Phenotypic adaptations in human muscle fibers 6 and 24 wk after spinal cord injury.

The effects of spinal cord injury (SCI) on the profile of sarco(endo) plasmic reticulum calcium-ATPase (SERCA) and myosin heavy chain (MHC) isoforms in individual vastus lateralis (VL) muscle fibers were determined. Biopsies from the VL were obtained from SCI subjects 6 and 24 wk postinjury (n = 6). Biopsies from nondisabled (ND) subjects were obtained at two time points 18 wk apart (n = 4). In ND subjects, the proportions of VL fibers containing MHC I, MHC IIa, and MHC IIx were 46 +/- 3, 53 +/- 3, and 1 +/- 1%, respectively. Most MHC I fibers contained SERCA2. Most MHC IIa fibers contained SERCA1. All MHC IIx fibers contained SERCA1 exclusively. SCI resulted in significant increases in fibers with MHC IIx (14 +/- 4% at 6 wk and 16 +/- 2% at 24 wk). In addition, SCI resulted in high proportions of MHC I and MHC IIa fibers with both SERCA isoforms (29% at 6 wk and 54% at 24 wk for MHC I fibers and 16% at 6 wk and 38% at 24 wk for MHC IIa fibers). Thus high proportions of VL fibers were mismatched for SERCA and MHC isoforms after SCI (19 +/- 3% at 6 wk and 36 +/- 9% at 24 wk) compared with only ~5% in ND subjects. These data suggest that, in the early time period following SCI, fast fiber isoforms of both SERCA and MHC are elevated disproportionately, resulting in fibers that are mismatched for SERCA and MHC isoforms. Thus the adaptations in SERCA and MHC isoforms appear to occur independently.     

Selected contribution: High-altitude natives living at sea level acclimatize to high altitude like sea-level natives.

Sea-level (SL) natives acclimatizing to high altitude (HA) increase their acute ventilatory response to hypoxia (AHVR), but HA natives have values for AHVR below those for SL natives at SL (blunting). HA natives who live at SL retain some blunting of AHVR and have more marked blunting to sustained (20-min) hypoxia. This study addressed the question of what happens when HA natives resident at SL return to HA: do they acclimatize like SL natives or revert to the characteristics of HA natives? Fifteen HA natives resident at SL were studied, together with 15 SL natives as controls. Air-breathing end-tidal Pco(2) and AHVR were determined at SL. Subjects were then transported to 4,300 m, where these measurements were repeated on each of the following 5 days. There were no significant differences in the magnitude or time course of the changes in end-tidal Pco(2) and AHVR between the two groups. We conclude that HA natives normally resident at SL undergo ventilatory acclimatization to HA in the same manner as SL natives.     

Body water metabolism in high altitude natives during and after a stay at sea level

Body fluid compartments were studied in a group of high altitude natives after a stay of two months at sea level and during 12 days at an altitude of 3,500 m. Measurements of total body water and extracellular water were made on day 3 and 12 of reinduction to altitude, while plasma volume was measured on day 12 only. The intracellular water, blood volume and red cell mass were computed from the above parameters. Total body water and intracellular water decreased by 3.3% (P<0.001) and 5.0% (P<0.001) respectively by the 3rd day at altitude and did not change thereafter. Extracellular water increased progressively at altitude, but the increase was not significant. Blood volume and red cell mass increased significantly while plasma volume decreased at altitude. These data were compared with that of low landers. This study suggested body hypohydration on high altitude induction in low landers as well as in high altitude natives on reinduction.     

Sleep of Andean high altitude natives.

The structure of sleep in lowland visitors to altitudes greater than 4000 m is grossly disturbed. There are no data on sleep in long-term residents of high altitudes. This paper describes an electroencephalographic study of sleep in high altitude dwellers who were born in and are permanent residents of Cerro de Pasco in the Peruvian Andes, situated at 4330 m. Eight healthy male volunteers aged between 18 and 69 years were studied. Sleep was measured on three consecutive nights for each subject. Electroencephalographs, submental electromyographs and electro-oculograms were recorded. Only data from the third night were used in the analysis. The sleep patterns of these subjects resembled the normal sleep patterns described by others in lowlanders at sea level. There were significant amounts of slow wave sleep in the younger subjects and rapid eye movement sleep seemed unimpaired.     

Cardiovascular response to hypoxia after endurance training at altitude and sea level and after detraining.

The purpose of this study was to elucidate 1) the effects of endurance exercise training during hypoxia or normoxia and of detraining on ventilatory and cardiovascular responses to progressive isocapnic hypoxia and 2) whether the change in the cardiovascular response to hypoxia is correlated to changes in the hypoxic ventilatory response (HVR) after training and detraining. Seven men (altitude group) performed endurance training using a cycle ergometer in a hypobaric chamber of simulated 4,500 m, whereas the other seven men (sea-level group) trained at sea level (K. Katayama, Y. Sato, Y. Morotome, N. Shima, K. Ishida, S. Mori, and M. Miyamura. J. Appl. Physiol. 86: 1805-1811, 1999). The HVR, systolic and diastolic blood pressure responses (DeltaSBP/DeltaSa(O(2)), DeltaDBP/DeltaSa(O(2))), and heart rate response (DeltaHR/DeltaSa(O(2)); Sa(O(2)) is arterial oxygen saturation) to progressive isocapnic hypoxia were measured before and after training and during detraining. DeltaSBP/DeltaSa(O(2)) increased significantly in the altitude group and decreased significantly in the sea-level group after training. The changed DeltaSBP/DeltaSa(O(2)) in both groups was restored during 2 wk of detraining, as were the changes in HVR, whereas there were no changes in the DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) throughout the experimental period. The changes in DeltaSBP/DeltaSa(O(2)) after training and detraining were significantly correlated with those in HVR. These results suggest that DeltaSBP/DeltaSa(O(2)) to progressive isocapnic hypoxia is variable after endurance training during hypoxia and normoxia and after detraining, as is HVR, but DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) are not. It also suggests that there is an interaction between the changes in DeltaSBP/DeltaSa(O(2)) and HVR after endurance training or detraining.     

Cardiovascular adaptations to mechanical overload

The cardiac changes resulting from mechanical overload of the left ventricle have been well documented and a variety of compensatory mechanisms described. These include a decrease in maximum velocity (V₀) of shortening in the absence of reduction in active tension (P₀), and a reversible decrease in myofibrillar adenosine triphosphatase activity resulting from isoenzymic shift from, predominantly, a form of myosin with high ATPase activity (V₁) to another with low (V₃). The thermodynamic advantage of the transition is the hypertrophied muscle possesses a more energy-efficient form of contraction. These reversible transitions resulted from altered gene expression of isoenzymic forms of myosin heavy chain. It must be borne in mind that the adaptational modifications just described appear to occur only in smaller animals such as the rat, that possesses several myosin isozymes. In large mammals it is mainly the V₃ form of myosin that is present, which does not change with altered contractile state. Responses of the large arteries to hypertension have been poorly studied. This is surprising when one recalls that degenerative disease of such vessels, that include the aorta, carotids and ileo-femoral arteries is almost an obligatory concomitant of hypertension. Such studies as have been carried out indicate that hyperplasia is specific for abdominal aortic stenosis while hypertrophy is found in aortic smooth muscle in rats with systemic hypertension. Mechanically, an increase in V₀ with no change in P₀ have been reported; an increase in myofibrillar ATPase activity was also reported. Though two myosin heavy chain isozymes have been found in aortic smooth muscle densitometry did not reveal any difference in distribution between tissues from control and hypertensive rats. The cause of the increased ATPase activity must be in increased phosphorylation of the muscles' 20,000 dalton light chain.     

Metabolic and work efficiencies during exercise in Andean natives

Maximum O2 and CO2 fluxes during exercise were less perturbed by hypoxia in Quechua natives from the Andes than in lowlanders. In exploring how this was achieved, we found that, for a given work rate, Quechua highlanders at 4,200 m accumulated substantially less lactate than lowlanders at sea level normoxia (approximately 5-7 vs. 10-14 mM) despite hypobaric hypoxia. This phenomenon, known as the lactate paradox, was entirely refractory to normoxia-hypoxia transitions. In lowlanders, the lactate paradox is an acclimation; however, in Quechuas, the lactate paradox is an expression of metabolic organization that did not deacclimate, at least over the 6-wk period of our study. Thus it was concluded that this metabolic organization is a developmentally or genetically fixed characteristic selected because of the efficiency advantage of aerobic metabolism (high ATP yield per mol of substrate metabolized) compared with anaerobic glycolysis. Measurements of respiratory quotient indicated preferential use of carbohydrate as fuel for muscle work, which is also advantageous in hypoxia because it maximizes the yield of ATP per mol of O2 consumed. Finally, minimizing the cost of muscle work was also reflected in energetic efficiency as classically defined (power output per metabolic power input); this was evident at all work rates but was most pronounced at submaximal work rates (efficiency approximately 1.5 times higher than in lowlander athletes). Because plots of power output vs. metabolic power input did not extrapolate to the origin, it was concluded 1) that exercise in both groups sustained a significant ATP expenditure not convertible to mechanical work but 2) that this expenditure was downregulated in Andean natives by thus far unexplained mechanisms.     

Physiological and molecular adaptations to drought in Andean potato genotypes

The drought stress tolerance of two Solanum tuberosum subsp. andigena landraces, one hybrid (adgxtbr) and Atlantic (S. tuberosum subsp. tuberosum) has been evaluated. Photosynthesis in the Andigena landraces during prolonged drought was maintained significantly longer than in the Tuberosum (Atlantic) line. Among the Andigena landraces, 'Sullu' (SUL) was more drought resistant than 'Negra Ojosa' (NOJ). Microarray analysis and metabolite data from leaf samples taken at the point of maximum stress suggested higher mitochondrial metabolic activity in SUL than in NOJ. A greater induction of chloroplast-localized antioxidant and chaperone genes in SUL compared with NOJ was evident. ABA-responsive TFs were more induced in NOJ compared with SUL, including WRKY1, mediating a response in SA signalling that may give rise to increased ROS. NOJ may be experiencing higher ROS levels than SUL. Metabolite profiles of NOJ were characterized by compounds indicative of stress, for example, proline, trehalose, and GABA, which accumulated to a higher degree than in SUL. The differences between the Andigena lines were not explained by protective roles of compatible solutes; hexoses and complex sugars were similar in both landraces. Instead, lower levels of ROS accumulation, greater mitochondrial activity and active chloroplast defences contributed to a lower stress load in SUL than in NOJ during drought.     

Alveolar PCO2 and PO2 of high-altitude natives living at sea level

León-Velarde, Fabiola, Manuel Vargas, Carlos Monge-C.,Robert W. Torrance, and Peter A. Robbins. AlveolarPCO₂ andPO₂ of high-altitude natives livingat sea level. J. Appl.Physiol. 81(4): 1605-1609, 1996.Thisstudy was designed to determine whether subjects born at high altitude(HA; 2,000 m or above) who subsequently move to near sea level (SL)develop end-tidal PCO₂(PET_CO2) andPO₂(PET_O2) valuesthat equal those of SL natives living near SL. A total of 108 male HAnatives living near SL were identified by survey of a district in Lima,Peru, and a further 108 male SL natives from the same district wereidentified as control subjects. Of these subjects, satisfactory datafor inclusion in the study were obtained from 93 HA and 82 SL subjects.Mean PET_CO2 and PET_O2 values were 37.7 ± 2.5 (SD) and 104.7 ± 3.2 Torr, respectively, in HA subjects and37.7 ± 2.2 and 104.8 ± 3.0 Torr, respectively, in SL subjects.The average difference between SL natives and HA natives forPET_CO2 was 0.07 Torr(0.64 to 0.78; 95% confidence interval) and forPET_O2 was 0.05 Torr(0.89 to 0.99, 95% confidence interval). The average age andweight of the SL and HA subjects did not differ, but the HA subjectswere shorter and tended to have larger vital capacities, consistentwith their origin at HA. We conclude that thePET_CO2 andPET_O2 near SL of SL nativesand HA natives do not differ.

     

Cardiovascular adaptations to exercise training in the elderly

Maximal O2 uptake (VO2max) and left ventricular function decrease with age. Endurance exercise training of sufficient intensity, frequency, and duration increases VO2max in the elderly. The mechanisms underlying the increased VO2max in the elderly are enhanced O2 extraction of trained muscle during maximal exercise leading to a wider arteriovenous O2 difference, and higher cardiac output in the trained state. However, increased cardiac output during true maximal exercise has not been documented in elderly subjects. Endurance exercise training results in a lower heart rate and rate pressure product during submaximal exercise at a given intensity. However, no improvement in left ventricular function has been reported in the elderly after exercise training. Highly trained master athletes exhibit proportional increases in the left ventricular end-diastolic dimension and wall thickness suggestive of volume-overload hypertrophy compared with age-matched sedentary controls. The magnitude of left ventricular enlargement is similar to that in young athletes. The failure of exercise training to alter the age-related deterioration of left ventricular function in the elderly may reflect an insufficient training stimulus rather than the inability of the heart to adapt to training in elderly subjects.     

Carbonic anhydrase activity in the red blood cells of sea level and high altitude natives

Red blood cell carbonic anhydrase (CA) activity has not been studied in high altitude natives. Because CA is an intraerythocytic enzyme and high altitude natives are polycythemic, it is important to know if the activity of CA per red cell volume is different from that of their sea level counterparts. Blood was collected from healthy subjects living in Lima (150m) and from twelve subjects from Cerro de Pasco (4330m), and hematocrit and carbonic anhydrase activity were measured. As expected, the high altitude natives had significantly higher hematocrits than the sea level controls (p = 0.0002). No difference in the CA activity per milliliter of red cells was found between the two populations. There was no correlation between the hematocrit and CA activity.     

Lower limb skeletal muscle function after 6wk of bed rest

Berg, H. E., L. Larsson, and P. A. Tesch. Lower limbskeletal muscle function after 6 wk of bed rest. J. Appl. Physiol. 82(1): 182-188, 1997.Force,electromyographic (EMG) activity, muscle mass, and fibercharacteristics were studied in seven healthy men before and after 6 wkof bed rest. Maximum voluntary isometric and concentric knee extensortorque decreased (P < 0.05)uniformly across angular velocities by 25-30% after bed rest.Maximum quadricep rectified EMG decreased by 19 ± 23%, whereassubmaximum (100-Nm isometric action) EMG increased by 44 ± 28%.Knee extensor muscle cross-sectional area (CSA), assessed by usingmagnetic resonance imaging, decreased by 14 ± 4%. Maximum torqueper knee extensor CSA decreased by 13 ± 9%. Vastus lateralis fiberCSA decreased 18 ± 14%. Neither type I, IIA, and IIB fiberpercentages nor their relative proportions of myosin heavy chain (MHC)isoforms were altered after bed rest. Because the decline in strengthcould not be entirely accounted for by decreased muscle CSA, it issuggested that the strength loss is also due to factors resulting indecreased neural input to muscle and/or reduced specifictension of muscle, as evidenced by a decreased torque/EMG ratio.Additionally, it is concluded that muscle unloading in humans does notinduce important changes in fiber type or MHC composition or in vivomuscle contractile properties.

     

Selected contribution: Acute and sustained ventilatory responses to hypoxia in high-altitude natives living at sea level.

High-altitude (HA) natives have blunted ventilatory responses to hypoxia (HVR), but studies differ as to whether this blunting is lost when HA natives migrate to live at sea level (SL), possibly because HVR has been assessed with different durations of hypoxic exposure (acute vs. sustained). To investigate this, 50 HA natives (>3,500 m, for >20 yr) now resident at SL were compared with 50 SL natives as controls. Isocapnic HVR was assessed by using two protocols: protocol 1, progressive stepwise induction of hypoxia over 5-6 min; and protocol 2, sustained (20-min) hypoxia (end-tidal Po(2) = 50 Torr). Acute HVR was assessed from both protocols, and sustained HVR from protocol 2. For HA natives, acute HVR was 79% [95% confidence interval (CI): 52-106%, P = not significant] of SL controls for protocol 1 and 74% (95% CI: 52-96%, P < 0.05) for protocol 2. By contrast, sustained HVR after 20-min hypoxia was only 30% (95% CI: -7-67%, P < 0.001) of SL control values. The persistent blunting of HVR of HA natives resident at SL is substantially less to acute than to sustained hypoxia, when hypoxic ventilatory depression can develop.     

Pulmonary gas exchange in Andean natives with excessive polycythemia--effect of hemodilution

Pulmonary gas exchange in Andean natives (n = 8) with excessive high-altitude (3,600-4,200 m) polycythemia (hematocrit 65.1 +/- 6.6%) and hypoxemia (arterial PO2 45.6 +/- 5.6 Torr) in the absence of pulmonary or cardiovascular disease was investigated both before and after isovolemic hemodilution by use of the inert gas elimination technique. The investigations were carried out in La Paz, Bolivia (3,650 m, 500 mmHg barometric pressure). Before hemodilution, a low ventilation-perfusion (VA/Q) mode (VA/Q less than 0.1) without true shunt accounted for 11.6 +/- 5.5% of the total blood flow and was mainly responsible for the hypoxemia. The hypoventilation with a low mixed venous PO2 value may have contributed to the observed hypoxemia in the absence of an impairment in alveolar capillary diffusion. After hemodilution, cardiac output and ventilation increased from 5.5 +/- 1.2 to 6.9 +/- 1.2 l/min and from 8.5 +/- 1.4 to 9.6 +/- 1.3 l/min, respectively, although arterial and venous PO2 remained constant. VA/Q mismatching fell slightly but significantly. The hypoxemia observed in subjects suffering from high-altitude excessive polycythemia was attributed to an increased in blood flow perfusing poorly ventilated areas, but without true intra- or extrapulmonary shunt. Hypoventilation as well as a low mixed venous PO2 value may also have contributed to the observed hypoxemia.     

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia

Desplanches, D., H. Hoppeler, L. Tüscher, M. H. Mayet,H. Spielvogel, G. Ferretti, B. Kayser, M. Leuenberger, A. Grünenfelder, and R. Favier. Muscle tissue adaptations ofhigh-altitude natives to training in chronic hypoxia or acute normoxia.J. Appl. Physiol. 81(5):1946-1951, 1996.Twenty healthy high-altitude natives, residentsof La Paz, Bolivia (3,600 m), participated in 6 wk of enduranceexercise training on bicycle ergometers, 5 times/wk, 30 min/session, aspreviously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl.Physiol. 59: 320-327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometricpressure = 500 mmHg; inspired O₂fraction = 0.209); a second group of 10 subjects was trained in acutenormoxia (NT; barometric pressure = 500 mmHg; inspired O₂ fraction = 0.314). Theworkloads were adjusted to ~70% of peak O₂ consumption(O_{2 peak}) measuredeither in hypoxia for the HT group or in normoxia for the NT group.O_{2 peak} determination and biopsies of the vastus lateralis muscle were taken before and afterthe training program.O_{2 peak} in the HTgroup was increased (14%) in a way similar to that in NT sea-levelnatives with the same protocol. Moreover,O_{2 peak} in the NTgroup was not further increased by additionalO₂ delivery during the training session. HT or NT induced similar increases in musclecapillary-to-fiber ratio (26%) and capillary density (19%) as well asin the volume density of total mitochondria and citrate synthaseactivity (45%). It is concluded that high-altitude natives have areduced capillarity and muscle tissue oxidative capacity; however,their training response is similar to that of sea-level residents,independent of whether training is carried out in hypobaric hypoxia orhypobaric normoxia.

     

Central nervous adaptations following 1 wk of wrist and hand immobilization.

Plastic neural changes have been documented in relation to different types of physical activity, but little is known about central nervous system plasticity accompanying reduced physical activity and immobilization. In the present study we investigated whether plastic neural changes occur in relation to 1 wk of immobilization of the nondominant wrist and hand and a corresponding period of recovery in 10 able-bodied volunteers. After immobilization, maximal voluntary contraction torque decreased and the variability of submaximal static contractions increased significantly without evidence of changes in muscle contractile properties. Hoffmann (H)-reflex amplitudes and the ratios of H-slope to M-slope increased significantly in flexor carpi radialis and abductor pollicis brevis at rest and during contraction without changes in corticospinal excitability, estimated from motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation. Corticomuscular coherence measures were derived from EEG and EMG obtained during static contractions. After immobilization, corticomuscular coherence in the 15- to 35-Hz range associated with maximum negative cumulant values at lags corresponding to MEP latencies decreased. One week after cast removal, all measurements returned to preimmobilization levels. The increased H-reflex amplitudes without changes in MEPs may suggest that presynaptic inhibition or postactivation depression of Ia afferents is reduced following immobilization. Reduced corticomuscular coherence may be caused by changes in afferent input at spinal and cortical levels or by changes in the descending drive from motor cortex. Further studies are needed to elucidate the mechanisms underlying the observed increased spinal excitability and reduced coupling between motor cortex and spinal motoneuronal activity following immobilization.     

Cardiovascular adaptations to 10days of cycle exercise

Mier, Constance M., Michael J. Turner, Ali A. Ehsani, andRobert J. Spina. Cardiovascular adaptations to 10 days of cycleexercise. J. Appl. Physiol. 83(6):1900-1906, 1997.We hypothesized that 10 days of training wouldenhance cardiac output (CO) and stroke volume (SV) during peak exerciseand increase the inotropic response to -adrenergic stimulation. Tensubjects [age 26 ± 2 (SE) yr] trained on a cycleergometer for 10 days. At peak exercise, training increasedO₂ uptake, CO, and SV(P < 0.001). Left ventricular (LV)size and function at rest were assessed with two-dimensional echocardiography before (baseline) and after atropine injection (1.0 mg) and during four graded doses of dobutamine. LV end-diastolic diameter increased with training (P < 0.02), whereas LV wall thickness was unchanged. LV contractileperformance was assessed by relating fractional shortening (FS) to theestimated end-systolic wall stress(_ES). Training increased theslope of the FS-_ES relationship (P < 0.05), indicating enhancedsystolic function. The increase in slope correlated with increases inCO (r = 0.71,P < 0.05) and SV(r = 0.70,P < 0.05). The increase in bloodvolume also correlated with increases in CO(r = 0.80, P < 0.01) and SV (r = 0.85, P < 0.004). These datashow that 10 days of training enhance the inotropic response to-adrenergic stimulation, associated with increases in CO and SVduring peak exercise.