Evidence for Classically Conditioned Fatigue Responses in Patients Receiving Chemotherapy Treatment for Breast Cancer

Fatigue is the most common side effect of chemotherapy for cancer. Not yet explored is the possibility that patients may develop conditioned fatigue responses to clinic cues as a result of the repeated pairing of the clinic environment (conditioned stimulus) with infusions of chemotherapy (unconditioned stimulus) that cause fatigue (unconditioned response). As a first critical test of this possibility, breast cancer patients (N = 82) were studied across their first four cycles of chemotherapy. Consistent with conditioning: (1) fatigue levels in the clinic environment significantly increased with repeated pairings of the clinic environment and chemotherapy administration; (2) fatigue responses in the clinic environment prior to the fourth infusion (CR) were predicted by patients’ previous experiences of post-infusion fatigue (UR) above and beyond effects of concurrent emotional distress. These results provide the first evidence in the literature that fatigue can be conditioned. Additional research is warranted to determine the clinical importance of this source of fatigue in chemotherapy patients.     

Detection of skeletal muscle fatigue using an accelerometer in dynamic cardiomyoplasty

 An animal experiment was done using six mongrel dogs that weighed 28 ± 3 kg to show that an accelerometer could detect skeletal muscle fatigue in dynamic cardiomyoplasty. Through left-side thoracotomy, the heart was exposed and an electrode to sense the heartbeat was positioned on the left ventricle. A left latissimus dorsi muscle flap (LDMF) was inserted into the left chest cavity and rolled around the heart. An accelerometer was put on the rolled LDMF to sense the ventricular acceleration by contraction of the LDMF and the heart. The LDMF was stimulated under these settings: pulse width, 210 μs; stimulation output, 6 V; burst frequency, 30 Hz; burst duration, 200 ms; synchronous ratio, 1 : 4; and synchronous delay, 66 ms. Output voltage from the accelerometer was recorded 1, 3, 5, 10, and 15 min after the beginning of stimulation. Percentages of the amplitude in all dogs after 3, 5, 10, and 15 min were 81 ± 10%, 63 ± 12%, 48 ± 11%, and 45 ± 14% of the values after 1 min, respectively. Significant differences were found between the values after 1 min and those after 3 min, between the values after 3 min and those after 5 min, and between the values after 5 min and those after 10 min. This study suggests that muscle fatigue is detectable with an accelerometer in actual dynamic cardiomyoplasty. Received: May 11, 2001 / Accepted: September 10, 2002 Acknowledgments This work was financially supported in a part by a Grant in Aid for Scientific Research (05671113) from the Ministry of Education, Science, and Culture of Japan. Correspondence to:H. Kuroda     

Influence of synchronous and sequential stimulation on muscle fatigue

In acute experiments the sciatic nerve of the rat is electrically stimulated to induce fatigue in the medial Gastrocnemius muscle. Fatigue tests are carried out using intermittent stimulation of different compartments (sequential) or a single compartment (synchronous) of the sciatic nerve. The activation of different compartments is achieved by dividing nerve fibres into subbundles and placing them in separate grooves in a multigroove electrode. The aim of the investigation is to quantify the effect of sequential contra synchronised stimulation in reducing muscle fatigue, with no overlap between compartments. Overlap between two compartments is calculated using the combined and individual forces from both compartments. Sequential stimulation of two and three compartments is investigated. There is a significant decrease of fatigue in sequential stimulation compared to synchronous. After 2 min of intermittent stimulation the force time level is significantly increased in sequential stimulation, than in synchronous stimulation. The rate of force time decrease is significantly slower in sequential stimulation than in synchronous stimulation. With sequential stimulation it takes significantly longer before the maximal force time is reached than with synchronous stimulation.     

Recuperation after muscular fatigue by “diverting activities”

Summary Diverting activity is defined as any physical or mental activity performed between or simultaneously with bouts of exhaustive, local muscular work. In the present experiments bouts of exhaustive work consisting of rhythmic lifting of weights were performed with the elbow flexors or with the flexors of the middle finger. Pauses of 2 min duration spent in complete rest or while performing diverting activities alternated between the bouts of work. As diverting activities were used: Physical activity, dynamic or static, performed with big or small muscle groups (other than the fatigued group), or mental activity (problem solving). It was found that the amount of work that could be performed after a pause with diverting activity was always larger than the amount of work performed after a passive pause. The beneficial effect was seen also when the blood flow to the exhausted muscles was interrupted by pneumatic cuffs. Determination of the blood flow in the exhausted muscles by means of Xe-133 clearance showed no systematic blood flow increases caused by the diverting activity. It is concluded that recuperation after local muscle fatigue is influenced by a central nervous factor (Setchenov phenomenon) that is largely independent of the local blood flow.     

Role of potassium in the regulation of systemic physiological function during exercise

In exercise, potassium (K⁺) is released from contracting muscle predominately through K⁺ channels associated with the repolarization phase of the action potential. Increases in extracellular K⁺ are directly related to increases in metabolic rate and may reach concentrations as high as 8–9 mm in the arterial blood during exhaustive work. Exercise-induced hyperkalaemia has been implicated in several physiological processes, in particular skeletal muscle fatigue, hyperaemia, pressor reflex, arterial chemosensitivity and myocardial stability. There is no direct evidence to show that hyperkalaemia causes muscle fatigue, although raised extracellular [K⁺] may contribute to fatigue during prolonged tetani by depressing the propagation of the action potential down the t-tubule system, thus impairing the release of Ca²⁺ from the sarcoplasmic reticulum. The vasodilating properties of K⁺ may transiently contribute to the early phase of exercise hyperaemia and interact synergistically with other vasoactive substances to cause relaxation by hyperpolarizing K⁺ channels in vascular smooth muscle. Hyperkalaemia has been implicated in the regulation of arterial blood pressure through activation of the muscle afferent reflex where potassium-depolarized C fibres may contribute to a reflex increase in arterial blood pressure. K⁺ can also increase ventilation and the sensitivity of the ventilatory response to hypoxia through direct excitation of the arterial chemoreceptors. Finally, to maintain myocardial electrical stability in exercise, there is a beneficial interaction between raised K⁺ and catecholamines on the heart, so that when they combine, each offsets the other's deleterious effects.     

Relationships between muscle lactate accumulation and surface EMG activities during isokinetic contractions in man

Summary In order to investigate the relationship between metabolic state and myoelectrical activity in working muscle during short term intense exercise, eleven healthy males performed isokinetic knee extensions at an angular velocity of 180 deg · sec^–1 for 30 and 60 s. The median frequency (MF) of the surface electromyogram (EMG) recorded from vastus lateralis was decreased while the time lag of torque production after the onset of electrical activity (EMD) was increased during exercise. These changes (MF and EMD) corresponded well to muscle lactate accumulation in the same muscle. Over the exercise period, the integrated EMG/knee extension peak torque ratio (E/T ratio) was increased, which indicated a decrease in the efficiency of electrical activity. It was concluded that the changes in the frequency components of the EMG and in the contractile property of the muscle during short term intense exercise correlated with lactate accumulation in the identical muscle, and that the decrease in efficiency of the electrical activity in the muscle suggested peripheral fatigue.     

Effect of arm-shoulder fatigue on carpenters at work

Summary The purpose of the study was to analyse the effect of arm-shoulder fatigue on manual performance. Ten experienced carpenters performed three standardized tasks (nailing, sawing and screwing). Electromyographic activity was recorded from six arm-shoulder muscles and the performances were video-filmed. After 45 min of standardized arm-cranking (arm-shoulder-fatiguing exercise of approximately 70%–80% maximal oxygen consumption), the tasks were repeated. The number of work movements and the time taken for each task were recorded and the quality of the work performed was compared. After the fatiguing exercise, only nailing was perceived as being harder and more mistakes were made during nailing and sawing. Movement performance was not influenced during nailing but was slightly slower during sawing and faster during screwing. However, there were increased mean EMG amplitudes in the upper trapezius and biceps muscles during nailing, in the upper trapezius, anterior deltoid and infraspinatus muscles during sawing and in the anterior deltoid muscle during screwing. Of the muscles studied the upper trapezius and anterior deltoid muscles increased their activity most after the arm-shoulder-fatiguing exercise.     

Comparison of Euroqol EQ-5D and SF-36 in patients with chronic fatigue syndrome

The objective of the study was to compare the Euroqol EQ-5D (Euroqol) and short-form 36 (SF-36) health questionnaires in patients with chronic fatigue syndrome (CFS). One hundred and twenty-seven out-patients referred to a hospital-based infectious disease clinic with a diagnosis of CFS were contacted by post and asked to complete both questionnaires. Additional data were determined from hospital casenotes. Eighty-five patients returned correctly completed questionnaires. Euroqol health values and visual analogue scale (VAS) scores were strongly and significantly correlated with all dimensions of the SF-36, with the exception of physical limitation of role. SF-36 dimensions were in turn strongly and significantly correlated with each other, with the same exception. Patients reported a high degree of physical disability and a moderate degree of emotional or psychological ill-health. The Euroqol elements dealing with mobility and self-care referred to inappropriately severe degrees of disability for these patients with CFS. Similarly some dimensions in the SF-36 were oversensitive and did not discriminate between patients with moderate or severe disability. It was concluded that Euroqol scores correlated strongly with SF-36 scores and provided useful information about patients with CFS and that Euroqol would be a useful tool for the rapid assessment of health status in CFS. The current Euroqol instrument refers to inappropriately severe degrees of disability for patients with CFS and would need to be modified to be maximally useful in this situation.     

Are voice endurance tests able to assess vocal fatigue?

Voice endurance tests are often used to evaluate vocal fatigue or to test the suitability of an individual for voice demands. It is assumed that these tests help to identify subjects with laryngeal or vocal fatigue out of a population of persons with complaints of discomfort in the throat, recurrent hoarseness and decreased voice power. In this study we evaluated the Voice Interval Test with respect to its discriminative power by comparison of voice performances in 20 patients with a history of vocal fatigue with that in 12 healthy subjects. Voice performance was studied during the Voice Interval Test as well as during regular use of the voice on a working day by electroglottography (EGG), acoustic analysis and a self-rating scale for pain and fatigue. Despite the number of tests the data did not reveal any significant difference between the patients and the healthy subjects. Voice fatigue could therefore not be identified and the clinical relevance of the Voice Interval Test appears to be questionable.     

A comparison between long-term survivors of Hodgkin's disease and their siblings on fatigue level and factors predicting for increased fatigue.

PURPOSE: To compare the level of fatigue in survivors of Hodgkin's disease and their siblings, and to explore factors associated with increased fatigue. METHODS: Survivors of Hodgkin's disease 5 years or more from diagnosis and their siblings completed a questionnaire study. Fatigue level was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) instrument, with lower scores reflecting increased fatigue. Multiple regression models were used to identify factors associated with fatigue level in the two populations. RESULTS: Five hundred and eleven survivors (median age 44 years; range 16-82) and 224 siblings (median age 44 years; range 16-79) returned the completed questionnaire. The response rates were 61% and 58%, respectively. Compared with siblings, survivors were significantly more likely to report the presence of cardiac disease (26% versus 16%; P = 0.001) and hypothyroidism (65% versus 3%; P <0.001), and had a significantly lower mean FACIT-F score (40.7 and 42.2; P = 0.05). On multivariable analysis, factors significantly associated with increased fatigue in survivors were reports of cardiac disease (P <0.001), psychiatric condition (P <0.001), history of tobacco use (P = 0.004) and low exercise frequency (P = 0.03). For siblings, the only independent factor associated with increased fatigue was low exercise frequency (P = 0.03). CONCLUSIONS: Survivors of Hodgkin's disease were more fatigued than their siblings. The difference was modest but statistically significant. The significant association between fatigue and cardiac disease suggests the importance of screening for underlying cardiac dysfunction in survivors with symptoms of fatigue. The association between fatigue and smoking history may be due to exacerbation of late medical complications of Hodgkin's disease by tobacco use.