Michael I. Lindinger

Lactate and glucose interactions during rest and exercise in men: effect of exogenous lactate infusion

To test the hypothesis that lactate plays a central role in the distribution of carbohydrate (CHO) potential energy for oxidation and glucose production (GP), we performed a lactate clamp (LC) procedure during rest and moderate intensity exercise. Blood [lactate] was clamped at ≈4 mm by exogenous lactate infusion. Subjects performed 90 min exercise trials at 65 % of the peak rate of oxygen consumption (V̇O2,peak; 65 %), 55 % V̇O2,peak (55 %) and 55 % V̇O2,peak with lactate clamped to the blood [lactate] that was measured at 65 % V̇O2,peak (55 %‐LC). Lactate and glucose rates of appearance (Ra), disappearance (Rd) and oxidation (Rox) were measured with a combination of [3‐13C]lactate, H13CO3−, and [6,6‐2H2]glucose tracers. During rest and exercise, lactate Ra and Rd were increased at 55 %‐LC compared to 55 %. Glucose Ra and Rd were decreased during 55 %‐LC compared to 55 %. Lactate Rox was increased by LC during exercise (55 %: 6.52 ± 0.65 and 55 %‐LC: 10.01 ± 0.68 mg kg−1 min−1) which was concurrent with a decrease in glucose oxidation (55 %: 7.64 ± 0.4 and 55 %‐LC: 4.35 ± 0.31 mg kg−1 min−1). With LC, incorporation of 13C from tracer lactate into blood glucose (L → GNG) increased while both GP and calculated hepatic glycogenolysis (GLY) decreased. Therefore, increased blood [lactate] during moderate intensity exercise increased lactate oxidation, spared blood glucose and decreased glucose production. Further, exogenous lactate infusion did not affect rating of perceived exertion (RPE) during exercise. These results demonstrate that lactate is a useful carbohydrate in times of increased energy demand.

POTASSIUM REGULATION DURING EXERCISE AND RECOVERY

SummaryThe concentrations of extracellular and intracellular potassium (K+) in skeletal muscle influence muscle cell function and are also important determinants of cardiovascular and respiratory function.Several studies over the years have shown that exercise results in a release of K+ ions from contracting muscles which produces a decrease in intracellular K+ concentrations and an increase in plasma K+ concentrations. Following exercise there is a recovery of intracellular K+ concentrations in previously contracting muscle and plasma K+ concentrations rapidly return to resting values.The cardiovascular and respiratory responses to K+ released by contracting muscle produce some changes which aid exercise performance. Increases in the interstitial K+ concentrations of contracting muscles stimulate CIII and CIV afferents to directly stimulate heart rate and the rate of ventilation. Localised K+ release causes a vasodilatation of the vascular bed within contracting muscle. This, together with the increase in cardiac output (through increased heart rate), results in an increase in blood flow to isometrically contracted muscle upon cessation of contraction and to dynamically contracting muscle. This exercise hyperaemia aids in the delivery of metabolic substrates to, and in the removal of metabolic endproducts from, contracting and recovering muscle tissues.In contrast to the beneficial respiratory and cardiovascular effects of elevations in interstitial and plasma K+ concentrations, the responses of contracting muscle to decreases in intracellular K+ concentrations and increases in intracellular Na+ concentrations and extracellular K+ concentrations contribute to a reduction in the strength of muscular contraction. Muscle K+ loss has thus been cited as a major factor associated with or contributing to muscle fatigue.The sarcolemma, because of changes in intracellular and extracellular K+ concentrations and Na+ concentrations on the membrane potential and cell excitability, contributes to a fatigue ‘safety mechanism’. The purpose of this safety mechanism would be to prevent the muscle cell from the self-destruction which is evident upon overload (metabolic insufficiency) of the tissues. The net loss of K+ and associated net gain of Na+ by contracting muscles may contribute to the pain and degenerative changes seen with prolonged exercise.During exercise, mechanisms are brought into play which serve to regulate cellular and whole body K+ homeostasis. Increased rates of uptake of K+ by contracting muscles and inactive tissues through activation of the Na+-K+ pump serve to restore active muscle intracellular K+ concentrations towards precontraction levels and to prevent plasma K+ concentrations from rising to toxic levels. These effects are at least partially mediated by exercise-induced increases in plasma catecholamines, particularly adrenaline. Upon cessation of exercise intracellular K+ concentrations rapidly recover towards resting values, and this is associated with improvements in muscle contraction.Training may result in an increase in intracellular K+ concentrations of resting muscle and relatively lower plasma K+ concentrations compared to values reported in untrained individuals. Also, a blunting of the exercise-induced hyperkalaemia in trained individuals is associated with a decrease in the net loss of K+ from contracting muscle; these observations have been attributed to an upregulation of Na+-K+ pump activity in both inactive tissues and active muscle.

Do multiple ionic interactions contribute to skeletal muscle fatigue

During intense exercise or electrical stimulation of skeletal muscle the concentrations of several ions change simultaneously in interstitial, transverse tubular and intracellular compartments. Consequently the functional effects of multiple ionic changes need to be considered together. A diminished transsarcolemmal K+ gradient per se can reduce maximal force in non‐fatigued muscle suggesting that K+ causes fatigue. However, this effect requires extremely large, although physiological, K+ shifts. In contrast, moderate elevations of extracellular [K+] ([K+]o) potentiate submaximal contractions, enhance local blood flow and influence afferent feedback to assist exercise performance. Changed transsarcolemmal Na+, Ca2+, Cl− and H+ gradients are insufficient by themselves to cause much fatigue but each ion can interact with K+ effects. Lowered Na+, Ca2+ and Cl− gradients further impair force by modulating the peak tetanic force–[K+]o and peak tetanic force–resting membrane potential relationships. In contrast, raised [Ca2+]o, acidosis and reduced Cl− conductance during late fatigue provide resistance against K+‐induced force depression. The detrimental effects of K+ are exacerbated by metabolic changes such as lowered [ATP]i, depleted carbohydrate, and possibly reactive oxygen species. We hypothesize that during high‐intensity exercise a rundown of the transsarcolemmal K+ gradient is the dominant cellular process around which interactions with other ions and metabolites occur, thereby contributing to fatigue.

Potassium regulation during exercise and recovery in humans: Implications for skeletal and cardiac muscle

This review summarizes the main cellular mechanisms involved in potassium regulation in plasma and skeletal muscle during exercise. The effects of exercise-induced hyperkalemia and post-exercise hypokalemia on the cardiac action potential are reviewed in light of recent research on Na+ and K+ channel activity. Specific consideration is given to K+ release from contracting skeletal muscle, K+ uptake by contracting skeletal muscle, K+ uptake by non-contracting tissues during the period of exercise, and K+ uptake by skeletal muscle recovering from contractile activity. The onset of exercise is associated with a net release of K+ from contracting skeletal muscle that results in an increase in plasma [K+]. Resultant decreases in intracellular [K+] and increases in interstitial [K+] in contracting skeletal muscle have been implicated in the fatigue process. The rate and magnitude of increase in plasma [K+] is dependent on exercise intensity, trained state of the individual, and on drugs such as beta-adrenoceptor blockers and caffeine. During exercise, the uptake of K+ from the blood by non-contracting tissues may be important in preventing plasma [K+] from rising to excessive levels that will impair skeletal muscle and myocardial excitability and contractility. Cessation of exercise results in a rapid decrease in plasma [K+], often to 3 mEq/l or less with intense exercise, that may be maintained for prolonged periods. The rapid increases and decreases in plasma [K+] with onset and cessation of exercise, respectively, has been implicated in altered myocardial function and sudden cardiac death. Recent studies suggest that increases in catecholamines during exercise are cardioprotective to the arrhythmogenic effects of hyperkalemia.

Pulmonary Gas Exchange and Acid‐Base Balance During Exercise

As the first step in the oxygen-transport chain, the lung has a critical task: optimizing the exchange of respiratory gases to maintain delivery of oxygen and the elimination of carbon dioxide. In healthy subjects, gas exchange, as evaluated by the alveolar-to-arterial PO2 difference (A-aDO2), worsens with incremental exercise, and typically reaches an A-aDO2 of approximately 25 mmHg at peak exercise. While there is great individual variability, A-aDO2 is generally largest at peak exercise in subjects with the highest peak oxygen consumption. Inert gas data has shown that the increase in A-aDO2 is explained by decreased ventilation-perfusion matching, and the development of a diffusion limitation for oxygen. Gas exchange data does not indicate the presence of right-to-left intrapulmonary shunt developing with exercise, despite recent data suggesting that large-diameter arteriovenous shunt vessels may be recruited with exercise. At the same time, multisystem mechanisms regulate systemic acid-base balance in integrative processes that involve gas exchange between tissues and the environment and simultaneous net changes in the concentrations of strong and weak ions within, and transfer between, extracellular and intracellular fluids. The physicochemical approach to acid-base balance is used to understand the contributions from independent acid-base variables to measured acid-base disturbances within contracting skeletal muscle, erythrocytes and noncontracting tissues. In muscle, the magnitude of the disturbance is proportional to the concentrations of dissociated weak acids, the rate at which acid equivalents (strong acid) accumulate and the rate at which strong base cations are added to or removed from muscle.

Fluid and electrolyte supplementation after prolonged moderate-intensity exercise enhances muscle glycogen resynthesis in Standardbred horses

We hypothesized that postexercise rehydration using a hypotonic electrolyte solution will increase the rate of recovery of whole body hydration, and that this is associated with increased muscle glycogen and electrolyte recovery in horses. Gluteus medius biopsies and jugular venous blood were sampled from six exercise-conditioned Standardbreds on two separate occasions, at rest and for 24 h following a competitive exercise test (CET) designed to simulate the speed and endurance test of a 3-day event. After the CETs, horses were given water ad libitum, and either a hypotonic commercial electrolyte solution (electrolyte) via nasogastric tube, followed by a typical hay/grain meal, or a hay/grain meal alone (control). The CET resulted in decreased total body water and muscle glycogen concentration of 8.4 +/- 0.3 liters and 22.6%, respectively, in the control treatment, and 8.2 +/- 0.4 liters and 21.9% in the electrolyte treatment. Electrolyte resulted in an enhanced rate of muscle glycogen resynthesis and faster restoration of hydration (as evidenced by faster recovery of plasma protein concentration, maintenance of plasma osmolality, and greater muscle intracellular fluid volume) during the recovery period compared with control. There were no differences in muscle Na, K, Cl, or Mg contents between the two treatments. It is concluded that oral administration of a hypotonic electrolyte solution after prolonged moderate-intensity exercise enhanced the rate of muscle glycogen resynthesis during the recovery period compared with control. It is speculated that postexercise dehydration may be one key contributor to the slow muscle glycogen replenishment in horses.

Oral acetate supplementation after prolonged moderate intensity exercise enhances early muscle glycogen resynthesis in horses

Oral acetate supplementation enhances glycogen synthesis in some mammals. However, while acetate is a significant energy source for skeletal muscle at rest in horses, its effects on glycogen resynthesis are unknown. We hypothesized that administration of an oral sodium acetate–acetic acid solution with a typical grain and hay meal after glycogen‐depleting exercise would result in a rapid appearance of acetate in blood with rapid uptake by skeletal muscle. It was further hypothesized that acetate taken up by muscle would be converted to acetyl CoA (and acetylcarnitine), which would be metabolized to CO2 and water via the tricarboxylic acid cycle, generating ATP within the mitochondria and thereby allowing glucose taken up by muscle to be preferentially incorporated into glycogen. Gluteus medius biopsies and jugular venous blood were sampled from nine exercise‐conditioned horses on two separate occasions, at rest and for 24 h following a competition exercise test (CET) designed to simulate the speed and endurance test of a 3 day event. After the CETs, horses were allowed water ad libitum and either 8 l of a hypertonic sodium acetate–acetic acid solution via nasogastric gavage followed by a typical hay–grain meal (acetate treatment) or a hay–grain meal alone (control treatment). The CET significantly decreased muscle glycogen concentration by 21 and 17% in the acetate and control treatments, respectively. Acetate supplementation resulted in a rapid and sustained increase in plasma [acetate]. Skeletal muscle [acetyl CoA] and [acetylcarnitine] were increased at 4 h of recovery in the acetate treatment, suggesting substantial tissue extraction of the supplemented acetate. Acetate supplementation also resulted in an enhanced rate of muscle glycogen resynthesis during the initial 4 h of the recovery period compared with the control treatment; however, by 24 h of recovery there was no difference in glycogen replenishent between trials. It is concluded that oral acetate could be an alternative energy source in the horse.

Low quality of evidence for glucosamine-based nutraceuticals in equine joint disease: review of in vivo studies.

Nutraceuticals are increasingly applied to the management of equine arthritis and joint disease, particularly those based upon glucosamine and chondroitin sulphate. While the first report of using glucosamine in horses appeared more than 25 years ago, it was not until 1992 that isolated studies began to be reported. Since that time, 15 in vivo papers have been published in the equine literature, usually on products already commercially available and often seeking evidence for efficacy. These studies demonstrate an encouraging trend to manufacturers of these products investing in research, but most do not meet a quality standard that provides sufficient confidence in the results reported. This review discusses the entirety of published in vivo research on glucosamine-based nutraceuticals (GBN) for horses, including that on Cosequin, Cortaflex, Synequin, Sashas EQ, Myristol, chondroitin sulphate, glucosamine sulphate and glucosamine hydrochloride; and considers experimental limitations of this research along with their impact on interpretation of results. A quality score was calculated for each paper according to preset quality criteria. A minimum quality standard of 60% was set as the threshold for confidence in interpretation of results. Of the 15 papers reviewed, only 3 met the minimum quality standard. Experimental limitations of each research paper are discussed. It is concluded that the quality of studies in this area is generally low, prohibiting meaningful interpretation of the reported results. New high quality research on GBN for horses is needed and recommendations for future research are discussed.

Effects of Gas Exchange on Acid‐Base Balance

This paper describes the interactions between ventilation and acid-base balance under a variety of conditions including rest, exercise, altitude, pregnancy, and various muscle, respiratory, cardiac, and renal pathologies. We introduce the physicochemical approach to assessing acid-base status and demonstrate how this approach can be used to quantify the origins of acid-base disorders using examples from the literature. The relationships between chemoreceptor and metaboreceptor control of ventilation and acid-base balance summarized here for adults, youth, and in various pathological conditions. There is a dynamic interplay between disturbances in acid-base balance, that is, exercise, that affect ventilation as well as imposed or pathological disturbances of ventilation that affect acid-base balance. Interactions between ventilation and acid-base balance are highlighted for moderate- to high-intensity exercise, altitude, induced acidosis and alkalosis, pregnancy, obesity, and some pathological conditions. In many situations, complete acid-base data are lacking, indicating a need for further research aimed at elucidating mechanistic bases for relationships between alterations in acid-base state and the ventilatory responses.

Role of skeletal muscle in plasma ion and acid-base regulation after NaHCO3 and KHCO3 loading in humans

This paper examines the time course of changes in plasma electrolyte and acid-base composition in response to NaHCO3 and KHCO3 ingestion. It was hypothesized that skeletal muscle is involved in the correction of the ensuing plasma disturbance by exchanging ions, gasses, and fluids between cells and extracellular fluids. Five male subjects, with catheters in a brachial artery and antecubital vein, ingested 3.57 mmol/kg body mass NaHCO3 or KHCO3. While seated, blood samples were taken 30 min before ingestion of the solution, at 10-min intervals during the 60-min ingestion period, and periodically for 210 min after ingestion was complete. Blood was analyzed for gases, hematocrit, plasma ions, and total protein. With NaHCO3, arterial plasma Na+ concentration ([Na+]) increased from 143 ± 1 to 147 ± 1 (SE) meq/l, H+ concentration ([H+]) decreased by 6 ± 1 neq/l, and [Formula: see text] increased by 5 ± 1 mmHg. There was no detectable net Na+ uptake by tissues. An increased plasma strong ion difference ([SID]) accounted fully for the decrease in plasma [H+]. With KHCO3, K+ concentration increased from 4.25 ± 0.10 to 7.17 ± 0.13 meq/l, plasma volume decreased by 15.5 ± 2.3%, [H+] decreased by 4 ± 1 neq/l, and there was no change in[Formula: see text]. The decrease in [H+] in the KHCO3 trial primarily arose in response to the increased [SID]. Net K+ uptake by tissues accounted for 37 ± 5% of the ingested K+. In conclusion, ingestion of NaHCO3and KHCO3 produced markedly different fluid and ionic disturbances and associated regulatory responses by skeletal muscle. Accordingly, the physicochemical origins of the acid-base disturbances also differed between treatments. The tissues did not play a role in regulating plasma [Na+] after ingestion of NaHCO3. In contrast, the net influx of K+ to tissues played an important role in removing K+ from the extracellular compartment after ingestion of KHCO3.