Muscle Failure Research Articles

Reflections for October

It took a few seconds to realize that the phone was ringing and I wasn't dreaming. “Doc, this is Julie. I'm sorry to waken you but thought you would want to know. Kyle just died.” Kyle's death was not unexpected—he had advanced muscular dystrophy with respiratory muscle failure. As I searched for words to comfort Julie, I was astonished by my own profound sadness. Physicians are cautioned to maintain professional distance from patients and their families, but my long history with Kyle and Julie caused me to break the rules. I realized I'd known Kyle most of my professional life. Our connection punctuated many significant chapters in my career as I helped him navigate one obstacle after another. Although he struggled to breathe, he refused a ventilator. Despite growing weaker, he viewed each loss of a function as a hurdle to overcome—“It's no different than repairing an old car, Doc; just keep me running.” I thought of many parallels in the way we approached life. While mine don't compare with his, we both faced inevitable disappointments, losses, and the need to adapt to new circumstances as optimists—people who saw life as a glass of water “half full”—not “half empty.” My mind drifted back 35 years when I first met Kyle. Like many other economically disadvantaged recruits who lacked formal education and vocational skills, Kyle was attracted to the glamorous portrayals of a military career. A high school dropout, at age 17 he had married Julie, who was pregnant with Rachel. Unemployed and with limited skills, the local Army recruiter's training opportunities and monetary incentives were tempting. He loved to repair cars and wanted to be in the Army's transportation pool. To save money, Julie and Rachel moved in with her parents in Greeley, Colorado. Kyle headed off to basic training …

Neurohypophyseal Dysfunction During Septic Shock

Septic shock is characterized by vasodilation and hypotension despite increased vasoconstrictors. While nitric oxide is known to be responsible for vasodilation, failure of vascular smooth muscle to constrict may be due in part to low plasma levels of vasopressin, a neurohypophyseal hormone. In the initial phase of septic shock, vasopressin concentration usually increases but then decreases to a significantly lower concentration after onset of septic shock. In this review, we discuss the neural mechanisms for the regulation of vasopressin secretion during septic shock.

Myocardial inflammation in Duchenne Muscular Dystrophy as a precipitating factor for heart failure: a prospective study

BackgroundIn patients with Duchenne Muscular Dystrophy (DMD), the absent or diminished dystrophin leads to progressive skeletal muscle and heart failure. We evaluated the role of myocardial inflammation as a precipitating factor in the development of heart failure in DMD.Methods20 DMD patients (aged 15-18 yrs) and 20 age-matched healthy volunteers were studied and followed-up for 2 years. Evaluation of myocarditis with cardiovascular magnetic resonance imaging (CMR) was performed using STIR T2-weighted (T2W), T1-weighted (T1W) before and after contrast media and late enhanced images (LGE). Left ventricular volumes and ejection fraction were also calculated. Myocardial biopsy was performed in patients with positive CMR and immunohistologic and polymerase chain reaction (PCR) analysis was employed.ResultsIn DMD patients, left ventricular end-diastolic volume (LVEDV) was not different compared to controls. Left ventricular end-systolic volume (LVESV) was higher (45.1 ± 6.6 vs. 37.3 ± 3.8 ml, p < 0.001) and left ventricular ejection fraction (LVEF) was lower (53.9 ± 2.1 vs. 63 ± 2.4%, p < 0.001). T2 heart/skeletal muscle ratio and early T1 ratio values in DMD patients presented no difference compared to controls. LGE areas were identified in six DMD patients. In four of them with CMR evidence of myocarditis, myocardial biopsy was performed. Active myocarditis was identified in one and healing myocarditis in three using immunohistology. All six patients with CMR evidence of myocarditis had a rapid deterioration of left ventricular function during the next year.ConclusionsDMD patients with myocardial inflammation documented by CMR had a rigorous progression to heart failure.

Adaptation of Skeletal Muscle O2 Transport and Utilization in Rats with Right Heart Failure

Exercise intolerance is a cardinal symptom in patients with heart failure (HF), resulting from energetic failure in both cardiac and skeletal muscles. HF is known to be associated with skeletal muscle atrophy and a shift towards fast fatigable fibers (Vescovo et al. Int J Cardiol 104:298-, 2005). Additionally, right HF is associated with peripheral edema which may impair convective and diffusive O2 transport. However, structural changes in the pathways determining diffusive O2 transport and utilization are not well understood in right HF. PURPOSE: We therefore determined capillarization, oxidative enzyme activity, fiber area and type in skeletal muscle from rats with right HF. METHODS: Right ventricle hypertrophy was induced by monocrotaline treatment (MCT; 60 mg/kg) in 6 rats, compared to saline control (CON; n=6). After 23±1 (mean, SD) days decompensated HF was verified by weight loss and clinical symptoms. Serial sections (10 μm) of the plantaris muscle were stained for ATPase activity (fiber type), succinate dehydrogenase (SDH) activity (oxidative capacity) and capillaries. Glycolytic and oxidative regions were analyzed separately and compared between conditions by two-way ANOVA. RESULTS: In MCT whole body and liver weights were less (p<0.01), and right ventricle and lung weights were greater (p<0.01) than CON. The plantaris was heavier in CON than MCT: 273±19 vs. 242±5 mg (p<0.05); but mean fiber cross-sectional area was not different: 2143±405 vs. 2045±287 μm2. The area occupied by type IIa fibers tended to be lower and the area of hybrid (IIa/x) fibers was significantly greater (p<0.05) in MCT. SDH activity was 15% lower in MCT independent of region and fiber type (p=0.06) and capillary to fiber ratio was greater in CON than MCT: 2.3±0.3 vs. 1.9±0.2 (p<0.05). CONCLUSIONS: As expected, there was a shift towards fast fatigable fibers in MCT treated rats. However, there was a similar reduction in SDH activity in both oxidative and glycolytic regions independent of fiber type, suggesting different remodeling pathways. The lower oxidative capacity in MCT was concurrent with a lower potential for diffusive O2 transport, as evidenced by fewer capillaries per fiber, but without fiber atrophy. These reductions in diffusive O2 transport and utilization may contribute to the energetic failure of skeletal muscles in right HF.

Respiratory disorders in type-1 hereditary motor and sensory neuropathy

Type-1 hereditary motor and sensory neuropathy (HMSN I) is a slowly progressive disease resulting in distal muscle weakness with atrophy, and in sensory disturbance. Restrictive lung disease and respiratory muscle failure, common in many advanced neuromuscular disorders, is not a predominant feature of HMSN-I. Recently, there have been several reports of respiratory dysfunction in patients with HMSN I, complicated by diaphragmatic weakness. In five patients with HMSN I (3 men and 2 women, mean age 55.4 yrs), we measured spirometric variables, maximal inspiratory pressure, and maximal expiratory pressure, in both sitting and supine positions. We also studied phrenic nerve conduction by cutaneous stimulation at the posterior border of the sternocleidomastoid muscle. Four of five patients had low maximal inspiratory pressure and abnormally long phrenic nerve latency. Two patients showed evidence of a restrictive lung disorder and daytime alveolar hypoventilation. All-night polysomnography in those two patients revealed periodic decreases in arterial blood oxygen saturation, and episodes of central apnea. We conclude that diaphragmatic dysfunction is not rare in HMSN I, and that maximal inspiratory pressure and phrenic nerve conduction may be useful in the early detection of phrenic nerve involvement.

Physiologische Atmungsparameter und der Effekt der nicht invasiven Beatmung (NIV) bei Patienten mit amyotropher Lateralsklerose (ALS)

Amyotrophic lateral sclerosis (ALS), as a consequence of the progressive failure of respiratory muscles, often causes chronic ventilatory failure (CVF), indicated by hypercapnia. This study analyses the physiological parameters of breathing in patients with ALS over time and the variables which influence survival time. In this observational study we analysed the data of physiological parameters (respiratory function, blood gas levels and breathing during sleep), as well as survival rate (according to Kaplan-Meier) of all 85 ALS patients who stayed in our hospital during the period of 1st January 2003 until 31st December 2007. After ALS had been diagnosed, all patients ran through standardised pneumological diagnostics during the observation period, this procedure was repeated every 3-6 months. If hypercapnia (carbon dioxide tension pCO(2) > 45 mm Hg) was detected, non-invasive ventilation (NIV) was indicated and offered to the respective patients. In the course of the observation, the parameters of respiratory function IVC (inspiratory vital capacity) and FEV1 (forced expiratory volume after 1 second) have shown a significant reduction by 14-15% per year. Half of the patients died within 3.1 years after ALS had been diagnosed. IVC and FEV1 had no impact on the survival time. In contrast, pCO(2) correlates negatively with the survival time. The period between diagnosis of ALS and manifestation of hypercapnia is about 1.9 +/- 2.4 years. In spite of a clear indication, some of the patients did not comply with NIV or did not accept it (19 patients, 22%). Twenty-eight patients (33%) started NIV with a good compliance. The survival rate of patients with NIV was 1.27 years on average--after the initial measurement of hypercapnia. The survival time of hypercapnic patients without NIV was only 0.12 years. Hypercapnia has a significant impact on the prognosis for ALS patients. In the case of CVF (hypercapnia), the survival time of ALS patients is significantly reduced. NIV is able to significantly increase the survival time of ALS patients with hypercapnia.

Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm

Respiratory failure is a major cause of mortality during septic shock and is due in part to decreased ventilatory muscle contraction. Ventilatory muscles have high energy demands; fatty acid (FA) oxidation is an important source of ATP. FA oxidation is regulated by nuclear hormone receptors; studies have shown that the expression of these receptors is decreased in liver, heart, and kidney during sepsis. Here, we demonstrate that lipopolysaccharide (LPS) decreases FA oxidation and the expression of lipoprotein lipase (LPL), FA transport protein 1 (FATP-1), CD36, carnitine palmitoyltransferase beta, medium chain acyl-CoA dehydrogenase (MCAD), and acyl-CoA synthetase, key proteins required for FA uptake and oxidation, in the diaphragm. LPS also decreased mRNA levels of PPARalpha and beta/delta, RXRalpha, beta, and gamma, thyroid hormone receptor alpha and beta, and estrogen related receptor alpha (ERRalpha) and their coactivators PGC-1alpha, PGC-1beta, SRC1, SRC2, Lipin 1, and CBP. Zymosan resulted in similar changes in the diaphragm. Finally, in PPARalpha deficient mice, baseline CPT-1beta and FATP-1 levels were markedly decreased and were not further reduced by LPS suggesting that a decrease in the PPARalpha signaling pathway plays an important role in inducing some of these changes. The decrease in FA oxidation in the diaphragm may be detrimental, leading to decreased diaphragm contraction and an increased risk of respiratory failure during sepsis.

LRT, a tendon-specific leucine-rich repeat protein, promotes muscle-tendon targeting through its interaction with Robo

Correct muscle migration towards tendon cells, and the adhesion of these two cell types, form the basis for contractile tissue assembly in the Drosophila embryo. While molecules promoting the attraction of muscles towards tendon cells have been described, signals involved in the arrest of muscle migration following the arrival of myotubes at their corresponding tendon cells have yet to be elucidated. Here, we describe a novel tendon-specific transmembrane protein, which we named LRT due to the presence of a leucine-rich repeat domain (LRR) in its extracellular region. Our analysis suggests that LRT acts non-autonomously to better target the muscle and/or arrest its migration upon arrival at its corresponding tendon cell. Muscles in embryos lacking LRT exhibited continuous formation of membrane extensions despite arrival at their corresponding tendon cells, and a partial failure of muscles to target their correct tendon cells. In addition, overexpression of LRT in tendon cells often stalled muscles located close to the tendon cells. LRT formed a protein complex with Robo, and we detected a functional genetic interaction between Robo and LRT at the level of muscle migration behavior. Taken together, our data suggest a novel mechanism by which muscles are targeted towards tendon cells as a result of LRT-Robo interactions. This mechanism may apply to the Robo-dependent migration of a wide variety of cell types.

Amyotrophic lateral sclerosis (ALS): three letters that change the people's life. For ever

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor nervous system. It causes progressive and cumulative physical disabilities in patients, and leads to eventual death due to respiratory muscle failure. The disease is diverse in its presentation, course, and progression. We do not yet fully understand the cause or causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. Currently, we rely on a multidisciplinary approach to symptomatically manage and care for patients who have ALS. Although amyotrophic lateral sclerosis and its variants are readily recognized by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with Riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. Multiple problems require a multidisciplinary approach including aggressive symptomatic management, rehabilitation to maintain motor function, nutritional support (enteric feeding, gastrostomy), respiratory support (non invasive home ventilation, invasive ventilation, tracheotomy), augmentative communication devices, palliative care, psychological support for both patients and families (because family members so often play a central role in management and care), communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. Social, bioethical, and financial issues as well as advance directives should be addressed. A plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice. The multidisciplinary team has changed the history of disease, with still no curative therapy available.

A High-resolution View of Achalasia

High-resolution manometry (HRM) makes it possible to better evaluate spatial and temporal characteristics of esophageal motor function. This technology is revealing new observations regarding disordered motor function in esophageal diseases. The aim of this study was to define the essential features of achalasia using HRM. We performed HRM on 27 patients with achalasia, 10 patients with gastroesophageal reflux disease, and 10 controls. Ten 5 mL water swallows were recorded with a solid-state manometric assembly incorporating 36 circumferential sensors spaced at 1-cm intervals. The resting lower esophageal sphincter pressure was greater in achalasia than in controls or gastroesophageal reflux disease. There was an absence of peristalsis in the smooth muscle esophagus and failure of lower esophageal sphincter relaxation. The resting upper esophageal sphincter pressure was not different among the 3 groups. In addition to the typical manometric findings of achalasia, new observations are included. Esophageal shortening, pressurization of the esophagus, and rhythmic contractions of the upper esophageal sphincter and striated muscle esophagus were frequently observed. HRM demonstrates alterations of esophageal motor function in achalasia that are not easily observed with other manometric techniques.

Muscle Activation Patterns And Repetitions-to-failure Performance In The Bench Press Exercise

The bench press (BP) exercise is used to determine and develop upper-body muscular strength and work capacity. PURPOSE: To examine the muscle activation pattern during performance of a bench press repetitions-to-failure (RTF) test. METHODS: Subjects (n=16; Age: 21+2 yr; ht: 179+6 cm; wt: 78+7 kg) performed BP one-repetition maximum (1-RM) and RTF (60% 1-RM) test. Surface EMG was collected during each repetition of both tests from the pectoralis major (PM), triceps brachii (TB), anterior (AD) and posterior (PD) deltoid, latissimus dorsi (LD), and biceps brachii (BB) muscle groups. The concentric phase EMG signals were integrated (iEMG) and normalized to muscle group specific EMG activity collected during a maximal voluntary isometric contraction (EMGMVC) performed at the mid-range of the BP exercise and prior to initiating testing. Mean power frequency (MPF) was also determined for the concentric phase. RESULTS: 1-RM BP (92.2+24.3 kg) was moderately correlated with body mass (r=0.74), fat-free mass (r=0.64) and fat mass (r=0.71). Subjects performed 23.4+2.5 reps during RTF. Although 1-RM was highly correlated with work capacity (load.reps; 1388+330 kg. reps; r=0.89) the relationship with RTF was negative and low (r=-0.22). During RTF concentric contraction time increased (0.69 +0.21 to 1.81 +0.83 sec), while range of motion (242+8° to 254+19°) and excentric contraction time (0.640-.900 sec) did not change from the first to the last repetition. iEMG/ EMGMVC increased progressively from the beginning (∼0.16-0.30) to the end (∼0.21-0.51) of each concentric contraction in PM, TB, AD and LD during RTF. At failure iEMG/ EMGMVC increased at the beginning (∼0.21-0.46) and end (∼0.39-0.83) of the concentric contraction; the latter activity was equal to iEMG/ EMGMVC activity observed during 1-RM. MPF decreased in PM (55.2+8.1 to 47.1+5.6 Hz) and TB (55.7+5.3 to 49.4+6.8 Hz), while AD (54.2+4.4 to 53.5+3.5 Hz) and LD (50.8+8.1 to 47.4+6.8 Hz) remained unchanged. CONCLUSION: There was a progressive increase in concentric contraction time and EMG activity and a decrease in MPF associated with muscle failure during RTF testing. The pattern and magnitude of EMG activity relative to EMGMVC was similar in PM, TB, AD and LD muscle groups. Supported in part by PEO Soldier Grant # AHS1131

An analytical phantom for the evaluation of medical flow imaging algorithms

Blood flow characteristics (e.g. velocity, pressure, shear stress, streamline and volumetric flow rate) are effective tools in diagnosis of cardiovascular diseases such as atherosclerotic plaque, aneurism and cardiac muscle failure. Noninvasive estimation of cardiovascular blood flow characteristics is mostly limited to the measurement of velocity components by medical imaging modalities. Once the velocity field is obtained from the images, other flow characteristics within the cardiovascular system can be determined using algorithms relating them to the velocity components. In this work, we propose an analytical flow phantom to evaluate these algorithms accurately. The Navier–Stokes equations are used to derive this flow phantom. The exact solution of these equations obtains analytical expression for the flow characteristics inside the domain. Features such as pulsatility, incompressibility and viscosity of flow are included in a three-dimensional domain. The velocity domain of the resulted system is presented as reference images. These images could be employed to evaluate the performance of different flow characteristic algorithms. In this study, we also present some applications of the obtained phantom. The calculation of pressure domain from velocity data, volumetric flow rate, wall shear stress and particle trace are the characteristics whose algorithms are evaluated here. We also present the application of this phantom in the analysis of noisy and low-resolution images. The presented phantom can be considered as a benchmark test to compare the accuracy of different flow characteristic algorithms.

Rosuvastatin-induced Rhabdomyolysis Probably via CYP2C9 Saturation

A 66 year-old woman with no history of renal or liver disease presented with progressive asthenia and diffuse myalgia. She cited 5 months history of mild hyperlipidemia under treatment with rosuvastatin (10 mg/day). Clinical examination documented both an increase in liver size and proximal muscle weakness, with difficulty in raising arms above the head. Blood tests showed the presence of renal, liver and muscle failure, with no evidence of virological, immunological or haematological diseases. Rosuvastatin treatment was stopped and blood values normalised within five days; but because of an increase in cholesterol plasma levels, rosuvastatin (10 mg/day) was restarted. Two days later, the patient returned to our observation due to the development of asthenia and muscle weakness, with an increase in creatine phosphokinase, 12,165 U/l. Rosuvastatin was discontinued and replaced with pravastatin (40 mg/day) with a complete resolution of clinical and laboratory findings in about six days. Our patient was taking rosuvastatin, warfarin and telmisartan, which are metabolised by CYP2C9; we therefore hypothesised that the rosuvastatin-induced rhabdomyolysis was probably by CYP2C9 enzyme saturation.

Analogien zwischen Herz- und Atemmuskelinsuffizienz

Heart failure is an established diagnosis. Respiratory muscle or ventilatory pump failure, however, is less well known. The latter becomes obvious through hypercapnia, caused by hypoventilation. The respiratory centre tunes into hypercapnea in order to prevent the danger of respiratory muscle overload (hypercapnic ventilatory failure). Hypoventilation will consecutively cause hypoxemia but this will not be responsible for performance limitation. One therefore has to distinguish primary hypoxemia evolving from diseases in the lung parenchyma. Here hypoxemia is the key feature and compensatory hyperventilation usually decreases PaCO2 levels. The cardiac as well as the respiratory pump adapt to an inevitable burden caused by chronic disease. In either case organ muscle mass will increase. If the burden exceeds the range of possible physiological adaptation, compensatory mechanisms will set in that are similar in both instances. During periods of overload either muscle system is mainly fueled by muscular glycogen. In the recovery phase (e. g. during sleep) stores are replenished, which can be recognized by down-regulation of the blood pressure in case of the cardiac pumb or by augmentation of hypercapnia through hypoventilation in case of the respiratory pump. The main function of cardiac and respiratory pump is maintenance of oxygen transport. The human body has developed certain compensatory mechanisms to adapt to insufficient oxygen supply especially during periods of overload. These mechanisms include shift of the oxygen binding curve, expression of respiratory chain isoenzymes capable of producing ATP at lower partial pressures of oxygen and the development of polyglobulia. Medically or pharmacologically the cardiac pump can be unloaded with beta blockers, the respiratory pump by application of inspired oxygen. Newer forms of therapy augment the process of recovery. The heart can be supported through bypass surgery or intravascular pump systems, while respiratory muscles may be supported through elective ventilatory support (mainly non-invasive) in the patient's home. The latter treatment in particular will increase patient endurance and quality of life and decrease mortality. Heart and respiratory pump failure share many common features. Since both take care of oxygen supply to the body, their function and compensatory mechanisms are closely related and linked.

Bench-to-bedside review: ventilatory abnormalities in sepsis.

In septic patients increased central drive and increased metabolic demands combine to increase energy demands on the ventilatory muscles. This occurs at a time when energy supplies are limited and energy production hindered, and it leads to an energy supply-demand imbalance and often ventilatory failure. Problems related to contractile function of the ventilatory muscles also contribute, especially when the clinical course is prolonged. The increased ventilatory activity increases interactions between the ventilatory and cardiovascular systems, and when ventilatory muscles fail and mechanical ventilatory support is required a new set of problems emerges. In this review I discuss factors related to ventilatory muscle failure, giving emphasis to mechanical and supply demand aspects. I also review the implications of changes in ventilatory patterns for heart-lung interactions.

Successful use of short‐term mechanical ventilation to manage respiratory failure secondary to profound hypokalemia in a cat with hyperaldosteronism

AbstractObjective – To report successful management of respiratory failure due to severe hypokalemia in a cat with hyperaldosteronism, including short‐term mechanical ventilation strategies and aspects of medical and surgical treatment.Case Summary – A cat presented with bilateral pelvic limb weakness that rapidly progressed to tetraparesis and respiratory muscle failure. Point‐of‐care testing revealed severe hypokalemia (1.9 mmol/L) and mild azotemia. Initial management included endotracheal intubation, mechanical ventilation, and aggressive potassium supplementation. Spironolactone was started due to a high index of suspicion for hyperaldosteronism. A right adrenal mass visualized during abdominal ultrasonographic examination and a serum aldosterone level greater than 3329 pmol/L confirmed the diagnosis. The cat made a full recovery following surgical removal of a right adrenal adenoma.New or Unique Information Provided – We report successful management of respiratory failure in a cat with hyperaldosteronism using short‐term mechanical ventilation. Respiratory failure due to severe hypokalemia should be considered a complication of hyperaldosteronism in cats and may require mechanical ventilation. However, full recovery is possible.

Nav1.4 Deregulation in Dystrophic Skeletal Muscle Leads to Na+ Overload and Enhanced Cell Death

Duchenne muscular dystrophy (DMD) is a hereditary degenerative disease manifested by the absence of dystrophin, a structural, cytoskeletal protein, leading to muscle degeneration and early death through respiratory and cardiac muscle failure. Whereas the rise of cytosolic Ca2+ concentrations in muscles of mdx mouse, an animal model of DMD, has been extensively documented, little is known about the mechanisms causing alterations in Na+ concentrations. Here we show that the skeletal muscle isoform of the voltage-gated sodium channel, Nav1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na+ concentrations found in muscle from mdx mice. The absence of dystrophin modifies the expression level and gating properties of Nav1.4, leading to an increased Na+ concentration under the sarcolemma. Moreover, the distribution of Nav1.4 is altered in mdx muscle while maintaining the colocalization with one of the dystrophin-associated proteins, syntrophin α-1, thus suggesting that syntrophin is an important linker between dystrophin and Nav1.4. Additionally, we show that these modifications of Nav1.4 gating properties and increased Na+ concentrations are strongly correlated with increased cell death in mdx fibers and that both cell death and Na+ overload can be reversed by 3 nM tetrodotoxin, a specific Nav1.4 blocker.

Testing for maximum oxygen consumption has produced a brainless model of human exercise performance

The measurement of the maximum oxygen consumption (VO2max) is probably the most widely used test in the applied sports sciences. Yet this test includes three features that are foreign to...

NIV - Modi und Prognose

Non-invasive (NIV) as well as invasive mechanical ventilation are established for the treatment of ventilatory failure in neuromuscular diseases. The EUROVENT study provides data about mechanical ventilation at home. In this survey there is a trend towards pressure-derived ventilation in these patient groups. Volume-cycled ventilators had been used in 41% patients with neuromuscular diseases. During the past decade a remarkable change towards pressure-cycled ventilation has occurred. Two recently published, randomised cross-over studies demonstrated equal efficacy of volume-cycled ventilation compared to pressure-cycled ventilation in terms of gas exchange and sleep efficacy in chronic ventilatory failure. In both groups the median survival times were equal. In respiratory muscle failure, assisted ventilation, assist/controlled ventilation as well as controlled ventilation are applied. Between 1977 and 2001, long-term survival improved in patients with Duchenne muscular dystrophy (DMD) in Denmark based on a strict organisation of care, home ventilation as standard treatment and the establishment of centres for home ventilation. The proportion of ventilated patients rose from 0.9% to 43.4% of all DMD patients. The median survival of an untreated DMD patient is 9.7 months. Simonds demonstrated a 5-year survival rate of 73% in these groups of patients under home mechanical ventilation. In patients with the more rapidly deteriorating amyotrophic lateral sclerosis, the efficacy of home ventilation is less impressive and bulbar involvement serves as an independent negative predictor.

Impact of breathing pattern on work of breathing in healthy subjects and patients with COPD

The impact of the respiratory pattern on respiratory muscle workload represents an unresolved controversy and is important for the treatment of patients with respiratory disorders and respiratory muscle failure. We designed this study to investigate the relationship of respiratory pattern and inspiratory workload. We measured esophageal pressure and inspiratory flow and calculated work of breathing, tidal volume and respiratory rate. Ten healthy subjects and 10 COPD patients participated and performed five different breathing patterns starting from respiratory rate 12 and tidal volume 1l or quiet breathing, respectively. They were instructed to increase respiratory rate by 50 and 100% as well as tidal volume by 50 and 100% while maintaining constant minute-ventilation. In healthy subjects Delta VT was the single best parameter to predict Delta WOB (R=0.958, R(2)=0.918, p<0.0001). The relationships of changes in tidal volume, respiratory rate and rapid shallow breathing index to changes in WOB were linear. In the COPD Delta VT was also the single best parameter to predict changes in work of breathing (R=0.777, R(2)=0.604, p<0.0001), however the relation of respiratory rate and rapid shallow breathing index to work of breathing was exponential (e-function) with lower indices generating higher workload. We conclude that rapid shallow breathing might be a strategy to compensate for burdensome respiratory mechanics. In COPD patients however we observed a critical threshold where any further increases in rapid shallow breathing index will be of no further benefit.