George Heigenhauser

George Heigenhauser
McMaster University | McMaster · Department of Medicine

PhD Physiology University of Michigan

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336
Publications
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Publications

Publications (336)
Article
A lag in the increase of oxygen consumption (MO2) occurs at the start of sustainable exercise in trout. Waterborne dichloroacetate (DCA, 0.58 and 3.49 mmol L‐1), a compound which activates pyruvate dehydrogenase (PDH) by inhibiting PDH kinase in muscle, accelerates the increase in MO2 during the first 10 min of sustainable exercise when velocity is...
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Omega‐3 polyunsaturated fatty acids (PUFAs) have unique properties purported to influence several aspects of metabolism, including energy expenditure and protein function. Supplementing with n‐3 PUFAs may increase whole‐body resting metabolic rate (RMR), by enhancing Na+/K+ ATPase (NKA) activity and reducing the efficiency of sarcoplasmic reticulum...
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Introduction: In skeletal muscle, the Na/K ATPase (NKA) plays essential roles in processes linked to muscle contraction, fatigue, and energy metabolism; however, very little information exists regarding the regulation of NKA activity. The scarcity of information regarding NKA function in skeletal muscle likely stems from methodological constraints...
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Fish oil (FO) supplementation in humans results in the incorporation of omega-3 fatty acids (FAs) eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C20:6) into skeletal muscle membranes. However, despite the importance of membrane composition in structure-function relationships, a paucity of information exists regarding how differen...
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General anesthesia (GA) can cause abnormal lung fluid redistribution. Pulmonary circulation transvascular fluid fluxes (J VA ) are attributed to changes in hydrostatic forces and erythrocyte volume (EV) regulation. Despite the very low hydraulic conductance of pulmonary microvasculature it is possible that GA may affect hydrostatic forces through c...
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We examined whether slower pulmonary O2uptake (V̇O2p) kinetics in hypoxia is a consequence of: a) hypoxia alone (lowered arterial O2pressure), b) hyperventilation-induced hypocapnia (lowered arterial CO2pressure), or c) a combination of both. Eleven participants performed 3-5 repetitions of step-changes in cycle ergometer power output from 20W to 8...
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This study determined whether ingesting a carbohydrate-electrolyte solution (CES) vs. progressive dehydration affected skeletal muscle glycogen use and performance in ice hockey players during simulated ice hockey exercise comprised of 3 active “periods”. Seven males (21.3±0.3 years, 184.7±1.2 cm, 84.2±3.9 kg, and 49.6±1.8 mL·kg−1·min−1) performed...
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The mechanistic target of rapamycin (mTOR) is a central mediator of protein synthesis in skeletal muscle. We utilized immunofluorescence approaches to study mTOR cellular distribution and protein-protein co-localisation in human skeletal muscle in the basal state as well as immediately, 1 and 3 h after an acute bout of resistance exercise in a fed...
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Purpose: To examine the effects of 7-d of beetroot juice (BRJ) supplementation on SkM contractile characteristics and function. Methods: Recreationally active males (n=8) underwent transcutaneous electrical muscle stimulation of the vastus lateralis for evaluation of contractile characteristics before (pre) and after (post) 7-d of BRJ supplement...
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This study determined whether mild dehydration influenced skeletal muscle glycogen use, core temperature or performance during high-intensity, intermittent cycle-based exercise in ice hockey players vs. staying hydrated with water. Eight males (21.6 ± 0.4 yr, 183.5 ± 1.6 cm, 83.9 ± 3.7 kg, 50.2 ± 1.9 mL·kg(-1)·min(-1)) performed two trials separate...
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Key points: Oral consumption of nitrate (NO3(-)) in beetroot juice has been shown to decrease the oxygen cost of submaximal exercise; however, the mechanism of action remains unresolved. We supplemented recreationally active males with beetroot juice to determine if this altered mitochondrial bioenergetics. Despite reduced submaximal exercise oxyg...
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This study combined overnight fluid restriction with lack of fluid intake during prolonged cycling to determine the effects of dehydration on substrate oxidation, skeletal muscle metabolism, heat shock protein 72 (Hsp72) response, and time trial (TT) performance. Nine males cycled at ~65% VO2peak for 90 min followed by a TT (6 kJ/kg BM) either with...
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Mitochondrial ADP transport may represent a convergence point unifying two prominent working models for the development of insulin resistance, as reactive lipids (specifically palmitoyl-CoA; P-CoA) can inhibit ADP transport and subsequently increase mitochondrial ROS emissions. In the current study we aimed to determine if exercise training in huma...
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Mitochondrial Pyruvate Dehydrogenase (PDH) regulates the delivery of carbohydrate-derived substrate to the mitochondrial tricarboxylic acid cycle and electron transport chain. PDH activity at rest and its activation during exercise is attenuated following high-fat (HFAT) compared to high-carbohydrate (HCHO) diets. Given the reliance on carbohydrate...
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Elimination of CO2 from skeletal muscle (mCO2) during exercise is important for the regulation of intramuscular [H+] ([mH+]). Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO2 to facilitate its elimination. We hypothesised that extracellular CA inhibition and subsequent increase in PCO2 will result in increased m[H+] and d...
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Studies have shown increased incorporation of omega-3s into whole skeletal muscle following supplementation, however little has been done to investigate the potential impact on the fatty acid composition of mitochondrial membranes and the functional consequences on mitochondrial bioenergetics. Therefore, we supplemented young healthy male subjects...
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Pulmonary O2 uptake (VO2p) and leg blood flow (LBF) kinetics were examined at the onset of moderate-intensity exercise (MOD), during hyperventilation with and without associated hypocapnic alkalosis. Seven male subjects (25 ± 6 yrs; mean ± SD) performed alternate-leg knee-extension exercise from baseline to MOD (80% of estimated lactate threshold),...
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During intense exercise in horses the transvascular fluid flux in the pulmonary circulation (JV-A) represent 4% of cardiac output (Q). This fluid flux has been attributed to an increase in pulmonary transmural hydrostatic forces, increases in perfused microvascular surface area, and reversible alterations in capillary permeability under conditions...
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This study investigated the effects of progressive mild dehydration during cycling on whole-body substrate oxidation and skeletal-muscle metabolism in recreationally active men. Subjects (N = 9) cycled for 120 min at ~65% peak oxygen uptake (VO2peak 22.7 °C, 32% relative humidity) with water to replace sweat losses (HYD) or without fluid (DEH). Blo...
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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 reache...
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Abstract In skeletal muscle, mitochondria exist as two subcellular populations known as subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. SS mitochondria preferentially respond to exercise training, suggesting divergent transcriptional control of the mitochondrial genomes. The transcriptional co-activator peroxisome proliferator-activat...
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Energy transfer between mitochondrial and cytosolic compartments is predominantly achieved by creatine-dependent phosphate shuttling (PCr/Cr) involving miCK. However ADP/ATP diffusion through adenine nucleotide translocase (ANT) and voltage-dependent anion carriers (VDAC) are also involved in this process. To determine if exercise alters the regula...
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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 quantif...
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This study investigated the effects of progressive dehydration on the time course of changes to whole body substrate oxidation and skeletal muscle metabolism during 120 min of cycling in hydrated females. Subjects (n = 9) cycled for 120 min at approximately 65% V˙O2peak on two occasions: with no fluid (DEH) and with fluid (HYD) replacement to match...
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Fatty acid transport proteins are present on the plasma membrane and are involved in the uptake of long-chain fatty acids into skeletal muscle. The present study determined whether acute endurance exercise increased the plasma membrane content of fatty acid transport proteins in rat and human skeletal muscle and whether the increase was accompanied...
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Frusemide (Fru) is widely prescribed for management of racehorses experiencing EIPH. The effect of Fru in the lung appears to be a reduction in transcapillary pressures and inhibition of the erythrocyte anion exchange, which may lead to attenuation of transpulmonary fluid fluxes during exercise. Treatment with Fru will attenuate transpulmonary flui...
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Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in hu...
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Silent mating type information regulator 2 homolog 1 (SIRT1)-mediated peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) deacetylation is potentially key for activating mitochondrial biogenesis. Yet, at the whole muscle level, SIRT1 is not associated with mitochondrial biogenesis (Gurd, BJ, Yoshida Y, Lally J, Holloway GP, Bon...
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Glycogen depletion was used as an experimental tool to examine the relationship between excess post-exercise oxygen consumption and lactate metabolism in 6-g rainbow trout. A 5-day starvation period reduced whole-body glycogen stores by 50% and slightly lowered resting lactate levels; resting oxygen consumption, glucose, ATP, and creatine phosphate...
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β-Adrenoceptor blockers are widely used clinically and can be classified as nonselective (β1 and β2) or selective (β1). Impairment of exercise performance is a well-known side effect of this group of drugs. This paper reviews mechanisms that could potentially be responsible for this impairment. In addition to cardiovascular and metabolic effects, β...
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Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl(-) and HCO(3)(-) exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses. To determine the effects o...
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Exercise training induces mitochondrial biogenesis, but the time course of molecular sequelae that accompany repetitive training stimuli remains to be determined in human skeletal muscle. Therefore, throughout a seven-session, high-intensity interval training period that increased (12%), we examined the time course of responses of (a) mitochondrial...
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Fatty acid oxidation is highly regulated in skeletal muscle and involves several sites of regulation, including the transport of fatty acids across both the plasma and mitochondrial membranes. Transport across these membranes is recognized to be primarily protein mediated, limited by the abundance of fatty acid transport proteins on the respective...
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The effects of training on silent mating-type information regulator 2 homolog 1 (SIRT1) activity and protein in relationship to peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and mitochondrial content were determined in human skeletal muscle. Six weeks of high-intensity interval training ( approximately 1 h of 10 x...
Article
Introduction: This study investigated the effects of progressive dehydration on the time course of changes to whole body substrate oxidation and skeletal muscle metabolism during 120 min of cycling in hydrated females. Methods: Subjects (n = 9) cycled for 120 min at approximately 65% V ˙ O 2peak on two occasions: with no fluid (DEH) and with fluid...
Article
The effect of hyperventilation-induced hypocapnic alkalosis (Hypo) on the adjustment of pulmonary O2 uptake (VO2p) and leg femoral conduit artery ("bulk") blood flow (LBF) during moderate-intensity exercise (Mod) was examined in eight young male adults. Subjects completed four to six repetitions of alternate-leg knee-extension exercise during norma...
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Apoptosis in skeletal muscle plays an important role in age- and disease-related tissue dysfunction. Physical activity can influence apoptotic signaling; however, this process has not been well studied in human skeletal muscle. The purpose of this study was to perform a comprehensive analysis of apoptosis-related proteins/enzymes, DNA fragmentation...
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The effect of hyperventilation-induced hypocapnic alkalosis (HYPO) and prior heavy-intensity exercise (HVY) on pulmonary O(2) uptake (VO(2p)) kinetics were examined in young adults (n = 7) during moderate-intensity exercise (MOD). Subjects completed leg cycling exercise during (1) normal breathing (CON, P(ET)CO(2) approximately 40 mmHg) and (2) con...
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Skeletal muscle lipid content is increased in obesity. Recent evidence suggests that fatty acid (FA) storage as triacylglycerol (TAG) represents a metabolically safe pool compared to the more bioactive diacylglycerol (DAG) and ceramide. The purpose of this study was to compare the expression of lipogenic proteins and ceramide and DAG content in ske...
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Pyruvate dehydrogenase (PDH) regulates oxidative carbohydrate disposal in skeletal muscle and is downregulated by reversible phosphorylation catalyzed by PDH kinase (PDK). Previous work has demonstrated increased PDK activity and PDK4 expression in human skeletal muscle following a high-fat low-carbohydrate (HF) diet, which leads to decreased PDH i...
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The adaptation of pulmonary oxygen uptake (VO(2)(p)) kinetics during the transition to moderate-intensity exercise is slowed in older compared with younger adults; however, this response is faster following a prior bout of heavy-intensity exercise. We have examined VO(2)(p) kinetics, pyruvate dehydrogenase (PDH) activation, muscle metabolite conten...
Article
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-de...
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High-intensity aerobic interval training (HIIT) is a compromise between time-consuming moderate-intensity training and sprint-interval training requiring all-out efforts. However, there are few data regarding the ability of HIIT to increase the capacities of fat and carbohydrate oxidation in skeletal muscle. Using untrained recreationally active in...
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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 t...
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to the editor: The acidification of blood during muscular exercise cannot be understood from an analysis of blood from a single site, nor from examination of only arterial (or arterialized) blood. Acidification of blood during muscular contraction occurs as a result of rapid and marked increases in
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to the editor: This debate ([1][1], [4][2]) focused on whether the increase in plasma [lactate] was the sole contributor to the acidosis associated with exercise at sufficiently high intensities to generate increased plasma [lactate−]. It remains puzzling that many physiologists continue to
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Reduced skeletal muscle mitochondrial content and fatty acid oxidation are associated with obesity and insulin resistance. Although the exact mechanisms remain elusive, this may result from impaired mitochondrial biogenesis or reductions in the mitochondrial reticulum network. Therefore, the purpose of this study was to determine whether the protei...
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Exposure to high fatty acids (FAs) induces whole body and skeletal muscle insulin resistance. The globular form of the adipokine, adiponectin (gAd), stimulates FA oxidation and improves insulin sensitivity; however, its ability to prevent lipid-induced insulin resistance in humans has not been tested. The purpose of this study was to determine 1) w...
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The adaptation of pulmonary O(2) uptake (Vo(2)(p)) kinetics is slowed in older compared with young adults during the transition to moderate-intensity exercise. In this study, we examined the relationship between Vo(2)(p) kinetics and mitochondrial pyruvate dehydrogenase (PDH) activity in young (n = 7) and older (n = 6) adults. Subjects performed cy...
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Pyruvate dehydrogenase (PDH) is an important regulator of carbohydrate oxidation during exercise, and its activity can be downregulated by an increase in dietary fat. The purpose of this study was to determine the acute metabolic effects of differential dietary fatty acids on the activation of the PDH complex (PDHa activity) at rest and at the onse...
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It is unclear whether the beneficial effects of habitual exercise on insulin resistance are due to concomitant weight loss, changes in diet or whether they are simply related to the transient effects of the last bout of exercise. Moreover, patients with coronary artery disease (CAD) have not been studied. Randomized controlled trial. To determine t...
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The present study used the physicochemical approach to characterize the changes in acid–base status that occur in Standardbreds after post-exercise electrolyte supplementation. Jugular venous blood was sampled from six conditioned Standardbreds on two separate occasions, at rest and for 24 h following a competitive exercise test (CET) designed to s...
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The interactions between nutrition, energy status and acid–base balance during exercise are poorly understood. Exercise, under conditions of prior glycogen depletion (GD) and low-carbohydrate diet, results in a decreased rate of skeletal muscle glycogenolysis, greatly decreased muscle pyruvate and lactate contents with decreased plasma [lactate] (P...
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The effect of voluntary hyperventilation-induced hypocapnic alkalosis (RALK) on pulmonary O2 uptake (VO2) kinetics and muscle deoxygenation was examined in young male adults (n=8) during moderate-intensity exercise. Subjects performed five repetitions of a step-transition in work rate from 20 W cycling to a work rate corresponding to 90% of the est...
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The transport of long-chain fatty acids (LCFAs) across mitochondrial membranes is regulated by carnitine palmitoyltransferase I (CPTI) activity. However, it appears that additional fatty acid transport proteins, such as fatty acid translocase (FAT)/CD36, influence not only LCFA transport across the plasma membrane, but also LCFA transport into mito...