The effect of acid–base balance on fatigue of skeletal muscle

H+ ions are generated rapidly when muscles are maximally activated. This results in an intracellular proton load. Typical proton loads in active muscles reach a level of 20–25 μmol∙g−1, resulting in a fall in intracellular pH of 0.3–0.5 units in mammalian muscle and 0.6–0.8 units in frog muscle. In isolated frog muscles stimulated to fatigue a proton load of this magnitude is developed, and at the same time maximum isometric force is suppressed by 70–80%. Proton loss is slowed when external pH is kept low. This is paralleled by a slow recovery of contractile tension and seems to support the idea that suppression results from intracellular acidosis. Nonfatigued muscles subjected to similar intracellular proton loads by high CO2 levels show a suppression of maximal tension by only about 30%. This indicates that only a part of the suppression during fatigue is normally due to the direct effect of intracellular acidosis. Further evidence for a component of fatigue that is not due to intracellular acidosis is provided by the fact that some muscle preparations (rat diaphragm) can be fatigued with very little lactate accumulation and very low proton loads. Even under these conditions, a low external pH (6.2) can slow recovery of tension development 10-fold compared with normal pH (7.4). We must conclude that there are at least two components to fatigue. One, due to a direct effect of intracellular acidosis, acting directly on the myofibrils, accounts for a part of the suppression of contractile force. A second, which in many cases may be the major component, is not dependent on intracellular acidosis. This component seems to be due to a change of state in one or more of the steps of the excitation–contraction coupling process. Reversal of this state is sensitive to external pH which suggests that this component is accessible from the outside of the cell.

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Use of Intravenous Sodium Bicarbonate in Neonatal Intensive Care Units in Italy: A Nationwide Survey

10.21203/rs.3.rs-48558/v1 ◽

2020 ◽

Author(s):

Luca Massenzi ◽

Roberto Aufieri ◽

Silvia Donno ◽

Rocco Agostino ◽

Andrea Dotta

Keyword(s):

Sodium Bicarbonate ◽

Neonatal Intensive Care ◽

Current Knowledge ◽

Nationwide Survey ◽

Intracellular Acidosis ◽

Acid Base Balance ◽

Metabolic Disturbances ◽

Attitudes And Practices ◽

Base Balance ◽

Intravenous Sodium

Abstract Background Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. Methods A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. Results The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8% and 32.5% of the NICUs). Conclusion This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

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Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey

Italian Journal of Pediatrics ◽

10.1186/s13052-021-00955-3 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Luca Massenzi ◽

◽

Roberto Aufieri ◽

Silvia Donno ◽

Rocco Agostino ◽

...

Keyword(s):

Sodium Bicarbonate ◽

Neonatal Intensive Care ◽

Current Knowledge ◽

Nationwide Survey ◽

Intracellular Acidosis ◽

Acid Base Balance ◽

Metabolic Disturbances ◽

Attitudes And Practices ◽

Base Balance ◽

Intravenous Sodium

Abstract Background Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. Methods A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. Results The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8 and 32.5% of the NICUs). Conclusion This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

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Use of intravenous sodium bicarbonate in neonatal intensive care units in Italy: a nationwide survey.

10.21203/rs.3.rs-48558/v2 ◽

2020 ◽

Author(s):

Luca Massenzi ◽

Roberto Aufieri ◽

Silvia Donno ◽

Rocco Agostino ◽

Andrea Dotta

Keyword(s):

Sodium Bicarbonate ◽

Neonatal Intensive Care ◽

Current Knowledge ◽

Nationwide Survey ◽

Intracellular Acidosis ◽

Acid Base Balance ◽

Metabolic Disturbances ◽

Attitudes And Practices ◽

Base Balance ◽

Intravenous Sodium

Abstract Background: Metabolic Acidosis (MA) is a disturbance of the acid-base balance that can occur in preterm and critically ill term neonates due to different etiologies. Intravenous sodium bicarbonate (SB) has been traditionally used to correct such unbalance, despite the lack of evidence about its safety and efficacy. In literature, reported undesirable effects of treatment with SB in neonates include worsening of intracellular acidosis, impairment of myocardial function, cerebral blood flow fluctuations and intracranial hemorrhage. A national survey was conducted by the Neonatal Pharmacotherapy Study Group of the Italian Society of Neonatology with the aim to assess and describe attitudes and practices concerning the use of SB, particularly for the treatment of MA in Italian NICUs. Methods: A questionnaire regarding treatment of MA and SB prescription habits was sent to the directors of 120 Italian NICUs from June 2017 to March 2018. Results: The survey response rate was 97.5% (117/120 centers). Findings showed that in 55% of the surveyed NICUs (64/117 units) it is common practice to correct MA with intravenous SB. On the other hand, the remaining 45% of the units try to solve the metabolic disturbances adopting different approaches (improving perfusion, adjusting ventilation parameters or increasing blood volume). Moreover, to prevent the occurrence of MA, 37.6% of the NICUs (44/117) include buffer salts (lactate, acetate or both) in parenteral nutrition prescriptions. SB is also used as a treatment for other conditions, mainly pathologies with bicarbonate loss and tubular acidosis (respectively in 53.8% and 32.5% of the NICUs). Conclusion: This survey showed how SB is a commonly used treatment for MA in more than half of Italian NICUs, with indications and prescription criteria that significantly vary across centers. Based on current knowledge, it is reasonable to suggest that the management of neonatal MA should be firstly directed to identify the underlying disorders. Thus, the use of SB should be reserved only for selected cases, also considering the severity of SB adverse effects and the lack of evidence about its efficacy. Guidance for the management of MA is required to harmonize practices and reduce the use of potentially inappropriate and unsafe treatments.

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Differential expression and acid-base regulation of glutaminase mRNAs in gluconeogenic LLC-PK1-FBPase+ cells

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.2.f227 ◽

2000 ◽

Vol 278 (2) ◽

pp. F227-F237 ◽

Cited By ~ 23

Author(s):

Gerhard Gstraunthaler ◽

Thomas Holcomb ◽

Elisabeth Feifel ◽

Wenlin Liu ◽

Nikolaus Spitaler ◽

...

Keyword(s):

Acidic Medium ◽

Molecular Mechanisms ◽

Mrna Levels ◽

Ammonia Production ◽

Intracellular Acidosis ◽

Acid Base Balance ◽

Acid Base ◽

Permeable Membrane ◽

Base Balance

LLC-PK1-FBPase+ cells, which are a gluconeogenic substrain of porcine renal LLC-PK1cells, exhibit enhanced oxidative metabolism and increased levels of phosphate-dependent glutaminase (PDG) activity. On adaptation to acidic medium (pH 6.9, 9 mM [Formula: see text]), LLC-PK1-FBPase+ cells also exhibit a greater increase in ammonia production and respond with an increase in assayable PDG activity. The changes in PDG mRNA levels were examined by using confluent cells grown on plastic dishes or on permeable membrane inserts. The latter condition increased the state of differentiation of the LLC-PK1-FBPase+ cells. The levels of the primary porcine PDG mRNAs were analyzed by using probes that are specific for the 5.0-kb PDG mRNA (p2400) or that react equally with both the 4.5- and 5.0-kb PDG mRNAs (p930 and r1500). In confluent dish- and filter-grown LLC-PK1-FBPase+ cells, the predominant 4.5-kb PDG mRNA is increased threefold after 18 h in acidic media. However, in filter-grown epithelia, which sustain an imposed pH and [Formula: see text] gradient, this adaptive increase is observed only when acidic medium is applied to both the apical and the basolateral sides of the epithelia. Half-life experiments established that induction of the 4.5-kb PDG mRNA was due to its stabilization. An identical pattern of adaptive increases was observed for the cytosolic PEPCK mRNA. In contrast, no adaptive changes were observed in the levels of the 5.0-kb PDG mRNA in either cell culture system. Furthermore, cultures were incubated in low-potassium (0.7 mM) media for 24–72 h to decrease intracellular pH while maintaining normal extracellular pH. LLC-PK1-FBPase+ cells again responded with increased rates of ammonia production and increased levels of the 4.5-kb PDG and PEPCK mRNAs, suggesting that an intracellular acidosis is the initiator of this adaptive response. Because all of the observed responses closely mimic those characterized in vivo, the LLC-PK1-FBPase+ cells represent a valuable tissue culture model to study the molecular mechanisms that regulate renal gene expression in response to changes in acid-base balance.

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Muscle metabolic status and acid-base balance during 10-s work:5-s recovery intermittent and continuous exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.01059.2011 ◽

2012 ◽

Vol 113 (3) ◽

pp. 410-417 ◽

Cited By ~ 10

Author(s):

Glen R. Belfry ◽

Graydon H. Raymer ◽

Gregory D. Marsh ◽

Donald H. Paterson ◽

R. Terry Thompson ◽

...

Keyword(s):

Power Output ◽

Plantar Flexion ◽

Average Power ◽

Rest Period ◽

Exercise Bout ◽

Peak Exercise ◽

Resonance Spectroscopy ◽

Intracellular Acidosis ◽

Acid Base Balance ◽

Base Balance

Gastrocnemius muscle phosphocreatine ([PCr]) and hydrogen ion ([H+]) were measured using 31P-magnetic resonance spectroscopy during repeated bouts of 10-s heavy-intensity (HI) exercise and 5-s rest compared with continuous (CONT) HI exercise. Recreationally active male subjects ( n = 7; 28 yr ± 9 yr) performed on separate occasions 12 min of isotonic plantar flexion (0.75 Hz) CONT and intermittent (INT; 10-s exercise, 5-s rest) exercise. The HI power output in both CONT and INT was set at 50% of the difference between the power output associated with the onset of intracellular acidosis and peak exercise determined from a prior incremental plantar flexion protocol. Intracellular concentrations of [PCr] and [H+] were calculated at 4 s and 9 s of the work period and at 4 s of the rest period in INT and during CONT exercise. [PCr] and [H+] (mean ± SE) were greater at 4 s of the rest periods vs. 9 s of exercise over the course of the INT exercise bout: [PCr] (20.7 mM ± 0.6 vs. 18.7 mM ± 0.5; P < 0.01); [H+] (370 nM ± 13.50 vs. 284 nM ± 13.6; P < 0.05). Average [H+] was similar for CONT vs. INT. We therefore suggest that there is a glycolytic contribution to ATP recovery during the very short rest period (<5 s) of INT and that the greater average power output of CONT did not manifest in greater [H+] and greater glycolytic contribution compared with INT exercise.

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Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000207 ◽

2014 ◽

Vol 84 (3-4) ◽

pp. 0206-0217 ◽

Cited By ~ 8

Author(s):

Seyedeh-Elaheh Shariati-Bafghi ◽

Elaheh Nosrat-Mirshekarlou ◽

Mohsen Karamati ◽

Bahram Rashidkhani

Keyword(s):

Calcium Intake ◽

Dietary Calcium ◽

Dietary Calcium Intake ◽

Dietary Intakes ◽

Iranian Women ◽

Acid Base Balance ◽

Mineral Density ◽

Acid Base ◽

Base Balance ◽

Dietary Acid

Findings of studies on the link between dietary acid-base balance and bone mass are relatively mixed. We examined the association between dietary acid-base balance and bone mineral density (BMD) in a sample of Iranian women, hypothesizing that a higher dietary acidity would be inversely associated with BMD, even when dietary calcium intake is adequate. In this cross-sectional study, lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50 - 85 years were measured using dual-energy x-ray absorptiometry. Dietary intakes were assessed using a validated food frequency questionnaire. Renal net acid excretion (RNAE), an estimate of acid-base balance, was then calculated indirectly from the diet using the formulae of Remer (based on dietary intakes of protein, phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the residual method. After adjusting for potential confounders, multivariable adjusted means of the lumbar spine BMD of women in the highest tertiles of RNAERemer and RNAEFrassetto were significantly lower than those in the lowest tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for RNAEFrassetto: mean difference - 0.088 g/cm2; P=0.004). Similar results were observed in a subgroup analysis of subjects with dietary calcium intake of >800 mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is associated with greater intake of acid-generating foods and lower intake of alkali-generating foods, may be involved in deteriorating the bone health of postmenopausal Iranian women, even in the context of adequate dietary calcium intake.

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