Muscle and femoral vein temperatures during short-term maximal exercise in heart failure

Core temperature decreases throughout short-term maximal exercise in heart-failure patients. To investigate possible causes for this unusual response to exercise, we studied core (pulmonary arterial blood), femoral vein, muscle, and skin temperatures in eight patients with severe heart failure who performed maximal upright incremental bicycle exercise to 50 W. A normal group (n = 4) was exercised for comparison. In the heart-failure patients, core temperature was 36.95 +/- 0.37 degrees C at rest, significantly (P less than 0.05) decreased at 25 W of exercise to 36.59 +/- 0.40 degrees C, and at 50 W remained decreased to 36.57 +/- 0.40 degrees C. In comparison, we found that the resting core temperature in the normal subjects was 37.28 +/- 0.34 degrees C, was the same at 25 W (37.29 +/- 0.41 degrees C), and increased significantly (P less than 0.05) to 37.50 +/- 0.32 degrees C at 50 W of exercise. Femoral vein temperature in heart-failure patients (n = 6) was below core temperature throughout exercise to 25 and 50 W (36.22 +/- 0.62 and 36.34 +/- 0.65 degrees C, respectively). Muscle temperature (n = 7) was significantly (P less than 0.05) lower in the heart-failure patients (34.8 +/- 1.1 degrees C) at rest compared with the normal subjects (36.2 +/- 1.0 degrees C). During exercise, muscle temperature increased above core temperature in only four of the heart-failure patients and was significantly (P less than 0.05) lower (36.5 +/- 1.3 degrees C) compared with the normal subjects (38.0 +/- 0.2 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle triglyceride utilization during exercise: effect of training

The respiratory exchange ratio (RER) is lower during exercise of the same intensity in the trained compared with the untrained state, even though plasma free fatty acids (FFA) and glycerol levels are lower, suggesting reduced availability of plasma FFA. In this context, we evaluated the possibility that lipolysis of muscle triglycerides might be higher in the trained state. Nine adult male subjects performed a prolonged bout of exercise of the same absolute intensity before and after adapting to a strenuous 12-wk program of endurance exercise. The exercise test required 64% of maximum O2 uptake before training. Plasma FFA and glycerol concentrations and RER during the exercise test were lower in the trained than in the untrained state. The proportion of the caloric expenditure derived from fat, calculated from the RER, during the exercise test increased from 35% before training to 57% after training. Muscle glycogen utilization was 41% lower, whereas the decrease in quadriceps muscle triglyceride concentration was roughly twice as great (12.7 +/- 5.5 vs. 26.1 +/- 9.3 mmol/kg dry wt, P less than 0.001) in the trained state. These results suggest that the greater utilization of FFA in the trained state is fueled by increased lipolysis of muscle triglyceride.     

Muscle mechanoreceptor sensitivity in heart failure

Prior work in animals suggests that muscle mechanoreceptor control of sympathetic activation (MSNA) during exercise in heart failure (HF) is heightened and that muscle mechanoreceptors are sensitized by metabolic by-products. We sought to determine whether 1) muscle mechanoreceptor control of MSNA is enhanced in HF patients and 2) lactic acid sensitizes muscle mechanoreceptors during rhythmic handgrip (RHG) exercise in healthy humans and patients with HF. Dichloroacetate (DCA), which reduces the production of lactic acid, or saline control was infused in 12 patients with HF and 13 controls during RHG. MSNA was recorded (microneurography). After saline was administered and during exercise thereafter, MSNA increased earlier in HF compared with controls, consistent with baseline-heightened mechanoreceptor sensitivity. In both HF and controls, MSNA increased during the 3-min exercise protocol, consistent with further sensitization of muscle mechanoreceptors by metabolic by-product(s). During posthandgrip circulatory arrest, MSNA returned rapidly to baseline levels, excluding the muscle metaboreceptors as mediators of the sympathetic excitation during RHG. To isolate muscle mechanoreceptors from central command, we utilized passive exercise in 8 HF and 11 controls, and MSNA was recorded. MSNA increased significantly during passive exercise in HF but not in controls. In conclusion, muscle mechanoreceptors mediate the increase in MSNA during low-level RHG exercise in healthy humans, and this muscle mechanoreceptor control is augmented further in HF. Neither lactate generation nor the fall in pH during RHG plays a central role in muscle mechanoreceptor sensitization. Finally, muscle mechanoreceptors in patients with HF have heightened basal sensitivity to mechanical stimuli resulting in exaggerated early increases in MSNA.     

Cellular remodeling in heart failure disrupts K(ATP) channel-dependent stress tolerance

ATP-sensitive potassium (K(ATP)) channels are required for maintenance of homeostasis during the metabolically demanding adaptive response to stress. However, in disease, the effect of cellular remodeling on K(ATP) channel behavior and associated tolerance to metabolic insult is unknown. Here, transgenic expression of tumor necrosis factor alpha induced heart failure with typical cardiac structural and energetic alterations. In this paradigm of disease remodeling, K(ATP) channels responded aberrantly to metabolic signals despite intact intrinsic channel properties, implicating defects proximal to the channel. Indeed, cardiomyocytes from failing hearts exhibited mitochondrial and creatine kinase deficits, and thus a reduced potential for metabolic signal generation and transmission. Consequently, K(ATP) channels failed to properly translate cellular distress under metabolic challenge into a protective membrane response. Failing hearts were excessively vulnerable to metabolic insult, demonstrating cardiomyocyte calcium loading and myofibrillar contraction banding, with tolerance improved by K(ATP) channel openers. Thus, disease-induced K(ATP) channel metabolic dysregulation is a contributor to the pathobiology of heart failure, illustrating a mechanism for acquired channelopathy.     

Variation in heart rate during submaximal exercise: implications for monitoring training

A change in heart rate at a controlled submaximal exercise intensity is used as a marker of training status. However, the standard error of measurement has not been studied systematically, and therefore a change in heart rate, which can be considered relevant, has not been determined. Forty-four subjects (26.5 +/- 5.4 years; mean +/- standard deviation) participated in a submaximal running test at the same time of day for 5 consecutive days. Heart rates were determined during each of the 4 exercise intensities (2 minutes each) of increasing intensity and during the 1-minute recovery period after each stage. The repeatability of the heart rate on a day-to-day basis during the stages and recovery periods were high (intraclass correlation coefficient: 95% confidence interval R = 0.94- 0.99). The lowest variation in heart rate occurred in the fourth stage ( approximately 90% maximum heart rate) with heart rate varying 5 +/- 2 b.min(-1) (95% confidence interval for coefficient of variation = 1.1-1.4%). In conclusion, the standard error of measurement of submaximal heart rate is 1.1-1.4%. This magnitude of measurement error needs to be considered when heart rate is used as a marker of training status.     

Electrophysiological changes in heart failure and their implications for arrhythmogenesis

Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors. Diet and ventricular wall stretch are discussed as modulating factors. Finally, emphasis is placed on the hitherto poorly studied aspects of right ventricular failure. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.     

Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise

Exercise increases permeability of muscle to glucose. Normally, the effects of exercise and a maximal insulin stimulus on glucose transport are additive. However, the combined effect on rat epitrochlearis muscle permeability to 3-O-methylglucose (3-MG) of a maximal insulin stimulus followed by in vitro contractile activity of 1.24 +/- 0.06 mumol.10 min-1.ml intracellular water-1 was no greater than that of either stimulus alone. We found that this absence of an additive effect was caused by prolonged exposure to an unphysiologically high insulin concentration (20,000 microU/ml for 60 min), which, in addition to stimulating glucose transport, appears to prevent further increases in permeability to glucose. When the treatments were reversed and muscles were first stimulated to contract and then incubated with 20,000 microU/ml insulin, 3-MG uptake (mumol.10 min-1.ml intracellular water-1) increased from a control value of 0.26 +/- 0.03 to 1.80 +/- 0.15, compared with 1.04 +/- 0.06 for contractile activity alone, 1.21 +/- 0.08 for insulin, and 1.88 +/- 0.11 for exercise (swimming) plus insulin. Swimming plus in vitro contractile activity did not have a greater effect than contractile activity alone. Our results provide evidence that 1) the effect of exercise on muscle permeability to glucose is mediated solely by a process associated with contractile activity, and 2) it is advisable to avoid the use of unphysiologically high insulin concentrations in studies designed to elucidate in vivo actions of insulin.     

A novel cardiopulmonary exercise test protocol and criterion to determine maximal oxygen uptake in chronic heart failure

Cardiopulmonary exercise testing for peak oxygen uptake (Vo(2peak)) can evaluate prognosis in chronic heart failure (CHF) patients, with the peak respiratory exchange ratio (RER(peak)) commonly used to confirm maximal effort and maximal oxygen uptake (Vo(2max)). We determined the precision of RER(peak) in confirming Vo(2max), and whether a novel ramp-incremental (RI) step-exercise (SE) (RISE) test could better determine Vo(2max) in CHF. Male CHF patients (n = 24; NYHA class I-III) performed a symptom-limited RISE-95 cycle ergometer test in the format: RI (4-18 W/min; ～10 min); 5 min recovery (10 W); SE (95% peak RI work rate). Patients (n = 18) then performed RISE-95 tests using slow (3-8 W/min; ～15 min) and fast (10-30 W/min; ～6 min) ramp rates. Pulmonary gas exchange was measured breath-by-breath. Vo(2peak) was compared within patients by unpaired t-test of the highest 12 breaths during RI and SE phases to confirm Vo(2max) and its 95% confidence limits (CI(95)). RER(peak) was significantly influenced by ramp rate (fast, medium, slow: 1.21 ± 0.1 vs. 1.15 ± 0.1 vs. 1.09 ± 0.1; P = 0.001), unlike Vo(2peak) (mean n = 18; 14.4 ± 2.6 ml·kg(-1)·min(-1); P = 0.476). Group Vo(2peak) was similar between RI and SE (n = 24; 14.5 ± 3.0 vs. 14.7 ± 3.1 ml·kg(-1)·min(-1); P = 0.407); however, within-subject comparisons confirmed Vo(2max) in only 14 of 24 patients (CI(95) for Vo(2max) estimation averaged 1.4 ± 0.8 ml·kg(-1)·min(-1)). The RER(peak) in CHF was significantly influenced by ramp rate, suggesting its use to determine maximal effort and Vo(2max) be abandoned. In contrast, the RISE-95 test had high precision for Vo(2max) confirmation with patient-specific CI(95) (without secondary criteria), and showed that Vo(2max) is commonly underestimated in CHF. The RISE-95 test was well tolerated by CHF patients, supporting its use for Vo(2max) confirmation.     

Exhaled nitric oxide and exercise performance in heart failure

BACKGROUND: In heart failure abnormalities of pulmonary function are frequently observed particularly during exercise, which is characterized by hyperpnea, low tidal volume, early expiratory flow limitation and reduced lung compliance. Exhaled nitric oxide (NO) is increased in asthma. We evaluated whether a correlation between exhaled NO and lung mechanics exists during exercise in heart failure. METHODS: We studied 33 chronic heart failure patients and 11 healthy subjects with: a) standard pulmonary function, b) lung diffusion for carbon monoxide (DLCO) including its subcomponents, capillary volume and membrane resistance and eNO both at rest and during light exercise, c) maximal cycloergometer cardiopulmonary exercise test. RESULTS: Forced expiratory volume in 1 second (FEV1) was reduced in heart failure patients (83 +/- 17% of predicted) as was DLCO (75 +/- 18% of predicted) due to reduced membrane resistance (32.6 +/- 10.3 ml/mmHg/min vs. 39.9 +/- 6.9 in patients vs. controls, p < 0.02). eNO was lower in patients vs. controls (9.7 +/- 5.4 ppm vs. 14.4 +/- 6.4, p < 0.05) and was, during exercise, constant in patients and reduced in controls. No significant correlation was found between eNO and lung function. Vice-versa eNO changes during exercise were correlated with peak exercise oxygen consumption (r = 0.560, p < 0.001). CONCLUSIONS: The hypothesis of a link between eNO and lung function in heart failure was not proved. The correlation between eNO changes during exercise and peak VO2 might be due to hemoglobin oxygenation which binds NO to hemoglobin.     

Cognitive decline in heart failure: Biomolecular mechanisms and benefits of exercise

By definition, heart failure (HF) is a pathological condition affecting the structure and function of all organs in the body, and the brain is not an exception to that. Failure of the heart to pump enough blood centrally and peripherally is at the foundation of HF patients' inability to attend even the most ordinary daily activities and progressive deterioration of their cognitive capacity. What is more, between heart and brain exists a bidirectional relationship that goes well beyond hemodynamics and concerns bioelectric and endocrine signaling. This increasingly consolidated evidence makes the scenario even more complex. Studies have mainly chased how HF impairs cognition without focusing much on preventive measures, notably cardio-cerebral health proxies. Here, we aim to provide a brief account of known and hypothetical factors that may explain how exercise can help obviate cognitive dysfunction associated with HF in its different forms. As we shall see, there is a stringent need for a deeper grasp of such mechanisms. Indeed, gaining this new knowledge will automatically shed new light on the inner workings of HF itself, thus resulting in more effective prevention and treatment of this escalating syndrome.     

Muscle oxygen kinetics at onset of intense dynamic exercise in humans

The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/- 3.7 (means +/- SE) W]. The femoral arteriovenous blood mean transit time (MTT) and time from femoral artery to muscle microcirculation was determined to allow for an examination of the oxygen uptake at capillary level. MTT was 15.3 +/- 1.8 s immediately before exercise, 10.4 +/- 0.7 s after 6 s of exercise, and 4.7 +/- 0.5 s at the end of exercise. Arterial venous O(2) difference (a-v(diff) O(2)) of 18 +/- 5 ml/l before the exercise was unchanged after 2 s, but it increased (P < 0.05) after 6 s of exercise to 43 +/- 10 ml/l and reached 146 +/- 4 ml/l at the end of exercise. Thigh oxygen uptake increased (P < 0.05) from 32 +/- 8 to 102 +/- 28 ml/min after 6 s of exercise and to 789 +/- 88 ml/min at the end of exercise. The time to reach half-peak a-v(diff) O(2) and thigh oxygen uptake was 13 +/- 2 and 25 +/- 3 s, respectively. The difference between thigh oxygen delivery (blood flow x arterial oxygen content) and thigh oxygen uptake increased (P < 0.05) after 6 s and returned to preexercise level after 14 s. The present data suggest that, at the onset of exercise, oxygen uptake of the exercising muscles increases after a delay of only a few seconds, and oxygen extraction peaks after approximately 50 s of exercise. The limited oxygen utilization in the initial phase of intense exercise is not caused by insufficient oxygen availability.     

活性氧、钙和心力衰竭

活性氧信号和钙信号广泛存在于机体内,两者相互作用,共同参与调节机体多种生理功能及病理过程。本文对这两个信号系统之间的相互作用及相关机制、在心力衰竭过程中的作用及可能的临床应用前景进行了综述。     

Maximal oxygen uptake,sweating and tolerance to exercise in the heat

The purpose of this experiment was to determine if tolerance to exercise in the heat is related to maximal oxygen uptake (max ₀₂) and sweating. Seven men with max ₀₂ between 42 and 66 ml/(min·kg) underwent one 2-hr exposure at 24°C T_q while working on a bicycle ergometer at rel ₀₂ of 28% ( ₀₂ = 1.23 1/min). In the hot exposures the high capacity subjects had maximal sweat rates of 800 to 1,000 g/(hr·m²) while the lower capacity men sweated 300 to 400 g/(hr·m²). These differences in sweating were not related to neuromuscular stimuli, ₀₂ (metabolic rate), T_re, T_re, _s, _s or tolerance time. Tolerance to exercise in the heat was not related to maximal ₀₂ capacity when the subjects worked at the same relative load in spite of large differences in sweating. These results question the importance of the rate of sweating for predicting work performance in hot environments.

---

Zusammenfassung Das Ziel dieser Untersuchung war, zu prüfen, ob die Toleranz bei Arbeit in der Hitze in einer Beziehung steht zur maximalen O₂-Aufnahme und Schwitzen. Sieben Männer mit V₀₂ zwischen 42 – 66 ml/(min·kg) wurden belastet während 2 Stunden bei T_a 24°C und 3 × 2 Stunden bei 47°C mit Arbeit auf dem Fahrrad-Ergometer bei im Mittel von 28% V₀₂ = 1.23 1/min. Während der Hitzebelastung zeigten die leistungsfähigen Personen Schweissekretionsraten von 800 – 1000 g/(hr·m²) und die wenig leistungsfähigen 300 – 400 g/(hr·m²). Diese Unterschiede waren ohne Beziehung zu neuromuskulären Stimuli, Stoffwechselrate, T_re, T_re, _s, _s oder der Toleranzzeit. Ausdauer bei Arbeit in der Hitze war ohne Beziehung zur maximalen V₀₂-Kapazität, wenn die Personen bei der gleichen relativen Belastung arbeiteten tro grosser Unterschiede im Schwitzen. Die Ergebnisse stellen den Wert der Schweissekretionsrate zur Voraussage der Arbeitsleistung in der Hitze in Frage.

---

Resume Dans cette étude, on a cherché à voir si la tolérance au travail sous contrainte de chaleur était en relation avec la possibilité maximum d'absorption de O₂ ( ₀₂) d'une part, de transpirer d'autre part. 7 hommes présentant des ₀₂ compris entre 42 et 66 ml/(min · kg) ont pédalé sur un ergomètre pendant 2 heures par une T_a de 24°C et 3 × 2 heures par 47°C et cela par une ₀₂ relative de 28% ( ₀₂ = 1,25 1/min). Durant l'effort sous contrainte de chaleur, les plus actifs ont eu des sécrétions de sueur de 800 à 1.000 g h^–1 m^–2 et les moins actifs de 300 à 400 g/h · m². Ces différences étaient sans rapport avec les stimulus neuro-musculaires, le taux de métabolisme, T_re, T_re, T_s et T_s ou la durée de tolérance. L'endurance au travail sous contrainte de chaleur n'a pas été fonction de la capacité maximum de ₀₂, lorsque les personnes travaillaient dans des conditions analogues, même si l'on a noté de grandes différences dans la transpiration. Ces résultats mettent en doute la représentativité du taux de sécrétion de sueur comme indicatif des possibilités de travailler en atmosphère chaude.