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International audience; Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient–ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

The aim of the present study was to investigate the in vitro effects of the short-acting β2-adrenoceptor agonist salbutamol and the long-acting β2-adrenoceptor agonist salmeterol on hypoxia-induced rat diaphragm force reduction. In vitro diaphragm twitch force (Pt) and maximal tetanic force (Po) of isolated diaphragm muscle strips were measured for 90 min during hyperoxia (tissue bath [Formula: see text] 83.8 ± 0.9 kPa and [Formula: see text] 3.9 ± 0.1 kPa) or severe hypoxia ([Formula: see text] 7.1 ± 0.3 kPa and [Formula: see text] 3.9 ± 0.1 kPa) in the presence and absence of 1 μM salbutamol or 1 μM salmeterol. During hyperoxia, salbutamol and salmeterol did not significantly alter the time-related decreases in Pt and Po (to ∼50% of initial values). Salbutamol had no effects on Po or the Pt-to-Poratio. Salmeterol treatment significantly reduced Po and increased the Pt-to-Poratio during hyperoxia ( P < 0.05 compared with control value). Hypoxia resulted in a severe decrease in Pt (to ∼30% of initial value) and Po after 90 min. Both salbutamol and salmeterol significantly reduced the decline in Pt during hypoxia ( P < 0.05). The reduction in Po was not prevented. Salbutamol increased Pt rapidly but transiently. Salmeterol had a delayed onset of effect and a longer duration of action. Addition of 1 μM propranolol (a nonselective β-adrenoceptor antagonist) did not alter Pt, Po, or the Pt-to-Poratio during hypoxia but completely blocked the inotropic effects of salbutamol and salmeterol, indicating that these effects are dependent on β2-adrenoceptor agonist-related processes.

Hypoxia is known to reduce isometric contractile properties of isolated rat diaphragm bundles. Its effect on isotonic contractile properties (i.e. force-velocity relationship and power output) has not been studied. We hypothesized that hypoxia reduces velocity of shortening and consequently power output of the unfatigued muscle, and shortens endurance time during isotonic contractions. Force-velocity relationship, power output, and fatigue resistance of rat diaphragm muscle bundles were measured during hypoxia (PO2: 6.6 +/- 0.2 kPa) and compared with hyperoxia (PO2: 91.8 +/- 0.7 kPa). Force was clamped from 1 to 100% of maximal tetanic force (Po). Fatigue during isotonic contractions was induced by repeated stimulation every 2 s at a clamp level of 33% of Po. Hypoxia did not affect isometric force generation compared with hyperoxia, nor contraction or relaxation time. In contrast, maximum shortening velocity decreased significantly (hypoxia: 4.2 +/- 0.3, hyperoxia: 6.0 +/- 0.2 Lo/s, P < 0.05). The force-velocity curve shifted downwards (P < 0.05). Hypoxia lowered power output at each load compared with hyperoxia (P < 0.05). The isotonic endurance time was shorter during hypoxia compared with hyperoxia (80 +/- 2 vs. 130 +/- 3 s, P < 0.05). These data show that hypoxia depresses isotonic contractile properties and power output, and reduces endurance time during repeated isotonic contractions.

Doping is an area of ongoing public, legal, and medical debate and in recent years it has been reported to be connected with many sports including athletics, cycling, body building, soccer, and swimming. Ethical issues related to doping include the honesty of the sports competition and the safety of drugs and other methods applied to improve the physical performance. These issues are of increasing interest and importance since drugs on the prohibited list are easily accessible by medically uncontrolled means such as the Internet. According to the International Olympic Committee (IOC)1doping consists of (1) the administration of substances belonging to prohibited classes of pharmacological agents and/or (2) the use of various prohibited methods. There are five prohibited classes of substances: stimulants, narcotics, anabolic agents, diuretics, and peptide and glycoprotein hormones and their analogues (table 1). Prohibited methods include blood doping and pharmacological, chemical and physical manipulation. View this table: Table 1 Prohibited classes of substances and prohibited methods (shortened and adapted from IOC1) Several respiratory drugs are included in the list of prohibited substances unless they are administered by inhalation. This paper reviews the current literature concerning the effects of respiratory and some other drugs on the respiratory system in the broadest sense—that is, from the respiratory controllers to the respiratory muscles and the lungs themselves. We will focus on the effects in athletes and healthy trained and untrained subjects but, where appropriate, we will also refer to studies in patients, to animal studies, and to studies in peripheral skeletal muscles. In general, the respiratory system does not limit maximal oxygen consumption (V˙o 2max) in healthy subjects.2 3 Only in highly trained endurance athletes may blood oxygen saturation fall during heavy exercise.4 5 The maximal sustainable ventilation decreases with time, and the level that can be sustained …

Dysfunction of the respiratory muscles, especially the diaphragm, is known to occur in patients with severe chronic obstructive pulmonary disease (COPD).1-3 Weakness of the diaphragm is part of a generalised process involving all (respiratory and peripheral) skeletal muscles. Causative factors for respiratory muscle dysfunction in COPD include disturbances in electrolytes,4hypercapnia,5 forward failure,6 and prolonged use of oral corticosteroids.7 In addition, the altered geometry of the thorax in severe emphysema compromises the ventilatory pump function of the diaphragm.8 Malnutrition, which frequently occurs in moderate to severe COPD,9 could also play a part in respiratory muscle dysfunction. Recent studies have indicated that wasting of fat free mass in COPD is associated with peripheral skeletal muscle weakness.10 However, few data are available regarding the effects of malnutrition on respiratory muscle strength. Maximal inspiratory pressure (Pimax) in nutritionally depleted patients with COPD (forced expiratory volume in one second (FEV1) 45.5 (15.1)% predicted) was lower than in non-depleted patients, but this did not reach statistical significance.9 Little is known about the underlying mechanisms of muscle dysfunction and the structural alterations that occur in the diaphragm with COPD. Levine et al 11 have shown that the diaphragm in patients with severe COPD (FEV1 33 (4)% predicted) has a higher proportion of type I (slow) fibres and a lower proportion of type II (fast) fibres than in those without COPD. It has recently been shown that a strong correlation exists between pulmonary functional residual capacity and the proportion of slow myosin heavy chain fibres in the diaphragm.12 This fast to slow fibre transition in the diaphragm can be regarded as an advantageous adaptation since it will attenuate fatiguability of the diaphragm.13 However, eventually most patients with COPD die from respiratory muscle …