the weight in both groups toward the end of the experimental period. Otehr organs showed little change, although the weight of the heart and the adrenal glands were

somewhat increased toward the end of the experimental period in the altitude-acclimatized group. Moreover, there was a sign of cardiac hypertrophy in the experimental group. The bone Na content was reduced in both groups during the experimental period, while the bone K content In creased progressively during the experimental period in both groups, the magnitude of increase being significantly greater in the experimental group than in the control.

It appears from these results that the work capacity of the rat shows a remarkable improvement after a high altitude acclimatization. On the basis of blood gas analysis, one can easily see that this improvement in the work capacity is not

due to the improvement in the anaerobic work capacity. The fact that the work capacity is linearly proportional to the hematocrit ratio until it reaches 55% indicates that an increase in the oxygen saturation capacity is the main determinant of the work capacity. However, it is also evident that, when the hematocrit ratio is greater than 55%, the work capacity does not increase any further, possibly because of an increased blood viscosity.