Unexplained exertional limitation: characterization of patients with a mitochondrial myopathy.

Exercise intolerance is a common complaint, the cause of which often remains elusive after a comprehensive evaluation. In this report, we describe 28 patients with unexplained dyspnea or exertional limitation secondary to biopsy-proven mitochondrial myopathies. Patients were prospectively identified from a multidisciplinary dyspnea clinic at a tertiary referral center. All patients were without underlying pulmonary, cardiac, or other neuromuscular disorders. Patients underwent history, physical examination, complete pulmonary function testing, respiratory muscle testing, cardiopulmonary exercise testing, and muscle biopsy. Results were compared with a group of normal control subjects. The estimated period prevalence was 8.5% (28 of 331). Spirometry, lung volumes, and gas exchange were normal in patients and control subjects. Compared with control subjects, the patient group demonstrated decreased exercise capacity (maximum achieved V O(2) 67 versus 104% predicted; p < 0.0001) and respiratory muscle weakness (PI(max) 77 versus 115% predicted; p = 0.001). These patients have a characteristic exercise response that was hyperventilatory (peak VE/V CO(2); 55 versus 42) and hypercirculatory (maximum heart rate - baseline heart rate/V O(2)max - baseline V O(2)max; 91 versus 41) compared to control subjects. Patients stopping exercise due to dyspnea (n = 16) (as compared with muscle fatigue, n = 11) displayed weaker respiratory muscles (Pdi(max) 61 versus 115 cm H(2)O; p = 0.01) and were more likely to reach mechanical ventilatory limitation (V Emax/ MVV 0.81 versus 0.58; p = 0.02). The sensation of dyspnea was related to indices of respiratory muscle function including respiratory rate and inspiratory flow. We conclude that mitochondrial myopathies are more prevalent than previously reported. The characteristic physiological profile may be useful in the diagnostic evaluation of mitochondrial myopathy.

Clinical exercise testing.

Clinical exercise testing is increasingly being utilized in clinical practice because of the valuable, often unique information that it provides in patient diagnosis and management. This is also due to a growing awareness that resting cardiopulmonary measurements provide an unreliable estimate of functional capacity. A continuum of exercise testing modalities for functional evaluation from "low tech" to "high tech" will be discussed. These include the six minute walk test, shuttle walk test, exercise induced bronchoconstriction test, cardiac stress test, and cardiopulmonary exercise testing. The main focus of this article will be cardiopulmonary exercise testing including indications, important measurements, salient methodological considerations, and interpretation.

Advances in pulmonary laboratory testing.

This review examines emerging technologies that are of potential use in the routine clinical pulmonary laboratory. These technologies include the following: the measurement of exercise tidal flow-volume (FV) loops plotted within the maximal FV envelope for assessment of ventilatory constraint during exercise; the use of negative expiratory pressures to asses expiratory flow limitation in various populations and under various conditions; the potential use of expired nitric oxide for assessing airway inflammation; and the use of forced oscillation for assessment of airway resistance. These methodologies have been used extensively in the research setting and are gaining increasing popularity and clinical application due to the availability of commercially available, simplified, and automated systems. An overview of each technique, its potential advantages and limitations will be discussed, along with suggestions for further investigation that is considered necessary prior to extensive clinical use.

Emerging concepts in the evaluation of ventilatory limitation during exercise: the exercise tidal flow-volume loop.

Traditionally, ventilatory limitation (constraint) during exercise has been determined by measuring the ventilatory reserve or how close the minute ventilation (VE) achieved during exercise (i.e., ventilatory demand) approaches the maximal voluntary ventilation (MVV) or some estimate of the MVV (i.e., ventilatory capacity). More recently, it has become clear that rarely is the MVV breathing pattern adopted during exercise and that the VE/MVV relationship tells little about the specific reason(s) for ventilatory constraint. Although it is not a new concept, by measuring the tidal exercise flow-volume (FV) loops (extFVLs) obtained during exercise and plotting them according to a measured end-expiratory lung volume (EELV) within the maximal FV envelope (MFVL), more specific information is provided on the sources (and degree) of ventilatory constraint. This includes the extent of expiratory flow limitation, inspiratory flow reserve, alterations in the regulation of EELV (dynamic hyperinflation), end-inspiratory lung volume relative to total lung capacity (or tidal volume/inspiratory capacity), and a proposed estimate of ventilatory capacity based on the shape of the MFVL and the breathing pattern adopted during exercise. By assessing these types of changes, the degree of ventilatory constraint can be quantified and a more thorough interpretation of the cardiopulmonary exercise response is possible. This review will focus on the potential role of plotting the extFVL within the MFVL for determination of ventilatory constraint during exercise in the clinical setting. Important physiologic concepts, measurements, and limitations obtained from this type of analysis will be defined and discussed.

Comparison of pulmonary gas exchange measurements between incremental and constant work exercise above the anaerobic threshold.

STUDY OBJECTIVES: To compare arterial blood gas (ABG) and pulmonary gas exchange variables (alveolar-arterial oxygen pressure difference [P(A-a)O2] and physiologic dead space to tidal volume ratio [VD/VT]) measured during incremental exercise test (IET) and constant work (CW) exercise at a matched oxygen uptake (VO2). DESIGN: A comparison of IET and CW variables was accomplished using patient data from clinical referrals for cardiopulmonary exercise testing and control data not reported from a previous study. SETTINGS: El Paso, Tex, located at an altitude of 1,270 m (barometric pressure, 656 mm Hg). PARTICIPANTS: Sixteen patients with dyspnea on exertion/exercise intolerance and nine normal subjects were evaluated above the anaerobic threshold (AT); seven patients were also studied below the AT. INTERVENTIONS: Participants had a maximal IET followed in 1 h by a 5-min CW test. Arterial blood samples were obtained from a radial catheter every other minute during IET and during minute 5 of CW. Cardiopulmonary measurements were obtained using an automated system in a breath-by-breath fashion (60-s averaging). RESULTS: Above the AT, no differences were observed in normal subjects between IET and CW at a matched VO2 in the following: PaO2 (79 vs 79 mm Hg); arterial oxygen saturation (SaO2) (94% vs 94%); P(A-a)O2 (16 vs 16 mm Hg); and VD/VT (0.09 vs 0.09) (mean values). Similarly, no differences were observed in patients above the AT in PaO2 (69 vs 68), SaO2 (90 vs 90), and VD/VT (0.24 vs 0.23). PaCO2 was 2 mm Hg higher (36 vs 34) in normal subjects and in patients (34 vs 32) during IET. A significant (p<0.05), albeit clinically unimportant, difference was also observed in P(A-a)O2 (28 vs 29) in patients. No statistically significant differences were observed below the AT between IET and CW for any of the variables measured. CONCLUSIONS: These data demonstrate the reliability of ABG and pulmonary gas exchange variables measured during 1-min IET for clinical use in patients and normal subjects. However, PaCO2 tends to be slightly higher during IET vs CW.

ECG in sickle cell trait at rest and during exercise and hypoxia.

The electrocardiograms of 28 volunteers with sickle cell trait were compared to those of 28 control subjects. Tracings were recorded at rest, at peak exercise, at simulated sea level, and at a simulated altitude of 4,000 m. No differences between the subjects with sickle cell trait and control subjects were observed for the majority of electrocardiographic measurements. Several measurements had statistically significant differences that persisted after correcting for body surface area and physical fitness. The magnitude of the differences does not appear to have physiologic or clinical significance. The observation that the differences were greatest for resting and sea level recordings indicates that sickling is probably not responsible. Further investigation will be needed to substantiate these differences and determine whether these electrical observations have any physiologic implication.

Behind the scenes of cardiopulmonary exercise testing.

The benefits and advantages of automated systems for cardiopulmonary exercise testing are well appreciated. Overenthusiasm and overconfidence in computer "black box" generated information, however, has resulted in inadequate attention to important issues related to quality control. The objective of this article is to provide basic and practical information related to equipment, methodology, conduct of the test, and quality control that will help assure clinically reliable results. The authors elaborate on the most widely applied methodologies and current criteria and guidelines of exercise testing.

An integrated approach to the interpretation of cardiopulmonary exercise testing.

This article demonstrates how the impressive amount of information obtained during cardiopulmonary exercise testing can be reasonably managed and meaningfully applied in the clinical decision-making process. An integrative approach is highlighted that emphasizes patterns of abnormalities and limitations to exercise so that reliance on single measurements is reduced. Illustrative case studies demonstrate the integrative method to the interpretation of cardiopulmonary exercise testing that may be used routinely in clinical practice.

Comparison of cardiopulmonary responses to forward and backward walking and running.

Backward running has long been used in sports conditioning programs and has recently been incorporated into rehabilitative settings as a method of increasing quadriceps strength while decreasing the joint compressive forces about the knee. Although backward locomotion has been studied kinetically, the metabolic cost of backward walking and/or running has not to our knowledge been previously characterized. Oxygen consumption and other cardiopulmonary variables were measured under constant speed exercise during backward and forward walking at 107.2 m.min-1 and during backward and forward running at 160.8 m.min-1. Peak oxygen consumption (VO2peak) was also measured during maximal incremental backward and forward running. VO2, HR, and blood lactate were significantly higher (P < 0.001) during backward walking and running than during forward walking and running. During backward walking and backward running, subjects exercised at 60% and 84% of their forward VO2peak, respectively. In conclusion, for a given speed, backward locomotion elicits a greater metabolic demand and cardiopulmonary response than forward locomotion. In general, these data suggest that while undergoing rehabilitation, an injured athlete may continue to exercise using backward walking/running at an intensity sufficient enough to maintain cardiovascular fitness levels.

Use of arm crank exercise in the detection of abnormal pulmonary gas exchange in patients at low altitude.

BACKGROUND: The measurement of arterial blood gases, P(A-a)O2 and VD/VT, during cycle ergometry is the "gold standard" for the assessment of pulmonary gas exchange. However, some patients are unable to perform cycle ergometry because of other medical problems. STUDY OBJECTIVE: To determine whether arm crank exercise could be used to reliably detect gas exchange abnormalities compared to cycle ergometry. PARTICIPANTS: Fifteen patients with a variety of pulmonary disorders, who were referred for exertional dyspnea. DESIGN: All patients performed maximal arm crank and cycle exercise. Arterial blood gases, VO2, VCO2, and VE were measured at rest and during exercise. RESULTS: Compared to peak cycle exercise (mean +/- SD), PaO2 (85 +/- 14 vs 75 +/- 13 mm Hg), SaO2 (94 +/- 2 vs 91 +/- 4 percent), VD/VT (0.21 +/- 0.07 vs 0.19 +/- 0.08), and pH (7.37 +/- 0.04 vs 7.34 +/- 0.03) were significantly higher during peak arm crank exercise. The P(A-a)O2 (18 +/- 13 vs 29 +/- 12 mm Hg) was narrower, and PaCO2 (29 +/- 3 vs 29 +/- 4 mm Hg) and PAO2 (104 +/- 4 vs 103 +/- 4 mm Hg) were similar. Six patients had normal gas exchange during cycle exercise at low altitude (P[A-a]O2 less than or equal to 27 mm Hg, PaO2 greater than or equal to 65 mm Hg, VD/VT less than or equal to 0.18) and nine were abnormal. Utilizing criteria specific for arm crank at low altitude, the same six patients had normal gas exchange (P[A-a]O2 less than or equal to 13 mm Hg, PaO2 greater than or equal to 85 mm Hg, VD/VT less than or equal to 0.26), and the remaining nine were abnormal. The P(A-a)O2 during peak arm crank was the most useful criterion in identifying patients with abnormal gas exchange. CONCLUSION: Proposed criteria for arm crank exercise testing accurately identified all patients with normal and abnormal pulmonary gas exchange during cycle exercise. The data from the present study suggest that arm crank can be an acceptable alternative exercise testing modality for the assessment of pulmonary gas exchange.

Effects of simulated altitude and exercise upon ECGs of young black men.

Twenty-five healthy black men between 17 and 21 years of age were evaluated. Their resting and exercise electrocardiograms were recorded at simulated sea level and at a simulated altitude of 4,000 m. Sea level exercise caused a reduction in the amplitudes of R waves and a lowering of J points. Exercise at a simulated altitude of 4,000 m caused a lowering of the J point in several leads and a reduction of the R wave amplitude in lead aVF. Hypoxia caused a reduction in the amplitudes of the T waves and a lowering of the J points in several leads. These effects of exercise and altitude, to a great extent, eliminated the appearance of "early repolarization," which is very common among young black men.

Reliability of noninvasive oximetry in black subjects during exercise and hypoxia.

The effect of skin pigmentation on the reliability of noninvasive oximetry, especially during exercise and hypoxia, has not been thoroughly investigated. This is the first study, to our knowledge, that specifically addresses this question. Thirty-three young black men performed multistage, steady-state cycle ergometry, breathing gas mixtures simulating different altitudes: 33 breathed gas simulating sea level (PIO2 = 146 mm Hg), 11 breathed gas simulating 2,300 m (PIO2 = 110 mm Hg), and 22 breathed gas simulating 4,000 m (PIO2 = 85 mm Hg). Co-oximeter SaO2 determinations were performed in arterial blood samples obtained concurrently with ear oximetry that was measured using Hewlett-Packard 47201A (HP) and Blox IIA oximeters. The mean error or bias for the [HP - SaO2] and for [Biox IIA - SaO2] +/- 95% CI were: at simulated sea level (SaO2 greater than 96%): -0.4 +/- 0.3% and 2.1 +/- 0.3%; at simulated 2,300 m (range of SaO2 means, 89 to 94%): -0.8 +/- 0.5% and 3.5 +/- 0.9%; for simulated 4,000 m (range of SaO2 means, 75 to 84%): -4.8 +/- 1.6% and 9.8 +/- 1.8%, respectively. A better coefficient correlation was observed for all the pairs between SaO2 versus HP (r = 0.94, p less than 0.001, n = 279) than for the SaO2 versus Biox IIA (r = 0.80, p less than 0.001, n = 242). In conclusion, the HP oximeter appears to estimate SaO2 more accurately than the Biox IIA oximeter. The previously described overestimation for the Biox IIA ear oximeter and the underestimation for the HP ear oximeter at low SaO2 values in whites is exaggerated in blacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Gas exchange during maximal upper extremity exercise.

STUDY OBJECTIVE: to characterize gas exchange and cardiopulmonary performance during maximal progressive arm crank exercise. DESIGN: Cardiopulmonary variables were measured and arterial blood gases were determined in blood samples obtained from an indwelling radial arterial catheter during arm crank exercise (34 watts/min). Arm crank exercise was compared to maximal leg exercise performed by a different but comparable group of subjects from a previous study. PARTICIPANTS: 19 healthy young (mean +/- SEM: 20 +/- 1 yr) black males. RESULTS: Peak arm crank exercise resulted in lower values compared to peak leg exercise for: power (129 +/- 2 vs 253 +/- 10 W), VO2 (2.17 +/- 0.04 vs 3.26 +/- 0.14 L/min); VCO2 (2.9 +/- 0.11 vs 4.32 +/- 0.17 L/min); HR (168 +/- 3 vs 189 +/- 3 beats/min); AT (1.15 +/- 0.05 vs 1.83 +/- 0.07 L/min); and VE (101 +/- 2 vs 144 +/- 8 L/min), respectively. Arm crank exercise (baseline vs peak) elicited an impressive improvement in PaO2 (85 +/- 1 to 97 +/- 1 mm Hg), no change in SaO2 (96 +/- 0.2 to 96 +/- 0.2 percent), no significant increase in P(A-a)O2 (3 +/- 0.7 to 5 +/- 0.9 mm Hg) and an appropriate trending decrease in VD/VT (0.22 +/- 0.01 to 0.17 +/- 0.01). Peak arm crank values were significantly different from peak cycle exercise for PaO2 (82 +/- 2.2 mm Hg), SaO2 (93 +/- 0.4 percent), P(A-a)O2 (21 +/- 1.9 mm Hg) and VD/VT (0.08 +/- 0.01). At comparable levels of VO2 for arm crank and cycle exercise (2.17 +/- 0.04 vs 2.26 +/- 0.08 L/min), significant differences were observed for PaO2 (97 +/- 1.4 vs 81 +/- 1.9 mm Hg); SaO2 (96 +/- 0.2 vs 94 +/- 0.4 percent); P(A-a)O2 (5 +/- 0.9 vs 14 +/- 1.5 mm Hg); and VD/VT (0.17 +/- 0.01 vs 0.08 +/- 0.01), respectively. CONCLUSIONS: Maximal arm crank exercise represents a submaximal cardiopulmonary stress compared to maximal leg exercise. The differences in gas exchange observed at peak exercise between arm crank and leg exercise for the most part reflect the lower VO2 achieved. However, the persistence of these gas exchange differences even at a comparable level of VO2 suggests that factors other than VO2 may be operative. These factors may include differences in alveolar ventilation, CO2 production, ventilation-perfusion inequality, diffusion, and control of breathing.

Exercise and hypoxia increase sickling in venous blood from an exercising limb in individuals with sickle cell trait.

PURPOSE: The association between sickle cell trait (SCT) and complications related to exercise may be explained if exercise-induced sickling interferes with capillary blood flow and causes tissue ischemia and functional abnormalities. To test this hypothesis, we measured sickling and blood gas values in venous and arterial blood of an exercising limb in subjects with SCT and in controls. SUBJECTS AND METHODS: The study consisted of 15 subjects with hemoglobin AS (SCT group) and 15 subjects with hemoglobin AA (control group). Each performed two maximal arm crank exercise tests, one at 1,270 meters and one at simulated 4,000 meters. RESULTS: At 1,270 meters, axillary venous sickling increased significantly (p less than 0.05) from (mean +/- SD) 1.0 +/- 1.0% at rest to 2.3 +/- 2.6% during peak exercise. At simulated 4,000 meters, sickling increased significantly (p less than 0.001) from 1.5 +/- 1.2% to 8.5 +/- 7.1%. A wide range of sickling during peak exercise was observed (1% to 25%). One minute after exercise at simulated 4,000 meters, venous sickling remained elevated (7.2 +/- 7.8%) despite high levels of oxygen saturation. Arterial sickling (less than 1%) was present in only two subjects. There was no significant difference in oxygen consumption (29.4 +/- 3 versus 30.7 +/- 4 mL/kg/minute) between the subjects with SCT and the controls, nor was there a correlation between exercise performance and sickling (r less than 0.2). CONCLUSION: We conclude that exercise at 1,270 meters slightly, albeit significantly, increased sickling in blood from an exercising limb and that simulated 4,000 meters dramatically potentiated this effect. Sickling in the effluent blood of an exercising limb does not appear to measurably affect overall maximal arm crank exercise performance.