S163
Muscular Adaptations at Extreme Altitude: Metabolic Implications during Exercise H. J. Green
Abstract
H. J. Green, Muscular Adaptations at Extreme Altitude: Metabolic Implications during Exercise. IntJ SportsMed,Vo113,Suppll,ppSl63—S165, 1992.
come evident that the staining patterns and consequently the fibre type is based on the heavy chain composition of the fibre (19). On the basis of the human studies published to-date which have examined fibre type composition in only lowlanders acclimatized to extreme simulated altitude, Operation Everest 11(8) or to a moderate altitude of 4,300 m (10), it appears that shifts between the major fibre types do not occur.
Residence at extreme altitude results in pronounced reductions in muscle mass and the cross-sectional area of the slow and fast twitch fibre types. The reductions
The possibility that fibre type transformation can occur with altitude acclimatization, particularly for the
in muscle contractile proteins appear not to be accompanied by significant alterations in the proportion of the major fibre types and consequently in the myosin heavy
major fibre subtypes is suggested by animal studies (1, 22). Bigard et al. (1) have found increases in Type lIab fibre percentage in sedentary rats subjected to 14 weeks of hypobaric hy-
chain isozymes. Acclimatization to extreme altitude is also
accompanied by a marked reduction in mitochondrial potential that occurs regardless of activity status. At least during mountaineering expeditions, the maximal activity of cytosolic enzymes involved in anaerobic function appear to be unaffected. In contrast, extreme hypobaric hypoxia with low exercise appears to result in loss of the activities of cytosolic enzymes. The attentuation of glycolysis during exercise accompanying acclimatization does not appear to be
due to adaptations in fibre size, capillarization or mitochondrial potential. Rather, evidence from both acclimatization and training at sea level suggests that a depressed blood epinephrine concentration is involved.
poxia equivalent to an altitude of 4,000 m. This fact that the Type Ilab fibres apparently express two types of myosin heavy chains (19) would suggest that some alteration in myosin heavy chain expression is occurring. The major limitations in examining the effect of hypoxia on fibre type composition in humans, in addition to the general lack of studies examining both the highlander and the acclimatized lowlander has been the inability of the histochemical procedures that were used to
resolve a greater number of fibre subtypes. Indeed, with further refinement of histochemical techniques and the application of electrophoresis at the single fibre level, transitions may be detected with acclimatization. Changes in transitional fibres in the human are readily apparent with alterations in activity pattern (17, 23).
Key words
Altitude, muscle, fibre type, metabolic pathways, lactate
Introduction One conspicuous level at which to examine the effect of altitude residence on skeletal muscle is at the level of muscle fibre composition. The identification of muscle fibre
types is commonly based on the myofibrillar (actomyosin) ATPase reaction using histochemical procedures. Employing the basic Brooke and Kaiser technique (3) with appropriate modifications (19), two major fibre types, labelled as Type I or
slow twitch (ST) and Type II or fast twitch (FT) as well as a number of subtypes can be identified. On the basis of a number of studies which have performed histochemistry in conjunction with SDS gel electrophoresis on the same fibre, it has belnt.J.SportsMed. 13(1992)S163—S165 GeorgThieme Verlag Stuttgart New York
Changes in fibre type composition with hypoxia appear plausible. Increases in sympathetic activity have
been shown to effect increases in the proportion of Type II fibres (27) and resting catecholamine levels are elevated during both moderate acclimatization (18) and during severe hypobaric hypoxia (26). Reductions in arterial pO2 have also been implicated in altered heavy chain expression of the fibre (11), however it is uncertain whether the reduced arterial PO2 operates as an independent factor or via the hormonal milieu.
Muscle Fibre Area An unavoidable consequence of sustained residence at extremes of altitude or hypobaric hypoxia at least for the lowlander is a pronounced loss of muscle mass as indicated by computed tomography (20) and direct measures of muscle cell size obtained from samples of tissue by needle biopsy (9,
14). Data obtained from mountaineers participating in two Swiss expeditions, one to Lhotse Shar (8398 m) and one to Mount everest (8848 m) revealed a 10% reduction in the crosssectional area of the left thigh (14). Muscle fibre areas were reduced between 11 % (Lhotse Shar) and 27% (Mount Everest)
Downloaded by: University of Connecticut. Copyrighted material.
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
H. I Green
S164 mt. J. Sports Med. 13(1992)
types of the vastus lateralis muscle. With a less severe and more abbreviated hypoxic exposure, however, muscle fibre size appears to be well conserved. In a recent study, examining the ef-
fects of 24 days of exposure to 4,300 m, no significant alteration in the cross-sectional area of either of the major fibre types or subtypes was found (10). One difficulty in studying the effect of hypoxia on muscle mass is attempting to isolate the effects of hypoxia per Se from the numerous other potentially interacting factors encountered during mountaineering expeditions. Operation Everest II was in large part conceived to minimize the confounding influences (15) of factors other than hypoxia. The fact that substantial losses in muscle mass occurred during the
mountaineering expeditions as well as during Operation Everest II suggests that hypoxia acts as a primary determinant. This conclusion is also supported by the recent work of Bigard
(1) who found that sedentary rats acclimatized to simulated altitude lost muscle mass in proportion to body weight loss. Training at simulated altitude did not exaggerate the changes in muscle mass over that which occurred following training at sea level.
A common denominator which appears to correlate with the reduction in muscle mass is general body weight loss, suggesting that the loss of muscle mass is not restricted to specific muscles. With the exception of the Mount Everest expedition, where body weight loss (—4.8%) was relatively modest compared to the fibre area reductions (—27%), the other studies show a general parallel between body weight loss and reductions in muscle fibre area. Interestingly, during acclimatization to 4,300 m, no weight loss occurred and no reduction in fibre cross-sectional area was found (10).
The loss of a substantial fraction of the cellular
constituents could potentially influence composition and cellular morphology. Aside from the work performed by Hoppeler et al. (14) examining basically the mitochondrial and lipid ditribution, no information exists regarding the effect of altitude on contractile and regulatory proteins and the composition of structures involved in excitation and excitation-contraction coupling such as the sarcolemma and sarcoplasmic reticulum. The fact that major shifts in fibre type composition do not occur with acclimatization in the lowlander would suggest that at least at the level of the myosin heavy chain isoforms, the catabolic effects of hypoxia are not selective.
Energy Metabolic Pathways and Segments
Acclimatization to extreme environments in the lowlander is also accompanied by a substantial re-organization of the maximal activities of enzymes representative of the major metabolic pathways and segments. However, the na-
ture and the magnitude of the adaptations that occur may to some degree be dependent on factors in addition to hypoxia. In mountaineers sojourning to extreme altitudes, a disproportionate loss of mitochondria occurs (14). The loss of mitochondna is manifested in significant and substantial reductions in
the maximal activities of a range of enzymes of the citric acid cycle, the respiratory chain, n-oxidation and ketone body utilization (16). Mountaineering appears to have little effect on cytosolic enzyme activities involved in glycogenolysis, glycolysis, glycose phosphorylation, high energy phosphagen transfer and purine nucleotide metabolism (16). Serial measures of
enzyme activities obtained at different time points during Operation Everest II indicate that the catabolic effect at least on the oxidative potential is mainly manifested during extreme hypoxia (9). At higher barometric pressure, 380 Torr and 282 Torr, the maximal activities of succinic dehydrogenase and the critric acid cycle were unaffected. We have also confirmed (10) as have others (25) that 21 days of residence at
a moderate altitude of 4,300 m does not impair oxidative potential. The influence of extreme hypoxia on the activities of other enzymes representative of other metabolic pathways and segments is not as well defined. Hypobaric hypoxia similar to the studies of the mountaineers also appeared to be without effect on most of the cytosolic enzymes at least until the most severe hypobaric condition. During this period a
clear downward trend was evident for all of the cytosolic enzymes examined (9). Hexokinase appears to respond differently at different degrees of hypoxia compared to the other cytosolic enzymes. During Operation Everest II, an increase was found earlier in the acclimatization period. This result has also been confirmed on humans in a recent study examining acclimatization to 4,300 m (10) and during acclimatization to simulated altitude in rats (2). Interestingly, the increase in hexokinase activity is paralleled by increases in glucose utilization (4). With extreme hypobaric hypoxia, hexokinase activity was dramatically reduced (9).
For some enzymes, differences in activity pattern may influence the impact of hypoxia. Regular activity is known to result in substantial elevations in the enzymes of mitochondrial function (19, 21). Given the differences in activity patterns between the mountaineers and the subjects involved in Operation Everest II, it is apparent that activity cannot offset the mitochondrial loss that occurs. In contrast, it is possible that activity could have stabilized the cytosolic enzymes since in contrast to the findings of Operation Everest II, where clear
indications of reductions, occurred, high altitude mountaineers were able to maintain the activities of enzymes involved in anaerobic function. It is of potential significance that during the final stages of Operation Everest II subjects became more lethargic and inactive (15).
In the mountaineering studies, the subjects maintained the maximal activities of the cytosolic enzymes in spite of substantial loss of muscle cell mass. This would suggest that unlike the mitochondria the cytosolic enzymes are de-
graded in parallel with the contractile protein which represents the major constituent of the muscle cell. At least for some enzymes this might be expected given that several are bound to
actin and tropomyosin (6). Since the activities of other cytosolic enzymes not bound to the mitochondria did not change as well, it would appear that their degradation is also coordinated with loss of contractile protein. Whether inactivity can uncouple this relationship during residence at severe hypoxia remains to be determined.
Downloaded by: University of Connecticut. Copyrighted material.
in samples obtained from the vastus lateralis muscle. During Operation Everest II fibre size reductions averaged approximately 22% (9). The reductions in fibre appeared to be of a comparable magnitude for both the Type I and Type II fibre
mt. J. Sports Med. 13 (1992) S165
Muscular Adaptations at Extreme Altitude
It has been demonstrated that residence at altitude results in a blunting of blood and muscle lactate concentration during both submaximal (25) and maximal exercise (8, 24). Recently, it has been determined, at least during submaximal exercise in lowlanders acclimatized to moderate altitude, that the blunting of lactate is due to a reduction in glycolysis (5). The adaptive mechanisms, responsible for the reduction in glycolysis, termed the lactate paradox (12) remain questionable. Since exercise training at sea level also results in reductions in lactate accumulation during submaximal exercise and since these changaes have been associated with increases in mitochondrial potential (13), it has been reasoned that altitude
acclimatization also results in an enhancement of mitochondrial potential. However, it is apparent from recent work that no change in oxidative potential fibre size or capillarization is needed for the attentuation in glycolysis during exercise (10). Enhancement of oxidative flux during exercise is also not a requirement (18). Indeed, as evidenced by the results obtained during Operation Everest II and the Mount Everest and Lhotse Shar Expeditions, glycolysis appears to be reduced in the face of reductions in mitochondrial potential (9, 16). Other adaptations appear to be involved. One inviting possibility is the reduction in blood epinephrine concentration that occurs during exercise following acclimatization. Recently, Masseo et al. (18) has reported a close relationship between reductions in epinephrine and blood lactate concentration. The significance of epinephrine on muscle glycolysis may not be limited to acclimatization. We have been able to document that short term training involving two hours per day for 10 to 12 days also results in a substantial reduction in blood and muscle lactate concentration in the absence of increases in muscle oxidative potential (7). These adaptations are also accompanied by a reduction in blood epinephrine concentration. References 1 Bigard A. X., Brunet A., Guezennec C. Y., Monad H.: Effects of chronic hypoxia and endurance training on muscle capillarity in rats.Pfluger'sArch4l9:225—229, 1991. 2 Bigard A. X., Brunet A., Guezennec C. Y., Monod H.: Skeletal muscle changes after endurance training at high altitude. J Appi Physiol7l: 2114—2121,1991. Brooke M. H., Kaiser K. K.: Muscle fibre types. How many and what kind?Arch Neurol(Chicago) 23: 369—379, 1970. Brooks . A., Butterfield G. E., Wolfe R. R., Groves B. M., Masseo R. S., Sutton J. R., Wolfe] E. E., Reeves J. T.: Increased dependence on blood glucose after acclimatization to 4,300 m. JAppiPhysioI7O:919—927, 1991.
Brooks G. A., Butterfield G.E., Wolfe R. R., Groves B. M., Masseo R. S., Sutton J. R., Wolfel E. E., Reeves J. T.: Decreased reliance on lactate during exercise after acclimatization to 4,300 m exercise. J ApplPhysiol7l:333—341, 1991.
Clarke F., Stephan P., Morton D., Weidemann J.: Glycolytic enzyme organization via the cytoskeleton and its role in metabolic regulation. In: Regulation of Carbohydrate Metabolism, ed. by R. Beitner, Boca Raton, FL.: CRC, vol 1, 1985, pp 3—25. Green H. J., Jones S., Ball-Burnett E., Fraser I. G.: Early muscular and metabolic adaptations to prolonged exercise training in man. J ApplPhysiol7O: 2032—2038,1991.
8 Green H. J., Sutton J., Young P., Cymerman A., Houston C. S.: Operation Everest II: muscle energetics during maximal exhaustive exercise. JApplPhysio!66: 142—150, 1989. Green H. J., Sutton J. R., Cymerman A., Young P. M., Houston C.
S.: Operation Everest II: adaptations in human skeletal muscle. J ApplPhysiol66: 2454—2461,1989.
10
Green H. J., Sutton J. R., Wolfe] E. E. Reeves J. T., Butterfield G. E., Brooks G. A.: Altitude acclimatization and energy metabolic adaptations in skeletal muscle during submaximal exercise. JAppI Physiol: in press, 1992. Hildebrand I. L., Stylvén C., Esbjflrnsson M., Hellstrom K., Jans-
son E.: Does chronic hypoxaemia induce transformations of skeletal muscle fibre types. Acta Physiol Scand 141: 435—439, 1991.
12 Hochachka P. W.: The lactate paradox: analysis of underlying mechanisms.Ann Sports Med4: 184—188, 1988.
13 Holloszy J. 0., Coyle E. F.: Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. JAppiPhysiol 56:831—838,1984.
14 Hoppeler H., Kleinert E., Schlegel C., Claassen H., Howald H., Kayar S. R., Cerretelli P.: II. Morphologic adaptations of human skeletal muscle to chronic hypoxia. mt j Sports Med 11 (suppl I): 53— 59, 1990.
15 Houston C. S., SuttonJ. R.,CymermanA.,ReevesJ.T.: Operation Everest II. man at extreme altitude. JAppiPhysiol 63: 877—882, 1987. 16 Howald H., Pette D., Simoneau J. A., Uber A., Hoppeler H., Cerretelli P.: III. Effect of chronic hypoxia on muscle enzyme activities.IntJSportsMedl 1 (suppl 1): 510—514,1990. 17 Klitgaard H., Bergman 0., Betto R., Salviatti G., Schiaffino S., Clausen T., Saltin B.: Co-existence of myosin heavy chain land Ha isoforms in human skeletal muscle fibres with endurance training. PJlOger'sArch4l6:470—472, 1991. 18 Masseo R. S., Bender P. R., Brooks G. A., Butterfield G.E., Groves
B. M., Sutton J. R., Wolfel E. B., Reeves J. T.: Arterial catecholamine response with acute and chronic high-altitude exposure.AmJPhysiol26l:E4l9—E424, 1991. 19 Pette D., Staron B.: Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev Physiol Bioche,n Pharmacol 116: 1—75, 1990.
20 Rose M. S., Houston C. S., FuccoC. S., Coates G., SuttonJ. R., Cy-
merman A.: Operation Everest II: nutrition and body composition.JAppIPhysioI65: 2543—2549, 1988.
2! Saltin B., Golinick P. D.: Skeletal muscle adaptability: significance for metabolism and performance. In: Handbook of Physiology. Skeletal Muscle, ed. by L. D. Peachy, R. H. Adrian, S. R. Geiger. Baltimore: Williams and Wilkins, 1983, pp 551—631. 2.. Sillau A. H., Banchero N.: Effects of hypoxia on capillary density and fiber composition in rat skeletal muscle. PflOger's Arch 370: 227—232, 1977.
23 Staron R. S., Malicky E. S., Leonardi M. J., Falkel J. E., Hagerman F. C., Dudley G. A.: Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women. Europ J AppI Physiol 60:71—79, 1989. 24 West J. B.: Lactate during exercise in extreme altitude. Fed Proc 45: 2953—2957,1986. 25 Young A. J., Evans W. J., Fisher E. C., Sharp R. L., Costill D. L., Maher J. T.: Skeletal muscle metabolism of sea level natives following short-term high altitude residence. Europ JAppi Physiol 52: 463—466, 1984.
26 Young P. M., Rose M. S., Sutton J. R., Green H. J., Cymerman A., Houston C. S.: Operation Everest II. Plasma lipid and hormonal responses during a simulated ascent of Mt. Everest. JApplPhysiol 66:1430—1435,1985. 27 Zemen R. J., Cudemann R., Easton T. G., Etlinger J. D.: Slow to fast alterations in skeletal muscle fibres caused by clenbuterol, a 32-receptor agonist. Am JPhysiol254: E726—E732, 1988.
Howard I Green, Ph. D. Department of Kinesiology University of Waterloo Waterloo, Ontario Canada N2L 3G1
Downloaded by: University of Connecticut. Copyrighted material.
Energy Metabolic Behaviour during Exercise
Muscular Adaptations at Extreme Altitude: Metabolic Implications during Exercise H. J. Green
Abstract
H. J. Green, Muscular Adaptations at Extreme Altitude: Metabolic Implications during Exercise. IntJ SportsMed,Vo113,Suppll,ppSl63—S165, 1992.
come evident that the staining patterns and consequently the fibre type is based on the heavy chain composition of the fibre (19). On the basis of the human studies published to-date which have examined fibre type composition in only lowlanders acclimatized to extreme simulated altitude, Operation Everest 11(8) or to a moderate altitude of 4,300 m (10), it appears that shifts between the major fibre types do not occur.
Residence at extreme altitude results in pronounced reductions in muscle mass and the cross-sectional area of the slow and fast twitch fibre types. The reductions
The possibility that fibre type transformation can occur with altitude acclimatization, particularly for the
in muscle contractile proteins appear not to be accompanied by significant alterations in the proportion of the major fibre types and consequently in the myosin heavy
major fibre subtypes is suggested by animal studies (1, 22). Bigard et al. (1) have found increases in Type lIab fibre percentage in sedentary rats subjected to 14 weeks of hypobaric hy-
chain isozymes. Acclimatization to extreme altitude is also
accompanied by a marked reduction in mitochondrial potential that occurs regardless of activity status. At least during mountaineering expeditions, the maximal activity of cytosolic enzymes involved in anaerobic function appear to be unaffected. In contrast, extreme hypobaric hypoxia with low exercise appears to result in loss of the activities of cytosolic enzymes. The attentuation of glycolysis during exercise accompanying acclimatization does not appear to be
due to adaptations in fibre size, capillarization or mitochondrial potential. Rather, evidence from both acclimatization and training at sea level suggests that a depressed blood epinephrine concentration is involved.
poxia equivalent to an altitude of 4,000 m. This fact that the Type Ilab fibres apparently express two types of myosin heavy chains (19) would suggest that some alteration in myosin heavy chain expression is occurring. The major limitations in examining the effect of hypoxia on fibre type composition in humans, in addition to the general lack of studies examining both the highlander and the acclimatized lowlander has been the inability of the histochemical procedures that were used to
resolve a greater number of fibre subtypes. Indeed, with further refinement of histochemical techniques and the application of electrophoresis at the single fibre level, transitions may be detected with acclimatization. Changes in transitional fibres in the human are readily apparent with alterations in activity pattern (17, 23).
Key words
Altitude, muscle, fibre type, metabolic pathways, lactate
Introduction One conspicuous level at which to examine the effect of altitude residence on skeletal muscle is at the level of muscle fibre composition. The identification of muscle fibre
types is commonly based on the myofibrillar (actomyosin) ATPase reaction using histochemical procedures. Employing the basic Brooke and Kaiser technique (3) with appropriate modifications (19), two major fibre types, labelled as Type I or
slow twitch (ST) and Type II or fast twitch (FT) as well as a number of subtypes can be identified. On the basis of a number of studies which have performed histochemistry in conjunction with SDS gel electrophoresis on the same fibre, it has belnt.J.SportsMed. 13(1992)S163—S165 GeorgThieme Verlag Stuttgart New York
Changes in fibre type composition with hypoxia appear plausible. Increases in sympathetic activity have
been shown to effect increases in the proportion of Type II fibres (27) and resting catecholamine levels are elevated during both moderate acclimatization (18) and during severe hypobaric hypoxia (26). Reductions in arterial pO2 have also been implicated in altered heavy chain expression of the fibre (11), however it is uncertain whether the reduced arterial PO2 operates as an independent factor or via the hormonal milieu.
Muscle Fibre Area An unavoidable consequence of sustained residence at extremes of altitude or hypobaric hypoxia at least for the lowlander is a pronounced loss of muscle mass as indicated by computed tomography (20) and direct measures of muscle cell size obtained from samples of tissue by needle biopsy (9,
14). Data obtained from mountaineers participating in two Swiss expeditions, one to Lhotse Shar (8398 m) and one to Mount everest (8848 m) revealed a 10% reduction in the crosssectional area of the left thigh (14). Muscle fibre areas were reduced between 11 % (Lhotse Shar) and 27% (Mount Everest)
Downloaded by: University of Connecticut. Copyrighted material.
Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
H. I Green
S164 mt. J. Sports Med. 13(1992)
types of the vastus lateralis muscle. With a less severe and more abbreviated hypoxic exposure, however, muscle fibre size appears to be well conserved. In a recent study, examining the ef-
fects of 24 days of exposure to 4,300 m, no significant alteration in the cross-sectional area of either of the major fibre types or subtypes was found (10). One difficulty in studying the effect of hypoxia on muscle mass is attempting to isolate the effects of hypoxia per Se from the numerous other potentially interacting factors encountered during mountaineering expeditions. Operation Everest II was in large part conceived to minimize the confounding influences (15) of factors other than hypoxia. The fact that substantial losses in muscle mass occurred during the
mountaineering expeditions as well as during Operation Everest II suggests that hypoxia acts as a primary determinant. This conclusion is also supported by the recent work of Bigard
(1) who found that sedentary rats acclimatized to simulated altitude lost muscle mass in proportion to body weight loss. Training at simulated altitude did not exaggerate the changes in muscle mass over that which occurred following training at sea level.
A common denominator which appears to correlate with the reduction in muscle mass is general body weight loss, suggesting that the loss of muscle mass is not restricted to specific muscles. With the exception of the Mount Everest expedition, where body weight loss (—4.8%) was relatively modest compared to the fibre area reductions (—27%), the other studies show a general parallel between body weight loss and reductions in muscle fibre area. Interestingly, during acclimatization to 4,300 m, no weight loss occurred and no reduction in fibre cross-sectional area was found (10).
The loss of a substantial fraction of the cellular
constituents could potentially influence composition and cellular morphology. Aside from the work performed by Hoppeler et al. (14) examining basically the mitochondrial and lipid ditribution, no information exists regarding the effect of altitude on contractile and regulatory proteins and the composition of structures involved in excitation and excitation-contraction coupling such as the sarcolemma and sarcoplasmic reticulum. The fact that major shifts in fibre type composition do not occur with acclimatization in the lowlander would suggest that at least at the level of the myosin heavy chain isoforms, the catabolic effects of hypoxia are not selective.
Energy Metabolic Pathways and Segments
Acclimatization to extreme environments in the lowlander is also accompanied by a substantial re-organization of the maximal activities of enzymes representative of the major metabolic pathways and segments. However, the na-
ture and the magnitude of the adaptations that occur may to some degree be dependent on factors in addition to hypoxia. In mountaineers sojourning to extreme altitudes, a disproportionate loss of mitochondria occurs (14). The loss of mitochondna is manifested in significant and substantial reductions in
the maximal activities of a range of enzymes of the citric acid cycle, the respiratory chain, n-oxidation and ketone body utilization (16). Mountaineering appears to have little effect on cytosolic enzyme activities involved in glycogenolysis, glycolysis, glycose phosphorylation, high energy phosphagen transfer and purine nucleotide metabolism (16). Serial measures of
enzyme activities obtained at different time points during Operation Everest II indicate that the catabolic effect at least on the oxidative potential is mainly manifested during extreme hypoxia (9). At higher barometric pressure, 380 Torr and 282 Torr, the maximal activities of succinic dehydrogenase and the critric acid cycle were unaffected. We have also confirmed (10) as have others (25) that 21 days of residence at
a moderate altitude of 4,300 m does not impair oxidative potential. The influence of extreme hypoxia on the activities of other enzymes representative of other metabolic pathways and segments is not as well defined. Hypobaric hypoxia similar to the studies of the mountaineers also appeared to be without effect on most of the cytosolic enzymes at least until the most severe hypobaric condition. During this period a
clear downward trend was evident for all of the cytosolic enzymes examined (9). Hexokinase appears to respond differently at different degrees of hypoxia compared to the other cytosolic enzymes. During Operation Everest II, an increase was found earlier in the acclimatization period. This result has also been confirmed on humans in a recent study examining acclimatization to 4,300 m (10) and during acclimatization to simulated altitude in rats (2). Interestingly, the increase in hexokinase activity is paralleled by increases in glucose utilization (4). With extreme hypobaric hypoxia, hexokinase activity was dramatically reduced (9).
For some enzymes, differences in activity pattern may influence the impact of hypoxia. Regular activity is known to result in substantial elevations in the enzymes of mitochondrial function (19, 21). Given the differences in activity patterns between the mountaineers and the subjects involved in Operation Everest II, it is apparent that activity cannot offset the mitochondrial loss that occurs. In contrast, it is possible that activity could have stabilized the cytosolic enzymes since in contrast to the findings of Operation Everest II, where clear
indications of reductions, occurred, high altitude mountaineers were able to maintain the activities of enzymes involved in anaerobic function. It is of potential significance that during the final stages of Operation Everest II subjects became more lethargic and inactive (15).
In the mountaineering studies, the subjects maintained the maximal activities of the cytosolic enzymes in spite of substantial loss of muscle cell mass. This would suggest that unlike the mitochondria the cytosolic enzymes are de-
graded in parallel with the contractile protein which represents the major constituent of the muscle cell. At least for some enzymes this might be expected given that several are bound to
actin and tropomyosin (6). Since the activities of other cytosolic enzymes not bound to the mitochondria did not change as well, it would appear that their degradation is also coordinated with loss of contractile protein. Whether inactivity can uncouple this relationship during residence at severe hypoxia remains to be determined.
Downloaded by: University of Connecticut. Copyrighted material.
in samples obtained from the vastus lateralis muscle. During Operation Everest II fibre size reductions averaged approximately 22% (9). The reductions in fibre appeared to be of a comparable magnitude for both the Type I and Type II fibre
mt. J. Sports Med. 13 (1992) S165
Muscular Adaptations at Extreme Altitude
It has been demonstrated that residence at altitude results in a blunting of blood and muscle lactate concentration during both submaximal (25) and maximal exercise (8, 24). Recently, it has been determined, at least during submaximal exercise in lowlanders acclimatized to moderate altitude, that the blunting of lactate is due to a reduction in glycolysis (5). The adaptive mechanisms, responsible for the reduction in glycolysis, termed the lactate paradox (12) remain questionable. Since exercise training at sea level also results in reductions in lactate accumulation during submaximal exercise and since these changaes have been associated with increases in mitochondrial potential (13), it has been reasoned that altitude
acclimatization also results in an enhancement of mitochondrial potential. However, it is apparent from recent work that no change in oxidative potential fibre size or capillarization is needed for the attentuation in glycolysis during exercise (10). Enhancement of oxidative flux during exercise is also not a requirement (18). Indeed, as evidenced by the results obtained during Operation Everest II and the Mount Everest and Lhotse Shar Expeditions, glycolysis appears to be reduced in the face of reductions in mitochondrial potential (9, 16). Other adaptations appear to be involved. One inviting possibility is the reduction in blood epinephrine concentration that occurs during exercise following acclimatization. Recently, Masseo et al. (18) has reported a close relationship between reductions in epinephrine and blood lactate concentration. The significance of epinephrine on muscle glycolysis may not be limited to acclimatization. We have been able to document that short term training involving two hours per day for 10 to 12 days also results in a substantial reduction in blood and muscle lactate concentration in the absence of increases in muscle oxidative potential (7). These adaptations are also accompanied by a reduction in blood epinephrine concentration. References 1 Bigard A. X., Brunet A., Guezennec C. Y., Monad H.: Effects of chronic hypoxia and endurance training on muscle capillarity in rats.Pfluger'sArch4l9:225—229, 1991. 2 Bigard A. X., Brunet A., Guezennec C. Y., Monod H.: Skeletal muscle changes after endurance training at high altitude. J Appi Physiol7l: 2114—2121,1991. Brooke M. H., Kaiser K. K.: Muscle fibre types. How many and what kind?Arch Neurol(Chicago) 23: 369—379, 1970. Brooks . A., Butterfield G. E., Wolfe R. R., Groves B. M., Masseo R. S., Sutton J. R., Wolfe] E. E., Reeves J. T.: Increased dependence on blood glucose after acclimatization to 4,300 m. JAppiPhysioI7O:919—927, 1991.
Brooks G. A., Butterfield G.E., Wolfe R. R., Groves B. M., Masseo R. S., Sutton J. R., Wolfel E. E., Reeves J. T.: Decreased reliance on lactate during exercise after acclimatization to 4,300 m exercise. J ApplPhysiol7l:333—341, 1991.
Clarke F., Stephan P., Morton D., Weidemann J.: Glycolytic enzyme organization via the cytoskeleton and its role in metabolic regulation. In: Regulation of Carbohydrate Metabolism, ed. by R. Beitner, Boca Raton, FL.: CRC, vol 1, 1985, pp 3—25. Green H. J., Jones S., Ball-Burnett E., Fraser I. G.: Early muscular and metabolic adaptations to prolonged exercise training in man. J ApplPhysiol7O: 2032—2038,1991.
8 Green H. J., Sutton J., Young P., Cymerman A., Houston C. S.: Operation Everest II: muscle energetics during maximal exhaustive exercise. JApplPhysio!66: 142—150, 1989. Green H. J., Sutton J. R., Cymerman A., Young P. M., Houston C.
S.: Operation Everest II: adaptations in human skeletal muscle. J ApplPhysiol66: 2454—2461,1989.
10
Green H. J., Sutton J. R., Wolfe] E. E. Reeves J. T., Butterfield G. E., Brooks G. A.: Altitude acclimatization and energy metabolic adaptations in skeletal muscle during submaximal exercise. JAppI Physiol: in press, 1992. Hildebrand I. L., Stylvén C., Esbjflrnsson M., Hellstrom K., Jans-
son E.: Does chronic hypoxaemia induce transformations of skeletal muscle fibre types. Acta Physiol Scand 141: 435—439, 1991.
12 Hochachka P. W.: The lactate paradox: analysis of underlying mechanisms.Ann Sports Med4: 184—188, 1988.
13 Holloszy J. 0., Coyle E. F.: Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. JAppiPhysiol 56:831—838,1984.
14 Hoppeler H., Kleinert E., Schlegel C., Claassen H., Howald H., Kayar S. R., Cerretelli P.: II. Morphologic adaptations of human skeletal muscle to chronic hypoxia. mt j Sports Med 11 (suppl I): 53— 59, 1990.
15 Houston C. S., SuttonJ. R.,CymermanA.,ReevesJ.T.: Operation Everest II. man at extreme altitude. JAppiPhysiol 63: 877—882, 1987. 16 Howald H., Pette D., Simoneau J. A., Uber A., Hoppeler H., Cerretelli P.: III. Effect of chronic hypoxia on muscle enzyme activities.IntJSportsMedl 1 (suppl 1): 510—514,1990. 17 Klitgaard H., Bergman 0., Betto R., Salviatti G., Schiaffino S., Clausen T., Saltin B.: Co-existence of myosin heavy chain land Ha isoforms in human skeletal muscle fibres with endurance training. PJlOger'sArch4l6:470—472, 1991. 18 Masseo R. S., Bender P. R., Brooks G. A., Butterfield G.E., Groves
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Howard I Green, Ph. D. Department of Kinesiology University of Waterloo Waterloo, Ontario Canada N2L 3G1
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Energy Metabolic Behaviour during Exercise
