Effect of continuous and interval exercise training on the PETCO2 response during a graded exercise test in patients with coronary artery disease

OBJECTIVE: The purpose of this study was to evaluate the following: 1) the effects of continuous exercise training and interval exercise training on the end-tidal carbon dioxide pressure (PETCO2) response during a graded exercise test in patients with coronary artery disease; and 2) the effects of exercise training modalities on the association between PETCO2 at the ventilatory anaerobic threshold (VAT) and indicators of ventilatory efficiency and cardiorespiratory fitness in patients with coronary artery disease. METHODS: Thirty-seven patients (59.7 +/- 1.7 years) with coronary artery disease were randomly divided into two groups: continuous exercise training (n = 20) and interval exercise training (n = 17). All patients performed a graded exercise test with respiratory gas analysis before and after three months of the exercise training program to determine the VAT, respiratory compensation point (RCP) and peak oxygen consumption. RESULTS: After the interventions, both groups exhibited increased cardiorespiratory fitness. Indeed, the continuous exercise and interval exercise training groups demonstrated increases in both ventilatory efficiency and PETCO2 values at VAT, RCP, and peak of exercise. Significant associations were observed in both groups: 1) continuous exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.49; PETCO(2)VAT and ventilatory efficiency r = -0.80) and 2) interval exercise training (PETCO(2)VAT and cardiorespiratory fitness r = 0.39; PETCO(2)VAT and ventilatory efficiency r = -0.45). CONCLUSIONS: Both exercise training modalities showed similar increases in PETCO2 levels during a graded exercise test in patients with coronary artery disease, which may be associated with an improvement in ventilatory efficiency and cardiorespiratory fitness.

Exercise Training Restores Cardiac Protein Quality Control in Heart Failure

Exercise training is a well-known coadjuvant in heart failure treatment; however, the molecular mechanisms underlying its beneficial effects remain elusive. Despite the primary cause, heart failure is often preceded by two distinct phenomena: mitochondria dysfunction and cytosolic protein quality control disruption. The objective of the study was to determine the contribution of exercise training in regulating cardiac mitochondria metabolism and cytosolic protein quality control in a post-myocardial infarction-induced heart failure (MI-HF) animal model. Our data demonstrated that isolated cardiac mitochondria from MI-HF rats displayed decreased oxygen consumption, reduced maximum calcium uptake and elevated H2O2 release. These changes were accompanied by exacerbated cardiac oxidative stress and proteasomal insufficiency. Declined proteasomal activity contributes to cardiac protein quality control disruption in our MI-HF model. Using cultured neonatal cardiomyocytes, we showed that either antimycin A or H2O2 resulted in inactivation of proteasomal peptidase activity, accumulation of oxidized proteins and cell death, recapitulating our in vivo model. Of interest, eight weeks of exercise training improved cardiac function, peak oxygen uptake and exercise tolerance in MI-HF rats. Moreover, exercise training restored mitochondrial oxygen consumption, increased Ca2+-induced permeability transition and reduced H2O2 release in MI-HF rats. These changes were followed by reduced oxidative stress and better cardiac protein quality control. Taken together, our findings uncover the potential contribution of mitochondrial dysfunction and cytosolic protein quality control disruption to heart failure and highlight the positive effects of exercise training in re-establishing cardiac mitochondrial physiology and protein quality control, reinforcing the importance of this intervention as a nonpharmacological tool for heart failure therapy.

Activation of the mitochondrial ATP-sensitive K+ channel reduces apoptosis of spleen mononuclear cells induced by hyperlipidemia

Background We have previously demonstrated that increased rates of superoxide generation by extra-mitochondrial enzymes induce the activation of the mitochondrial ATP-sensitive potassium channel (mitoKATP) in the livers of hypertriglyceridemic (HTG) mice. The resulting mild uncoupling mediated by mitoKATP protects mitochondria against oxidative damage. In this study, we investigate whether immune cells from HTG mice also present increased mitoKATP activity and evaluate the influence of this trait on cell redox state and viability. Methods Oxygen consumption (Clark-type electrode), reactive oxygen species production (dihydroethidium and H2-DCF-DA probes) and cell death (annexin V, cytocrome c release and Trypan blue exclusion) were determined in spleen mononuclear cells. Results HTG mice mononuclear cells displayed increased mitoKATP activity, as evidenced by higher resting respiration rates that were sensitive to mitoKATP antagonists. Whole cell superoxide production and apoptosis rates were increased in HTG cells. Inhibition of mitoKATP further increased the production of reactive oxygen species and apoptosis in these cells. Incubation with HTG serum induced apoptosis more strongly in WT cells than in HTG mononuclear cells. Cytochrome c release into the cytosol and caspase 8 activity were both increased in HTG cells, indicating that cell death signaling starts upstream of the mitochondria but does involve this organelle. Accordingly, a reduced number of blood circulating lymphocytes was found in HTG mice. Conclusions These results demonstrate that spleen mononuclear cells from hyperlipidemic mice have more active mitoKATP channels, which downregulate mitochondrial superoxide generation. The increased apoptosis rate observed in these cells is exacerbated by closing the mitoKATP channels. Thus, mitoKATP opening acts as a protective mechanism that reduces cell death induced by hyperlipidemia.

Cardiac autonomic impairment and chronotropic incompetence in fibromyalgia

Abstract Introduction We aimed to gather knowledge on the cardiac autonomic modulation in patients with fibromyalgia (FM) in response to exercise and to investigate whether this population suffers from chronotropic incompetence (CI). Methods Fourteen women with FM (age: 46 ± 3 years; body mass index (BMI): 26.6 ± 1.4 kg/m2) and 14 gender-, BMI- (25.4 ± 1.3 kg/m2), and age-matched (age: 41 ± 4 years) healthy individuals (CTRL) took part in this cross-sectional study. A treadmill cardiorespiratory test was performed and heart-rate (HR) response during exercise was evaluated by the chronotropic reserve. HR recovery (deltaHRR) was defined as the difference between HR at peak exercise and at both first (deltaHRR1) and second (deltaHRR2) minutes after the exercise test. Results FM patients presented lower maximal oxygen consumption (VO2 max) when compared with healthy subjects (22 ± 1 versus CTRL: 32 ± 2 mL/kg/minute, respectively; P < 0.001). Additionally, FM patients presented lower chronotropic reserve (72.5 ± 5 versus CTRL: 106.1 ± 6, P < 0.001), deltaHRR1 (24.5 ± 3 versus CTRL: 32.6 ± 2, P = 0.059) and deltaHRR2 (34.3 ± 4 versus CTRL: 50.8 ± 3, P = 0.002) than their healthy peers. The prevalence of CI was 57.1% among patients with FM. Conclusions Patients with FM who undertook a graded exercise test may present CI and delayed HR recovery, both being indicative of cardiac autonomic impairment and higher risk of cardiovascular events and mortality.

Physical training prevents body weight gain but does not modify adipose tissue gene expression

The relationship of body weight (BW) with white adipose tissue (WAT) mass and WAT gene expression pattern was investigated in mice submitted to physical training (PT). Adult male C57BL/6 mice were submitted to two 1.5-h daily swimming sessions (T, N = 18), 5 days/week for 4 weeks or maintained sedentary (S, N = 15). Citrate synthase activity increased significantly in the T group (P < 0.05). S mice had a substantial weight gain compared to T mice (4.06 ± 0.43 vs 0.38 ± 0.28 g, P < 0.01). WAT mass, adipocyte size, and the weights of gastrocnemius and soleus muscles, lung, kidney, and adrenal gland were not different. Liver and heart were larger and the spleen was smaller in T compared to S mice (P < 0.05). Food intake was higher in T than S mice (4.7 ± 0.2 vs 4.0 ± 0.3 g/animal, P < 0.05) but oxygen consumption at rest did not differ between groups. T animals showed higher serum leptin concentration compared to S animals (6.37 ± 0.5 vs 3.11 ± 0.12 ng/mL). WAT gene expression pattern obtained by transcription factor adipocyte determination and differentiation-dependent factor 1, fatty acid synthase, malic enzyme, hormone-sensitive lipase, adipocyte lipid binding protein, leptin, and adiponectin did not differ significantly between groups. Collectively, our results showed that PT prevents BW gain and maintains WAT mass due to an increase in food intake and unchanged resting metabolic rate. These responses are closely related to unchanged WAT gene expression patterns.

Sanguineous normothermic, intermittent cardioplegia, effects on hypertrophic myocardium: morphometric, metabolic and ultrastructural studies in rabbits hearts

OBJECTIVES: The present investigation aimed to study the protective effect of intermittent normothermic cardioplegia in rabbit's hypertrophic hearts. METHODS: The parameters chosen were 1) the ratio heart weight / body weight, 2) the myocardial glycogen levels, 3) ultrastructural changes of light and electron microscopy, and 4) mitochondrial respiration. RESULTS: 1) The experimental model, coarctation of the aorta induced left ventricular hypertrophy; 2) the temporal evolution of the glycogen levels in hypertrophic myocardium demonstrates that there is a significant decrease; 3) It was observed a time-dependent trend of higher oxygen consumption values in the hypertrophic group; 4) there was a significant time-dependent decrease in the respiratory coefficient rate in the hypertrophic group; 5) the stoichiometries values of the ADP: O2 revealed the downward trend of the values of the hypertrophic group; 6) It was possible to observe damaged mitochondria from hypertrophic myocardium emphasizing the large heterogeneity of data. CONCLUSION: The acquisition of biochemical data, especially the increase in speed of glycogen breakdown, when anatomical changes are not detected, represents an important result even when considering all the difficulties inherent in the process of translating experimental results into clinical practice. With regard to the adopted methods, it is clear that morphometric methods are less specific. Otherwise, the biochemical data allow detecting alterations of glycogen concentrations and mitochondria respiration before the morphometric alterations should be detected

Acute inhibition of excessive mitochondrial fission after myocardial infarction prevents long-term cardiac dysfunction

BACKGROUND: Ischemia and reperfusion (IR) injury remains a major cause of morbidity and mortality and multiple molecular and cellular pathways have been implicated in this injury. We determined whether acute inhibition of excessive mitochondrial fission at the onset of reperfusion improves mitochondrial dysfunction and cardiac contractility postmyocardial infarction in rats. METHODS AND RESULTS: We used a selective inhibitor of the fission machinery, P110, which we have recently designed. P110 treatment inhibited the interaction of fission proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics in three different rat models of IR, including primary cardiomyocytes, ex vivo heart model, and an in vivo myocardial infarction model. Drp1 transiently bound to the mitochondria following IR injury and P110 treatment blocked this Drp1 mitochondrial association. Compared with control treatment, P110 (1 μmol/L) decreased infarct size by 28 ± 2% and increased adenosine triphosphate levels by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model resulted in improved mitochondrial oxygen consumption by 68% when measured 3 weeks after ischemic injury, improved cardiac fractional shortening by 35%, reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall mitochondrial functions. CONCLUSIONS: Together, we show that excessive mitochondrial fission at reperfusion contributes to long-term cardiac dysfunction in rats and that acute inhibition of excessive mitochondrial fission at the onset of reperfusion is sufficient to result in long-term benefits as evidenced by inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.

Skeletal muscle mitochondrial DNA content in exercising humans

[EN] Several weeks of intense endurance training enhances mitochondrial biogenesis in humans. Whether a single bout of exercise alters skeletal muscle mitochondrial DNA (mtDNA) content remains unexplored. Double-stranded mtDNA, estimated by slot-blot hybridization and real time PCR and expressed as mtDNA-to-nuclear DNA ratio (mtDNA/nDNA) was obtained from the vastus lateralis muscle of healthy human subjects to investigate whether skeletal muscle mtDNA changes during fatiguing and nonfatiguing prolonged moderate intensity [2.0-2.5 h; approximately 60% maximal oxygen consumption (Vo(2 max))] and short repeated high-intensity exercise (5-8 min; approximately 110% Vo(2 max)). In control resting and light exercise (2 h; approximately 25% Vo(2 max)) studies, mtDNA/nDNA did not change. Conversely, mtDNA/nDNA declined after prolonged fatiguing exercise (0.863 +/- 0.061 vs. 1.101 +/- 0.067 at baseline; n = 14; P = 0.005), remained lower after 24 h of recovery, and was restored after 1 wk. After nonfatiguing prolonged exercise, mtDNA/nDNA tended to decline (n = 10; P = 0.083) but was reduced after three repeated high-intensity exercise bouts (0.900 +/- 0.049 vs. 1.067 +/- 0.071 at baseline; n = 7; P = 0.013). Our findings indicate that prolonged and short repeated intense exercise can lead to significant reductions in human skeletal muscle mtDNA content, which might function as a signal stimulating mitochondrial biogenesis with exercise training.

Leg and arm lactate and substrate kinetics during exercise

[EN] To study the role of muscle mass and muscle activity on lactate and energy kinetics during exercise, whole body and limb lactate, glucose, and fatty acid fluxes were determined in six elite cross-country skiers during roller-skiing for 40 min with the diagonal stride (Continuous Arm + Leg) followed by 10 min of double poling and diagonal stride at 72-76% maximal O(2) uptake. A high lactate appearance rate (R(a), 184 +/- 17 micromol x kg(-1) x min(-1)) but a low arterial lactate concentration ( approximately 2.5 mmol/l) were observed during Continuous Arm + Leg despite a substantial net lactate release by the arm of approximately 2.1 mmol/min, which was balanced by a similar net lactate uptake by the leg. Whole body and limb lactate oxidation during Continuous Arm + Leg was approximately 45% at rest and approximately 95% of disappearance rate and limb lactate uptake, respectively. Limb lactate kinetics changed multiple times when exercise mode was changed. Whole body glucose and glycerol turnover was unchanged during the different skiing modes; however, limb net glucose uptake changed severalfold. In conclusion, the arterial lactate concentration can be maintained at a relatively low level despite high lactate R(a) during exercise with a large muscle mass because of the large capacity of active skeletal muscle to take up lactate, which is tightly correlated with lactate delivery. The limb lactate uptake during exercise is oxidized at rates far above resting oxygen consumption, implying that lactate uptake and subsequent oxidation are also dependent on an elevated metabolic rate. The relative contribution of whole body and limb lactate oxidation is between 20 and 30% of total carbohydrate oxidation at rest and during exercise under the various conditions. Skeletal muscle can change its limb net glucose uptake severalfold within minutes, causing a redistribution of the available glucose because whole body glucose turnover was unchanged.

Metabolic and thermodynamic responses to dehydration-induced reductions in muscle blood flow in exercising humans

[EN] 1. The present study examined whether reductions in muscle blood flow with exercise-induced dehydration would reduce substrate delivery and metabolite and heat removal to and from active skeletal muscles during prolonged exercise in the heat. A second aim was to examine the effects of dehydration on fuel utilisation across the exercising leg and identify factors related to fatigue. 2. Seven cyclists performed two cycle ergometer exercise trials in the heat (35 C; 61 +/- 2 % of maximal oxygen consumption rate, VO2,max), separated by 1 week. During the first trial (dehydration, DE), they cycled until volitional exhaustion (135 +/- 4 min, mean +/- s.e.m.), while developing progressive DE and hyperthermia (3.9 +/- 0.3 % body weight loss and 39.7 +/- 0.2 C oesophageal temperature, Toes). On the second trial (control), they cycled for the same period of time maintaining euhydration by ingesting fluids and stabilising Toes at 38.2 +/- 0.1 degrees C. 3. After 20 min of exercise in both trials, leg blood flow (LBF) and leg exchange of lactate, glucose, free fatty acids (FFA) and glycerol were similar. During the 20 to 135 +/- 4 min period of exercise, LBF declined significantly in DE but tended to increase in control. Therefore, after 120 and 135 +/- 4 min of DE, LBF was 0.6 +/- 0.2 and 1.0 +/- 0.3 l min-1 lower (P < 0.05), respectively, compared with control. 4. The lower LBF after 2 h in DE did not alter glucose or FFA delivery compared with control. However, DE resulted in lower (P < 0.05) net FFA uptake and higher (P < 0.05) muscle glycogen utilisation (45 %), muscle lactate accumulation (4.6-fold) and net lactate release (52 %), without altering net glycerol release or net glucose uptake. 5. In both trials, the mean convective heat transfer from the exercising legs to the body core ranged from 6.3 +/- 1.7 to 7.2 +/- 1.3 kJ min-1, thereby accounting for 35-40 % of the estimated rate of heat production ( approximately 18 kJ min-1). 6. At exhaustion in DE, blood lactate values were low whereas blood glucose and muscle glycogen levels were still high. Exhaustion coincided with high body temperature ( approximately 40 C). 7. In conclusion, the present results demonstrate that reductions in exercising muscle blood flow with dehydration do not impair either the delivery of glucose and FFA or the removal of lactate during moderately intense prolonged exercise in the heat. However, dehydration during exercise in the heat elevates carbohydrate oxidation and lactate production. A major finding is that more than one-half of the metabolic heat liberated in the contracting leg muscles is dissipated directly to the surrounding environment. The present results indicate that hyperthermia, rather than altered metabolism, is the main factor underlying the early fatigue with dehydration during prolonged exercise in the heat.

Muscle blood flow is reduced with dehydration during prolonged exercise in humans

[EN] 1. The present study examined whether the blood flow to exercising muscles becomes reduced when cardiac output and systemic vascular conductance decline with dehydration during prolonged exercise in the heat. A secondary aim was to determine whether the upward drift in oxygen consumption (VO2) during prolonged exercise is confined to the active muscles. 2. Seven euhydrated, endurance-trained cyclists performed two bicycle exercise trials in the heat (35 C; 40-50 % relative humidity; 61 +/- 2 % of maximal VO2), separated by 1 week. During the first trial (dehydration trial, DE), they bicycled until volitional exhaustion (135 +/- 4 min, mean +/- s.e.m.), while developing progressive dehydration and hyperthermia (3.9 +/- 0.3 % body weight loss; 39.7 +/- 0.2 C oesophageal temperature, Toes). In the second trial (control trial), they bicycled for the same period of time while maintaining euhydration by ingesting fluids and stabilizing Toes at 38.2 +/- 0.1 C after 30 min exercise. 3. In both trials, cardiac output, leg blood flow (LBF), vascular conductance and VO2 were similar after 20 min exercise. During the 20 min-exhaustion period of DE, cardiac output, LBF and systemic vascular conductance declined significantly (8-14 %; P < 0.05) yet muscle vascular conductance was unaltered. In contrast, during the same period of control, all these cardiovascular variables tended to increase. After 135 +/- 4 min of DE, the 2.0 +/- 0.6 l min-1 lower blood flow to the exercising legs accounted for approximately two-thirds of the reduction in cardiac output. Blood flow to the skin also declined markedly as forearm blood flow was 39 +/- 8 % (P < 0.05) lower in DE vs. control after 135 +/- 4 min. 4. In both trials, whole body VO2 and leg VO2 increased in parallel and were similar throughout exercise. The reduced leg blood flow in DE was accompanied by an even greater increase in femoral arterial-venous O2 (a-vO2) difference. 5. It is concluded that blood flow to the exercising muscles declines significantly with dehydration, due to a lowering in perfusion pressure and systemic blood flow rather than increased vasoconstriction. Furthermore, the progressive increase in oxygen consumption during exercise is confined to the exercising skeletal muscles.

Behavior of respiratory metabolism and pyridine nucleotide levels in Oxyrrhis marina during starvation

Máster en Oceanografía

Bottle effects, toxicity and cell viability during incubation experiments to asses community respiration

Máster en Oceanografía

A parallel future for Ocean research?

[EN] Today, science is difficult to pursue because funding is so tenuous. In such a financial climate, researchers need to consider parallel alternatives to ensure that scientific research can continue. Based on this thinking, we created BIOCEANSolutions, a company born of a research group. A great variety of environmental regulations and standards have emerged over recent years with the purpose of protecting natural ecosystems. These have enabled us to link our research to the market of environmental management. Marine activities can alter environmental conditions, resulting in changes in physiological states, species diversity, abundance, and biomass in the local biological communities. In this way, we can apply our knowledge, to plankton ecophysiology and biochemical oceanography. We measure enzyme activities as bio-indicators of energy metabolism and other physiological rates and biologic-oceanographic processes in marine organisms. This information provides insight into the health of marine communities, the stress levels of individual organisms, and potential anomalies that may be affecting them. In the process of verifying standards and complying with regulations, we can apply our analytic capability and knowledge. The main analyses that we offer are: (1) the activity of the electron transport system (ETS) or potential respiration (Φ), (2) the physiological measurement of respiration (oxygen consumption), (3) the activity of Isocitrate dehydrogenase (IDH), (4) the respiratory CO2 production, and (5) the activity of Glutamate dehydrogenase (GDH) and (6) the physiological measurement of ammonium excretion. In addition, our experience in a productive research group allows us to pursue and develop technical-experimental activities such as marine and freshwater aquaculture, oceanographic field sampling, as well as providing guidance, counseling, and academic services. In summary, this new company will permit us to create a symbiosis between public and private sectors that serve clients and will allow us to grow and expand as a research team.

Active mesopelagic prokaryotes support high respiration in the subtropical northeast Atlantic Ocean

[EN]Here we provide evidence, based on prokaryote metabolic proxies and direct estimates of oxygen consumption, that the mesopelagic prokaryote assemblage in the subtropical Northeast Atlantic is an active one. It supports a high respiration (0.22 ± 0.05 μmol O2 l−1 d−1, corresponding to 68 ± 8 mmol CO2 m−2 d−1), comparable to that of the epipelagic zone during the same period (64–97 mmol C m−2 d−1). Our findings suggest that mesopelagic prokaryotes in the NE subtropical Ocean, as well as in other eastern boundary regions, are important carbon sinks for organic matter advected from the highly productive coastal systems, and would play a key role in the global carbon cycle of the oceans.