Chronic or prolonged low-intensity loading of the inspiratory muscles has recently been shown to produce diaphragm injury. The present study was designed to examine whether an acute episode of inspiratory resistive loading (IRL) could produce secondary diaphragm inflammation and injury. On Day 1, three groups of anesthetized and intubated New Zealand White rabbits were subjected to moderate IRL (Pao of approximately 30 cm H2O), high IRL (Pao of approximately 45 cm H2O), or no load for 1.5 h. On Day 3, costal and crural diaphragms, parasternals, and gastrocnemius muscles were taken to assess injury by point counting. Normal muscle, abnormal and inflamed muscle, and connective tissue on hematoxylin and eosin-stained cross-sections were expressed as percentage of the total points for that cross-section. For the costal diaphragm, both the abnormal muscle (7.3 +/- 0.6% versus 1.1 +/- 0.2%; p < 0.001) and connective tissue (8.0 +/- 0.6% versus 5.7 +/- 0.2%; p < 0.01) in the high IRL group were higher than control, whereas in the moderate IRL group they were not significantly different from control. Total calpain-like activity was increased in the moderate IRL group but not in the high IRL group. Injury was observed in the parasternal muscles but to a lesser extent. No injury was observed in the gastrocnemius muscle. We conclude that secondary diaphragm injury occurs after acute IRL but only when the IRL exceeds the fatigue threshold.

The present study was designed to examine the effect of delayed diaphragm injury produced by inspiratory resistive loading (IRL) on diaphragm force production. On Day 1, three groups of anesthetized and intubated NZW rabbits (n = 7 in each group) were subjected to moderate IRL (Pao approximately 30 cm H2O), high IRL (Pao approximately 45 cm H2O), or no load for 1.5 h. On Day 3, the baseline twitch transdiaphragmatic pressure (Pdi) and Pdi at 10 to 80 Hz were measured during bilateral phrenic stimulation and these measurements were repeated after another IRL (high level) in all three groups. Diaphragm injury was assessed by the point-counting technique. Marked diaphragm injury was observed in the high-IRL group (p < 0.01), but no significant diaphragm injury was observed in the moderate-IRL or control groups. The baseline twitch Pdi was maintained in both IRL groups, whereas the baseline Pdi-frequency values in the high-IRL group were significantly reduced at most frequencies (p < 0.05). The decreases in twitch and Pdi at different frequencies were more pronounced after the IRL on Day 3 in the high-IRL group compared with controls. Moderate IRL did not decrease diaphragm force either before or after the high IRL on Day 3. We conclude that the diaphragm injury induced by high IRL has a significant impact on diaphragm force production and the attendant force loss produced by IRL is dependent on the intensity of inspiratory loading.

V Ve en nt ti il la at to or ry y m mu us sc cl le e s st tr re en ng gt th h a an nd d e en nd du ur ra an nc ce e i in n m my ya as st th he en ni ia a g gr ra av vi is s We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH 2 O (70% of predicted), MEP 86 cmH 2 O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH 2 O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response.We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally. The measurement of ventilatory muscle endurance by incremental threshold loading does not provide additional information to the measurement of ventilatory muscle strength in patients with generalized myasthenia gravis.

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Key Words: antitrypsin deficiency, chronic obstructive pulmonary disease (Clin J Sport Med 2005;15:183-185) A lpha-1 antitrypsin deficiency (a1-ATD) was first identified in the 1960s and was subsequently linked to chronic lung disease. a1-ATD is a genetically transmitted disorder resulting from mutations in the a1-AT gene, 1 and it is associated with a high risk for the development of early-onset pulmonary emphysema. It is estimated that a1-ATD is implicated in 2% to 3% of chronic obstructive pulmonary disease (COPD) cases. 2,3 Therapeutic modalities for a1-ATD are limited. Exercise as a therapeutic intervention is commonly viewed as an integral component of disease management for a variety of chronic conditions. Significant debilitation, impaired exercise tolerance, dyspnea during exercise, and a reduced quality of life are often present in COPD. 4 Exercise training has overwhelmingly been shown to elicit favorable responses in patients with COPD, 5 but little is known about the interactions among physical activity, a1-ATD, and disease management. In the case of a1-ATD, the phenotype is known, and the disease pathology well documented; however, treatment is limited, and the role of physical activity as a management strategy is not well described. This case reports on monozygotic twins as a natural experiment to understand the relationship between physical activity and the a1-ATD genetic disorder. CASE REPORTParticipants were male monozygotic twins (57 y; twin A, twin B) who were diagnosed with a1-ATD (PiZ phenotype) 16 years ago. All procedures were approved by the University of British Columbia, and written informed consent was obtained. Neither twin had a history of asthma, cardiac, vascular, or neuromuscular conditions. Neither used supplemental O 2 at rest or during exercise. Both were clinically stable for over 1-year prior to any testing. Both were exsmokers, had stopped smoking more than 15 years ago, and had similar smoking histories. Each received the same regular infusion of human a1-AT (25-30 g once/2 wk), and each took similar standard medications (Table 1). Neither participated in a structured pulmonary rehabilitation program. Twin A was habitually sedentary, and twin B regularly played golf (2-3 times/wk) and walked the golf course (18 holes). Although we were unable to perform a retrospective quantification of physical activity, it was clear from 10 to 15 years of physician-patient interviews that twin A was habitually sedentary and twin B was regularly physically active. The twins had vocationally similar physical activity patterns.Standard pulmonary function analyses were performed. Lean body mass was determined using dual-energy x-ray absorptiometry (4500 DXA; Hologic, Waltham, MA). Eccentric quadriceps strength was assessed using an isokinetic dynamometer (Chattanooga Group, Hixson, TN). Participants performed a graded cycle exercise test (GXT) to exhaustion. Expired gases, minute ventilation ( _ VE), and derived respiratory variables were recorded (2900; Sensor Medics, Yorba Linda, CA), an...