The cost of storing checkpoints to multiple volatile storage locations using at-least-k semantics

Using the volatile memory of other computers within a system to store checkpoints is an alternative to the traditional approach of using stable storage. The objective of this study is to develop a storage mechanism using at-least-k delivery semantics. This semantics allows data to be saved to a minimum number of computers simultaneously using group communications, without requiring that each group computer successfully acknowledge the receipt. The new storage mechanism is implemented in the GENESIS checkpointing facility v2.0. The results showed that at-least-k storage mechanisms provide low storage latency times; however, the incurred execution overheads on the applications executing within the system are higher than that when using remote stable storage to store checkpoints.

Chronic intermittent hypoxia and incremental cycling exercise independently depress muscle in vitro maximal Na+-K+-ATPase activity in well-trained athletes

Athletes commonly attempt to enhance performance by training in normoxia but sleeping in hypoxia [live high and train low (LHTL)]. However, chronic hypoxia reduces muscle Na⁺-K<sup>+-ATPase content, whereas fatiguing contractions reduce Na⁺-K<sup>+-ATPase activity, which each may impair performance. We examined whether LHTL and intense exercise would decrease muscle Na⁺-K<sup>+-ATPase activity and whether these effects would be additive and sufficient to impair performance or plasma K<sup>+ regulation. Thirteen subjects were randomly assigned to two fitness-matched groups, LHTL (n = 6) or control (Con, n = 7). LHTL slept at simulated moderate altitude (3,000 m, inspired O₂ fraction = 15.48%) for 23 nights and lived and trained by day under normoxic conditions in Canberra (altitude ~600 m). Con lived, trained, and slept in normoxia. A standardized incremental exercise test was conducted before and after LHTL. A vastus lateralis muscle biopsy was taken at rest and after exercise, before and after LHTL or Con, and analyzed for maximal Na⁺-K<sup>+-ATPase activity [K<sup>+-stimulated 3-O-methylfluorescein phosphatase (3-O-MFPase)] and Na⁺-K<sup>+-ATPase content ([³H]ouabain binding sites). 3-O-MFPase activity was decreased by –2.9 ± 2.6% in LHTL (P < 0.05) and was depressed immediately after exercise (P < 0.05) similarly in Con and LHTL (–13.0 ± 3.2 and –11.8 ± 1.5%, respectively). Plasma K<sup>+ concentration during exercise was unchanged by LHTL; [3H]ouabain binding was unchanged with LHTL or exercise. Peak oxygen consumption was reduced in LHTL (P < 0.05) but not in Con, whereas exercise work was unchanged in either group. Thus LHTL had a minor effect on, and incremental exercise reduced, Na⁺-K<sup>+-ATPase activity. However, the small LHTL-induced depression of 3-O-MFPase activity was insufficient to adversely affect either K<sup>+ regulation or total work performed.

Impaired K+ regulation contributes to exercise limitation in end-stage renal failure

Background

Patients with end-stage renal failure (ESRF) exhibit grossly impaired maximal exercise performance. This study investigated whether K+ regulation during exercise is impaired in ESRF and whether this is related to reduced exercise performance.

Methods

Nine stable hemodialysis patients and eight controls (CON) performed incremental cycling exercise to volitional fatigue, with measurement of peak oxygen consumption (VdotO2 peak). Arterial blood was sampled during and following exercise and analyzed for plasma [K+] (PK).

Results

The VdotO2 peak was approximately 44% less in ESRF than in CON (P < 0.001), whereas peak exercise PK was greater (7.23 plusminus 0.38 vs. 6.23 plusminus 0.14 mmol dot L-1, respectively, P < 0.001). In ESRF, the rate of rise in PK during exercise was twofold greater (0.43 plusminus 0.05 vs. 0.23 plusminus 0.03 mmol dot L-1dotmin-1, P < 0.005) and the ratio of rise in PK relative to work performed was 3.7-fold higher (90.1 plusminus 13.5 vs. 24.7 plusminus 3.3 nmol dot L-1dot J-1, P < 0.001). A strong inverse relationship was found between VdotO2 peak and the DeltaPKdot work-1 ratio (r = -0.80, N = 17, P < 0.001).

Conclusions

Patients with ESRF exhibit grossly impaired extrarenal K+ regulation during exercise, demonstrated by an excessive rise in PK relative to work performed. We further show that K+ regulation during exercise was correlated with aerobic exercise performance. These results suggest that disturbed K+ regulation in ESRF contributes to early muscle fatigue during exercise, thus causing reduced exercise performance.

Impaired muscle Ca2+ and K+ regulation contribute to poor exercise performance post-lung transplantation

Lung transplant recipients (LTx) exhibit marked peripheral limitations to exercise. We investigated whether skeletal muscle Ca2+ and K+ regulation might be abnormal in eight LTx and eight healthy controls. Peak oxygen consumption and arterialized venous plasma [K+] (where brackets denote concentration) were measured during incremental exercise. Vastus lateralis muscle was biopsied at rest and analyzed for sarcoplasmic reticulum Ca2+ release, Ca2+ uptake, and Ca2+-ATPase activity rates; fiber composition; Na+-K+-ATPase (K+-stimulated 3-O-methylfluorescein phosphatase) activity and content ([3H]ouabain binding sites); as well as for [H+] and H+-buffering capacity. Peak oxygen consumption was 47% less in LTx (P < 0.05). LTx had lower Ca2+ release (34%), Ca2+ uptake (31%), and Ca2+-ATPase activity (25%) than controls (P < 0.05), despite their higher type II fiber proportion (LTx, 75.0 ± 5.8%; controls, 43.5 ± 2.1%). Muscle [H+] was elevated in LTx (P < 0.01), but buffering capacity was similar to controls. Muscle 3-O-methylfluorescein phosphatase activity was 31% higher in LTx (P < 0.05), but [3H]ouabain binding content did not differ significantly. However, during exercise, the rise in plasma [K+]-to-work ratio was 2.6-fold greater in LTx (P < 0.05), indicating impaired K+ regulation. Thus grossly subnormal muscle calcium regulation, with impaired potassium regulation, may contribute to poor muscular performance in LTx.

Alkalosis increases muscle K+ release, but lowers plasma [K+] and delays fatigue during dynamic forearm exercise

Alkalosis enhances human exercise performance, and reduces K<sup>+ loss in contracting rat muscle. We investigated alkalosis effects on K<sup>+ regulation, ionic regulation and fatigue during intense exercise in nine untrained volunteers. Concentric finger flexions were conducted at 75% peak work rate (-3 W) until fatigue, under alkalosis (Alk, NaHCO₃, 0.3 g kg⁻¹) and control (Con, CaCO₃) conditions, 1 month apart in a randomised, double-blind, crossover design. Deep antecubital venous (v) and radial arterial (a) blood was drawn at rest, during exercise and recovery, to determine arterio-venous differences for electrolytes, fluid shifts, acid–base and gas exchange. Finger flexion exercise barely perturbed arterial plasma ions and acid–base status, but induced marked arterio-venous changes. Alk elevated [HCO₃⁻] and P^CO2, and lowered [H+] (P < 0.05). Time to fatigue increased substantially during Alk (25 ± 8%, P < 0.05), whilst both [K<sup>+]_a and [K<sup>+]_v were reduced (P < 0.01) and [K<sup>+]_a-v during exercise tended to be greater (P= 0.056, n= 8). Muscle K<sup>+ efflux at fatigue was greater in Alk (21.2 ± 7.6 µmol min⁻¹, 32 ± 7%, P < 0.05, n= 6), but peak K<sup>+ uptake rate was elevated during recovery (15 ± 7%, P < 0.05) suggesting increased muscle Na⁺,K<sup>+-ATPase activity. Alk induced greater [Na⁺]_a, [Cl⁻]_v, muscle Cl⁻ influx and muscle lactate concentration ([Lac⁻]) efflux during exercise and recovery (P < 0.05). The lower circulating [K<sup>+] and greater muscle K<sup>+ uptake, Na⁺ delivery and Cl⁻ uptake with Alk, are all consistent with preservation of membrane excitability during exercise. This suggests that lesser exercise-induced membrane depolarization may be an important mechanism underlying enhanced exercise performance with Alk. Thus Alk was associated with improved regulation of K<sup>+, Na⁺, Cl⁻ and Lac⁻.

Fatigue depresses maximal in vitro skeletal muscle Na+-K+-ATPase activity in untrained and trained individuals

This study investigated whether fatiguing dynamic exercise depresses maximal in vitro Na+-K+-ATPase activity and whether any depression is attenuated with chronic training. Eight untrained (UT), eight resistance-trained (RT), and eight endurance-trained (ET) subjects performed a quadriceps fatigue test, comprising 50 maximal isokinetic contractions (180°/s, 0.5 Hz). Muscle biopsies (vastus lateralis) were taken before and immediately after exercise and were analyzed for maximal in vitro Na+-K+-ATPase (K+-stimulated 3-O-methylfluoroscein phosphatase) activity. Resting samples were analyzed for [3H]ouabain binding site content, which was 16.6 and 18.3% higher (P < 0.05) in ET than RT and UT, respectively (UT 311 ± 41, RT 302 ± 52, ET 357 ± 29 pmol/g wet wt). 3-O-methylfluoroscein phosphatase activity was depressed at fatigue by −13.8 ± 4.1% (P < 0.05), with no differences between groups (UT −13 ± 4, RT −9 ± 6, ET −22 ± 6%). During incremental exercise, ET had a lower ratio of rise in plasma K+ concentration to work than UT (P < 0.05) and tended (P = 0.09) to be lower than RT (UT 18.5 ± 2.3, RT 16.2 ± 2.2, ET 11.8 ± 0.4 nmol · l−1 · J−1). In conclusion, maximal in vitro Na+-K+-ATPase activity was depressed with fatigue, regardless of training state, suggesting that this may be an important determinant of fatigue.

Maternal dietary supplementation with saturated, but not monounsaturated or polyunsaturated fatty acids, leads to tissue-specific inhibition of offspring Na+,K+-ATPase

In rats, a maternal diet rich in lard is associated with reduced Na+,K+-ATPase activity in adult offspring kidney. We have addressed the role of different fatty acids by evaluating Na+,K+-ATPase activity in offspring of dams fed diets rich in saturated (SFA), monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids. Female Sprague–Dawley rats were fed, during pregnancy and suckling, a control diet (4% w/w corn oil) or a fatty acid supplemented diet (24% w/w). Offspring were reared on chow (4% PUFA) and studied at 6 months. mRNA expression (real-time PCR) of Na+,K+-ATPase α subunit and protein expression of Na+,K+-ATPase subunits (Western blot) were assessed in kidney and brain. Na+,K+-ATPase activity was reduced in kidney (P < 0.05 versus all groups) and brain (P < 0.05 versus control and MUFA offspring) of the SFA group. Neither Na+,K+-ATPase α1 subunit mRNA expression, nor protein expression of total α, α1, α2, α3 or β1 subunits were significantly altered in kidney in any dietary group. In brains of SFA offspring α1 mRNA expression (P < 0.05) was reduced compared with MUFA and PUFA offspring, but not controls. Also in brain, SFA offspring demonstrated reduced (P < 0.05) α1 subunit protein and increased phosphorylation (P < 0.05) of the Na+,K+-ATPase modulating protein phospholemman at serine residue 63 (S63 PLM). Na+,K+-ATPase activity was similar to controls in heart and liver. In utero and neonatal exposure to a maternal diet rich in saturated fatty acids is associated with altered activity and expression of Na+,K+-ATPase in adulthood, but mechanisms appear tissue specific.