Maximal exercise and muscle energy metabolism after recovery from exercise hyperthermia syndrome.

Muscle energy metabolism was studied in 30 subjects after recovery from exercise hyperthermia syndrome (EHTS subjects) and 15 healthy men with identical physical activities. Blood lactate, free fatty acid (FFA), serum creatine kinase activity (CK), and glycerol and the temperature in the auditory duct (T(c)) and on the thumb pad (T(sk)) were measured at rest and during and after maximal exercise on a cycloergometer. The EHTS subjects had a limitation of physical performance, with lowered values for maximal oxygen uptake (VO(2max), P < 0.0005), maximal workload (P < 0.05), and ventilatory threshold (V(t), P < 0.0005). The discrepancy between high plasma concentrations of FFA and the lack of decrease in respiratory ratio (RR) suggests that, in EHTS subjects, a very active release of FFA was not balanced by a proportional increase in catabolism. The increased skin temperature was smaller in EHTS subjects (P < 0.05 at 180 and 200 W). At the end of exercise, auditory duct temperature increase was higher in EHTS subjects than in control subjects (P < 0.05). This study thus showed an impairment of muscle metabolism and an abnormality of thermoregulatory mechanisms. These results may provide insight into the underlying physiopathological disturbance.

Malignant hyperthermia susceptibility revealed by myalgia and rhabdomyolysis during fluoroquinolone treatment.

Fluoroquinolones cause myalgia, but this complication is not clearly documented. We describe a patient who developed myalgia and rhabdomyolysis during fluoroquinolone treatment. The patient was a 33-year-old man treated with norfloxacin for common cystitis. He complained of general muscular fatigue, tendon disorders, and articular pain during treatment. When the antimicrobial agent was stopped, symptoms decreased, with persistence of slight myalgia for 10 days. Rhabdomyolysis was detected. Six months later, investigation by 31P magnetic resonance spectroscopy revealed an oxidative disorder and an abnormal abundance of phosphomonoesters. In vitro contracture tests led to a diagnosis of malignant hyperthermia susceptibility. Our case shows that for any subject presenting myalgia with rhabdomyolysis triggered by fluoroquinolone treatment, the presence of a latent myopathy should be investigated.

Blood ammonia and ventilation at maximal exercise.

This study, intended to evaluate the role of ammonia (NH3) as a ventilatory stimulus, was conducted in three groups of subjects: 14 sedentary individuals, 12 triathletes, 5 patients with a glycolytic deficiency (Mc Ardle disease). All subjects performed maximal exercise tests on a cycle ergometer. Ventilation measured at maximal oxygen consumption (VE 100%) was correlated with lactatemia (lactate 100%) and ammonemia (NH3 100%) in the sedentary group, but only with ammonemia in triathletes, although NH3 100% and lactate 100% were correlated in both groups, which suggests that correlation between VE 100% and NH3 100% is not a false correlation. In patients with Mc Ardle disease, unable to produce lactate during exercise, VE 100% was correlated with NH3 100%. NH3 may act indirectly by increasing the production of lactate in cereberal tissue. Another hypothesis rests on the fact that the catabolism of ammonia leads to an increase in intracerebral glutamate which may act as a ventilatory stimulus.

Impairment of muscle energy metabolism in patients with sleep apnoea syndrome.

Impairment of muscle energy metabolism has been demonstrated in normal subjects with chronic hypoxaemia (altitude chronic respiratory failure). The purpose of this study was to verify the hypothesis that a comparable condition could develop in patients with sleep apnoea syndrome (SAS), considering that they are exposed to prolonged and repeated hypoxaemia periods. Muscle metabolism was assessed in 11 patients with SAS performing a maximal effort on cycloergometer. In comparison with normal subjects, SAS patients reached lower maximal loads [144 +/- 7 vs. 182 +/- 10 W (P < 0.005)] and lower peak oxygen uptakes [26.4 +/- 1.2 vs 33.2 +/- 1.4 ml kg-1 min-1 (P < 0.005)]. Abnormal metabolic features were found: maximal blood lactate concentration was significantly lower than in normal subjects [0.034 +/- 0.004 vs. 0.044 +/- 0.002 mmol l-1 W-1 (P < 0.05)]; and lactate elimination rate, calculated during a 30-min recovery period, was reduced [0.127 +/- 0.017 vs, 0.175 +/- 0.014 mmol l-1 min-1 (P < 0.025)]. The extent of these anomalies correlated with the severity of SAS. The patients also showed higher maximal diastolic blood pressures than normal subjects [104 +/- 5 vs. 92 +/- 4 mmHg (P < 0.05)]. These results can be interpreted as indications of an impairment of muscle energy metabolism in patients with SAS. Decrease in maximum blood lactate concentration suggests an impairment of glycolytic metabolism, while decrease in the rate of lactate elimination indicates a defect in oxidative metabolism. Since no respiratory pathology apart from SAS was found in this group of patients, it seems legitimate to link the genesis of these impairments to repeated bouts of nocturnal hypoxaemia.

Priapism following splenectomy in an unstable hemoglobin: hemoglobin Olmsted beta 141 (H19) Leu-->Arg.

We report a case of severe priapism occurring in a patient with an unstable hemoglobin, Hb Olmsted (beta 141 Leu-->Arg) This is a rare hemoglobin variant, which until now has been reported only once. The clinical course of the 12-year-old boy was characterized by severe hemolytic anemia leading to splenectomy and cholecystectomy at the of 3.5 years. The priapism occurred 8 years after splenectomy, during a hemolytic febrile episode and required aspiration of the corpora cavernosa. This report raises the question of the benefit of splenectomy in patients suffering from a chronic hemolytic anemia such as that due to an unstable hemoglobin. This treatment lowers the frequency and the severity of acute hemolytic attacks, but several cases of vascular complications have been reported after splenectomy.

[Sufficient autotransfusion with a single-use device in experimental vascular surgery]. / Autosuffisance transfusionnelle réalisée au moyen d'un dispositif à usage unique en chirurgie vasculaire expérimentale.

The authors used a disposable original system to recover total blood during surgery and realized 17 transfusions of autologous blood in sheep. No biological or clinical disturbance was observed.

Opposite effects of urea on hemoglobin-oxygen affinity in anemia of chronic renal failure.

We studied the action of urea on the spin-spin relaxation rate of 2,3-diphosphoglycerate (2,3-DPG) phosphorus atoms in normal and uremic erythrocytes. At concentrations from 10 to 60 mM, urea increased the relaxation rates of 2,3-DPG P-3 phosphorus atoms. This evidenced a stronger binding of 2,3-DPG to hemoglobin (Hb), suggesting that the deoxyform of Hb was stabilized. This hypothesis was confirmed by measurements of the association constant of oxygen to hemoglobin (K) in normal erythrocytes in presence of urea concentrations in the range of those observed in uremic patients (30 mM). Indeed, the observed decrease in K suggests that the T structure of hemoglobin is stabilized. By contrast, with higher urea concentrations (120 mM), measurements of P50 showed an increase in the hemoglobin affinity for oxygen (decrease in P50). Moreover, the relaxation rates of 2,3-DPG P-3 phosphorus atoms were not modified, which is consistent with the simultaneous increase of K. This may be attributed to the formation of carbamylated hemoglobin in presence of urea. These results suggest two opposite effects of urea on Hb-O2 affinity: the first reinforces 2,3-DPG-Hb binding and leads to a decrease in O2 affinity; the second, mediated by carbamylation of Hb, hinders the binding of 2,3-DPG and increases the O2 affinity. These findings are consistent with the fact that, despite the presence of carbamylated hemoglobin, uremic patients do not present increased Hb-O2 affinity.

Effect of recombinant human erythropoietin treatment in uremic patients on oxygen affinity of hemoglobin.

Anemia of chronic renal failure is associated with a reduced affinity of hemoglobin for oxygen (Hb-O2 affinity). It has been reported that the correction of renal anemia by recombinant human erythropoietin (rhuEPO) treatment could be associated paradoxically with a further decrease in Hb-O2 affinity. We investigated changes in the compensatory mechanisms of chronic renal anemia during 25 weeks of rhuEPO treatment, in 19 chronic hemodialyzed (HD) patients. There was no significant variation of mean standard P50 (P50std). Average 2,3-diphosphoglycerate (DPG) increased after 13 weeks and remained stable. The large interindividual variations prompted us to study delta P50std and delta Hb. We demonstrated a negative correlation between delta P50std and delta Hb. Thus, P50std increased in patients who did not immediately correct their anemia and decreased in patients whose Hb values rose. These data showed that the major factor influencing variations of Hb-O2 affinity in chronic HD patients treated by rhuEPO is the variation of Hb concentrations. In our study, it was demonstrated that the most important rise in P50std and 2,3-DPG occurred in patients who were late responders to rhuEPO.

Changes in blood ammonia induced by a maximum effort in trained and untrained subjects.

Twelve healthy male volunteers, either trained or untrained, performed a maximal exercise on a cycloergometer. Venous blood samples were taken for analysis during the effort and the following recovery. Blood concentrations of lactate and ammonia, and plasmatic concentrations of alanine, glutamate and glutamine were measured. At the beginning on the effort, ammonia decreased by 32% (P < 0.01) in comparison with its mean level at rest; at 77% and 78% of maximum load there was a steeper ascent of blood ammonia and lactate vs load curve. There was a high correlation (P < 0.001) between ammonia and lactate during exercise. At the end of the effort, these two variables had significantly increased in comparison with their values at rest (P < 0.01 for ammonia and P < 0.001 for lactate), but they did not correlate with VO2max. The negative correlation existing between ammonia and VO2max at the beginning of the recovery period may imply that muscle NH3 release is inversely proportional to the subject's sports training level, this relation being less evident when blood lactate vs VO2max correlation was considered. Increase in blood glutamate level was greater in trained subjects (P < 0.05). This finding suggests that ammonia elimination is favoured by physical training. In conclusion, ammonia measurements during exercise provide a valuable information about muscle cell oxidative capacity.

[The hyperammonemia of exercise; value of automatic measurement]. / L'hyperammoniémie d'effort; intérêt du dosage automatique.

Ammonia blood level (NH3) was measured during maximum exercise performed on cycloergometer, in 11 patients. NH3 measurements through an automatic chemical method (whole blood) were compared to those of the enzymatic reference method (plasma). Automatic analysis made it possible to quickly obtain [NH3] values, that were highly correlated with those of the enzymatic method (P < 0.001). Plasma [NH3] may be calculated from the following equation, where it is expressed versus [NH3] obtained with the automatic method (c anal): [NH3] mumol.l-1 = 0.795. [c] anal.microgram.dl-1 + 5.446.

31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies.

Two patients with mitochondrial encephalomyopathy due to complexes I and IV deficiencies received 150 mg/d of coenzyme Q10 (CoQ). We studied them with a bicycle ergometer exercise test and 31P NMR spectroscopy before and after 10 months of treatment. Before treatment, we observed a low phosphocreatine/inorganic phosphate (PCr/P(i)) resting value along with abnormally high resting lactate concentration. During exercise, there was a pronounced acidosis with delayed kinetics of postexercise recovery for blood lactate, pH, PCr, and PCr/P(i) ratio. Oxygen uptake during exercise was reduced while the lowering of the ventilatory threshold indicated an early activation of glycolysis. After treatment, the bicycle ergometer exercise test indicated a significant improvement with a decrease in resting blood lactate level, an increase in oxygen consumption during exercise, and an increase in the kinetics of lactate disappearance during the recovery period. A shift of the ventilatory threshold to higher workload was present. 31P NMR spectroscopy confirmed the improvement, showing a significant increase in the PCr/P(i) ratio at rest and in the kinetics of recovery for pH, PCr, and PCr/P(i) ratio following exercise in patient 1. For patient 2, we observed a less pronounced acidosis correlated with a lesser amount of Pi produced during exercise. These observations indicate an improvement of mitochondrial function and a shift from high to low glycolytic activity in both patients consequent to CoQ treatment.

[The contribution of effort tests in the evaluation of factors related to dyspnea in pneumonology]. / Apport de l'épreuve d'effort dans l'appréciation des facteurs de la dyspnée en pneumologie.

Forty nine patients suffering from respiratory disorders underwent an exercise test carried out on a bicycle ergometer (n = 45) or by walking rapidly on flat or inclined ground (n = 4). The respiratory restrictions on effort were correlated with a degree of dyspnoea (stages 1 to 4) established by a questionnaire. The analysis of the effort test had consequences of practical importance: in effect, in this study, nearly half the patients benefited from advice orientated in particular towards the level of activity which would be suitable for them, and to reduction in their weight.

[Influence of chronic smoking on leukocytes]. / Influence du tabagisme chronic sur les leucocytes.

The authors showed a significant increase in total leukocyte count (2p less than 0.001), neutrophil concentration (2p less than 0.001) and lymphocyte concentration (2p less than 0.01) in 21 chronic smokers compared to 22 non-smokers. However, only the total leukocyte count and the neutrophil count proved to be correlated to carboxyhemoglobin saturation. Slightly different hypotheses are proposed to explain the increase in leukocyte count: the carbon monoxide and/or the carboxyhemoglobin acts directly on peripheral blood leukocytes or indirectly, via the adrenalin secretion. The average leukocyte count in smokers corresponds to the upper borderline in nonsmokers; therefore, it seems pertinent to take into consideration the number of cigarettes smoked per day when assessing a smoker's leukocytosis.

[Polycythemia vera and 2,3-diphosphoglycerate deficiency. Apropos of 2 cases]. / Polyglobulie vraie et déficit en 2,3-diphosphoglycérate. A propos de deux observations.

Two cases of mistaken diagnosis of polycythemia vera leading to useless or dangerous treatments exemplify the old saying "primum non nocere". Absolute polycythemia which lacks both the specific characteristics of polycythemia vera and lacks both the specific characteristics of polycythemia vera and any tumoral etiology (particularly renal) but is accompanied with normal arterial oxygen saturation should suggest the possibility of an anomalous hemoglobin with increased affinity for oxygen. Two alternative mechanisms may be present: anomalous hemoglobins due to the substitution of an amino acid or, as in the two reported cases, a deficit in intraerythrocytic 2,3 diphosphoglyceride. In both cases, polycyhthemia is compensative and does not warrant therapy.

[Tobacco consumption and carboxyhemoglobin levels in blood donors]. / Tabagisme et carboxyhémoglobine chez les donneurs de sang.

The authors studied the tobacco consumption of 283 blood donors and its consequences. 151 were nonsmokers and 132 were smokers (47.7% smoke more than 10 g/day). Their mean HbCO level was 4.3 +/- 0.2% (highest level 15%). HbCO levels are significantly correlated with daily tobacco consumption (p less than 0.001) and can be estimated with the following regression equation: HbCO% = 0.176 (tobacco in grams/day) + 1.976. For a similar consumption, inhalers exhibit significantly (p less than 0.001) higher HbCO levels than noninhalers and the increase is significantly higher (p less than 0.02) in inhalers who smoked 1 h or less prior to blood sampling. High HbCO levels have two consequences: in the donors they have caused a tobacco polycythemia syndrome and in the recipients they have caused acute problems in cases of massive blood transfusion and cardiovascular surgery with extracorporeal circulation.

Assessment of the central chemosensitivity in man under transient or progressive hypercapnia.

In healthy man, the central chemosensitivity to CO2 was studied after depression of the arterial chemoreflex drive by inhalation of pure oxygen. The effectiveness of the functional decrease of arterial chemoreceptor function was assessed by the delayed hyperventilation which followed transient inhalation of hypercapnic gas mixtures for 3 or 5 breaths in hyperoxic conditions. In such a case the first significant increase in tidal volume (VT) occurred 13.9 +/- 3.2 (SE) sec later than the early change in this variable measured in normoxic conditions. The stimulus strength was estimated by the change in CO2 partial pressure in end-tidal alveolar gas (delta PETCO2). The central chemosensitivity (SCO2), defined as the ratio between change in ventilation (delta V) and delta PETCO2, was assessed either by transient inhalation of gas mixtures containing 5 to 8% CO2 in pure O2 ("varying transients") or by progressive hypercapnia (rebreathing in pure O2). In both cases, the first significant change in ventilation was due to an increase in VT, but, for a given delta PETCO2, VT changes were higher during rebreathing than after transient hypercapnia; (2) The respiratory frequency (fR) was progressively enhanced during rebreathing (shortening of expiratory duration in all cases and of inspiratory time in some subjects) but the ventilatory rhythm diminished after transient stimulation as soon as delta PETCO2 reached one kPa, and this was due to an increase in inspiratory duration; (3) The associated changes in VT and fR during rebreathing could explain that SCO2 values given by this method were 5.2 times greater than after transient hypercapnia ("varying tests"). The differences are discussed in terms of, (1) isolated changes in arterial PCO2 or associated decrease in pH of the cerebrospinal fluid; (2) changes in brain blood flow, and (3) stimulation of lung stretch receptors by the important increase in VT during rebreathing.

[Smoking and carbon monoxide consumption (author's transl)]. / Tabagisme et monoxyde de carbone.

Among 2,069 patients subjected to pulmonary function tests, 20% were smokers with a mean oxyhemoglobin (HbCO) level of 5.2%. Similar values for HbCO (2.4%) were found in non-smokers and ex-smokers. A positive correlation was observed between daily tobacco consumption and HbCO level, i.e. HbCO = 0.123 (g/day) + 3.433. For a similar consumption (16 g/day), smokers who inhaled the smoke had a significantly higher level of HbCO than smokers who did not (5.8 vs. 4.7%). The interval separating the time when the last cigarette was smoked from HbCO measurement is of utmost importance: for a similar tobacco consumption (10 g/day) HbCO ranged from 6.5 +/- 0.5% when the interval was 1 h to 4.6 +/- 0.3% when it was 3 h (p < 0.005). In some cases, there were discrepancies between the number of cigarettes smoked as indicated by the subjects and the measured levels of HbCO. Possible inhalation of exogenous CO from other sources than smoking or increased production of endogenous CO could account for these differences.

[Hemoglobin oxygen combining capacity power. Reproducibility, variability; the effect of carboxyhemoglobin (author's transl)]. / Le pouvoir oxyphorique. Précision et variabilité de la mesure; influence du taux de carboxyhémoglobine.

Hemoglobin oxygen combining power (HOCP) was measured in blood samples of 41 non smoking subjects and 36 smokers. The reproductibility and the varibility of this value were established (maximal variability was 2,5% in individual measurement). When the oxygen carrying capacity is reported to total hemoglobin (Hbt.), these two groups are not significantly different (1,344 +/- 0,004 ml O2 g-1 Hbt--n = 77-). However, when oxygen carrying capacity is reported to functional hemoglobin (Hbf = Hbt -- HbCO) there is a significative difference between smokers and non smokers (Student's t test 2 p less than 0,001) (1,404 +/- 0,005 ml O2 Hbf -- n = 77-).