Exercise following a sport induced concussion.

OBJECTIVE: To determine if an athlete's capacity to perform exercise is impaired following concussion and whether this would be reflected by an altered heart rate response. METHODS: Of the 14 concussed athletes, nine missed playing time as a direct result of their concussion and five did not. The concussed athletes performed an exercise protocol on a cycle ergometer within 72 hours of being asymptomatic at rest and a second test at 5 days following the previous assessment. Matched controls (n = 14) were tested using the same time line. The exercise protocol consisted of a 2 minute warm up, 10 minute, low-moderate intensity, steady state exercise session, and a high intensity interval protocol. The interval protocol consisted of a 40 second high intensity bout, followed by a 40 second rest period. This protocol continued until the participant had reached volitional fatigue. RESULTS: The number of exercise bouts completed was not significantly different from their matched controls. However, concussed athletes who missed playing time had a significantly higher heart rate during the steady state exercise session. During this same period, they also exhibited a greater rise in heart rate over time. CONCLUSION: These findings indicate that exercise capacity is unaffected in concussed athletes who are asymptomatic at rest. However, their heart rate response to submaximal exercise is increased.

Differential effects of des IGF-1 on Erks, AKT-1 and P70 S6K activation in mouse skeletal and cardiac muscle.

Alterations in the degree of the phosphorylation of ERKI/2, Akt-1 and p70 S6K in mouse skeletal and cardiac muscle was examined in vivo following an intraperitoneal injection of des IGF-I. Plasma levels of insulin, IGF-I and glucose were measured. The administration of des IGF-I had no effect on plasma levels of insulin, or IGF-I, but plasma glucose levels were decreased about 50% (p < 0.01). In both skeletal and cardiac muscle, des IGF-I increased the phosphorylation of Akt-1 at Ser 473 (p < 0.01) with no change in the phosphorylation of p44 and p42 MAP kinases at Thr202/Tyr204. The phosphorylation of p70 S6K at Thr421/Ser424 was increased in skeletal muscle (p < 0.01), but not in cardiac muscle. The phosphorylation of the nuclear transcription factor CREB phosphorylation at Ser 133 was not significantly changed in either skeletal or cardiac muscle. Des IGF-I increased the phosphorylation of the transcription factor FKHR in cardiac muscle only (p < 0.05). These data demonstrate that the administration of des IGF-I had differential effects on the activation of the MAP kinase and PI 3-kinase pathways in mouse skeletal and cardiac muscle.

Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats.

The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are responsible for >50% of nutrient-stimulated insulin secretion. After being released into the circulation, GIP and GLP-1 are rapidly inactivated by the circulating enzyme dipeptidyl peptidase IV (DP IV). The use of DP IV inhibitors to enhance these insulinotropic hormonal axes has proven effective on an acute scale in both animals and humans; however, the long-term effects of these compounds have yet to be determined. Therefore, we carried out the following study: two groups of fa/fa Zucker rats (n = 6 each) were treated twice daily for 3 months with the DP IV inhibitor P32/98 (20 mg.kg(-1).day(-1), p.o.). Monthly oral glucose tolerance tests (OGTTs), performed after drug washout, revealed a progressive and sustained improvement in glucose tolerance in the treated animals. After 12 weeks of treatment, peak OGTT blood glucose values in the treated animals averaged 8.5 mmol/l less than in the controls (12.0 +/- 0.7 vs. 20.5 +/- 1.3 mmol/l, respectively). Concomitant insulin determinations showed an increased early-phase insulin response in the treated group (43% increase). Furthermore, in response to an 8.8 mmol/l glucose perfusion, pancreata from controls showed no increase in insulin secretion, whereas pancreata from treated animals exhibited a 3.2-fold rise in insulin secretion, indicating enhanced beta-cell glucose responsiveness. Also, both basal and insulin-stimulated glucose uptake were increased in soleus muscle strips from the treated group (by 20 and 50%, respectively), providing direct evidence for an improvement in peripheral insulin sensitivity. In summary, long-term DP IV inhibitor treatment was shown to cause sustained improvements in glucose tolerance, insulinemia, beta-cell glucose responsiveness, and peripheral insulin sensitivity, novel effects that provide further support for the use of DP IV inhibitors in the treatment of diabetes.

Recovery of trout myocardial function following anoxia: preconditioning in a non-mammalian model.

Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout (Oncorhynchus mykiss) working heart preparation at 10 degrees C to examine whether prior exposure to 5 min of anoxia (PO(2) < or = 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low P(out) [15 min of anoxia at an output pressure (P(out)) of 10 cmH(2)O]; 2) anoxia with high P(out) [10 min of anoxia at a P(out) of 10 cmH(2)O, followed by 5 min of anoxia at P(out) = 50 cmH(2)O]; and 3) preconditioning [5 min of anoxia at P(out) = 10 cmH(2)O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high P(out) group]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low P(out) decreased maximum stroke volume (V(s max)) by 15% and maximum cardiac output (Q(max)) by 23%. When the anoxic workload was increased by raising P(out) to 50 cmH(2)O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in V(s max) and Q(max) that were observed in the anoxia with high P(out) group and any anoxia-related increases in the input pressure (P(in)) required to maintain resting Q (16 ml. min(-1). kg(-1)). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.

Aging and glucose transporter plasticity in response to hypobaric hypoxia.

In order to gain a better understanding of tissue plasticity with aging, we investigated the adaptive responses of young and adult animals to both 7 and 28 days of hypobaric hypoxia. Senescence is associated with a decreased tolerance to hypoxia that may be related to an age-associated decline in glucose transporter system plasticity. In addition, elucidation of the factors contributing to the decreased hypoxia tolerance with aging may provide insights into ischemia for older individuals. Following 7 days of hypobaric hypoxia, soleus and plantaris muscle Glut-4 contents were increased 23-45% with a greater increase in the soleus muscle for both ages. A parallel decline in insulin receptor content was observed in both the young (soleus 56%; plantaris 74%) and adult (soleus 26%; plantaris 37%) animals over 7 days. Similar responses were observed in cardiac muscle over 7 days, with increases in content for both Glut-4 (young 25%; adult 23%) and Glut-1 (young 33%; adult 44%) and a decline in insulin receptor (young 27%; adult 15%). Following 28 days of hypobaric hypoxia, adult soleus, and both age groups plantaris muscle Glut-4 and insulin receptor contents were similar to control. However, the young soleus muscle Glut-4 and insulin receptor contents were still significantly different from control but only altered about half as much as following 7 days of exposure to hypobaric hypoxia. In contrast to what was observed for skeletal muscle, cardiac Glut-4 content was further elevated in both young (33%) and adult (44%) animals with longer exposure to hypobaric hypoxia. The young animals also showed a further decrease in heart insulin receptor content, while the adult did not. Interestingly, cardiac Glut-1 levels returned to normal values for both young and adult animals with prolonged exposure. An adaptive coregulation of Glut-4 and insulin receptor content appears to optimize the use of glucose during chronic hypobaric hypoxia within these tissues. Differences are apparent in the magnitude and time course of the response between young and adult animals.

IGF-1 bioavailability is increased by resistance training in older women with low bone mineral density.

We investigated if long-term resistance training would increase insulin-like growth factor-1 (IGF-1) bioavailabilty at rest in older women (68+/-1 years) with low bone mineral density. IGF-1 levels were significantly lower (P<0.05), and insulin-like growth factor binding proteins -1 and -3 (IGFBP-1 and IGFBP-3) significantly higher than an age-matched healthy normal group. Resistance training resulted in significant (P<0.05) increases in repetition maximums across all exercises (range 41-78%). Resting IGF-1 levels were significantly (P<0.05) elevated (70%) by the resistance training whereas no significant changes occurred in IGFBP-1 and IGFBP-3 levels. IGFBP-1/IGF-1 and IGFBP-3/IGF-1 ratios were significantly decreased (approximately - 50%) as a result of resistance training (P<0.05). Thus, IGF-1 bioavailability was increased as a result of resistance training induced increases in IGF-1 levels in older women with low bone mineral density. These alterations in the IGF-1 system may be contributing to the significant strength gain observed with the resistance training in this population.

Resistance of the aged myocardium to exercise-induced chronic changes in glucose transport related protein content.

The effects of acute exercise on myocardial content of glut-1 and glut-4 transporters, insulin and IGF-1 receptors were assessed in control and chronically exercised 24-month-old C57B1/6 mice. Myocardial glut-1, glut-4, insulin receptor (Ins R) and insulin like growth factor-1 receptor (IGF-1 R) protein levels were unaffected by 36 weeks of chronic exercise. However, myocardial protein content of glut-1, but not glut-4, was increased 12 h following an acute exercise bout in control (46%) and chronically exercised (83%) aged animals. This increased glut-1 response following acute exercise occurred despite the finding that the chronic exercise failed to increase cardiac or skeletal muscle oxidative capacity as indicated by no change in citrate synthase activity. Myocardial IGF-1 R content was unaffected by acute exercise whereas Ins R protein content was decreased 12 h following the acute exercise bout in the chronically exercised (-52%) and control (-28%) animals. The effect of acute exercise on the protein content of glut-1 and Ins R was 80 and 84% greater respectively, in the chronically exercised animals. This suggests that the amplitude of the expression of these two proteins may be increased by chronic exercise, thus constituting a form of adaptation.

Influence of physical activity on plasma insulin-like growth factor-1 and insulin-like growth factor binding proteins in healthy older women.

It was examined whether physical activity could alter the bioavailability of insulin-like growth factor-1 (IGF-1) which is dependent upon plasma IGF-1 and insulin-like growth factor binding protein (IGFBPs) levels. The potential role that growth hormone (GH) and insulin play in this process was also examined. Seven healthy 62-69-year-old women performed four bouts of physical activity on separate occasions at either a low (L; heart rate = 100 bpm) or moderate intensity (M; heart rate = 120 bpm) for either 25 (S) or 50 (L) min (LS, low intensity/short duration; LL, low intensity/long duration; MS, moderate intensity/short duration; ML, moderate intensity/long duration). GH levels were elevated immediately following the physical activity from 1.3 to 2.6-fold (P < 0.05) whereas IGF-1 levels were not affected by any activity condition. Plasma insulin levels decreased about 35% under all activity conditions (P < 0.05). Plasma levels of IGFBP-1 (BP-1) were decreased immediately following the ML (-47%; P < 0.05) and the LL (-21%) activity bouts and remained lower than initial values 1 h after these activity bouts (-25 and 34%, respectively, P < 0.05). The ML exercise bout resulted in significant (P < 0.05) increases in IGFBP-2 (BP-2) and IGFBP-3 (BP-3) immediately following activity (+31, and +30%, respectively) and these binding proteins remained elevated following the activity (+28, and +48%, respectively). No relationship was found between any changes in plasma GH or insulin, and changes in plasma IGFBPs. Thus, moderate intensity physical activity of long duration may modulate the bioavailability of IGF-1 in the elderly via alterations in BP-1, -2 and -3. However, changes in circulating levels of GH, insulin or IGF-1 do not appear to be regulating IGF-1 bioavailability in response to physical activity.

Age-associated alterations in cardiac and skeletal muscle glucose transporters, insulin and IGF-1 receptors, and PI3-kinase protein contents in the C57BL/6 mouse.

We investigated potential age-related changes in cardiac and skeletal muscle protein contents of glut-4 and glut-1 transporters, insulin and insulin-like growth factor-1 (IGF-1) receptors, and phosphatidylinositol 3-kinase (PI3-kinase) in the C57B1/6 mouse. Myocardial glut-4 content increased four- to five-fold between mid- to late-adulthood with no further age-related changes. Increases in myocardial glut-1 preceded the increase in glut-4 and was of a much smaller magnitude (25-40%). Skeletal muscle glut-4 was also increased (38-49%) and no further changes were noted between adulthood and old age. Cardiac insulin receptor and the p85 alpha subunit of PI3-kinase both declined by about 40%, whereas the skeletal muscle content of these two proteins were unaffected by aging. Cardiac (-23 to -24%) and skeletal muscle (-40 to -62%) IGF-1 receptor levels were decreased in adult and old animals with senescence being associated with a further decrease in cardiac IGF-1 receptor levels to 20% of controls. A two- to three-fold increase in both basal and maximal in vitro autophosphorylation of the cardiac insulin and IGF-1 receptors by their respective ligands was observed with senescence. It appears that cardiac and skeletal muscle demonstrate differential responses in terms of the magnitude and temporal responses of age-associated alterations in glucose transport related protein contents in the C57B1/6 mouse.

Restoration of insulin-like growth factor I action in skeletal muscle of old mice.

This study examined the effects of long-term chronic voluntary wheel exercise on the ability of insulin-like growth factor I (IGF-I) to stimulate rates of protein synthesis in the soleus muscle of old C57Bl/6 mice. Factors contributing to any changes in hormone action were analyzed at the level of hormone receptor binding, protein content, and gene expression. Chronic exercise resulted in an increased skeletal muscle mass (10-22%) and a 56% increase in IGF-I-stimulated rates of protein synthesis (P < 0.05). IGF-I receptor mRNA was increased 46%, IGF-I receptor protein was increased 65%, and the binding capacity of the IGF-I high-affinity site was increased sixfold (P < 0.05) with chronic wheel exercise. Insulin receptor protein content was decreased 35% (P < 0.05), whereas GLUT-4 content was increased 47% with chronic exercise (P < 0.05). This study demonstrates that old animals retain a plasticity for IGF I receptor and glucose transporter expression that may have valuable physiological consequences.

Exercise during puberty and NMU induced mammary tumorigenesis in rats.

Previously we have shown that exercising rats prior to administration of 50 mg NMU/kg (high dose) significantly decreased tumor multiplicity, but not incidence or latency. We hypothesized that the dose of NMU saturated the system such that the exercise intervention was overshadowed. Therefore, the purpose of this investigation was to determine if exercise would have a more pronounced effect with a moderate dose of 37.5 mg NMU/kg. Female Sprague Dawley rats were divided into sedentary and exercised groups. The rats were exercised five times per week from 21 to 50 days of age on a progressive treadmill training program with a final workload of 18 m/min at 15% incline for 60 min a day. At 50 days of age all rats were given an i.p. injection of NMU at 37.5 mg/kg body weight. The experiment was terminated 22 weeks post carcinogen administration. Although there was no difference in terms of tumor incidence, multiplicity, or latency between the two groups, the tumor growth rate (0.107+/-0.025 vs. 0.043+/-0.009 g/day) and final tumor weight (3.2+/-0.74 vs. 1.2+/-0.34 grams) were significantly higher in the exercised animals. IGF-I receptor (9.4+/-96 vs. 10.5+/-57 per microg protein) and estrogen receptor (18.4+/-1.14 vs. 19.6 + 1.6 per microg protein) levels were not significantly different in tumors from exercised animals compared to those from sedentary animals. For both sets of tumors, correlation between estrogen receptor content and growth rate is positive, while the correlation between IGF-I receptor content and growth rate is negative. The results of this study suggest that exercise prior to NMU administration does not affect tumor burden but does alter tumor growth rate, which is not due to differences in estrogen receptor or IGF-I receptor content.

Acute exercise attenuates age-associated resistance to insulin-like growth factor I.

This study examined the influence of acute exercise on the ability of insulin-like growth factor I (IGF-I) to stimulate protein synthesis in an isolated in vitro soleus muscle preparation in female C57Bl/6 mice aged 5, 12, and 24 mo. Gastrocnemius muscles were analyzed for IGF-I receptor mRNA levels, IGF-I receptor number, and IGF-I receptor binding capacities and affinity constants. IGF-I (20 nM) was unable to stimulate rates of protein synthesis in the 12- and 24-mo-old control animals. These animals demonstrated declines in IGF-I receptor protein. After acute exercise, IGF-I receptor mRNA was elevated, IGF-I receptor protein levels were unaffected, and rates of protein synthesis were stimulated by IGF-I in the 12- and 24-mo-old animals. Acute exercise significantly increased IGF-I receptor binding capacity and affinity constants in the 24- but not the 12-mo-old animals. We conclude that acute exercise can restore the action of IGF-I in aged muscle, potentially by increasing the IGF-I receptor binding capacity and affinity or as a result of factors downstream of the IGF-I receptor.

The potential role of insulin-like growth factors in skeletal muscle regeneration.

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues have been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed.

Exercise during adolescence and its effects on mammary gland development, proliferation, and nitrosomethylurea (NMU) induced tumorigenesis in rats.

The purpose of this investigation was to determine the effects of moderate intensity exercise training during peripuberty on nitrosomethylurea (NMU) induced mammary tumorigenesis and to assess the effects of this activity on mammary epithelial cell proliferation and mammary gland development in rats. Female Sprague Dawley rats were divided into two groups, sedentary and exercised. The rats were exercised five times per week from 21 to 50 days of age on a progressive treadmill training program with a final workload of 18 m/min at 15% incline for 60 min a day. At fifty days of age eight rats from each group were sacrificed to determine the effects of exercise on mammary gland labelling index and development scores. The remaining animals were given NMU at a concentration of 50 mg/kg body weight. The experiment was terminated 24 weeks post carcinogen administration, and cancer incidence, multiplicity, and latency were analyzed. The total tumor number per group was reduced by exercise (58 vs. 33 carcinomas p < 0.05). This corresponded to a significantly higher number of tumors/animal in the sedentary rats compared to those that were exercised prior to NMU administration. However latency period (124.9 +/- 4.3 vs. 125.2 +/- 6.4) and final incidence (68.9% vs. 61.5%) were not significantly different in sedentary vs. exercised rats. There were no significant differences in mammary gland developmental scores (4.1 +/- 0.24 vs. 4.4 +/- 0.26) or labelling index of mammary epithelial cells in either ducts or lobuloaveolar units (ductal 41.5 +/- 4.7 vs. 39.4 +/- 5.7; lobuloalveolar 38.5 +/- 4.1 vs. 47.7 +/- 5.7) between the two groups. The results of this study suggest that although exercise prior to carcinogen administration has an effect on mammary tumorigenesis, these effects do not appear to be related to exercise-induced changes in mammary gland development.

The effects of ATP, inorganic phosphate, protons, and lactate on isolated myofibrillar ATPase activity.

The purpose of this study was to examine the effects of lactate, protons, inorganic phosphate, and ATP on myofibrillar ATPase activity. Myofibrils were isolated from carp (Cyprinius carpio L.) fast-twitch white muscle, and myofibrillar ATPase activities were assessed under maximal activating calcium levels (pCa 4.0) at 10 degrees C in reaction media containing metabolic profiles similar to those seen in fatiguing muscles. The Ca(2+)-activated ATPase activity was assessed by an ATP regenerating assay that coupled the myofibrillar ATPase to pyruvate kinase and lactate dehydrogenase. This assay allowed the effects of ATP, inorganic phosphate, protons, and lactate on myofibrillar ATPase activity to be assessed. The coupled assay was found to give similar myofibrillar ATPase kinetics, with the exception of higher maximal activities, to those seen with a standard end-point assay. Myofibrillar ATPase activity was depressed by 35% when ATP concentrations were lowered to 2.5 mM. Lowering ATP levels to 0.5 mM reduced the myofibrillar ATPase activities by 85%. Lactate had no effect on myofibrillar ATPase activities. Inorganic phosphate levels up to about 20 mM significantly decreased the myofibrillar ATPase activities, after which further increases in inorganic phosphate content had minimal effects. The changes in ATPase activities were related to total inorganic phosphate, not to the content of diprotonated inorganic phosphate. Myofibrillar ATPase activity was highest at pH 7.5 and lowest at pH 6.0. The interactive effects of low ATP, decreased pH, and high inorganic phosphate levels were not additive, giving similar decreases in activity to those produced by increased inorganic phosphate levels alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of skeletal muscle metabolism by enzyme binding.

The random diffusion mechanism is usually assumed in analyzing the energetics of specific pathways despite the findings that enzymes associate with each other and (or) with various membranous and contractile elements of the cell. Successive glycolytic enzymes have been shown to associate in the cytosol as enzyme complexes or bind to the thin filaments. Furthermore, the degree of glycolytic enzyme interactions have been shown to change with altered rates of carbon flux through the pathway. In particular, the proportions of aldolase, phosphofructokinase, and glyceraldehyde phosphate dehydrogenase bound to the contractile proteins have been found to increase with increased rates of glycolysis. In addition, decreasing pH and ionic strength are also associated with an increase in glycolytic enzyme interactions. The kinetics displayed by interacting enzymes generally serve to enhance their catalytic efficiencies. The associations of the glycolytic enzymes serve to enhance metabolite transfer rates, increase the local concentrations of intermediates, and provide for regulation of activity via effectors. Therefore these interactions provide an additional mechanism for regulating glycolytic flux in skeletal muscle.

Overall and regional lung function in Andean natives after descent to low altitude.

Overall lung volumes, regional residual volume to total lung capacity ratio (RVr/TLCr), regional ventilation (V/V) and perfusion (Q/V) were measured at 670 m in six Quechua Indians on days 2 and 37 after leaving their high-altitude homes (3500-4500 m). On day 2 the lung volumes averaged between 124 and 137% of those predicted for low-altitude residents (LAR) and there were no significant changes on day 37. Although overall RV/TLC was not different from the predicted value for LAR, RVr/TLCr on day 2 was higher at the top and lower at the bottom of the lungs compared to LAR. Regional Q/V and V/V were not different from LAR on day 2, or on day 37. However, the ratio of Q/V at the bottom to Q/V at the top was 2.36 on day 2 and 2.84 on day 37 (P less than 0.05). On day 2 hemoglobin- and volume-corrected diffusing capacity was 145% of the value predicted for LAR and this fell to 135% predicted on day 37 (P less than 0.05). Natives of high altitude reportedly have more alveoli that LAR and this could explain the greater vital capacity toward the bottom of the lung if the alveolar proliferation is concentrated there. This might also lower pulmonary vascular resistance at the bottom which would explain the normal Q/V distribution, even though pulmonary artery pressure may be increased.

On the role of actomyosin ATPases in regulation of ATP turnover rates during intense exercise.

Actomyosin ATPase is the dominant ATP sink during muscle work. Its catalytic capacities in fast-twitch oxidative glycolytic fibers have long been known to exceed by about 3-fold those of slow-twitch oxidative fibers, but the relative contributions to control of metabolic rates during exercise have never been closely examined. We compared fast-twitch oxidative glycolytic and slow-twitch oxidative fibers that displayed similar mitochondrial abundance (similar activities of mitochondrial marker enzymes). During short-term, but near maximum, aerobic exercise, fast-twitch oxidative glycolytic fibers displayed ATP turnover rates that were 2-4 times higher than for slow-twitch oxidative fibers (despite similar mitochondrial metabolic capacities), implying a large ATPase contribution to control of maximum metabolic rate. Fluxes through the ATP in equilibrium ADP + Pi cycle were extremely well regulated; at the lower limit, the forward flux exceeded the backward flux by only 0.06%, whereas at the upper limit, ATPase rates exceeded ATP synthesis rates by 0.12%. This very high precision of energy coupling could not be easily explained by standard metabolic regulation models.

Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level.

Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.

Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders.

Two metabolic features of altitude-adapted humans are the maximal O2 consumption (VO2max) paradox (higher work rates following acclimatization without increases in VO2max) and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at increasing altitude). To assess underlying mechanisms, we studied six Andean Quechua Indians in La Raya, Peru (4,200 m) and at low altitude (less than 700 m) immediately upon arrival in Canada. The experimental strategy compared whole-body performance tests and single (calf) muscle work capacities in the Andeans with those in groups of sedentary, power-trained, and endurance-trained lowlanders. We used 31P nuclear magnetic resonance spectroscopy to monitor noninvasively changes in concentrations of phosphocreatine [( PCr]), [Pi], [ATP], [PCr]/[PCr] + creatine ([Cr]), [Pi]/[PCr] + [Cr], and pH in the gastrocnemius muscle of subjects exercising to fatigue. Our results indicate that the Andeans 1) are phenotypically unique with respect to measures of anaerobic and aerobic work capacity, 2) despite significantly lower anaerobic capacities, are capable of calf muscle work rates equal to those of highly trained power- and endurance-trained athletes, and 3) compared with endurance-trained athletes with significantly higher VO2max values and power-trained athletes with similar VO2max values, display, respectively, similar and reduced perturbation of all parameters related to the phosphorylation potential and to measurements of [Pi], [PCr], [ATP], and muscle pH derivable from nuclear magnetic resonance. Because the lactate paradox may be explained on the basis of tighter ATP demand-supplying coupling, we postulate that a similar mechanism may explain 1) the high calf muscle work capacities in the Andeans relative to measures of whole-body work capacity, 2) the VO2max paradox, and 3) anecdotal reports of exceptional work capacities in indigenous altitude natives.