The isokinetic assessment of peripheral muscle function in patients with coronary artery disease: correlations with cardiorespiratory capacity

Materials and methods Fifteen CAD patients and 15 age-matched healthy subjects (mean age 60 ± 6 vs. 57 ± 3.5 years) underwent maximal laboratory exercise testing, a 6-min walking test and an assessment of peripheral skeletal muscle function by use of an isokinetic apparatus. Quadricep and hamstring function was tested at two angular velocities, 150 and 180°s −1 with simultaneous electrocardiography monitoring. The cardiorespiratory and mechanical parameters (VO 2 , ventilatory threshold [VT], heart rate [HR], and power) were measured at VT and at maximal effort. Results Quadricep and hamstring peak torque was impaired in CAD patients, with quadriceps peak torque at 180° being 71.13 ± 14 vs. 91.13 ± 23 Nm ( P < 0.01) and hamstring peak torque 46.50 ± 10 vs. 59.86 ± 12 Nm ( P < 0.01). CAD subjects presented a deficient aerobic capacity as compared with the healthy subjects at maximal effort. At VT, the VO 2 , ventilation, and HR were significantly lower in CAD patients, at 13.77 ± 2.33 vs. 17.08±3.59 ml min −1  kg −1 ( P < 0.05), 29.64 ± 664 vs. 37.76 ± 7.2 ml min −1 ( P < 0.05), and 86 ± 14 vs. 111 ± 15 beats min −1 ( P = 0.001), respectively. The 6-min walking distance was significantly shorter for CAD patients than healthy subjects (425.93 ± 52.77 vs. 551.46 ± 57.94 m; P < 0.01). In CAD patients quadriceps and hamstring strength was not correlated with VO 2 at maximal effort and at VT. Total distance walked during the 6-min walk and VO 2 max were correlated ( r = 0.869; P < 0.001) but not at VT. Conclusion CAD patients showed impaired cardiorespiratory capacity accompanied by increased muscle fatigability as compared with healthy subjects. An isokinetic muscle assessment in these patients must be achieved systematically and seems to have value in cardiovascular rehabilitation. Keywords Coronary artery disease patients Cardiorespiratory capacity Skeletal muscle fatigue Isokinetic assessment Aerobic capacity 1 Introduction The impaired physical capacity of cardiac patients is directly related to cardiovascular disorders because of myocardial ischemia but also physical inactivity and sedentary way of life, changes in health called “deconditioning.” This immobilization adversely affects muscular and cardiovascular function and ventilation. These disorders are responsible for exercise intolerance that could provoke perturbation of the cardiorespiratory and peripheral skeletal muscle function. Patients often feel a progressive muscle fatigue, which, with dyspnoea, are the essential symptoms of exercise intolerance [1,2,38] . Dyspnoea has several origins and might come from cardiorespiratory and/or muscular factors [3] . Metabolic gas exchange analysis during maximal exercise testing is the most widely used method for the assessment of aerobic performance and effort tolerance in cardiac patients [6,19,20] . Cardiorespiratory capacity was largely studied in healthy subjects and patients with coronary artery disease (CAD) [4,5,19,20,31] . However, peripheral skeletal muscle dysfunction has been largely studied among patients with chronic heart failure (CHF) and was described as a cause of exercise intolerance and dyspnoea [3,8,10] . Isokinetic strength of the knee extensor muscles is markedly impaired in patients with CHF and those with chronic obstructive pulmonary disease; this alteration is related to a smaller muscle cross-sectional area [26] . Anker et al. [8] found reduced muscle strength in patients with cachectic as well as noncachectic heart failure as compared with age-matched controls. Isokinetic dynamometry provides a dynamic physiological assessment of muscle strength. A fixed angular velocity is imposed on the limb movement through a dynamic resistance, allowing for the determination of the considered muscle group [24] . The determination of isokinetic strength may be important for clinical purposes in these conditions. Indeed its potential application to evaluate the benefits of an isokinetic centered rehabilitation program might be of particular interest. We aimed to determine whether the diminished cardiorespiratory capacity of CAD patients is accompanied by impaired skeletal muscle function measured by an isokinetic dynamometer. As well, we evaluated the correlation between isokinetic strength and aerobic capacity in these patients. 2 Materials and methods 2.1 Subjects A total of 15 consecutive patients with CAD (mean age 60.33 ± 6 years) undergoing cardiac survey (coronary artery bypass grafting) or coronary angioplasty were studied for 3 months following the intervention. Patients all received angiotensin-converting enzyme inhibitors ( N = 8), beta blockers ( N = 15), aspegic ( N = 15), cordarone ( N = 6), calcium inhibitors ( N = 1) and statins ( N = 9) ( Table 1 ). During this period, the medical treatment was not changed to minimize its influence on maximal laboratory exercise testing data. The healthy age-matched control subjects (mean age 57.33 ± 3.5 years) were volunteers recruited through our consultation. They underwent a physical examination by a physician to ensure no cardiac disease ( Table 2 ). Exclusion criteria were severe systemic hypertension, left-ventricular ejection fraction < 40% (angiographic determination), severe rhythm disorder, and all noncardiovascular exercise limitation causes (e.g. total prosthesis of the hip, hemiplegia, paraplegia or inability to pedal). Healthy subjects had to have normal clinical exam results and perform regular physical activity as assessed by the Physical Activity Scale for the Elderly (PASE) [13,37] . All subjects underwent a maximal exercise testing session on an electromagnetic ergocycle and an evaluation of the peripheral muscular function on an isokinetic appartus. For CAD subjects, tests were performed before any rehabilitation program. All subjects gave their informed consent for the study procedures. 2.2 Isokinetic strength analysis Peripheral skeletal muscle performance was measured for the knee extensor (quadriceps) and flexors (hamstrings) by use of an isokinetic dynamometer (Cybex Norm II; Medimex [France]). Subjects were seated upright on the chair of the dynamometer with back support. At the level of the chest, pelvis and thigh, subjects were restrained with straps. The hip joint was between 90° and 100° of flexion during testing. The lever arm was attached to the distal part of the tibia, and its axis of rotation was visually aligned with the anatomic axis of flexion of the knee joint. Subjects were instructed to keep their hands on their thighs during testing. The isokinetic tests were performed at two angular velocities, 180 and 150°s –1 . Subjects underwent a period of adaptation to the movement and the appartus to limit the learning effect. The isokinetic testing protocol consisted of two sets of five repetitions for each velocity and for each lower extremity. The two sets were separated by 1 min of recovery. Subjects were encouraged to achieve the best possible performance. The maximal isokinetic strength was defined as the mean of the highest value of peak torque (in Newton meters [Nm]) of each set. The test was performed by the same examiner and under the same conditions (in the morning before any physical activity, without consumption of caffeine or tobacco in the previous hour) ( Fig. 1 ). This assessment was accompanied by electrocardiography (Sicard 460; Simens; Germany), heart rate (HR) and blood pressure (BP) monitoring. 2.3 Maximal exercise testing with metabolic gas exchange analysis Maximal exercise testing was realized by use of an electromagnetic ergocycle (Ergometrics 800; Sensor Medics) with an incremental protocol under physician supervision. The initial power was fixed at 20% of the theoretical maximal oxygen uptake (VO 2 max) and increased by 10–15% every min. The theoretical VO 2 max was calculated by the Wasserman formula: VO 2 max uptake = weight × (50.72–0.372 age) for male subjects; from this value we deduced the maximal theoretical power = (VO 2 max – VO 2 rest)/10.3 [27] . Oxygen uptake was determined by an open circuit technique. During the entire exercise test, expired gases were analyzed by breath-by-breath analysis through a rubber mouthpiece attached to a one-way valve with low resistance and small dead space (Vmax; Legacy 229). Flow was calibrated by introducing a calibrated volume of air at several flow rates with a 3-l pump. HR and systolic/diastolic BP were continuously checked by electrocardiography (Corina; CardioSoft; Version 0.3). The same protocol was used for control subjects, and all were encouraged to cycle at 60 revolutions per min until exhaustion. The test lasted until fatigue or dyspnoea occurred. No subjects stopped exercise due to angina or claudication. For both groups, the VO 2 max obtained at the end of the maximal exercise testing was considered as the maximal VO 2 uptake. At the end of the test, each patient had 3 min of active recovery and 3 min of passive recovery. Tolerance to exercise was measured by cardiorespiratory variables (VO 2 , ventilation [VE], HR) at ventilatory threshold (VT) and at maximal effort. The VT was determined according to the Beaver et al. [9] method. The pedaling mechanical power was also measured at ventilatory threshold (Pvt) and at maximal effort (Pmax). 2.4 The 6-min walking test A 6-min walking test was performed on a 30-m level hallway surface. Allowing the patients to set the place of ambulation with rests and stops as needed, they were asked to walk as far as possible for 6 min without running. Before the first test, patients were familiarized with the test and the environment by their taking one pass along the corridor (forwards and backwards) in a natural way. Then subjects sat at rest in a chair located near the starting position for 10 min before the test started. During this time we measured pulse and BP. To guarantee a standardized and reproducible procedure, the time elapsed was called out after each minute, but no additional encouragement was offered during the test. The total distance walked during the 6-min walk test was recorded in meters (6′ WT). HR and saturation in oxygen were measured every minute [7,33] . The test was repeated at least 30 min later, and the highest value of the two measurements was taken as an estimate of the walking performance of each subject. 2.5 Statistical analysis Results are given as mean ± S.D. for continuous variables. Data analyses involved use of SPSS 11.0 software. The cardiorespiratory fitness and peripheral skeletal muscle function of the healthy subjects and CAD patients were compared with use of Student's t -test. The Spearman correlation coefficient was used to determine correlation between VO 2 max and muscle strength. Statistical significance was set at P < 0.05. 3 Results 3.1 Peripheral skeletal muscle function data All subjects performed the whole protocol without any complications. No cardiac arrhythmic event or abnormal hemodynamic responses were observed in either group. As compared with healthy subjects, CAD patients showed impaired quadriceps peak torque at 150° angular velocity (76.93 ± 16 vs. 98.96 ± 23 Nm for healthy subjects; P < 0.01) and at 180° angular velocity (71.13 ± 14 vs. 91.13 ± 23 Nm; P < 0.01). The hamstring peak torque was impaired at 150° angular velocity (49.46 ± 16 vs. 65.86 ± 14 Nm; P < 0.01) and at 180° angular velocity (46.50 ± 10 vs. 59.86 ± 12 Nm; P < 0.01) ( Fig. 2 ). The mean power at 180° angular velocity was impaired in CAD patients and in quadriceps was 103.59 ± 26.33 vs. 134.76 ± 46.96 W ( P < 0.05) and in hamstrings was 68.41 ± 18.72 vs. 91.63 ± 22.05 W ( P < 0.01). 3.2 Cardiorespiratory data At maximal effort, CAD subjects presented a deficient aerobic capacity compared with healthy subjects ( Fig. 3 ). The VO 2 max was 20.34 ± 4.95 vs. 29.16 ± 7.68 ml min −1  kg −1 ( P = 0.01); maximal ventilation (VEmax) was 58.18 ± 16.28 vs. 84±24.45 ml min −1 ( P < 0.05); and maximal HR (HR max) was 118 ± 21 vs. 152 ± 13 beats min −1 ( P < 0.001). The maximal power (P max) was 102 ± 31 vs. 153 ± 33 W ( P < 0.001). At VT, VO 2 max was of 13.77 ± 2.33 vs. 17.08 ± 3.59 ml min −1  kg −1 ( P < 0.05); VE was 29.64± 6.64 vs. 37.76 ± 7.2 ml min −1 ( P < 0.05); HR was 86 ± 14 vs. 111 ± 15 beats min −1 ( P = 0.001); and Pvt was 61 ± 12 vs. 76 ± 24 W (NS). No difference was found in systolic and diastolic BP at rest and at effort. 3.3 The 6-min test No subjects slowed down, stopped or took a rest during the 6-min test. The 6-min distance walked was significantly shorter for CAD patients than for healthy subjects (425.93 ± 52.77 vs. 551.46 ± 57.94 m; P < 0.01). The groups did not differ in HR at rest (74 ± 11 vs. 78 ± 9 beats min −1 ), but HR was diminished in the CAD group at the end of the test (114 ± 11 vs. 102 ± 10 beats min −1 ; P < 0.01). 3.4 Correlation between isokinetic strength and aerobic capacity In CAD patients, quadricep and hamstring strength was not correlated with the VO 2 at maximal effort and at VT (data not shown). Total distance walked during the 6-min walk test was correlated with VO 2 max ( r = 0.869; P < 0.001) but not at the VT. HRmax in CAD patients was not correlated with VO 2 max and VO 2 at VT. 4 Discussion The results of this study show that cardiorespiratory capacity (oxygen uptake, ventilation and HR) measured at maximal effort and at ventilatory threshold is decreased in CAD patients as compared with healthy subjects. This decreased oxygen uptake of CAD patients at maximal and sub-maximal levels of effort was demonstrated in the literature [3,19,20] . The maximal exercise testing represents the most appropriate method to determine decreased physical performance in patients with cardiovascular disease, and fatigue represents the usual limiting factor during this test [34] . Measurement of gas exchange during the exercise test allows for investigation of the entire chain of oxygen binding, transport and utilization, essential for oxidative phosphorylation. It is a validated criterion of cardiopulmonary and metabolic performance [12] . The VT corresponds to a hyperventilation phenomenon during the progressive exercise test and provides complementary information to peak VO 2 ; it is a sub-maximal parameter independent of patient motivation [30] . The essential limitation of this metabolic analysis remains the difficulty in distinguishing between the peripheral component (muscle) and the central component (cardiac) of exercise intolerance [12] . It is well known that maximal oxygen uptake (VO 2 max) is related to age, physical activity and cardiovascular clinical status [20] . In our study, CAD patients did not differ from health subjects in age. The healthy subjects were considered a physically active group in terms of their PASE score, so age does not explain the difference observed in the maximal oxygen uptake for the two groups. The cardiac event implies a period of physical inactivity for the CAD patient. This negative affect is added to the sedentary way of life and bad life habits (smoking and consuming food rich in saturated fat). This physical inactivity strongly decreases the values of VO 2 max [3,29] . The aerobic power is related to oxygen consumption. Oxygen uptake increases in a linear way with power (Watts) imposed to subjects [19,20] . This aerobic power was found impaired in our CAD patients. Values of maximal ventilation were lower for our CAD patients. This observation can be explained not only by thoracic surgical trauma but also by associated pectoral angina phenomena [2] . The difference observed between HR at VT and at maximal effort and between HRmax at maximal exercise testing and during the 6-min walking test can be explained by the medication prescribed to the CAD patients. Indeed, all our CAD patients took beta blockers to prevent abnormal HR elevation [19,20] . The 6-min walk test is a complement test for evaluating exercise capacity. The procedure has been used extensively for patients with cardiovascular or pulmonary disease. The shortest walking distances were observed for patients with angina, previous myocardial infarction, congestive heart failure and decreased lung function. Also psychological factors such as depression and cognitive impairment all have a negative effect on timed walking distance [36] . The distance walked during the test was correlated with peak VO 2 . Several studies showed good correlation between the distance covered by patients during the test and the laboratory measurement of aerobic exercise function such as VO 2 max or ventilatory anaerobic threshold [12,36] . Although the distance walked is usually considered an index of sub-maximal exercise capacity, we found no correlation with the anaerobic threshold. Indeed, some authors [17,18] showed that in patients with CHF, the peak VO 2 during the 6-min walk test was similar to that reached during the cardiopulmonary exercise test and a similar anaerobic threshold was also detected [17] . Cahalin et al. [11] observed that in some cases, HRmax and BP reached during the 6-min walk test were near their respective peak values at maximal exercise test. Therefore, instead of being a measure of sub-maximal capacity, in some cases, the 6-min walk test may reflect maximal exercise tolerance, and the energy required may also be provided by anaerobic metabolism. The reduced aerobic capacity of CAD patients is associated with decreased maximal concentric isokinetic muscle strength and peak torque of the two muscular groups (quadriceps, hamstrings), which shows a more important local muscle fatigability. This impaired muscular strength can be explained by a smaller muscle cross-sectional area but also by an important decrease of the activity of local muscular oxidative enzymes [21,15] . In general, maximal muscle strength is decreased during cardiovascular disease, mainly when associated with left-ventricular dysfunction. Thus, maximal quadricep strength has been shown to be reduced by 30% in CHF patients [12] for isometric [10] and isokinetic [28] contractions. Peripheral muscle deconditioning induces poor adaptation to exercise. This form of exercise intolerance is dominated by alteration of muscle oxidative metabolism. The deconditioning is often worsened by a sedentary life style but also by cardiac patients limiting their physical activity to avoid inducing anxiogenic painful symptoms. The methodology used for measurement of maximal isokinetic muscle strength and peak torque of knee extensors and flexors in severe stable CHF patients has proved to be valid and reproducible [35] . Muscle fatigue can be more accurately quantified by spectral analysis applied to surface electromyography. In patients with CAD, this abnormal muscle fatigue is reflected by a premature increase of motoneuron recruitment [22] . Only weak correlations were reported in the literature between exercise capacity and maximal isokinetic muscle strength in patients with stable CHF [32] . The relation between peak VO 2 and muscle strength, if it exists, is probably weak in CAD patients. We did not observe such a result in the present study, which argues for a lack of relation between these two physical capabilities. Another study found the same results concerning the relation between VO 2 max and maximal isokinetic quadricep and hamstring muscle strength in patients with CHF and chronic obstructive pulmonary disease [14] . This conclusion seems logical, because VO 2 peak is a major result of general aerobic condition, whereas isokinetic muscle strength reflects mainly short and intense metabolic demands. The results by Gayda et al. [23] on maximal voluntary isokinetic force showed that the capacity of CAD patients to develop a maximal force is long preserved as compared with aerobic capacity. Minotti et al. [28] showed this in patients with CHF: skeletal muscular fatigue did not come from an impaired central nervous system command or from abnormalities of the neuromuscular junction but rather from perturbations of the muscular energy metabolism, independent of the reduction of local blood flow during muscular exercise [28] . Therefore, the isolated assessment of one physical capacity, VO 2 peak or isokinetic muscle strength, cannot be used as an indication of the other. Both need to be assessed separately, yielding complementary information that might help obtain a better comprehensive approach for rehabilitation aims. Isokinetic strength training can also be planned as endurance training, with a circuit-training program with isokinetic exercises for different muscle groups. Such a program can increase aerobic power. Further studies should deal with the evaluation of an optimal training program. Furthermore, recent studies have found that isokinetic strength training and isokinetic strength testing appeared to be safe and reliable for CHF patients [16,25,26] . 5 Conclusion CAD patients, compared with healthy subjects, have impaired cardiorespiratory capacities accompanied by increased muscle fatigability in quadriceps and hamstrings. 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