More Impaired Dynamic Ventilatory Muscle Oxygenation in Congestive Heart Failure than in Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF) often have dyspnea. Despite differences in primary organ derangement and similarities in secondary skeletal muscle changes, both patient groups have prominent functional impairment. With similar daily exercise performance in patients with CHF and COPD, we hypothesized that patients with CHF would have worse ventilatory muscle oxygenation than patients with COPD. This study aimed to compare differences in tissue oxygenation and blood capacity between ventilatory muscles and leg muscles and between the two patient groups. Demographic data, lung function, and maximal cardiopulmonary exercise tests were performed in 134 subjects without acute illnesses. Muscle oxygenation and blood capacity were measured using frequency-domain near-infrared spectroscopy (fd-NIRS). We enrolled normal subjects and patients with COPD and CHF. The two patient groups were matched by oxygen-cost diagram scores, New York Heart Association functional classification scores, and modified Medical Research Council scores. COPD was defined as forced expired volume in one second and forced expired vital capacity ratio ≤0.7. CHF was defined as stable heart failure with an ejection fraction ≤49%. The healthy subjects were defined as those with no obvious history of chronic disease. Age, body mass index, cigarette consumption, lung function, and exercise capacity were different across the three groups. Muscle oxygenation and blood capacity were adjusted accordingly. Leg muscles had higher deoxygenation (HHb) and oxygenation (HbO2) and lower oxygen saturation (SmO2) than ventilatory muscles in all participants. The SmO2 of leg muscles was lower than that of ventilatory muscles because SmO2 was calculated as HbO2/(HHb+HbO2), and the HHb of leg muscles was relatively higher than the HbO2 of leg muscles. The healthy subjects had higher SmO2, the patients with COPD had higher HHb, and the patients with CHF had lower HbO2 in both muscle groups throughout the tests. The patients with CHF had lower SmO2 of ventilatory muscles than the patients with COPD at peak exercise (p < 0.01). We conclud that fd-NIRS can be used to discriminate tissue oxygenation of different musculatures and disease entities. More studies on interventions on ventilatory muscle oxygenation in patients with CHF and COPD are warranted.

Respiratory gas levels interact to control ventilatory motor patterns in isolated locust ganglia

Large insects actively ventilate their tracheal system even at rest, using abdominal pumping movements, which are controlled by a central pattern generator (CPG) in the thoracic ganglia. We studied the effects of respiratory gases on the ventilatory rhythm by isolating the thoracic ganglia and perfusing its main tracheae with various respiratory gas mixtures. Fictive ventilation activity was recorded from motor nerves controlling spiracular and abdominal ventilatory muscles. Both hypoxia and hypercapnia increased the ventilation rate, with the latter being much more potent. Sub-threshold hypoxic and hypercapnic levels were still able to modulate the rhythm as a result of interactions between the effects of the two respiratory gases. Additionally, changing the oxygen levels in the bathing saline affected ventilation rate, suggesting a modulatory role for haemolymph oxygen. Central sensing of both respiratory gases as well as interactions of their effects on the motor output of the ventilatory CPG reported here indicate convergent evolution of respiratory control among terrestrial animals of distant taxa.Summary statementTight control over respiratory gas supply to the isolated locust CNS reveals interactions of oxygen and carbon dioxide effects on central ventilatory output.

Pulmonary function and ventilatory muscle strengh in Myasthenia Gravis.

Introduction: Myasthenia gravis (MG) is a neuromuscular autoimmune disease of unknown etiology, characterized by generalized muscle weakness and fatigue, especially after repetitive physical activities, with consequent improvement after rest. The MG follows a slowly progressive course, which can be fatal failure of the ventilatory muscles. The manifestations of the respiratory system are generally attributed to the weakness of the diaphragm and also accessory muscles of ventilation. Objetive: The objective was to evaluate the volumes and lung capacities and maximum pressure ventilation in patients with clinically stable MG. Methods: This is an observational study involving 15 patients (2 men) with MG. Subjects were recruited consecutively and screened for eligibility using the standardized protocol. Results: Spirometry, only two patients showed abnormalities of respiratory pattern, being a moderate restrictive pattern (50-60% predicted), and another patient with the congenital form showed a severe restrictive pattern. Not obstructive patterns were observed. Our results of spirometry showed an average value of FVC: 3.15 ± 0.77 and FEV1: 2.64 ± 0.65. Regarding the maximum pressure generated by the ventilatory muscles, the average value for the MIP was 45.5 cmH2O among women and the value of 56 cmH2O for men was observed. To MEP it was observed the average value of 45 cmH2O for women and 55 cmH2O for men. Conclusion: We conclude that patients with MG have lower values of maximal inspiratory and expiratory ventilatory associated with normal lung function values.

Regulation of nitric oxide production in limb and ventilatory muscles during chronic exercise training

In this study, we evaluated the differential influence of chronic treadmill training (30 m/min, 15% incline, 1 h/day, 5 days/wk) on nitric oxide (NO) production and NO synthase (NOS) isoform expression as well as 3-nitrotyrosine formation (footprint of peroxynitrite) both in limb (gastrocnemius) and ventilatory (diaphragm) muscles. A group of exercise-trained rats and a control group (no training) were examined after a 4-wk experimental period. Exercise training elicited an approximate fourfold rise in gastrocnemius NOS activity and augmented protein expression of the endothelial (eNOS) and neuronal (nNOS) isoforms of NOS to ∼480% and 240%, respectively. Qualitatively similar but quantitatively smaller elevations in NOS activity and eNOS and nNOS expression were observed in the diaphragm. No detectable inducible NOS (iNOS) protein expression was found in any of the muscle samples. Training increased the intensity of 3-nitrotyrosine only in the gastrocnemius muscle. We conclude that whole body exercise training enhances both limb and ventilatory muscle NO production and that constitutive and not iNOS isoforms are responsible for increased protein tyrosine nitration in trained limb muscles.

Role of heme oxygenases in sepsis-induced diaphragmatic contractile dysfunction and oxidative stress

Heme oxygenases (HOs), essential enzymes for heme metabolism, play an important role in the defense against oxidative stress. In this study, we evaluated the expression and functional significance of HO-1 and HO-2 in the ventilatory muscles of normal rats and rats injected with bacterial lipopolysaccharide (LPS). Both HO-1 and HO-2 proteins were detected inside ventilatory and limb muscle fibers of normal rats. Diaphragmatic HO-1 and HO-2 expressions rose significantly within 1 and 12 h of LPS injection, respectively. Inhibition of the activity of inducible nitric oxide synthase (iNOS) in rats and absence of this isoform in iNOS−/− mice did alter sepsis-induced regulation of muscle HOs. Systemic inhibition of HO activity with chromium mesoporphyrin IX enhanced muscle protein oxidation and hydroxynonenal formation in both normal and septic rats. Moreover, in vitro diaphragmatic force generation declined substantially in response to HO inhibition both in normal and septic rats. We conclude that both HO-1 and HO-2 proteins play an important role in the regulation of muscle contractility and in the defense against sepsis-induced oxidative stress.

Bedrest alters respiratory muscle strength in patients immobilized due to fractured femurs

Bedrest produces decrements in the functioning of all physiological systems. Physiotherapists treat patients who are managed with Thomas splints following fractured femurs. The patients are generally compartmentally treated as orthopaedic patients. No attention is paid to the status of the respiratory system which can be the cause of morbidity in these patients. Since the ventilatory muscles play a major role in breathing and coughing the purpose of the present study was to determine the effect of a limited period of bedrest on the strength of the inspiratory and expiratory muscles.A sample of convenience consisting of 15 African male patients immobilized by Thomas’ Splint for fractured mid-shaft femurs participated in the study by voluntary consent. All patients had been confined to bed for at least 3 weeks. Maximal inspiratory pressures (PiMAX) and Maximal expiratory pressures (PeMAX) were recorded using a Boehringer Force Meter at functional residual capacity in the semi-recumbent position. The data were normalized and analyzed using the student t-test at the 0.05% level.The results showed a significant reduction in both PiMAX and PeMAX compared to age predicted normal values. The decrease in PeMAX was greater than that of PiMAX.We conclude that respiratory muscle strength decays with bedrest.