Muscle pH recovery after high intensity cycle exercise in malignant hyperthermia susceptible subjects.
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Biomedical subjects
Publications and source records attributed to L Jorfeldt.
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Six subjects susceptible to malignant hyperthermia (MHS) and seven control subjects exercised for 4 min at 120% of their calculated maximal oxygen uptake on a bicycle ergometer. Mean (SEM) muscle pH, measured with a needle-tipped electrode in the vastus lateralis muscle, decreased from a resting value of 7.16 (0.04) to 6.78 (0.04) after exercise in the control group, and from 7.15 (0.05) to 6.56 (0.05) in the MHS group (P less than 0.01 compared with control group). A further decrease in muscle pH to 6.68 (0.06) by 5 min after exercise occurred in the control group, followed by incomplete recovery to 7.06 (0.04) 30 min after exercise. In the MHS group, however, muscle pH decreased to 6.45 (0.05) 5 min after exercise before recovering slowly to only 6.64 (0.07) after 30 min (P less than 0.01 compared with control group). There was no difference in muscle temperature, venous pH or venous lactate concentrations between the two groups. The results show that there is abnormal recovery of muscle pH after short-duration, high-intensity exercise in MHS subjects.
10 subjects with Hb Linköping (beta 36 Pro greater than Thr), a high-affinity hemoglobin variant, with a P50 of 2.2 kPa (16.5 mm Hg) were investigated before and 3-4 days after normovolemic hemodilution. Blood hemoglobin concentration decreased from 176 +/- 13 (SD) to 146 +/- 15 g l-1 and the red cell volume from 2.77 +/- 0.83 to 2.23 +/- 0.67 l. Maximal oxygen consumption decreased slightly by 2.7 +/- 3.8 ml min-1 kg-1 and maximal exercise power by 11 +/- 23 W; these changes were, however, not statistically significant. Maximal heart rate was unchanged (-1.1 +/- 6.4 beats min-1) while submaximal heart rate was consistently increased on comparable loads after hemodilution compared to before. The exercise ECG was normal both before and after hemodilution. Capillary lactate levels at exercise were always higher after hemodilution than before. Cerebral blood flow was normal both before and after hemodilution in all subjects but one who had a high flow. The grey matter blood flow increased slightly but significantly by 8.6 +/- 10.3 ml min-1 100 g-1 from before to after hemodilution. The results indicate that subjects with Hb Linköping have only limited benefit from their increased blood hemoglobin concentration.
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We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.
The impact of the bolus dose and the basal infusion during insulin pump treatment on pre- and post-prandial hyperinsulinemia was investigated in 8 insulin-dependent diabetic patients. Frequent determinations of free insulin in blood and simultaneous determination of glucose consumption with euglycaemic clamp technique were made after a bolus of 5 U with or without basal infusion and after 10 U with basal infusion. The maximum free insulin level was reached after 75, 65 and 105 min respectively (median; NS), whereas 50% of the maximum was reached already after 15, 10, and 12.5 min (NS). The fall in free insulin after the peak was slower in all protocols compared to the breakfast induced peak in healthy subjects and it was slower with than without basal infusion (p less than 0.03). Glucose consumption followed the free insulin profiles. We conclude, that administration of a subcutaneous bolus with an insulin pump gives a dose-related free insulin peak that is unphysiological in comparison with the normal meal-related insulin secretion. Preprandial hyperinsulinemia, found after a prescribed interval of 30 min between injection and meal, as well as postprandial hyperinsulinemia, increased with a greater bolus indicating that adjustments of timing of meals and snacks may be necessary when the dose is changed. Furthermore, the insulin substitution with external pumps would probably be more physiological if the basal supply was interrupted after a bolus.
Post-operative fatigue is a well-known clinical problem even after uncomplicated surgery. In the multifaceted post-operative state, several factors other then the surgical trauma may influence muscular function, such as an insufficient nutritional intake. The aim of this study was to investigate the effect of fasting on work capacity and voluntary skeletal muscle function. Eight healthy lean volunteers, age range 25-43 years, were studied the day before starvation, at the end of the fasting period of 5 days, and after another 3-4 days on a normal diet. Hand grip strength was assessed as maximum voluntary contraction (MVC) and physical working capacity was investigated with successively increased work load on a cycle ergometer until near exhaustion. After 5 days of total starvation, MVC remained unchanged but physical working capacity was reduced from 220 +/- 18 watt to 199 +/- 22 watt (p < 0.05). Corresponding heart rate, estimated effort and leg tiredness were not changed. A poor nutritional intake per se may therefore be a less important factor causing post-operative muscle fatigue than the operation itself.
1. In eight healthy volunteers we compared leg blood flow, as determined in a calf segment by strain-gauge plethysmography, with the flow measured by a constant-rate infusion of Indocyanine Green dye into the femoral artery. The representativeness of the calf segment was evaluated by complementary measurements with additional strain gauges attached around the proximal and distal crural and the distal thigh segments (n = 6). Furthermore, we investigated the influence of the catheterization procedure and a simulated vascular puncture, as well as repeated venous occlusions, on blood flow and on arterial and femoral venous substrate concentrations and blood gases (n = 8). 2. The leg blood flow measured by dye dilution was 0.31 +/- 0.03 litre/min (mean +/- SEM). The blood flow in the calf segments was 14.8 +/- 1.6 ml min-1 litre-1 and no difference between the legs was observed. Extended to the whole leg the plethysmographic blood flow was 0.17 +/- 0.01 litre/min and thus lower (43 +/- 7%, P less than 0.001) than the flow determined by the indicator-dilution method. Blood flow in the legs was not influenced by catheterization or sham punctures of the vessels or by repeated venous occlusions. 3. The concentrations of glucose, lactate and glycerol, as well as blood gas variables, in arterial and femoral venous blood did not change during the study or decreased so slightly (pH and lactate) that the arteriovenous difference was not influenced. 4. We conclude that the blood flow of the total leg cannot be satisfactorily estimated from strain-gauge plethysmography of a single calf segment.(ABSTRACT TRUNCATED AT 250 WORDS)
The metabolic effects of the local administration of propranolol were determined in seven patients undergoing cholecystectomy. Measurements were carried out in the early postoperative period before and after infusion of 2 mg of intraarterial propranolol into the femoral artery of one leg using the other leg as control. Blood flow and arterio-venous concentration differences for oxygen, glucose, lactate, alanine, glycerol and total FFAs were determined. Uptake and release of FFAs were determined by using a tracer technique. The statistical analyses were based on differences between the test and the control leg in changes following the blockade. Glycerol release was significantly more suppressed in the test leg than in the control leg. No difference between the legs was seen in the uptake of oxygen, FFA and glucose or the release of lactate and alanine. The arterial concentration of propranolol was 6.07 +/- 0.72 ng ml-1 (mean +/- SEM). This study indicates that a local beta-blockade by intra-arterial propranolol infusion after surgery slightly reduces the postoperative lipolysis in leg tissues but does not influence or only marginally influences leg blood flow and oxygen uptake or the exchange of glucose, lactate and alanine after moderate surgical trauma.
Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.
Eighteen patients with advanced chronic obstructive pulmonary disease (COPD), 8 with chronic respiratory failure (CRF group) and 10 without (NCRF group) were investigated using arterial blood analyses before, during and after progressive exercise. Dynamic spirometry was also performed. The arterial blood was analyzed for free fatty acids (FFA), glycerol, 3-hydroxybutyrate, alanine, glucose and lactate concentrations as well as PO2 and PCO2. In the CRF group the concentrations of FFA, glycerol and 3-hydroxybutyrate were lower and the concentrations of glucose and lactate higher than in the NCRF group. Analysis of the whole material revealed that the arterial FFA, glycerol and 3-hydroxybutyrate concentrations correlated positively to arterial PO2 and negatively to arterial PCO2 at rest, as well as during exercise and recovery. The results indicate that lipolysis is decreased in patients with advanced COPD with chronic respiratory failure. An altered glucose metabolism may also exist in these patients.
Eighteen patients with advanced COPD, 8 with chronic respiratory failure (RF) and 10 without (nonRF, NRF) were investigated using spirometry, arterial blood gas analysis and biopsies taken from the quadriceps femorls muscle. The biopsies were analysed for ATP, creatine phosphate (CrP), creatine (Cr), lactate and glycogen content. Muscle fibre composition was also studied. Low concentrations of ATP, glycogen and CrP were found in the RF patients. Significant correlations were found between muscle metabolites and arterial blood gas values with the strongest correlation between muscle glycogen and arterial PO2 (r = 0.70; p less than 0.001). A very low percentage of "oxidative" type I muscle fibres was found in both groups. Possible mechanisms causing depletion of muscle metabolites are discussed.
In order to investigate how vibration affects endurance during muscular contraction, knee-joint extension efforts were performed with and without superimposed vibrations. Fourteen healthy non-smoking 20-year-old males performed maximal isometric and sustained knee-joint extension efforts (angle 90 degrees) in sitting posture three times with each leg, with or without vibration. The tests were done once with each leg in a randomly chosen order. The frequency of the vibration was 20 Hz and the acceleration 20 m/s2 RMS, applied in a horizontal sagittal direction to the ankle. The endurance was defined as the time in seconds that it took for the exerted force to decrease by 10% of the initial value. The endurance time averages 22.5 s without vibration and 15.8 s with vibration. The vibratory stress reduced endurance by 6.7 +/- 1.84 s (mean +/- SEM) (P less than 0.005). The difference in maximal force recorded initially was 34 +/- 1.9 N (P less than 0.1). Our conclusion is that vibration may decrease the endurance of maximal och sustained isometric muscular contraction.
With a view to investigating how vibration affects dynamic working capacity, exercise tests were performed both with and without superimposed vibration. The performance of 8 healthy, non-smoking 20-year-old males exercising on a cycle ergometer at a constant load was studied on four occasions, with and without vibration in a randomly chosen order. The frequency of the vibration, which was applied vertically through the pedals, was 20 Hz and the acceleration was 20 m/s2 RMS. The handlebars and saddle of the cycle were insulated from the vibration. The exercise time averaged 47 min with vibration and 60 min without. The vibratory stress reduced the exercise time by 13 +/- 2.9 min (mean +/- SEM) (P less than 0.005). The average heart rate when the exercise was stopped was 180.3 beats/min with vibration and 180.7 beats/min without. The systolic blood pressure after 20 min averaged 188 mm Hg with vibration and 187 mm Hg without vibration. Both with and without vibration, 6 of the 8 subjects stated that leg fatigue was the cause of their inability to continue pedalling longer. Our conclusion is that in the performance of dynamic muscular work endurance may decrease under the influence of vibration.
Twelve healthy men drank 0.8 g of ethanol per kilogram of body weight during 30 min after an overnight (10 h) fast. At nine exactly timed intervals (30-390 min after the start of drinking), blood was sampled through indwelling catheters in cubital veins on the left and right arms. Immediately thereafter, capillary blood was sampled from fingertips on the left and right hands. The blood ethanol concentration (BAC) was determined by headspace gas chromatography. The SD for alcohol determinations in venous blood, including the left vs right arm sampling variation, was 30 mg/L (range 8.3-83 mg/L), whereas for capillary blood the SD was 35 mg/L (range 11-60 mg/L). This difference much exceeded the purely analytical errors: SD = 2.67 mg/L for venous blood and 14.2 mg/L for fingertip blood. During the first 60 min after the subjects started to drink, capillary BAC exceeded venous BAC, the mean difference at 30 min being 136 mg/L (range 36-216 mg/L). In the postabsorptive state later than 60 min after drinking, venous BAC exceeded capillary BAC [mean difference 58 mg/L (range 0.0-170 mg/L]), the values for venous and capillary BAC crossing 37 min (range 6-77 min) after the end of drinking. Apparently, the source of blood analyzed, venous or capillary, must be considered in clinical pharmacokinetic studies of ethanol.
The relationship between striated muscle tissue oxygenation during hyper- and hypocapnia, and lactate levels and venous pO2 (pvO2) was studied in a rabbit model. Seven rabbits were ventilated with constant volume during ether anesthesia, and arterial pCO2 (paCO2) was varied by addition of CO2. Muscle tissue oxygenation was measured with a multichannel electrode on the striated muscle surface, the results presented as oxygen pressure distributions (OPD:s). The principal result during hypercapnia (paCO2 9.9 kPa) was a tendency toward increased mean oxygen pressure (ptxO2) of the OPD; OPD shape was normal in 5/7 runs. Arterial lactates (aLa) decreased. During duplicate hypocapnia to paCO2 2.9 and 2.8 kPa ptxO2 decreased, but only in 4/14 runs were tissue oxygen pressures (ptO2) below 0.6 kPa found. OPD shape was scattered in 6/14 runs indicating disturbance in regulation of tissue oxygenation (but without signs of hypoxia). An increase in aLa was found, as well as a decrease in arterio-venous lactate difference (avDLa). Lacking direct blood flow measurements, these two results could not be interpreted as increased lactate efflux per se. Muscle lactates (mLa) were high but, on average, not higher than a control group. A decrease in pvO2 was seen during hypocapnia. Subgrouping OPD:s according to shape and presence of low ptO2 values did, however, suggest that lactate was released in cases with low ptO2 values: a covariation was seen in runs with low oxygen pressures between high arterial and muscle lactates, decreased avDLa and pvO2; runs with scattered OPD:s had only intermediately high lactates and low avDLa and pvO2 when compared to normally shaped OPD:s. In this study, hypercapnia influenced striated muscle tissue oxygenation only to a minor degree while hypocapnia influenced it more but not as much as expected. Only when low oxygen pressures were present in the OPD:s were there indications of peripheral lactate release.
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It has been speculated that, in malignant hyperthermia-susceptible (MHS) individuals, an abnormality of sympathetic activity is seen during stressful situations, such as exercise. The authors investigated whether muscle metabolism in eight MHS subjects, at rest and during moderate and heavy short-term exercise, is different then that in normals. Leg exchange of energy substrates (glucose, lactate, and glycerol) was quantified by measuring leg blood flow and arterial-venous concentration differences. Muscle biopsies were also performed, and ATP, glycogen, and lactate were analyzed. Catecholamines and oxygen uptake were also measured. The study was performed at rest with subjects in the supine position and during two periods (40% and 80% of the subjects maximal oxygen uptake, respectively) on a bicycle ergometer. The principal finding of the study was that there was no major difference in oxygen uptake or leg exchange of glucose, lactate, and glycerol between MHS-subjects and previously standard normals during different grades of exercise. Furthermore, muscle metabolites and plasma catecholamines did not differ between the groups. This study indicates a normal sympathetic activity and muscle metabolism in MHS subjects during rest, as well as during moderate and severe exercise. The authors' results do not support the opinion that persons with positive in vitro tests for MH should restrict their physical activity.