Total Body Oxygen Consumption Research Articles

COMET: monitoring mitochondrial shock in anesthesiology and intensive care medicine

AbstractMitochondria, as the cellular end-users of oxygen and responsible for approximately 98% of total body oxygen consumption, play a significant role in the development of organ dysfunction during shock. Therefore, integrating information on mitochondrial oxygen homeostasis with macroscopic observations of macrocirculation and microcirculation is crucial for monitoring critically ill patients or those undergoing high-risk surgery. However, current clinical practice still lack reliable surrogate parameters for assessing mitochondrial function. The Cellular Oxygen METabolism (COMET) monitor, utilizing the protoporphyrin IX triplet state lifetime technique (PpIX-TSLT), represents the first clinical device capable of non-invasive, in vivo measurement of mitochondrial oxygen pressure and oxidative phosphorylation. Recent research suggests that implementing this real-time bedside monitoring will provide additional insights into microcirculatory dynamics and enhance patient management. This review will comprehensively detail the rationale, methodologies, evolution, and clinical applications of the technique, aiming at improving the understanding of mitochondrial pathology in daily clinical practice and facilitating the development of targeted therapeutic strategies. Graphical Abstract

High Intensity Interval Exercise Causes Acute Microvascular Dysfunction in Elderly Individuals with Low Cardiorespiratory Fitness - A Pilot Study

Background: Frailty is strongly associated with low physical and cardiorespiratory fitness, and unfortunately is observed in 20-50% of the ~50 million adults that experience surgical stress in the U.S. each year. The peripheral microvasculature may serve as a potential target to increase resilience to stress and improve postoperative outcomes. A better understanding of how the microvasculature responds to stress in elderly individuals with low fitness is thus needed. Objective: To define the relationship between cardiorespiratory fitness and microvascular resiliency to stress in elderly individuals. Hypothesis: Elderly individuals with low cardiorespiratory fitness will show acute reductions in acetylcholine (Ach)-mediated dilation of the skin microvasculature following the physiological stressful stimulus of high intensity interval exercise (HIIE). Methods: This was a prospective, observational study that enrolled elderly individuals aged 65-85 years from the community. Each participant was asked to complete two study visits. During visit 1, participants completed the Frailty Index and performed a graded cardiopulmonary exercise test (CPET) on a cycle ergometer with a metabolic cart to measure peak total body oxygen consumption (VO2 Peak). During visit 2, laser Doppler flowmetry with dermal microdialysis was performed on the ventral forearm to measure peak cutaneous microvascular vasodilation to Ach (10 mM). After baseline assessment, the participants performed a HIIE protocol where they repetitively switched between exercising at 70% of the peak workload achieved during the CPET for 60 seconds, followed by a 60 second active recovery at 10 watts. These intervals were repeated 12 times, for a total exercise duration of 24 min. Thirty minutes following exercise, Ach-mediated dilation of the cutaneous microvasculature was reassessed. Maximum dilator capacity of each site was assessed by infusing sodium nitroprusside (28 mM) and heating the skin to 43 °C. Results: Six individuals (1 male, 5 females; mean age 68 ±4 years) completed all study procedures. Based on age- and sex-predicted normative values for VO2 Max, three of the individuals had high physical fitness while three had low fitness (mean VO2 Peak = 27.5±1.1 vs. 13.6±3.4 ml/kg/min, respectively). Prior to HIIE there was no difference in peak dilation to Ach between the individuals with high vs. low fitness (% max dilation = 72±13 vs. 83±13, respectively). During HIIE, the individuals reached a Borg rating of perceived exertion of 15±4 (out of 20) and their peak heart rate was 74±15% of their age-predicted maximum. Ach-mediated dilation of the dermal microvasculature was reduced following HIIE in elderly individuals with low cardiorespiratory fitness (pre vs. post % maximum dilation = 82±13 vs. 49±27, respectively; mean change = -34±40 %) but unchanged in those with high fitness (pre vs. post % maximum dilation = 72±13 vs. 78±10, respectively; mean change = 5±3 %). Using Pearson correlation tests there was a strong correlation between the change in peak Ach-mediated dilation pre vs. post HIIE and both VO2 Peak (r=0.82, p=0.04) and Frailty Index score (r=-0.98, p<0.001). Conclusion: Microvascular resilience to acute stress is decreased in elderly individuals with low cardiorespiratory fitness compared to those with high fitness. None. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of Oxidative DNA Damage and the Role of DNA Glycosylases in Neurological Dysfunction.

The human brain requires a high rate of oxygen consumption to perform intense metabolic activities, accounting for 20% of total body oxygen consumption. This high oxygen uptake results in the generation of free radicals, including reactive oxygen species (ROS), which, at physiological levels, are beneficial to the proper functioning of fundamental cellular processes. At supraphysiological levels, however, ROS and associated lesions cause detrimental effects in brain cells, commonly observed in several neurodegenerative disorders. In this review, we focus on the impact of oxidative DNA base lesions and the role of DNA glycosylase enzymes repairing these lesions on brain function and disease. Furthermore, we discuss the role of DNA base oxidation as an epigenetic mechanism involved in brain diseases, as well as potential roles of DNA glycosylases in different epigenetic contexts. We provide a detailed overview of the impact of DNA glycosylases on brain metabolism, cognition, inflammation, tissue loss and regeneration, and age-related neurodegenerative diseases based on evidence collected from animal and human models lacking these enzymes, as well as post-mortem studies on patients with neurological disorders.

Preparation for Advanced Airway Management: Pre-oxygenation and Positioning

Preoxygenation allows a margin of safety prior to establishing control of a patient’s airway. Effective preoxygenation is influenced by careful technique, respiratory physiology, blood oxygen content, and total body oxygen consumption. Total body oxygen consumption is increased in the pregnant, pediatric, and obese populations, making maintenance of oxygenation more difficult during apnea. In addition to a standard facemask, advanced equipment such as high-flow nasal cannula, THRIVE, and various mask variants may be used. Positioning of a patient for advanced airway management affects preoxygenation, respiratory mechanics, and the conditions for establishing a definitive airway. The “triple airway support” maneuver consists of head extension, neck flexion, and protrusion of the mandibular teeth over the upper teeth; and provides effective mechanics for positive-pressure mask ventilation. Patients with potentially unstable cervical spines present additional challenges and, especially in emergency situations, require careful negotiation of priorities. Common maneuvers such as head tilt, jaw thrust, cricoid pressure, and manual in-line stabilization can cause motion in the unstable cervical spine with uncertain effects. This review contains 7 figures, 5 tables, and 43 references. Keywords: preoxygenation, functional residual capacity, blood oxygen content, alveolar fraction of oxygen, total body oxygen consumption, high-flow nasal cannula, apneic oxygenation, sniffing position, triple airway support maneuver, manual in-line stabilization

Liquid Sucrose Consumption Promotes Liver Lipid Accumulation, Fat Mass, and Glucose Intolerance without Altering Circulating Insulin Levels

A variety of factors contribute to the rising rates of obesity and to difficulties in weight reduction that exist in the worldwide population. One factor that contributes to weight gain is caloric intake via consumption of sugar‐sweetened beverages (SSBs). Therefore, in this study, we investigated specific metabolic outcomes associated with ad libitum liquid sucrose intake over 12 weeks in male C57BL/6J mice. Mice consuming 30% sucrose in liquid form gained 39.6% more weight (p < 0.001) with a 51% increase in fat mass (p< 0.01), stored 3.5‐fold more fat in liver (p< 0.05), and had impaired glucose tolerance relative to control mice (AUC p < 0.01). Intriguingly, all of these metabolic perturbations occurred without alterations in circulating insulin levels and with no detectable changes in physical activity of the mice. In addition, liver and muscle glycogen content did not increase with sucrose consumption. However, sucrose intake produced higher RQ values (p < 0.01), increased serum FGF21 levels (5.9 fold; p < 0.01), promoted browning of white adipose tissue, and enhanced whole body energy expenditure (22% increase; p < 0.01). A correlation analysis based on Pearson's correlation coefficient r indicated that energy expenditure (EE) correlated with total body mass (TBM: r = 0.91, p<0.0001), oxygen consumption (VO2: r=0.75, p<0.001), lean mass (LBM: r=0.94, p<0001) and fat‐free mass (FFM: r=0.94, p<0.0001). Oxygen consumption (VO2) also correlated with fat‐free mass (Pearson r = 0.76; p < 0.001), moderately with total body mass (Pearson r = 0.60; p < 0.05), but not with fat mass (Pearson r = 0.31; p = 0.25). Analysis of covariance (ANCOVA) for treatment effects on EE with TBM, VO2, LBM, and FFM taken as potential covariates for EE revealed that VO2 was the preferred single covariate. When the treatment means for EE were covariate adjusted for VO2, the EE mean for sucrose was significantly elevated (p<0.025). When multiple covariates were considered, TBM and VO2 were significant, but the difference between covariate‐adjusted treatment means was not significant. Congruent with the increase in RQ, there was a marked increase in the glycolytic enzyme gene expression profile in skeletal muscle, but not in epididymal white adipose tissue. We further found that sucrose consumption downregulated the expression of the dgat1 and dgat2 genes in inguinal white adipose tissue (iWAT). By contrast, dgat1 and dgat2 expression are not suppressed in iWAT from db/db mice, a separate model of obesity that displays hyperinsulinemia. Taken together, we conclude that sucrose‐induced weight gain occurs without an increase in circulating insulin and is associated with enhanced lipid accumulation in liver, but not skeletal muscle. This study shows that obesity driven by enhanced consumption of carbohydrate calories in liquid form is distinct from the hyperinsulinemia promoted by high‐fat diet or by obesity driven secondary to deficiencies in leptin receptor signaling. Thus, molecular mechanisms responsible for the obese state are likely to be dependent on the macronutrient source of calories and route of delivery.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of zilpaterol hydrochloride on methane production, total body oxygen consumption, and blood metabolites in finishing beef steers.

An indirect calorimetry experiment was conducted to determine the effects of feeding zilpaterol hydrochloride (ZH) for 20 d on total body oxygen consumption, respiratory quotient, methane production, and blood metabolites in finishing beef steers. Sixteen Angus steers (initial BW = 555 ± 12.7 kg) were individually fed at ad libitum intake and used in a completely randomized design. The model included the fixed effects of dietary treatment, day, and treatment × day. Dry matter intake did not differ between the treatments ( = 0.89), but was greater on d 0 than any other day ( < 0.01). Oxygen consumption was not different between treatments ( = 0.79), but was different across day ( < 0.01) on d 7, 14, 21, and 28. Respiratory quotient was less for cattle fed ZH than control ( < 0.01), and also different across day ( < 0.01), being greater on d 7, 21, and 28 than d 3 or 21. Methane production (L/kg of DMI) was greater for steers fed the control vs. the ZH diet ( < 0.01), and it also differed by day ( < 0.01), being greater on d 21 and 28 than d 0, 3, 7, and 14. Nonesterified fatty acids were not different across treatments ( = 0.82), and there was no effect of treatment on β-hydroxybutyrate concentration ( = 0.45). Whole blood glucose concentrations were not affected by feeding ZH in this experiment ( = 0.76); however, lactate concentrations were reduced by feeding ZH ( = 0.03). Additionally, there was no treatment effect on ɑ-amino-N, blood glutamate, or glutamine ( ≥ 0.16). Plasma NH was not affected by ZH ( = 0.07), but plasma urea nitrogen was reduced by ZH ( < 0.01). Urinary creatinine was increased by steers receiving ZH ( = 0.01), and urine 3-methylhistidine (3-MH) concentrations were normalized to creatinine, the 3-MH:creatinine ratio decreased from d 0 to d 3 in steers fed ZH, and remained less than control steers until d 28. These data provide insight into how β-agonists alter nutrient partitioning and improve the efficiency of tissue accretion, mainly through decreased muscle protein turnover and altering the catabolic fuel for peripheral tissues.

Effects of zilpaterol hydrochloride on methane production, total body oxygen consumption, and blood metabolites in finishing beef steers

Effects of zilpaterol hydrochloride on methane production, total body oxygen consumption, and blood metabolites in finishing beef steers

Central venous oxygenation: when physiology explains apparent discrepancies.

Central venous oxygen saturation (ScvO2) >70% or mixed venous oxygen saturation (SvO2) >65% is recommended for both septic and non-septic patients. Although it is the task of experts to suggest clear and simple guidelines, there is a risk of reducing critical care to these simple recommendations. This article reviews the basic physiological and pathological features as well as the metrological issues that provide clear evidence that SvO2 and ScvO2 are adaptative variables with large inter-patient variability. This variability is exemplified in a modeled population of 1,000 standard ICU patients and in a real population of 100 patients including 15,860 measurements. In these populations, it can be seen how optimizing one to three of the four S(c)vO2 components homogenized the patients and yields a clear dependency with the fourth one. This explains the discordant results observed in large studies where cardiac output was increased up to predetermined S(c)vO2 thresholds following arterial oxygen hemoglobin saturation, total body oxygen consumption needs and hemoglobin optimization. Although a systematic S(c)vO2 goal-oriented protocol can be statistically profitable before ICU admission, appropriate intensive care mandates determination of the best compromise between S(c)vO2 and its four components, taking into account the specific constraints of each individual patient.

Extracorporeal Membrane Oxygenation Versus Counterpulsatile, Pulsatile, and Continuous Left Ventricular Unloading for Pediatric Mechanical Circulatory Support*

Despite progress with adult ventricular assist devices, limited options exist to support pediatric patients with life-threatening heart disease. Extracorporeal membrane oxygenation remains the clinical standard. To characterize (patho)physiologic responses to different modes of mechanical unloading of the failing pediatric heart, extracorporeal membrane oxygenation was compared to intra-aortic balloon pump, pulsatile-flow ventricular assist device, or continuous-flow ventricular assist device support in a pediatric heart failure model. Experimental. Large animal laboratory operating room. Yorkshire piglets (n = 47; 11.7 ± 2.6 kg). In piglets with coronary ligation-induced cardiac dysfunction, mechanical circulatory support devices were implanted and studied during maximum support. Left ventricular, right ventricular, coronary, carotid, systemic arterial, and pulmonary arterial hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption and total-body oxygen consumption were calculated from arterial, venous, and coronary sinus blood sampling. Blood flow was measured in 17 organs with microspheres. Paired Student t tests compared baseline and heart failure conditions. One-way repeated-measures analysis of variance compared heart failure, device support mode(s), and extracorporeal membrane oxygenation. Statistically significant (p < 0.05) findings included 1) an improved left ventricular blood supply/demand ratio during pulsatile-flow ventricular assist device, continuous-flow ventricular assist device, and extracorporeal membrane oxygenation but not intra-aortic balloon pump support, 2) an improved global myocardial blood supply/demand ratio during pulsatile-flow ventricular assist device and continuous-flow ventricular assist device but not intra-aortic balloon pump or extracorporeal membrane oxygenation support, and 3) diminished pulsatility during extracorporeal membrane oxygenation and continuous-flow ventricular assist device but not intra-aortic balloon pump and pulsatile-flow ventricular assist device support. A profile of systems-based responses was established for each type of support. Each type of pediatric ventricular assist device provided hemodynamic support by unloading the heart with a different mechanism that created a unique profile of physiological changes. These data contribute novel, clinically relevant insight into pediatric mechanical circulatory support and establish an important resource for pediatric device development and patient selection.

Cocoa, neurovascular coupling, and neurodegeneration

Though the human brain is only ∼2% of body mass, it represents more than 20% of total body oxygen and energy consumption,1,2 and the supply of blood to the active neurons must match their metabolic demand. Fortunately, the tight coupling between capillary endothelial cells, astrocytes, pericytes, and neurons—dubbed the neurovascular unit—ensures precise modulation of regional blood flow in response to local metabolic demand. This integration of supply and demand, termed neurovascular coupling (NVC), is critical to neurophysiologic health. Indeed, accumulating evidence shows an important role for cerebral vascular insufficiency in neurodegenerative diseases ranging from vascular cognitive impairment3 to Alzheimer disease.4 Therefore, targeting cerebral vascular pathology is a promising option for primary and secondary prevention of neurodegenerative diseases and subsequent cognitive impairments.

Cerebral oxygen desaturation monitored by intraoperative near-infrared spectroscopy, and incidence of post-operative cognitive dysfunction: a systematic review protocol

Review question/objective The objective of this systematic review is to determine if there is a direct relationship between cerebral oxygen desaturation using intraoperative near-infrared spectroscopy monitoring, and the incidence of post-operative cognitive dysfunction (POCD). Inclusion criteria Types of participants This systematic review will consider all patients over the age of eight years old receiving general anesthesia for any surgical procedure, since patients younger than this age usually have different anesthetic emergence and transfer processes than patients older than eight years of age. Patients with pre-existing neurologic disease including stroke, alcohol abuse, history of psychiatric disorders, and emergency cases will be excluded, since a baseline neurologic test cannot be performed appropriately. Focus of the review The systematic review considers studies that examine the use of NIRS or cerebral oximetry as a monitor for cerebral oxygen saturation and desaturation in patients receiving general anesthesia. Types of outcomes The systematic review will consider studies that included measurements of postoperative neurological deficit, and POCD related to cerebral oxygen desaturation as outcome measures. This cognitive decline is measured throughout the literature with various tools including the (MMSE), this test measures neurocognitive functions such as orientation, attention, and calculation, memory and language. Another tool is the Logical Memory Subtest of the Rivermead, which examines the immediate and delayed memory as well as the recovery capacity. Other tools include The Rey Auditory Verbal Learning Test and The Verbal Fluency Test and others. 8

The neuroprotective effects of electrolyzed reduced water and its model water containing molecular hydrogen and Pt nanoparticles

Human brain is the biggest energy consuming tissue in human body. Although it only represents 2% of the body weight, it receives 20% of total body oxygen consumption and 25% of total body glucose utilization. For that reason, brain is considered to be the most vulnerable part of human body against the reactive oxygen species (ROS), a by-product of aerobic respiration. Oxidative stress is directly related to a series of brain dysfunctional disease such as Alzheimer’ sd isease, Parkinson’s disease etc. Electrolyzed reduced water (ERW) is a functional drinking water containing a lot of molecular hydrogen and a small amount of platinum nanoparticles (Pt NPs, Table 1). ERW is known to scavenge ROS and protect DNA from oxidative damage [1]. We previously showed that ERW was capable of extending lifespan of Caenorhabditis elegans by scavenging ROS [2]. Molecular hydrogen could scavenge ROS and protected brain from oxidative stress [3]. Pt NPs are also a new type of multi-functional ROS scavenger [4]. Materials and methods In this research, we used TI-200S ERW derived from 2 mM NaOH solution produced by a batch type electrolysis device and model waters containing molecular hydrogen and synthetic Pt NPs of 2-3 nm sizes as research models of ERW to examine the anti-oxidant capabilities of ERW on several kinds of neural cells such as PC12, N1E115, and serum free mouse embryo (SFME) cells. We pretreated the ERW and 200 μM H2O2 and examined the neuroprotective effects of ERW on PC12, N1E115 and SFME cells, using WST-8 method. We also examined the intracellular ROS scavenging effects of ERW on N1E115 cells after pretreated cells with ERW and H2O2 using DCFH-DA. We checked the protective effects of ERW on mitochondria and cytoplasm by Rh123 and Fuo-3 AM stain. We also examined the ATP production of SFME cells after pretreated with ERW and H2O2 by Bioluminescence Assay Kit. Finally, we used dissolved hydrogen (DH) and Pt NPs as research models to examine their neuroprotective effects. Results

A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: Reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low flow in a porcine model

Cerebral ischemia can occur during cardiopulmonary bypass, especially during low flow. HBOC-201 (OPK Biotech, Cambridge, Mass) is a hemoglobin-based oxygen-carrying solution that enhances oxygen delivery. This project evaluated the benefits on total body and cerebral oxygen delivery and consumption using HBOC-201 during cardiopulmonary bypass. Twelve immature swine were assigned to one of 2 groups. One group used HBOC-201 in pump prime, and the other used donor porcine blood. Cardiopulmonary bypass was initiated and then flow was serially decreased from 100% to 75%, to 50%, and then back to full flow. At each interval, (15)O positron emission tomographic analysis was performed, and blood was collected. Total body and cerebral oxygen delivery and consumption were calculated. Statistical analysis was performed with a Tukey-Kramer adjusted P value based on a repeated measures linear model on log-transformed data. Total and plasma hemoglobin levels were higher in the HBOC-201 group. Oxygen delivery and consumption were not statistically different but did tend to be higher in the HBOC-201 group. Mixed venous saturation was lower in the HBOC-201 group but not significant. Mild metabolic acidosis with increased lactate levels developed in the blood group. Mean cerebral blood flow decreased in both groups when total flow was 50%. In the HBOC-201 group cerebral oxygen metabolism was maintained. The addition of HBOC-201 for cardiopulmonary bypass appears to improve oxygen use and minimize anaerobic metabolism. Cerebral oxygen use was preserved in the HBOC-201 group, even during decrease in blood flow. These findings support the reported improved oxygen-unloading properties of HBOC-201 and might provide a benefit during cardiopulmonary bypass.

EAAT expression by macrophages and microglia: still more questions than answers

Glutamate is the main excitatory amino acid, but its presence in the extracellular milieu has deleterious consequences. It may induce excitotoxicity and also compete with cystine for the use of the cystine-glutamate exchanger, blocking glutathione neosynthesis and inducing an oxidative stress-induced cell death. Both mechanisms are critical in the brain where up to 20% of total body oxygen consumption occurs. In normal conditions, the astrocytes ensure that extracellular concentration of glutamate is kept in the micromolar range, thanks to their coexpression of high-affinity glutamate transporters (EAATs) and glutamine synthetase (GS). Their protective function is nevertheless sensitive to situations such as oxidative stress or inflammatory processes. On the other hand, macrophages and microglia do not express EAATs and GS in physiological conditions and are the principal effector cells of brain inflammation. Since the late 1990s, a number of studies have now shown that both microglia and macrophages display inducible EAAT and GS expression, but the precise significance of this still remains poorly understood. Brain macrophages and microglia are sister cells but yet display differences. Both are highly sensitive to their microenvironment and can perform a variety of functions that may oppose each other. However, in the very particular environment of the healthy brain, they are maintained in a repressed state. The aim of this review is to present the current state of knowledge on brain macrophages and microglial cells activation, in order to help clarify their role in the regulation of glutamate under pathological conditions as well as its outcome.

Counterpoint: Humans do not demonstrate selective brain cooling during hyperthermia

Selective brain cooling is an attractive idea for protection of the central nervous system against fatigue ([17][1]) and potentially cellular damage. Several factors influence fatigue, but brain temperature appears to be of utmost importance for hyperthermia-induced fatigue during prolonged exercise

Effects of Maintained Weight Loss on Sleep Dynamics and Neck Morphology in Severely Obese Adults

The goals of the study were to determine if moderate weight loss in severely obese adults resulted in (i) reduction in apnea/hypopnea index (AHI), (ii) improved pharyngeal patency, (iii) reduced total body oxygen consumption (VO(2)) and carbon dioxide production (VCO(2)) during sleep, and (iv) improved sleep quality. The main outcome was the change in AHI from before to after weight loss. Fourteen severely obese (BMI > 40 kg/m(2)) patients (3 males, 11 females) completed a highly controlled weight reduction program which included 3 months of weight loss and 3 months of weight maintenance. At baseline and postweight loss, patients underwent pulmonary function testing, polysomnography, and magnetic resonance imaging (MRI) to assess neck morphology. Weight decreased from 134 +/-6.6 kg to 118 +/- 6.1 kg (mean +/- s.e.m.; F = 113.763, P < 0.0001). There was a significant reduction in the AHI between baseline and postweight loss (subject, F = 11.11, P = 0.007). Moreover, patients with worse sleep-disordered breathing (SDB) at baseline had the greatest improvements in AHI (group, F = 9.00, P = 0.005). Reductions in VO(2) (285 +/- 12 to 234 +/-16 ml/min; F = 24.85, P < 0.0001) and VCO(2) (231 +/- 9 to 186 +/- 12 ml/min; F = 27.74, P < 0.0001) were also observed, and pulmonary function testing showed improvements in spirometry parameters. Sleep studies revealed improved minimum oxygen saturation (minSaO(2)) (83.4 +/- 61.9% to 89.1 +/- 1.2%; F = 7.59, P = 0.016), and mean SaO(2) (90.4 +/- 1.1% to 93.8 +/- 1.0%; F = 6.89, P = 0.022), and a significant increase in the number of arousals (8.1 +/- 1.4 at baseline, to 17.1 +/- 3.0 after weight loss; F = 18.13, P = 0.001). In severely obese patients, even moderate weight loss (approximately 10%) boasts substantial benefit in terms of the severity of SDB and sleep dynamics.

The effects of aerobic fitness and β1-adrenergic receptor blockade on cardiac work during dynamic exercise

The purpose of this investigation was to determine whether cardiovascular adaptations characteristic of long-term endurance exercise compensate more effectively during cardioselective beta(1)-adrenergic receptor blockade-induced reductions in sympathoadrenergic-stimulated contractility. Endurance-trained (ET) athletes (n = 8) and average-trained (AT; n = 8) subjects performed submaximal cycling exercise at moderate [45% maximum oxygen uptake (Vo(2max))] and heavy (70% Vo(2max)) workloads, with and without metoprolol. Cardiac output (Qc), heart rate (HR), and systolic blood pressure were recorded at rest and during exercise. Cardiac work was calculated from the triple product of HR, stroke volume, and systolic blood pressure, and myocardial efficiency is represented as cardiac work for a given total body oxygen consumption. Metoprolol reduced Qc at 45% Vo(2max) (P = 0.004) and 70% Vo(2max) (P = 0.022) in ET subjects, but did not alter Qc in the AT subjects. In ET subjects at 45% Vo(2max), metoprolol-induced reductions in Qc were a result of decreases in HR (P < 0.05) and the absence of a compensatory increase in stroke volume (P > 0.05). The cardiac work and calculated cardiac efficiency were reduced with metoprolol in ET subjects at both exercise intensities and in the AT subjects during the high-intensity workload (P < 0.01). The cardiac work and the calculated cardiac efficiency were not affected by metoprolol in the AT subjects during the 45% Vo(2max) exercise. Therefore, in AT subjects, beta-blockade reduced the amount of pressure generation necessary to produce the same amount of work during moderate-intensity exercise. In patients with heart disease receiving metoprolol, a decrease in the generation of cardiac pressure necessary to perform a given amount of work during mild-to-moderate exercise would prove to be beneficial.

Potential therapeutic applications of thyroid hormone analogs

Thyroid hormone (T3 and T4) has many beneficial effects including enhancing cardiac function, promoting weight loss and reducing serum cholesterol. Excess thyroid hormone is, however, associated with unwanted effects on the heart, bone and skeletal muscle. We therefore need analogs that harness the beneficial effects of thyroid hormone without the untoward effects. Such work is largely based on understanding the cellular mechanisms of thyroid hormone action, specifically the crystal structure of the nuclear receptor proteins. In clinical studies, use of naturally occurring thyroid hormone analogs can suppress TSH levels in patients with thyroid cancer without producing tachycardia. Many thyromimetic compounds have been tested in animal models and shown to increase total body oxygen consumption, and to lower weight and serum cholesterol and triglyceride levels while having minor effects on heart rate. Alternatively, analogs that specifically enhance both systolic and diastolic function are potentially useful in the treatment of chronic congestive heart failure. In addition to analogs that are thyroid hormone receptor agonists, several compounds that are thyroid hormone receptor antagonists have been identified and tested. This Review discusses the potential application of thyroid hormone analogs (both agonists and antagonists) in a variety of human disease states.

Circuit Resistance Training in Chronic Heart Failure Improves Skeletal Muscle Mitochondrial ATP Production Rate—A Randomized Controlled Trial

We aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF). Thirteen CHF patients (New York Heart Association functional class 2.3 +/- 0.5; Left ventricular ejection fraction 26 +/- 8%; age 70 +/- 8 years) underwent testing for peak total body oxygen consumption (VO(2peak)), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO(2peak) and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO(2peak), P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO(2peak)) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO(2peak). These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.

Health risks associated with overweight and obesity

The intra-abdominal visceral deposition of adipose tissue,which characterizes upper body – central – obesity(assessed by waist circumference and/or waist : hip ratio)is a major contributor to the development of hypertension,elevated plasma insulin concentrations and insulin resis-tance, hyperglycaemia and hyperlipidaemia (metabolic syn-drome). The concept of the metabolic syndrome refers tothe phenomenon of risk-factor clustering – a collection ofmetabolic traits occurring in the same individual with theclustering presumably reflecting a unifying underlyingpathophysiology that requires a holistic approach to theirmanagement (5–7).Many of the health risks associated with increasing bodyweight begin to appear in children and young people. Ofgreat concern is the increasing prevalence of type 2 diabetesand associated medical complications in childhood (8–10).This early onset needs to be reflected by active managementand research priorities to reduce the consequential healthand economic burdens (11).