Ergometer exercise in myoadenylate deaminase deficient patients

Summary Three patients with primary myoadenylate deaminase deficiency were subjected to exercise on a bicycle ergometer at 125 W for 30 minutes. Blood samples prior to, during, and at the end of exercise were analyzed for lactate, ammonia, and hypoxanthine. In addition, urinary hypoxanthine excretion was measured. In these patients the serum lactate level increased to concentrations between 7.9 and 9.0 mmol/1 at the end of exercise whereas the mean lactate level in nine control subjects at the end of exercise was 3.3 mmol/l (range 1.1–8.1 mmol/l). There was no difference to control subjects in the exercise-induced increase in plasma levels of ammonia and hypoxanthine or in the increase in urinary hypoxanthine excretion. The findings support the hypothesis of a reduced substrate supply to the citric acid cycle in myoadenylate deaminase deficiency. The normal formation of ammonia and hypoxanthine excludes a marked loss of adenine nucleotides in working muscles in these patients.Abbreviations ATP adenosine triphosphate - AMP adenosine monophosphate - IMP inosine monophosphate - MAD myoadenylate deaminase - NCP non-collagen protein Dedicated to Prof. Dr. N. Zöllner on the occasion of his 70th birthday     

Metabolism of D-ribose administered continuously to healthy persons and to patients with myoadenylate deaminase deficiency

Summary D-ribose was administered orally or intravenously over at least 5 h to eight healthy volunteers and five patients with myoadenylate deaminase deficiency. Intravenous administration rates were 83, 167, and 222 mg/kg/h, which were well tolerated but oral administration of more than 200 mg/kg/h caused diarrhea. The average steady state serum ribose level ranged between 4.8 mg/100 ml (83 mg/kg/h, oral administration) and 81.7 mg/100 ml (222 mg/kg/h, intravenous administration). Serum glucose level decreased during ribose administration. The intestinal absorption rate of orally administered ribose was 87.8%–99.8% of the intake at doses up to 200 mg/kg/h without first pass effect. Urinary losses were 23% of the intravenously administered dose at 222 mg/kg/h. Ribose appeared to be excreted by glomerular filtration without active reabsorption; a renal threshold could not be demonstrated. The amount of ribose transported back from the tubular lumen depended on the serum ribose level. There was no difference in ribose turnover in healthy subjects and patients with MAD deficiency.Abbreviations MAD myoadenylate deaminase - i.v. intravenous(ly)     

Effects of prolonged exercise at a similar percentage of maximal oxygen consumption in trained and untrained subjects

Summary Six trained male cyclists and six untrained but physically active men participated in this study to test the hypothesis that the use of percentage maximal oxygen consumption (% , as a normalising independent variable is valid despite significant differences in the absolute of trained and untrained subjects. The subjects underwent an exercise test to exhaustion on a cycle ergometer to determine and lactate threshold. The subjects were grouped as trained (T) if their exceeded 60 ml ·kg^–1 ·min^–1, and untrained (UT) if their was less than 50 ml · kg^–1 · min-^–1. The subjects were required to exercise on the ergometer for up to 40 min at power outputs that corresponded to approximately 50% and 70% The allocation of each exercise session (50% or 70% was random and each session was separated by at least 5 days. During these tests venous blood was taken 10 min before exercise (–10 min), just prior to the commencement of exercise (–10 min), after 20 min of exercise (20 min), at the end of exercise and 10 min postexercise (+ 10 min) and analysed for concentrations of cortisol, [Na⁺], [K⁺], [CI^–], glucose, free fatty acid, lactate [la-], [NH₃], haemoglobin [Hb] and for packed cell volume. The oxygen consumption ( ) and related variables were measured at two time intervals (14–15 and 34–35 min) during the prolonged exercise tests. Rectal temperature was measured throughout both exercise sessions. There was a significant interaction effect between the level of training and exercise time at 50% for heart rate ( _c:) and venous [la^–]. At 70% and ventilation ( ) for the T group and and carbon dioxide production for the UT group increased significantly with time and there was a significant interaction effect forf _c, ]Ia^–1], [Hb] and [NH₃]. The change in body mass at 50% and 70% was significantly greater in the T group. The present study found that when two groups of male subjects with different absolute exercised at a similar percentage of some effector responses were significantly different, questioning the validity of selecting % as a normalising independent variable.     

Muscle metabolism and red cell ATP/ADP concentration during bicycle ergometer in patients with AMPD-deficiency

Summary 6 patients with AMPD-deficiency and 6 control subjects performed exercise on a bicycle ergometer until heart rate was 200 minus age. During exercise the increase of ammonia plasma concentrations was reduced in AMPD-deficient patients compared with that of control subjects. Plasma concentrations of lactate, pyruvate, inosine, hypoxanthine and xanthine increased during exercise in both groups. The concentrations of lactate, inosine and hypoxanthine were lower in AMPD-deficient patients during exercise, the difference was not significant. In AMPD-deficient patients the ATP-concentrations of red blood cells increased during exercise in contrast to control subjects, whereas the ADP amount did not change significantly.Our data suggest that in AMPD-deficient-patients AMP is mainly reduced to adenosine during exercise resulting in decreased ammonia concentrations. The increased concentrations of ATP in red blood cells may be the consequence of increased phosphorylation.Abbreviations AMP, ADP, ATP adenosine-5-monophosphate, -diphosphate, -triphosphate - AMPD AMP deaminase (myoadenylate deaminase)     

Lipid metabolism during exercise I: Physiological and biochemical characterization of normal healthy male subjects in relation to their physical fitness

Summary On the basis of maximal oxygen uptake ( O₂ max) 18 normal, healthy men were divided into two groups of equal size: moderately trained subjects (MTR) each having O₂ max below 65.0 ml·min^–1·kg^–1 body weight (54.0±8.3) and well trained subjects (WTR), whose O₂ max exceeded 65.0 ml·min^–1·kg^–1 body weight (69.2±4.1). The WTR group had slightly (non significant, n.s.) higher percentage of slow twitch, oxidative (SO) fibers in M. vastus lateralis and higher (n.s.) activities of cytochrome c oxidase (CytOx), succinate dehydrogenase (SDH), 3-hydroxyacyl-CoA-dehydrogenase (HADH), and citrate synthase (CS), while lactate dehydrogenase (LDH) activity was lower (n.s.). In the MTR group only, the SO-%, and the activities of CytOx, SDH and HADH correlated positively with O₂ max, and LDH negatively with O₂ max. These correlations were not significant in the WTR group possibly because of the adaptations produced by training in this group. Multiple regression analysis was used to elucidate the best combination of variables to explain the variance in O₂ max. The best model consisted of the sum of relative activities of oxidative muscle enzymes (CytOx, SDH, HADH, CS), muscle LDH activity, body fat content (% F) and lean body mass. This model explained 69% of the variance in O₂ max; and of the individual variables % F was of utmost importance.     

Fat and carbohydrate metabolism during low intensity exercise: Effects of the availability of muscle glycogen

Summary Four subjects were studied during exercise at 50% of maximum oxygen uptake after a normal diet, after a low carbohydrate (CHO) diet following exercise-induced glycogen depletion, and after a high CHO diet. This regime has previously been shown to cause changes in the amount of glycogen stored in the exercising muscles. Metabolic and respiratory parameters were measured during the exercise. The respiratory exchange ratio, blood lactate, blood pyruvate, blood glucose and plasma triglycerides were lower than normal following the low CHO diet and higher than normal following the high CHO diet. Plasma free fatty acids and plasma glycerol were higher than normal after the low CHO diet and lower than normal after the high CHO diet. The contribution of CHO to metabolism was less than normal after the low CHO diet and greater than normal after the high CHO diet. The altered availability of FFA does not appear to be a result of the variations in the blood lactate content. R. J. M. is in receipt of a Science Research Council Postgraduate Studentship award     

Effects of various beverages on the hormones involved in energy metabolism during exercise in the heat in previously dehydrated subjects

The objective of our study was to examine the effects of beverage content on hormone responses involved in fuel substrate metabolism (catecholamines, insulin and glucagon) in previously dehydrated subjects exercising at a moderate intensity in the heat. Six healthy men walked for 60-min on five occasions at 50% maximal oxygen uptake in a warm environment (dry bulb temperature 35?±?0.2°C, relative humidity 20%). On each occasion, the subjects were dehydrated before exercise (loss of 2% body mass) by passive controlled hyperthermia, which led to a reduction in plasma volume (PV) of about ?5% to ?9%. In one session, the subjects exercised without rehydration (Dh). In the other sessions, four beverages (650?ml) were given just before the exercise: mineral water (W), a 60?g?·?l^?1 glucose and 1.2?g?·?l^?1 NaCl solution (GS), a 60?g?·?l^?1 maltodextrin solution, and a 60?g?·?l^?1 maltodextrin and 1.2?g?·?l^?1 NaCl solution. Compared to Dh and W, carbohydrate supply with or without NaCl induced a higher glycaemia (P?P?P?P?P?相似文献   

Effect of endurance and sprint exercise on the sensitivity of glucose metabolism to insulin in the epitrochlearis muscle of sedentary and trained rats

Summary The effects of two types of acute exercise (1 h treadmill running at 20 m· min^–1, or 6 × 10-s periods at 43 m · min^–1, 0° inclination), as well as two training regimes (endurance and sprint) on the sensitivity of epitrochlearis muscle [fast twitch (FT) fibres] to insulin were measured in vitro in rats. The hormone concentration in the incubation medium producing the half maximal stimulation of lactate (la) production and glycogen synthesis was determined and used as an index of the muscle insulin sensitivity. A single period of moderate endurance as well as the sprint-type exercise increased the sensitivity of la production to insulin although the rate of la production enhanced markedly only after sprint exercise at 10 and 100 U· ml^–1 of insulin. These effects persisted for up to 2 h after the termination of exercise. Both types of exercise significantly decreased the muscle glycogen content, causing a moderate enhancement in the insulin-stimulated rates of glycogen synthesis in vitro for up to 2 h after exercise. However, a significant increase in the sensitivity of this process to insulin was found only in the muscle removed 0.25 h after the sprint effort. Training of the sprint and endurance types increased insulin-stimulated rates of glycolysis 24 h after the last period of exercise. The sensitivity of this process to insulin was also increased at this instant. Both types of training increased the basal and maximal rates of glycogen snythesis, as well as the sensitivity of this process to insulin at the 24^th following the last training session. It was concluded that in the epitrochlearis muscle, containing mainly FT fibres, both moderate and intensive exercise (acute and repeated) were effective in increasing sensitivity of glucose utilization to insulin. Thus, the response in this muscle type to increased physical activity differs from that reported previously in the soleus muscle, representing the slow-twitch, oxidative fibres in which sprint exercise did not produce any changes in the muscle insulin sensitivity.     

The effects of a high carbohydrate diet on postprandial energy expenditure during exercise in rats

Summary Whether or not a high intake of carbohydrate increases postprandial energy expenditure during exercise was studied in rats. The rats were meal-fed regularly twice a day (0800–0900 hours and 1800–1900 hours) on either a high carbohydrate (CHO) (carbohydrate/fat/protein = 70/5/25, % of energy) or high fat (FAT) (35/40/25) diet for 12 days. On the final day of the experiment, all of the rats in each dietary group were fed an evening meal containing equal amounts of energy (420 kJ · kg^–1 body mass). After the meal, they were divided into three subgroups: pre-exercise control (PC), exercise (EX), and resting control (RC). The PC-CHO and PC-FAT groups were sacrificed at 2030 hours. The EX-CHO and EX-FAT groups were given a period of 3-h swimming, and then sacrificed at 2330 hours. The RC-CHO and RC-FAT groups rested after the meal and were sacrificed at 2330 hours. Total energy expenditure during the period 1.5 h from the commencement of exercise was higher in EX-CHO than in EX-FAT. The respiratory exchange ratio was also higher in EX-CHO than in EX-FAT, suggesting enhanced carbohydrate oxidation in the former. Compared with both PC-FAT and RC-FAT, the liver glycogen content of EX-FAT rats was significantly decreased by exercise. On the other hand, the liver glycogen content of both EX-CHO and RC-CHO was higher than that of PC-CHO rats. The glycogen content of soleus muscle of EX-FAT was slightly decreased during exercise, however, that of EX-CHO increased significantly. Thus postprandial energy expenditure during exercise was higher in the rats fed the CHO diet than in those fed the FAT diet, which could have been related to the increase of both liver and muscle glycogen storage during exercise in the former.     

Effects of exercise on nasal airflow resistance in healthy subjects and in patients with asthma and rhinitis

We studied the effect of exercise on nasal airflow resistance (Rnaw) and the relationship between exercise-induced asthma (EIA) and Rnaw. Rnaw was obtained by measurement of flow through the nose and mouth (in series) at constant inflow pressure. In seven healthy subjects, there were statistically significant decreases in Rnaw (39.5 +/- 6.3 and 49.0 +/- 8.2%; p less than 0.05) and no change in forced expired volume immediately after exercise on a bicycle ergometer at both 75 W and 100 W, but there was no significant difference between these two resistance changes. At 75 W, Rnaw returned to pre-exercise level at 15-20 min after exercise. At 100 W, Rnaw remained below the pretest value 30 min after exercise. In eleven asthmatics, treadmill running for 1, 2 and 6 min caused significant decreases (p less than 0.05) in Rnaw up to 44.8 +/- 3.3%, reaching levels similar to those of controls after exercise. With 6 min exercise, four of nine patients developed EIA; these subjects had allergic rhinitis as well, and recovery to pretest valued tended to be quicker than in those without EIA. In healthy subjects at both ergometer workloads, there was a rebound increase in Rnaw in 40-50% of the subjects appearing 20-30 min after exercise. In the patients, there was a rebound increase in Rnaw in about 60% of the subjects 5-10 min after exercise. Both for healthy subjects and patients, the rebound increase in Rnaw was smaller at the higher workloads.     

Effects of methionine sulphoximine treatment on renal amino acid and ammonia metabolism in rats

Renal glutamine metabolism in relation to ammoniagenesis has been extensively studied during chronic metabolic acidosis, when arterial glutamine levels are reduced. However, little is known about the effects of reduced glutamine delivery on renal glutamine and ammonia metabolism at physiological systemic pH values. Therefore, a model of decreased arterial glutamine concentrations at normal pH values was developed using methionine sulphoximine (MSO). Renal glutamine and ammonia metabolism was measured by determining fluxes and intracellular concentrations after an overnight fast in ether anaesthetized normal rats, MSO-treated rats and their pair-fed controls. Moreover, fluxes and intracellular concentrations of several other amino acids were determined concomitantly. After 2 and 4 days of MSO treatment, arterial glutamine concentrations were reduced to 55%, while arterial ammonia concentrations increased by 70%. Kidney glutamine uptake reduced, but systemic pH was unchanged. Fractional extraction of glutamine remained unchanged, suggesting that also in vivo net uptake of glutamine by the kidney at subnormal levels is related to arterial glutamine concentrations. As a result, at day 2 but not at day 4, the kidney reduced the net release of ammonia into the renal vein and thus reduced net renal ammonia addition to body ammonia pools. Therefore at day 2, the kidney seems to play an important role in adaptation to both hyperammonaemia and hypoglutaminaemia.     

Effects of a rapid change in muscle glycogen availability on metabolic and hormonal responses during exercise

Summary To evaluate the metabolic and hormonal adaptations following a rapid change in muscle glycogen availability, 14 subjects had their muscle glycogen content increased in one leg (IG) and decreased in the other (DG). In group A (n=7), subjects exercised on a bicycle ergometer at 70% maximal oxygen uptake for 20 min using the DG leg. Without resting these same subjects exercised another 20 min using the IG leg. Subjects in group B (n=7) followed the same single-leg exercise protocol but in the reverse order. In order to get some information on the time sequence of these possible adaptations, blood samples were collected at rest and at the beginning and the end of each exercise period (min 5, 20, 25, and 40). Results indicated that 5 min after the switch from the DG leg to the IG leg. transient increases in plasma free fatty acids (1.20 to 1.39 meq·l^–1) and serum insulin (10.1 to 12 mU·l^–1) concentrations occured. Between minute 25 and 40 of exercise, the DG to IG switch was accompanied by a decrease in free fatty acids and glycerol concentrations as well as an increase in lactate levels. An opposite response was observed in the IG to DG condition during the same time span. Plasma norepinephrine, epinephrine, glucagon, and serum cortisol concentrations were not significantly affected by the leg change. These results suggest a rapid preferential use of muscle glycogen when available and a time lag in the response of the extramuscular substrate mobilization factors.     

大鼠烧伤早期肝细胞能量代谢改变及药物作用的观察

目的观察烧伤早期不同复苏条件下，肝细胞能量代谢的变化以及保护细胞药物-爱维治对肝细胞结构和能量代谢的影响。方法采用30％TBSAⅢ度大鼠烧伤模型，检测烧伤后立即补液、延迟补液及药物治疗情况下，肝组织及全血ATP含量、血清戊二醛水平的变化，并应用电镜观察肝细胞结构的改变。结果不论立即补液还是延迟补液，伤后肝组织ATP含量均明显下降，以延迟补液组为重，血清丙二醛水平升高，在延迟补液组还观察到肝细胞结构的明显异常；应用爱维治治疗可明显升高肝组织及全血ATP含量，降低血清丙二醛水平，并使肝细胞结构得到改善。结论烧伤早期肝细胞能量代谢受到抑制，延迟补液加重能量代谢紊乱；早期应用爱维治具有改善肝细胞能量代谢和保护细胞结构的作用。     

Influence of codeine on lobeline-induced respiratory reflexes and sensations and on ventilation with exercise in healthy subjects

In 15 healthy subjects, the effect of 60 mg oral codeine and placebo was examined on intravenously injected lobeline-elicited respiratory reflexes and sensations. Its influence was also studied on ventilation and appearance of distressful respiratory sensations with modest but incremental exercise. After placebo, tachypnoea and respiratory sensations were evoked with 12.1 ± 1.9 μg/kg of lobeline i.v. (mean threshold dose) and after codeine, by significantly higher doses i.e., 18.0 ± 3.1 μg/kg (P < 0.05). Additionally after codeine, in response to incremental doses of lobeline the respiratory reflex was notably attenuated and the magnitude of respiratory sensations, subdued. Dry cough seen in 66% of the subjects with suprathreshold doses of lobeline i.e., 22.0 ± 3.4 μg/kg (mean), appeared post codeine, with significantly higher doses i.e., 27.0 ± 3.9 μg/kg (mean) (P < 0.05) and in a fewer subjects (60%). Mean increase in minute ventilation at the end of 8 min of incremental treadmill walking after codeine was 21% less than after placebo (P < 0.05); 60% of the subjects continued to walk for an additional 4 min and the onset of respiratory discomfort was delayed by 1-5 min. This is the first report of an attenuation of lobeline-elicited respiratory reflexes and sensations that are attributable to J receptors (pulmonary C fibres) by a pharmacological entity. It also suggests that codeine decreased these receptors' known contribution to respiratory augmentation and motor inhibition during exercise, which was seen as a delay in the onset of, and a decrease in the magnitude of respiratory discomfort during treadmill walking and an increase in the duration walked by more than half the subjects.     

Effects of alpha-phenyl-N-tert-butyl nitrone (PBN)on brain cell membrane function and energy metabolism during transient global cerebral hypoxia-ischemia and reoxygenation-reperfusion in newborn piglets

We sought to know whether a free radical spin trap agent, alpha-phenyl-N-tert-butyl nitrone (PBN) influences brain cell membrane function and energy metabolism during and after transient global hypoxia-ischemia (HI) in the newborn piglets. Cerebral HI was induced by temporary complete occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min, followed by release of carotid occlusion and normoxic ventilation for 1 hr (reoxygenation-reperfusion,RR). PBN (100 mg/kg) or vehicle was administered intravenously just before the induction of HI or RR. Brain cortex was harvested for the biochemical analyses at the end of HI or RR. The level of conjugated dienes significantly increased and the activity of Na+, K+ -ATPase significantly decreased during HI,and they did not recover during RR. The levels of ATP and phosphocreatine (PCr)significantly decreased during HI, and recovered during RR. PBN significantly decreased the level of conjugated dienes both during HI and RR, but did not influence the activity of Na+, K+ -ATPase and the levels of ATP and PCr. We demonstrated that PBN effectively reduced brain cell membrane lipid peroxidation, but did not reverse ongoing brain cell membrane dysfunction nor did restore brain cellular energy depletion, in our piglet model of global hypoxic-ischemic brain injury.     

Effects of magnesium sulfate on dynamic changes of brain glucose and its metabolites during a short-term forced swimming in gerbils

This investigation examined the acute effects of magnesium on the dynamic changes of brain glucose, lactate, pyruvate and magnesium levels in conscious gerbils during forced swimming. Gerbils were pretreated with saline (control group) and magnesium sulfate (90 mg kg⁻¹, intraperitoneal injection) before a 15 min forced swimming period. The basal levels of glucose, pyruvate, lactate, and magnesium in brain dialysates were 338 ± 18, 21 ± 2, 450 ± 39, and 2.1 ± 0.1 μM, respectively, with no significant difference between groups. Magnesium levels were found slightly higher (but not significant) in the magnesium-treated group. However, brain glucose and pyruvate levels in the control group decreased to about 50 and 60% of the basal level (P = 0.01) after swimming, respectively. Pretreatment with magnesium sulfate immediately increased glucose levels to about 140% of the basal level, and increased pyruvate levels to about 150% of the basal level during forced swimming (P = 0.01). Both glucose and pyruvate levels returned to the basal level after 30 min of the recovery. The lactate levels of the control group increased to about 160% of the basal level (P = 0.01) during swimming, whereas pretreatment with magnesium sulfate attenuated lactate levels to 130% of the basal level (P = 0.01). Magnesium supplementation may be beneficial because it provides an additional glucose source and may also promote the recovery of energy substrates in the brain during and after forced exercise. In order to achieve optimal physical performance, further investigation as to dosage of magnesium supplementation is needed.     

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease

Aim: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. Methods: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. Results: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent K_m for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 μm , P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts (P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O₂ kg^?1 min^?1 (P < 0.05) only in the COPD group. Conclusion: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power.     

High-energy phosphate metabolism in the calf muscle of healthy humans during incremental calf exercise with and without moderate cuff stenosis

It is known that the relevance of a peripheral stenosis for muscle function increases with exercise. Our intention was to investigate the impact of a moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on high-energy phosphate (HEP) metabolism during isotonic, incremental calf exercise. Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity-encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten healthy male volunteers. Each leg underwent four increments of calf exercise (2, 3, 4 and 5 W) followed by recovery during separate exercise sessions with and without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution of 10 s. VEPC MRI was performed at the end of each increment during separate sessions. During all increments, we detected significant differences (P < 0.05) in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis between the sessions without and with CS. Regarding the time courses of the PCr, inorganic phosphate (Pi) and pH level, we observed significant differences (P < 0.002) during exercise and recovery. During both conditions, the end-increment PCr levels as well as blood flow correlated significantly with the mechanical power. The PCr time constants during exercise significantly correlated with the intramuscular pH, but not with blood flow or mechanical power. However, the PCr recovery time constants correlated significantly with blood flow and end-exercise pH. Our study shows that reduction of blood flow due to a peripheral stenosis results in a prolongation of PCr time constants, decreased PCr and pH level as well as increased Pi level during exercise. We believe that 31P MRS during incremental exercise might provide additional information for assessing the relevance of a peripheral stenosis and its impact on muscle function.     

Effects of dead space loading on neuro-muscular and neuro-ventilatory coupling of the respiratory system during exercise in healthy adults: implications for dyspnea and exercise tolerance

We examined the effects of dead space loading (DSL) on ventilation (V˙E), neural respiratory drive (EMGdi%max, diaphragm EMG expressed as a % of maximal EMGdi), contractile respiratory muscle effort (Pes,tidal%P(Imax), tidal esophageal pressure swing expressed as a % of maximal inspiratory Pes) and exertional dyspnea intensity ratings in 11 healthy adults with normal spirometry. Subjects completed, in random order, symptom-limited incremental cycle exercise tests under control (CTRL) and DSL (500 ml) conditions. Compared with CTRL, DSL decreased exercise tolerance by 20-25%; increased exertional dyspnea intensity ratings in direct proportion to concurrent increases in EMGdi%max, Pes,tidal%P(Imax) and V˙E; and had little/no effect on the inter-relationships between EMGdi%max, Pes,tidal%P(Imax) and V˙E during exercise. In conclusion, DSL was associated with an earlier onset of intolerable dyspnea; however, neuro-muscular and neuro-ventilatory coupling of the respiratory system remained relatively preserved during exercise in the presence of an increased external dead space. Under these circumstances, DSL-induced increases in exertional dyspnea intensity ratings reflected, at least in part, the awareness of increased neural respiratory drive, contractile respiratory muscle effort and ventilatory output.     

Experimental acute hypoxia in healthy subjects: evaluation of systolic and diastolic function of the left ventricle at rest and during exercise using echocardiography

To clarify whether or not systolic and diastolic function of the human left ventricle (LV) were decreased during acute hypoxia, at rest and with exercise, 14 healthy male volunteers [age 25.9 (SD 3.0) years, height 182.9 (SD 7.1) cm, body mass 75.9 (SD 6.9)kg] were examined using M-mode and 2D-mode echocardiography to determine the systolic LV function as well as Doppler-echocardiography for the assessment of diastolic LV function on 2 separate test days. In random order, the subjects breathed either air on 1 day (N) or a gas mixture with reduced oxygen content on the other (H; oxygen fraction in inspired gas 0.14). Measurements on either day were made at rest, several times during incremental cycle exercise in a supine position (6-min increments of 50 W, maximal load 150 W) and in 6th min of recovery. Corresponding measurements during N and H were compared statistically. Arterial O₂ tension (P _aO₂) was normal on N-day. All subjects showed a marked acute hypoxia at rest [P _aO₂, 54.5 (SD 4.6) mmHg], during exercise and recovery on H-day. The latter was associated with tachycardia compared to N-day. All echocardiographic measurements at rest were within the limits of normal values on both test days. Ejection time, end-systolic and end-diastolic left ventricular dimensions as well as the thickness of left posterior wall and of interventricular septum showed no statistically significant influence of H either at rest or during exercise. Stroke volume and cardiac output were always higher on H-day, which could be attributed to a slight reduction in end-systolic volume with unaffected end-diastolic volume as well as to increased heart rates. Among the indices of systolic LV function the fractions of thickening in the left ventricular posterior wall and interventricular septum showed no differences between H and N at rest or during exercise. However, fibre shortening, ejection fraction and mean circumferential fibre shortening were increased on H-day on all occasions. The mitral-valve-Doppler ratio, the index of diastolic LV function, was decreased with H at rest, showed a more pronounced reduction during exercise and was still lower in 6th min of recovery compared to N-day. It was concluded that with acute hypoxia of the severity applied in this study left ventricular systolic function in our healthy subjects showed a pronounced improvement and left ventricular diastolic function was reduced, both at rest and with exercise.