Lactic acid levels in patients with chronic obstructive pulmonary disease accomplishing unsupported arm exercises

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1 Original paper Lactic acid levels in patients with chronic obstructive pulmonary disease accomplishing unsupported arm exercises Chronic Respiratory Disease 7(2) ª The Author(s) 2010 Reprints and permission: sagepub.co.uk/journalspermissions.nav DOI: / crd.sagepub.com Gérson F de Souza 1,2, Antonio AM Castro 1,3, Marcelo Velloso 1, Camille R Silva 4, and José R Jardim 5 Abstract Patients with chronic obstructive pulmonary disease (COPD) may suffer dyspnea when performing unsupported arm exercises (UAE). However, some factors related to the tolerance of the upper limbs during these exercises are not well understood. Our investigation was to determine if an unsupported arm exercise test in patients with COPD accomplishing diagonal movements increases lactic acid levels; also, we assessed the metabolic, ventilatory and cardiovascular responses obtained from the unsupported arm exercise test. The study used results of maximal symptom limited tests with unsupported arms and legs performed on 16 patients with COPD. In order to do the test, some metabolic, respiratory and cardiovascular parameters such as oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ), respiratory rate (RR), pulmonary ventilation (VE), heart rate (HR) and blood pressure (BP) were measured during the exercise tests. Furthermore, blood lactate concentration was measured during the arm test. We detected a significant increase in the mean blood lactate concentration, VO 2,VCO 2, VE and RR from the resting to the peak phase of the UAE test. The mean values of VO 2, VCO 2 and VE obtained at the peak of the UAE test corresponded to 52.5%, 50.0% and 61.2%, respectively, of the maximal values obtained at the peak of the leg exercise test. In comparison, the mean heart rate and systolic arterial blood pressure were significantly lower at the peak of the UAE test than at the peak leg exercise test and corresponded to 76.2% and 83.0%, respectively. Unsupported incremental arm exercises in patients with COPD increases blood lactic acid levels. Keywords unsupported arm exercise test, COPD, lactate concentration Introduction Patients with chronic obstructive pulmonary disease (COPD) may develop high ventilatory and metabolic output when accomplishing simple activities of daily living (ADL). 1 Upper limb exercises lead to dyspnea, especially when performed without support. 2 Factors related to low exercise tolerance of the upper limbs are not totally understood including severe airway obstruction, 3 dyssynchronous breathing and accessory ventilatory muscles recruitment. 4 Impaired skeletal muscle function has been reported in patients with COPD, 5 but this impairment may not be similar in the upper and the lower limbs. Results reported in the literature on upper-limb muscle adaptations are still unclear and the influences of 1 Research Fellow at Pulmonary Rehabilitation Center, Federal University of São Paulo, Unifesp, Brazil 2 Nove de Julho University and the Monte Serrat University, Brazil 3 Adventist University, Unasp, Brazil 4 Pulmonary Rehabilitation Center, Unifesp, Brazil 5 Respiratory Division, Director of the Pulmonary Rehabilitation Center, Unifesp, Brazil Corresponding author: José R Jardim, Respiratory Division (Pneumologia), Federal University of São Paulo, Rua Botucatu, andar, São Paulo/SP, Brazil, CEP joserjardim@yahoo.com.br 75

2 76 Chronic Respiratory Disease 7(2) muscle wasting to this particular muscle group are somehow controversial. Frassen et al. 6 showed that lower- and upper-limb muscle dysfunction is common in COPD patients, independently of the presence of fat free mass depletion. Despite this, the authors showed preserved arm endurance as an indicative for intrinsic differences in muscular adaptations between leg and arm muscles. It has been described that COPD patients develop early lactic acidosis during lower limb exercises, which enhances the ventilatory output and imposes certain limits to the exercise tolerance. 7 It is expected that the same would hold true for upper limb exercises in patients with COPD. However, the lactic acid levels in unsupported arm exercises still need to be described in COPD patients. Our investigation was to determine if unsupported arm exercise tests would lead to an increase in lactic acid levels in patients with COPD and also their metabolic, ventilatory and cardiovascular responses. Methods Patients were included if they fulfilled the criteria for COPD according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. 8 Patients had to be former smokers who had never participated in a rehabilitation program; they were recruited in a consecutive order; they had to be considered clinically stable without a history of infections or exacerbation and without changes in medication during the 4 weeks prior to the test. We also excluded all patients with any neurological, orthopedic, cardiovascular and/or rheumatological disease or those who had a SpO 2 lower than 80% during a 6-min walking test in a flat corridor. All participants in the study were previously oriented on the procedures and had a quick training on the treadmill and the correct rhythm of movement they should keep with their arms during the programmed tests. This procedure was approved by the Research Ethics Committee of the Federal University of São Paulo, Brazil, and formally consented by all patients in the group. Assessment protocol Initially, patients answered a questionnaire to assess their clinical stability and were submitted to a spirometry pre and post 400 mcg of salbutamol according to standard techniques 9 (Koko Spirometer, PDS Instrumentation, Louisville, KY, USA). Forced vital capacity (FVC), forced expiratory volume in the first Illustration 1. Second diagonal patterns of the proprioceptive neuromuscular facilitation techniques. second (FEV 1 ) and the FEV 1 /FVC ratio were reported as absolute and predicted percentage of reference values. 10 For the assessment of nutritional status, a body mass index (BMI) below 22 kg/m 2,from22to 27 kg/m 2 andhigherthan27kg/m 2 were considered malnutrition, eutrophia and overweight, respectively. 11 Unsupported arm exercise test The exercise consisted of lifting a weight with the dominant arm performing a diagonal movement based on the diagonal movements of the proprioceptive neuromuscular facilitation technique. The second diagonal technique include a flexion-abduction-external rotation motion (Illustration 1). 12 The rationale for the use of this exercise is based on the fact that the execution of movements in the diagonal are considered to recruit a larger number of muscle groups than other exercises. Bouts of 2 minutes exercise, followed by 1 minute resting interval, were repeated until exhaustion. The test started using a 250-g dumbbell, which was increased by 250 g at the beginning of each new bout. The frequency of the movements was imposed by a digital metronome (QT-3, Qwiktime, San Clemente, CA, USA), which was programmed to establish 20 repetitions per min. The test could be interrupted if the patient presented excessive dyspnea, arm fatigue 76

3 de Souza et al. 77 shoulder pain or thoracic compensatory movement that was considered as muscle fatigue. In the case of shoulder pain, the patient was excluded from the protocol. The total duration of the arm test included both the exercise itself and the interval periods. The test was carried out with the patients in the sitting position. Maximal cardiopulmonary exercise test The maximal cardiopulmonary exercise test was accomplished in order to calculate at which percentage of maximal ventilatory and metabolic rate the arm test was performed. The test was performed on a treadmill (Lifestride model 7500, Schiller Park, IL, USA) according to the Harbor protocol. 13 The procedure started with the patient walking on the treadmill at a fixed speed, without any inclination for the first 3 min, followed by a 1% inclination increment at the end of each following min. The test was continuously monitored with electrocardiographic CM5, AVF and V2 leads (EP-3 Dixtal, São Paulo, Brazil). The patient was encouraged to continue the exercise until exhaustion, but it could be immediately interrupted in the case of limiting symptoms such as dyspnea, fatigue and/or pain in the lower limbs, dizziness or discomfort, precordial pain, severe arrhythmia, no increase in systolic pressure or an exaggerated hypertensive response (systolic arterial pressure >260 mm Hg or diastolic pressure >120 mm Hg). Blood lactate was not measured during the maximal cardiopulmonary exercise test. Variables obtained in the exercise test Oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ), respiratory rate (RR) and pulmonary ventilation (VE) were measured at 30-sec intervals using an automated system (Vista Mini CPX, Vacumed, Ventura, CA, USA). Maximal voluntary ventilation ratio (MVV) was estimated by multiplying FEV 1 by Blood samples were collected for lactate analyses from the lateral pulp of the index finger of the upper limb performing the exercise at resting, at the end of the exercise and after 3 min of recovery. The collected blood was placed on test strips (BM-Lactate, Mannheim, Germany) for quantitative lactate determination. Lactate concentration was determined with a reflexion photometer based on a colorimetric reaction mediated by lactate oxidase, using a portable lactate analyzer (Accusport, Hawthorne, CA, USA). The results are reported as Table 1. Demographic and spirometric characteristics of the chronic obstructive pulmonary disease (COPD) patients submitted to a maximum unsupported arms exercise test Mean Age (years) Weight (Kg) Height (m) BMI (kg/m 2 ) FEV 1 (L) FEV 1 (%) FVC (L) FVC (%) FEV 1 /FVC (%) Standard deviation BMI, body mass index; FEV 1, forced expiratory volume at the first second in liters and percentage; FVC, forced vital capacity in liters and percentage; FEV 1 /FVC, forced expiratory volume at the first second/ forced vital capacity ratio in percentage. mmol/l. We have considered values higher than 2 mmol/l as the lactate threshold. 15 Oxyhemoglobin saturation was measured by a pulse oximeter (Model 920M, Healthdyne Technologies, Marietta, GA, USA). Heart rate was measured using a sport tester Polar T31 (Polar Electro OY, Kempele, Finland) during the arm exercise tests. Arterial blood pressure was measured using a sphygmomanometer (Becton Dickinson, Juiz de Fora, Brazil) at resting time and at the end of the test. Subjects were asked to quantify their perceived dyspnea and arm fatigue by pointing at a 10-point modified Borg scale before and at the completion of the test. Statistical analysis Due to the variability of the results, no parametric tests were used. Wilcoxon s test was used to assess resting and peak exercise variables obtained during the arm and leg exercise tests. Spearman s correlation analysis was applied to correlate blood lactate concentration with peak VO 2, peak VE, dyspnea and arm fatigue values. Results are shown as mean and standard deviation values. Sample size calculated according to lactate variation in the literature for an alpha error of 5% and beta error of 20% considered 16 patients as the minimum required sample. Results Sixteen patients with COPD (11 males, 68.8%) were enrolled in the study. Patient s anthropometric data are presented in Table 1. Six patients (37.5%) were 77

4 78 Chronic Respiratory Disease 7(2) Lactate (mmol/l) Rest Peak Recovery classified as malnourished, six (37.5%) as eutrophic, and four (25%) as overweight. Patient s airway obstruction severity was classified according to the GOLD classification 8 as: stage I 1 patient (6.2%), stage II 5 patients (31.3%), stage III 10 patients (62.5%) and none at stage IV. Responses to exercise tests * * Figure 1. Blood lactate values in milimol per liter, at rest, at the peak of the exercise with unsupported arms and 3 min after the end of the exercise in chronic obstructive pulmonary disease (COPD) patients (median and range). *p <.05 different from the rest value. The mean blood lactate increased from mmol/l at resting to mmol/l at the end of the arm exercise test and maintained at mmol/l during recovery time (p <.05; Figure 1). Blood lactate concentration equal to or higher than 2 mmol/l was obtained in 13 patients at the peak of the arm exercise test and in 15 at the recovery phase. We found that blood lactate at the peak of the arm exercise test did not correlate with the peak VE (r ¼.30, p ¼.25) and peak VO 2 (r ¼.32, p ¼.90). There was a significant increase in the mean VO 2, VCO 2, VE and RR from rest to the peak of the arm exercise test (Table 2). The mean VO 2, VCO 2 and VE values obtained at the peak of the arm exercise test corresponded to 52.5% %, 50.0% % and 61.2% %, respectively, of those obtained at the peak of the cardiopulmonary exercise test. The mean VE/MVV (pulmonary ventilation/ maximal voluntary ventilation ratio) obtained at the peak of the arm exercise test reached 56.2% %, with values higher than 60% in five patients, values between 50% and 60% in nine patients and values lower than 40% in two patients. The mean VE/MVV ratio at the peak of the cardiopulmonary exercise test was 90.9% %. The cardiovascular response to the arm exercise test was characterized by a significant increase in heart rate and systolic arterial blood pressure from resting to the peak of the exercise, while diastolic arterial blood pressure remained unaffected. The mean heart rate and systolic arterial blood pressure were significantly lower at the peak of the arm exercise test than at the peak of the cardiopulmonary exercise test and corresponded to 76.2% + 7% and 83.0% + 11%, respectively. None of the patients showed a variation higher than 3% in peripheral oxyhemoglobin saturation at the peak of the arm exercise test. On the other hand, 13 patients showed oxyhemoglobin desaturation in the maximal cardiopulmonary exercise test. The SpO 2 at the peak of the leg exercise test was higher than 90% in three patients, ranging from 85% to 90% in seven, from 80 to 84% in three and was lower than 80% in three (Table 3). The mean Borg score for dyspnea (Borg D) increased from at rest to at the peak of the arm exercise test (p ¼.001); a similar behavior was observed for arm fatigue with the Borg score increasing from at rest to at the peak of the arm exercise test (p ¼.001). In contrast, maximal cardiopulmonary exercise test showed a mean Borg D ranging from at rest and increased to at the peak of the exercise (p <.001) and dyspnea and leg fatigue increased from at rest to at the peak (p <.001). The mean duration of the arm exercise test was min. During the test, our patients reached the peak and steady state values for oxygen consumption and pulmonary ventilation (Figure 2). One patient ended the last load of the arm exercise test with 750 g, four with 1000 g, five with 1250 g, four with 1500 g, and two with 1750 g. All patients stopped the maximal cardiopulmonary exercise test due to dyspnea, while all arm exercise tests were interrupted only when the patient was no longer able to continue the exercise due to arm fatigue or compensation of movements. Discussion It is well known that enhancement of ventilatory output even in low intensity exercises is due to lactic acidosis and is one of the limiting factors during lower limb exercises in patients with COPD. 7,16 In respect to the low tolerance in patients during upper limb efforts, 78

5 de Souza et al. 79 Table 2. Metabolic and ventilatory response obtained in maximum treadmill and unsupported arms exercises in COPD patients (n ¼ 16) Rest Peak arms Peak legs Mean SD Mean SD Mean SD VO 2 (ml/min) a b 0.39 VCO 2 (ml/min) a b 0.43 VE (L/min) a b 12.9 VEO c 5.9 VECO d c 5.6 RR (rpm) a b 4.3 RR, respiratory rate; VO 2, oxygen consumption; VCO 2, carbon dioxide production; VE, pulmonary ventilation; VEO 2, pulmonary ventilation/oxygen consumption ratio; VECO 2, pulmonary ventilation/carbon dioxide production ratio. a p <.001 peak exercise rest. b p <.001 peak exercise legs arms. c p <.05 peak exercise legs arms. d p ¼.002 peak exercise rest. Table 3. Cardiovascular variables, oxyhemoglobin saturation, sensation of dyspnea and fatigue obtained from maximum unsupported arms exercise and treadmill incremental test in COPD patients (n ¼ 16) Rest Peak arms Peak legs Mean SD Mean SD Mean SD HR (bpm) a b 20.3 Systolic BP (mm Hg) c d 26.1 Diastolic BP (mm Hg) SpO 2 (%) a 6.3 Borg D e b 3.2 Borg F e b 3.3 a p <.001 peak exercise rest. b p <.001 peak exercise legs arms. c p <.05 peak exercise rest. d p ¼.001 peak exercise legs arms. e p ¼.001 peak exercise rest. Borg D, perceived dyspnea sensation (Borg scale); Borg F, perceived fatigue sensation (Borg scale); HR, heart rate; diastolic BP, diastolic blood pressure; systolic BP, systolic blood pressure; SpO 2, peripheral oxygen saturation. 0.8 Panel A 25 Panel B VO 2 (ml/min.) VE (L/min.) Rest End Rest End Load (grams) Load (grams) Figure 2. Mean changes in oxygen consumption (panel A) and pulmonary ventilation (panel B) during the upper limbs incremental test with the second diagonal in chronic obstructive pulmonary disease (COPD) patients. 79

6 80 Chronic Respiratory Disease 7(2) it is usually due to the occurrence of dyssynchronous contraction of the different ventilatory muscles compartments. However, poor attention has been given to blood lactate accumulation as a limiting factor during upper limb exercises in patients with COPD. Our results undoubtedly confirm that unsupported arm exercises produce increased blood lactic acid levels in patients with COPD. We showed a significant increase in lactate production at the end of and 3 min after the unsupported arm exercise. The lactate values at the peak of the arm exercise were lower than the values reported by Castagna et al. 17 during an incremental arm cranking test in COPD patients. We believe that this is due to the fact that our test was accomplished exclusively with the dominant upper limb as opposed to other studies that submitted their patients to a incremental test using both arms. Probably we found a smaller elevation of variables such as lactate production and VO 2 is due to the lesser muscle mass involved in the exercise. The increase in the lactic acid levels could be another reason for the limited arm effort as reported by COPD patients when performing activities with their arms. In fact, lactic acid production is a strong stimulus for the respiratory center, leading to increased ventilation. Increased breathing frequency associated to a short expiratory time is the basic mechanism for the development of dynamic hyperinflation, a known factor for respiratory discomfort and exercise limitation. 18 Our results showed some lactate values at rest higher than 2 mmols/l. This wide variation in lactate in COPD patients has been shown in the literature. The reason for this variability is believed to be due to hypoxemia, low blood flow to the muscles, abnormalities in the oxidative capacity of the skeletal muscles Lind et al. 22 showed that during a handgrip exercise, the increased muscle tension reduces the blood flow to the muscles of the forearm and this reduction was inversely correlated to the increase in pulmonary ventilation. Later, Bevegard et al. 23 showed that blood flow reduction during an arm exercises occurred because of adrenergic output and vasoconstriction; the authors concluded that there is a more intense reduction in blood flow to smaller muscle groups, such as the forearm, in relation to the lower limb exercises, leading to a higher blood lactate accumulation with greater pulmonary ventilation stimulation. It is possible that some of the lactate may be produced from the trunk and forearm. During a maximum arm exercise, the trunk has to be stabilized in order for the muscles of the shoulder girdle to accomplish maximal work. However, we believe that most of the work in this kind of exercise is done mainly by the arms and they should be the major source of lactate production. Kutsuzawa et al. 24 showed that patients with COPD when performing a handgrip exercise with a constant load presented a reduction in intracellular ph and low levels of phosphocreatine in the forearm muscles, suggesting that premature activation of anaerobic glycolysis and impaired oxidative phosphorylation occurred. However, Gea et al. 25 showed that oxidative and glycolytic enzyme activities in the deltoid muscles of patients with COPD were found to be normal. Therefore, more studies are necessary for a better understanding of what might occur in the upper limb muscles of patients with COPD during exercise. It is conceivable to think that the exercise response may be peculiar to different muscular territories involved within the exercise. The test used in our study involving unsupported upper limb movements was chosen as it resembles the movements accomplished during ADL such as combing the hair, brushing teeth and sweeping. 1 The peak values of VE, VO 2 and VCO 2 obtained by our patients in the unsupported arm exercise test corresponded to approximately 50% of the peak values obtained in the maximal leg exercise test. Velloso et al. 1 showed that patients with COPD presented a significant increase in both metabolic and respiratory requirements, reaching 55% of maximal oxygen uptake and 62.7% of MVV when performing simple activities of daily life with the arms within 5 min. Their VO 2 and VE values were similar to those found in our study showing that our test simulated the level of effort by COPD patients when accomplishing ADL. Therefore, it is possible that the accomplishment of ADL with unsupported arms by patients with COPD may result in premature blood lactate accumulation and fatigue. In contrast, recently, Castagna et al. 17 did not find a significant difference in VE and VO 2 between arm and leg cranking in COPD patients. Nevertheless, they found that for the same relative workload limb power, VO 2, respiratory exchange ratio (RER), VE, HR and blood lactate production were all significantly lower in the upper limbs of patients with COPD than in healthy controls. 17 We did not consider to recruit a control group to our protocol due to the documented literature that states superiority of exercise tolerance in healthy subjects against COPD patients. We chose an interval exercise protocol as it is closer to what patients accomplish in their ADL in the 80

7 de Souza et al. 81 real world. The diagonal arm movement, based on the second diagonal of the proprioceptive neuromuscular facilitation method was chosen for this study because it involves spiral and diagonal muscle movements, very similar to those required to perform ADL. Diagonal movements allow exercising at the same time and in one single movement a great number of muscles of the shoulder girdle. Ries et al. 26 have previously shown that modified proprioceptive neuromuscular facilitation exercise is an efficient way of arm training in patients with COPD. Our study has a few limitations. We measured the lactate from a finger blood sample with a portable device, as this method has shown a high correlation with lactate measurements from an arterial sample. 27 We observed that the lactate values were homogeneously distributed among all patients. We did not specifically look at the lactate production in the different groups of patient severity, as they were not homogeneously distributed and it was not our objective. We did not measure the lactate concentration during the maximal cardiopulmonary exercise test because this test was done with the sole purpose of having a reference value to point out the intensity of the arm exercise concerning the ventilation and oxygen consumption in relation to the maximum exercise capacity. It is already well known that maximal cardiopulmonary exercise tests may increase lactate as much as 3 to 4 times. 16 Finally, there was no control group to compare the data of the COPD patients as they served as their own controls. Our results lead us to conclude that interval exercise with unsupported arms in patients with COPD performing diagonal movements with progressive loads of increments up to tolerance produces increased lactic acid levels. We also conclude that the VE and VO 2 at the maximal tolerated effort with unsupported arms test accomplished by patients with COPD corresponds to approximately half of the VE and VO 2 obtained in the maximal lower limbs exercise test. It is possible that COPD patients doing repeated heavy arm tasks during their daily life may develop a similar metabolic and ventilatory response, which may potentially explain their fatigue. Conflict of Interest None of the authors had a conflict of interest to declare in relation to this work. We had no financial or personal relationships with other people or organizations that could inappropriately influence our work, such as employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations and grants or other funding. References 1. Velloso M, Stella SG, Cendon S, et al. Metabolic and ventilatory parameters of four activities of daily living accomplished with arms in COPD patients. Chest 2003; 123: Criner GJ, Celli BR. Effect of unsupported arm exercise on ventilatory muscle recruitment in patients with severe chronic airflow obstruction. Am Rev Respir Dis 1988; 138: Lebzelter J, Klainman E, Yarmolovsky A, et al. Relationship between pulmonary function and unsupported arm exercise in patients with COPD. Monaldi Arch Chest Dis 2001; 56: Celli BR, Rassulo J, Make BJ. Dyssynchronous breathing during arm but not leg exercise in patients with chronic airflow obstruction. N Engl J Med 1986; 314: Couillard A, Prefaut C. From muscle disuse to myopathy in COPD: potential contribution of oxidative stress. Eur Respir J 2005; 26: Franssen FM, Broekhuizen R, Janssen PP, et al. Limb muscle dysfunction in COPD: effects of muscle wasting and exercise training. Med Sci Sports Exerc 2005; 37: Sue DY, Wasserman K, Moricca RB, et al. Metabolic acidosis during exercise in patients with chronic obstructive pulmonary disease. Use of the V-slope method for anaerobic threshold determination. Chest 1988; 94: Fabbri L, Pauwels RA, Hurd SS. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD Executive Summary updated COPD 2004; 1: ; discussion Standardization of spirometry 1987 update. Statement of the American Thoracic Society. Am Rev Respir Dis 1987; 136: Knudson RJ, Slatin RC, Lebowitz MD, et al. The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. Am Rev Respir Dis 1976; 113: Lipschitz DA. Screening for nutritional status in the elderly. Prim Care 1994; 21: Surburg PR, Schrader JW. Proprioceptive neuromuscular facilitation techniques in sports medicine: A reassessment. J Athl Train 1997; 32:

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