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In this paper, we describe low-permeability components of a microfluidic drug delivery system fabricated with versatile micromilling and lamination techniques. The fabrication process uses laminate sheets which are machined using XY milling tables commonly used in the printed-circuit industry. This adaptable platform for polymer microfluidics readily accommodates integration with silicon-based sensors, printed-circuit, and surface-mount technologies. We have used these methods to build components used in a wearable liquid-drug delivery system for in vivo studies. The design, fabrication, and performance of membrane-based fluidic capacitors and manual screw valves provide detailed examples of the capability and limitations of the fabrication method. We demonstrate fluidic capacitances ranging from 0.015 to 0.15 [micro]L/kPa, screw valves with on/off flow ratios greater than 38 000, and a 45 x reduction in the aqueous fluid loss rate to the ambient due to permeation through a silicone diaphragm layer. [2008-0148] Index Terms--Fluidics, implantable biomedical devices, micromachining, permeability, polyimide films, printed-circuit fabrication.

We investigated whether digoxin lowered muscle Na+,K+‐ATPase (NKA), impaired muscle performance and exacerbated exercise K+ disturbances. Ten healthy adults ingested digoxin (0.25 mg; DIG) or placebo (CON) for 14 days and performed quadriceps strength and fatiguability, finger flexion (FF, 105%peak‐workrate, 3 × 1 min, fourth bout to fatigue) and leg cycling (LC, 10 min at 33% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ and 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$, 90% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ to fatigue) trials using a double‐blind, crossover, randomised, counter‐balanced design. Arterial (a) and antecubital venous (v) blood was sampled (FF, LC) and muscle biopsied (LC, rest, 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$, fatigue, 3 h after exercise). In DIG, in resting muscle, [3H]‐ouabain binding site content (OB‐Fab) was unchanged; however, bound‐digoxin removal with Digibind revealed total ouabain binding (OB+Fab) increased (8.2%, P = 0.047), indicating 7.6% NKA–digoxin occupancy. Quadriceps muscle strength declined in DIG (−4.3%, P = 0.010) but fatiguability was unchanged. During LC, in DIG (main effects), time to fatigue and [K+]a were unchanged, whilst [K+]v was lower (P = 0.042) and [K+]a‐v greater (P = 0.004) than in CON; with exercise (main effects), muscle OB‐Fab was increased at 67% VO2peak${\rm{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ (per wet‐weight, P = 0.005; per protein P = 0.001) and at fatigue (per protein, P = 0.003), whilst [K+]a, [K+]v and [K+]a‐v were each increased at fatigue (P = 0.001). During FF, in DIG (main effects), time to fatigue, [K+]a, [K+]v and [K+]a‐v were unchanged; with exercise (main effects), plasma [K+]a, [K+]v, [K+]a‐v and muscle K+ efflux were all increased at fatigue (P = 0.001). Thus, muscle strength declined, but functional muscle NKA content was preserved during DIG, despite elevated plasma digoxin and muscle NKA–digoxin occupancy, with K+ disturbances and fatiguability unchanged. Key points: The Na+,K+‐ATPase (NKA) is vital in regulating skeletal muscle extracellular potassium concentration ([K+]), excitability and plasma [K+] and thereby also in modulating fatigue during intense contractions. NKA is inhibited by digoxin, which in cardiac patients lowers muscle functional NKA content ([3H]‐ouabain binding) and exacerbates K+ disturbances during exercise.In healthy adults, we found that digoxin at clinical levels surprisingly did not reduce functional muscle NKA content, whilst digoxin removal by Digibind antibody revealed an ∼8% increased muscle total NKA content.Accordingly, digoxin did not exacerbate arterial plasma [K+] disturbances or worsen fatigue during intense exercise, although quadriceps muscle strength was reduced.Thus, digoxin treatment in healthy participants elevated serum digoxin, but muscle functional NKA content was preserved, whilst K+ disturbances and fatigue with intense exercise were unchanged. This resilience to digoxin NKA inhibition is consistent with the importance of NKA in preserving K+ regulation and muscle function. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the importance of training leading to repetition failure in the performance of 2 different tests: 6 repetition maximum (6RM) bench press strength and 40-kg bench throw power in elite junior athletes. Subjects were 26 elite junior male basketball players (n = 12; age = 18.6 [+ or -] 0.3 years; height = 202.0 [+ or -] 11.6 cm; mass = 97.0 [+ or -] 12.9 kg; mean [+ or -] SD) and soccer players (n = 14; age = 17.4 [+ or -] 0.5 years; height = 179.0 [+ or -] 7.0 cm; mass = 75.0 [+ or -] 7.1 kg) with a history of greater than 6 months' strength training. Subjects were initially tested twice for 6RM bench press mass and 40-kg Smith machine bench throw power output (in watts) to establish retest reliability. Subjects then undertook bench press training with 3 sessions per week for 6 weeks, using equal volume programs (24 repetitions x 80-105% 6RM in 13 minutes 20 seconds). Subjects were assigned to one of two experimental groups designed either to elicit repetition failure with 4 sets of 6 repetitions every 260 seconds ([RF.sub.4x6]) or allow all repetitions to be completed with 8 sets of 3 repetitions every 113 seconds ([NF.sub.8x3]). The [RF.sub.4x6] treatment elicited substantial increases in strength (7.3 [+ or -] 2.4 kg, +9.5%, p < 0.001) and power (40.8 [+ or -] 24.1 W, +10.6%, p < 0.001), while the [NF.sub.8x3] group elicited 3.6 [+ or -] 3.0 kg (+5.0%,p < 0.005) and 25 [+ or -] 19.0 W increases (+6.8%, p < 0.001). The improvements in the [RF.sub.4x6] group were greater than those in the repetition rest group for both strength (p < 0.005) and power (p < 0.05). Bench press training that leads to repetition failure induces greater strength gains than nonfailure training in the bench press exercise for elite junior team sport athletes. KEY WORDS. Smith machine, repetition maximum, typical error of measurement, smallest worthwhile change, fatigue

Purpose: The cardiac T-wave peak-to-end interval (Tpe) is thought to reflect dispersion in ventricular repolarisation, with abnormalities in Tpe associated with increased risk of arrhythmia. Extracellular K+ modulates cardiac repolarisation, and since arterial plasma K+ concentration ([K+]) rapidly increases during and declines following exercise, we investigated the relationship between [K+] and Tpe with exercise. Methods: Serial ECGs (Tpe, Tpe/QT ratio) and [K+] were obtained from 8 healthy, normokalaemic volunteers and 22 patients with end-stage renal disease (ESRD), at rest, during, and after exhaustive exercise. Results: Post-exercise [K+] nadir was 3.1 ± 0.1, 5.0 ± 0.2 and 4.0 ± 0.1 mmol.L−1 (mean ± SEM) for healthy participants and ESRD patients before and after haemodialysis, respectively. In healthy participants, compared to pre-exercise, recovery-induced low [K+] was associated with a prolongation of Tpe (110 ± 8 vs. 87 ± 5 ms, respectively, p = 0.03) and an increase in Tpe/QT ratio (0.28 ± 0.01 vs. 0.23 ± 0.01, respectively, p = 0.01). Analyses of serial data revealed [K+] as a predictor of Tpe in healthy participants (β = -0.54 ±0.05, p < 0.0001), in ESRD patients (β = -0.75 ± 0.06, p < 0.0001) and for all data pooled (β = -0.61 ± 0.04, p < 0.0001). The [K+] was also a predictor of Tpe/QT ratio in healthy participants and ESRD patients. Conclusions: Tpe and Tpe/QT ratio are predicted by [K+] during exercise. Low [K+] during recovery from exercise was associated with increased Tpe and Tpe/QT, indicating accentuated dispersion of ventricular repolarisation. The findings suggest that variations in [K+] with physical exertion may unmask electrophysiological vulnerabilities to arrhythmia. [ABSTRACT FROM AUTHOR]