Physical activity relies on muscular force. In adult skeletal muscle, force results from the contraction of postmitotic, multinucleated myofibres of different contractile and metabolic properties. Myofibres can adapt to (patho-)physiological conditions of altered functional demand by radial growth, longitudinal growth, and regulation of fibre type functional gene modules. The adaptation's specificity depends on the distinct molecular and cellular events triggered by unique combinations of conditional cues. In order to derive effective and tailored exercise prescriptions, it must be determined (1) which mechano-biological condition leads to what molecular/cellular response, and (2) how this molecular/cellular response relates to the structural, contractile, and metabolic adaptation. It follows that a thorough mechano-biological description of the loading condition is imperative. Unfortunately, the definition of (resistance) exercise conditions in the past and present literature is insufficient. It is classically limited to load magnitude, number of repetitions and sets, rest in-between sets, number of interventions/week, and training period. In this review, we show why the current description is insufficient, and identify new determinants of quantitative and/or qualitative effects on skeletal muscle with respect to resistance exercise in healthy, adult humans. These new mandatory determinants comprise the fractional and temporal distribution of the contraction modes per repetition, duration of one repetition, rest in-between repetitions, time under tension, muscular failure, range of motion, recovery time, and anatomical definition. We strongly recommend to standardise the design and description of all future resistance exercise investigations by using the herein proposed set of 13 mechano-biological determinants (classical and new ones).

Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia. J. Appl. Physiol. 66(4): [1785][1786][1787][1788] 1989.-This study was carried out to investigate the early changes in erythropoietin (EPO) formation in humans in response to hypoxia. Six volunteers were exposed to simulated altitudes of 3,000 and 4,000 m in a decompression chamber for 5.5 h. EPO was measured by radioimmunoassay in serum samples withdrawn every 30 min during altitude exposure and also in two subjects after termination of hypoxia (4,000 m). EPO levels during hypoxia were significantly elevated after 114 and 84 min (3,000 and 4,000 m), rising thereafter continuously for the period investigated. Mean values increased from 16.0 to 22.5 mu/ml (3,000 m) and from 16.7 to 28.0 mu/ml (4,000 m). This rise in EPO levels corresponds to 1.8-fold (3,000 m) and 3.0-fold (4,000 m) increases in the calculated production rate of the hormone. After termination of hypoxia, EPO levels continued to rise for ~1.5 h and after 3 h declined exponentially with an average half-life time of 5.2 h. simulated altitude; half-life time; radioimmunoassay THE ADJUSTMENT OF THE erythrocyte mass to the availability of 02 in the mammalian organism is brought about by renal secretion of erythropoietin (EPO). However, the regulation of renal EPO production is not completely understood. Present knowledge is mainly based on experiments in laboratory animals. Direct data related to the regulation of EPO production in humans are confined to two observations. First, it has been shown that in anemias serum EPO levels are inversely correlated with the hematocrit (5,7,9), and, second, it was demonstrated that a sojourn at high altitude increases EPO concentrations in blood and urine (1, 3, 8,(12)(13)(14) 17). However, when subjects travel to high altitude (1, 3,8, 12, 14), the interval required for ascent does not allow the precise study of early increase in EPO formation, because the onset of hypoxia is gradual and not clearly defined. During mountaineering expeditions (1, 12) additional factors, e.g., physical exercise, may also influence EPO formation in an unpredictable manner. Furthermore, with the exception of one study (12), in previous investigations in humans only bioassays for EPO that indicate a change in the serum EPO level at least threefold above the normal value were available.The present study was therefore carried out to show a more definitive association between hypoxia and EPO formation in humans. We measured serum EPO levels with a sensitive radioimmunoassay in healthy volunteers exposed to simulated altitudes of 3,000 (9,840 ft) and 4,000 m (13,120 ft) under controlled conditions in a decompression chamber. The changes in serum EPO levels after acute onset and after termination of hypoxia, as well as the relationship between alveolar partial pressure of 02 and EPO formation were determined. SUBJECTSANDMETHODSSubjects. Six male volunteers (24-39 yr) participated in the study after being informed about the aim of the investigation and the ex...

We examined the effects of respiratory muscle work [inspiratory (W r-insp); expiratory (W r-exp)] and arterial oxygenation (SpO 2 ) on exerciseinduced locomotor muscle fatigue in patients with chronic obstructive pulmonary disease (COPD). Eight patients (FEV, 48 Ϯ 4%) performed constant-load cycling to exhaustion (Ctrl; 9.8 Ϯ 1.2 min). In subsequent trials, the identical exercise was repeated with 1) proportional assist ventilation ϩ heliox (PAV); 2) heliox (He:21% O 2); 3) 60% O 2 inspirate (hyperoxia); or 4) hyperoxic heliox mixture (He: 40% O 2). Five age-matched healthy control subjects performed Ctrl exercise at the same relative workload but for 14.7 min (Ϸbest COPD performance). Exercise-induced quadriceps fatigue was assessed via changes in quadriceps twitch force (Q tw,pot) from before to 10 min after exercise in response to supramaximal femoral nerve stimulation. During Ctrl, absolute workload (124 Ϯ 6 vs. 62 Ϯ 7 W), W r-insp (207 Ϯ 18 vs. 301 Ϯ 37 cmH 2O·s·min Ϫ1 ), Wr-exp (172 Ϯ 15 vs. 635 Ϯ 58 cmH 2O·s·min Ϫ1 ), and SpO 2 (96 Ϯ 1% vs. 87 Ϯ 3%) differed between control subjects and patients. Various interventions altered W r-insp, W r-exp, and SpO 2 from Ctrl (PAV: Ϫ55 Ϯ 5%, Ϫ21 Ϯ 7%, ϩ6 Ϯ 2%; He:21% O 2: Ϫ16 Ϯ 2%, Ϫ25 Ϯ 5%, ϩ4 Ϯ 1%; hyperoxia: Ϫ11 Ϯ 2%, Ϫ17 Ϯ 4%, ϩ16 Ϯ 4%; He:40% O 2: Ϫ22 Ϯ 2%, Ϫ27 Ϯ 6%, ϩ15 Ϯ 4%). Ten minutes after Ctrl exercise, Q tw,pot was reduced by 25 Ϯ 2% (P Ͻ 0.01) in all COPD and 2 Ϯ 1% (P ϭ 0.07) in healthy control subjects. In COPD, ⌬Q tw,pot was attenuated by onethird after each interventional trial; however, most of the exerciseinduced reductions in Q tw,pot remained. Our findings suggest that the high susceptibility to locomotor muscle fatigue in patients with COPD is in part attributable to insufficient O 2 transport as a consequence of exaggerated arterial hypoxemia and/or excessive respiratory muscle work but also support a critical role for the well-known altered intrinsic muscle characteristics in these patients.work of breathing; arterial oxygenation; blood flow; chronic obstructive pulmonary disease PATIENTS WITH chronic obstructive pulmonary disease (COPD) are characterized by endurance exercise intolerance, a characteristic consequence of the disease that impairs their capability for physical rehabilitation and contributes to their poor quality of life. Given the pathophysiological heterogeneity of COPD including various comorbidities (31), controversy exists about the prevailing determinants of the impaired capability for exercise in patients with COPD (2, 18, 54). The traditional view of perceived respiratory difficulty (dyspnea) as a critical factor restricting exercise is important and certainly plays a significant limiting role in many patients with COPD (34, 50). However, substantial exercise-induced locomotor muscle fatigue also occurs in many of these patients (34, 39 -41), and their susceptibility to peripheral muscle fatigue is greater than in age-matched healthy control subjects exercising at the same work rate (39, 40). Peripheral muscle fatigue ha...