Vipa Bernhardt

Dyspnea on exertion in obese men.

Recently, we reported that dyspnea on exertion is strongly associated with an increased oxygen cost of breathing in otherwise healthy obese women; the mechanism of dyspnea on exertion in obese men is unknown. Obese men underwent measurements of body composition, fat distribution, pulmonary function, steady state and maximal graded cycle ergometry, and oxygen cost of breathing. Nine men (34 ± 8 years, 35 ± 4 BMI) with ratings of perceived breathlessness of ≤2 during cycling, and ten men (36 ± 9 years, 38 ± 5 BMI) with ratings of perceived breathlessness ≥4 were studied (ratings of perceived breathlessness: 1.8 ± 0.4 vs. 4.7 ± 0.8, respectively; p<0.0001). Groups had only minor differences in fat distribution, pulmonary function, and steady state exercise. There was no association between ratings of perceived breathlessness and oxygen cost of breathing; but ratings of perceived breathlessness was strongly correlated with ratings of perceived exertion (RPE, rho=0.87, p<0.0001). The differences in exercise intensity, ventilatory demand, cardiovascular conditioning and/or the quality of respiratory sensation did not appear to play a role in the development of dyspnea on exertion. The mechanism of dyspnea on exertion in obese men seems unrelated to the oxygen cost of breathing.

Tracheal Occlusion Conditioning in Conscious Rats Modulates Gene Expression Profile of Medial Thalamus

The thalamus may be the critical brain area involved in sensory gating and the relay of respiratory mechanical information to the cerebral cortex for the conscious awareness of breathing. We hypothesized that respiratory mechanical stimuli in the form of tracheal occlusions would modulate the gene expression profile of the thalamus. Specifically, it was reasoned that conditioning to the respiratory loading would induce a state change in the medial thalamus consistent with a change in sensory gating and the activation of molecular pathways associated with learning and memory. In addition, respiratory loading is stressful and thus should elicit changes in gene expressions related to stress, anxiety, and depression. Rats were instrumented with inflatable tracheal cuffs. Following surgical recovery, they underwent 10 days (5 days/week) of transient tracheal occlusion conditioning. On day 10, the animals were sacrificed and the brains removed. The medial thalamus was dissected and microarray analysis of gene expression performed. Tracheal obstruction conditioning modulated a total of 661 genes (p < 0.05, log2 fold change ≥0.58), 250 genes were down-regulated and 411 up-regulated. There was a significant down-regulation of GAD1, GAD2 and HTR1A, HTR2A genes. CCK, PRKCG, mGluR4, and KCJN9 genes were significantly up-regulated. Some of these genes have been associated with anxiety and depression, while others have been shown to play a role in switching between tonic and burst firing modes in the thalamus and thus may be involved in gating of the respiratory stimuli. Furthermore, gene ontology and pathway analysis showed a significant modulation of learning and memory pathways. These results support the hypothesis that the medial thalamus is involved in the respiratory sensory neural pathway due to the state change of its gene expression profile following repeated tracheal occlusions.

Weight loss reduces dyspnea on exertion in obese women

During submaximal exercise, some otherwise healthy obese women experience breathlessness, or dyspnea on exertion (+DOE), while others have mild or no DOE (-DOE). We investigated whether weight loss could reduce DOE. Twenty nine obese women were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60 W cycling: +DOE (n = 14, RPB ≥ 4, 34 ± 8 years, and 36 ± 3 kg/m(2)) and -DOE ( n= 15, RPB ≤ 2, 32 ± 8 years, and 36 ± 4 kg/m(2)) and then completed a 12-week weight loss program. Both groups lost a moderate amount of weight (+DOE: 6.6 ± 2.4 kg, -DOE: 8.4 ± 3.5 kg, and p < 0.001). RPB decreased significantly in the +DOE group (from 4.7 ± 1.1 to 3.1 ± 1.6) and remained low in the -DOE (from 1.5 ± 0.7 to 1.6 ± 1.1) (interaction p < 0.002). Most physiological variables measured (i.e. body composition, fat distribution, pulmonary function, oxygen cost of breathing, and cardiorespiratory measures) improved with weight loss; however, the decrease in RPB was not correlated with any of these variables (p > 0.05). In conclusion, moderate weight loss was effective in reducing breathlessness on exertion in obese women who experienced DOE at baseline.

Corrected End-Tidal P CO 2 Accurately Estimates Pa CO 2 at Rest and During Exercise in Morbidly Obese Adults

BACKGROUND Obesity affects lung function and gas exchange and imposes mechanical ventilatory limitations during exercise that could disrupt the predictability of Pa(CO(2)) from end-tidal P(CO(2)) (P(ETCO(2))), an important clinical tool for assessing gas exchange efficiency during exercise testing. Pa(CO(2)) has been estimated during exercise with good accuracy in normal-weight individuals by using a correction equation developed by Jones and colleagues (P(JCO(2)) = 5.5 + 0.9 x P(ETCO(2)) – 2.1 x tidal volume). The purpose of this project was to determine the accuracy of Pa(CO(2)) estimations from P(ETCO(2)) and P(JCO(2)) values at rest and at submaximal and peak exercise in morbidly obese adults. METHODS Pa(CO(2)) and P(ETCO(2)) values from 37 obese adults (22 women, 15 men; age, 39 ± 9 y; BMI, 49 ± 7; [mean ± SD]) were evaluated. Subjects underwent ramped cardiopulmonary exercise testing to volitional exhaustion. P(ETCO(2)) was determined from expired gases simultaneously with temperature-corrected arterial blood gases (radial arterial catheter) at rest, every minute during exercise, and at peak exercise. Data were analyzed using paired t tests. RESULTS P(ETCO(2)) was not significantly different from Pa(CO(2)) at rest (P(ETCO(2)) = 37 ± 3 mm Hg vs Pa(CO(2)) = 38 ± 3 mm Hg, P = .14). However, during exercise, P(ETCO(2)) was significantly higher than Pa(CO(2)) (submaximal: 42 ± 4 vs 40 ± 3, P < .001; peak: 40 ± 4 vs 37 ± 4, P < .001, respectively). Jones’ equation successfully corrected P(ETCO(2)), such that P(JCO(2)) was not significantly different from Pa(CO(2)) (submax: P(JCO(2)) = 40 ± 3, P = .650; peak: 37 ± 4, P = .065). CONCLUSION P(JCO(2)) provides a better estimate of Pa(CO(2)) than P(ETCO(2)) during submaximal exercise and at peak exercise, whereas at rest both yield reasonable estimates in morbidly obese individuals. Clinicians and physiologists can obtain accurate estimations of Pa(CO(2)) in morbidly obese individuals by using P(JCO(2)).

Effect of weight loss on operational lung volumes and oxygen cost of breathing in obese women

Background:The effects of moderate weight loss on operational lung volumes during exercise and the oxygen (O2) cost of breathing are unknown in obese women but could have important implications regarding exercise endurance.Methods:In 29 obese women (33±8 years, 97±14 kg, body mass index: 36±4 kg m−2, body fat: 45.6±4.5%; means±s.d.), body composition, fat distribution (by magnetic resonance imaging), pulmonary function, operational lung volumes during exercise and the O2 cost of breathing during eucapnic voluntary hyperpnea (([Vdot ]O2) vs ([Vdot ]E) slope) were studied before and after a 12-week diet and resistance exercise weight loss program.Results:Participants lost 7.5±3.1 kg or ≈8% of body weight (P<0.001), but fat distribution remained unchanged. After weight loss, lung volume subdivisions at rest were increased (P<0.05) and were moderately associated (P<0.05) with changes in weight. End-expiratory lung volume (percentage of total lung capacity) increased at rest and during constant load exercise (P<0.05). O2 cost of breathing was reduced by 16% (2.52±1.02–2.11±0.72 ml l−1; P=0.003). As a result, O2 uptake of the respiratory muscles ([Vdot ]O2Resp), estimated as the product of O2 cost of breathing and exercise ([Vdot ]E) during cycling at 60 W, was significantly reduced by 27±31 ml (P<0.001), accounting for 46% of the reduction in total body ([Vdot ]O2) during cycling at 60 W.Conclusions:Moderate weight loss yields important improvements in respiratory function at rest and during submaximal exercise in otherwise healthy obese women. These changes in breathing load could have positive effects on the exercise endurance and adherence to physical activity.

Tracheal occlusion modulates the gene expression profile of the medial thalamus in anesthetized rats

Conscious awareness of breathing requires the activation of higher brain centers and is believed to be a neural gated process. The thalamus could be responsible for the gating of respiratory sensory information to the cortex. It was reasoned that if the thalamus is the neural gate, then tracheal obstructions will modulate the gene expression profile of the thalamus. Anesthetized rats were instrumented with an inflatable cuff sutured around the trachea. The cuff was inflated to obstruct 2-4 breaths, then deflated for a minimum of 15 breaths. Obstructions were repeated for 10 min followed by immediate dissection of the medial thalamus. Following the occlusion protocol, 588 genes were found to be altered (P < 0.05; log(2) fold change ≥ 0.4), with 327 genes downregulated and 261 genes upregulated. A significant upregulation of the serotonin HTR2A receptor and significant downregulation of the dopamine DRD1 receptor genes were found. A pathway analysis was performed that targeted serotonin and dopamine receptor pathways. The mitogen-activated protein kinase 1 (MAPK1) gene was significantly downregulated. MAPK1 is an inhibitory regulator of HTR2A and facilitatory regulator for DRD1. Downregulation of MAPK1 may be related to the significant upregulation of HTR2A and downregulation of DRD1, suggesting an interaction in the medial thalamus serotonin-dopamine pathway elicited by airway obstruction. These results demonstrate an immediate change in gene expression in thalamic arousal, fear, anxiety motivation-related serotonin and dopamine receptors in response to airway obstruction. The results support the hypothesis that the thalamus is a component in the respiratory mechanosensory neural pathway.

Verification of Maximal Oxygen Uptake in Obese and Nonobese Children

Purpose The purpose of this study was to examine whether a supramaximal constant-load verification test at 105% of the highest work rate would yield a higher V˙O2max when compared with an incremental test in 10- to 12-yr-old nonobese and obese children. Methods Nine nonobese (body mass index percentile = 57.5 ± 23.2) and nine obese (body mass index percentile = 97.9 ± 1.4) children completed a two-test protocol that included an incremental test followed 15 min later by a supramaximal constant-load verification test. Results The V˙O2max achieved in verification testing (nonobese = 1.71 ± 0.31 L·min−1 and obese = 1.94 ± 0.47 L·min−1) was significantly higher than that achieved during the incremental test (nonobese = 1.57 ± 0.27 L·min−1 and obese = 1.84 ± 0.48 L·min−1; P < 0.001). There was no significant group (i.e., nonobese vs obese)–test (i.e., incremental vs verification) interaction, suggesting that there was no effect of obesity on the difference between verification and incremental V˙O2max (P = 0.747). Conclusion A verification test yielded significantly higher values of V˙O2max when compared with the incremental test in obese children. Similar results were observed in nonobese children. Supramaximal constant-load verification is a time-efficient and well-tolerated method for identifying the highest V˙O2 in nonobese and obese children.

Aerobic exercise training without weight loss reduces dyspnea on exertion in obese women.

Dyspnea on exertion (DOE) is a common symptom in obesity. We investigated whether aerobic exercise training without weight loss could reduce DOE. Twenty-two otherwise healthy obese women participated in a 12-week supervised aerobic exercise training program, exercising 30 min/day at 70-80% heart rate reserve, 4 days/week. Subjects were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60 W cycling: +DOE (n=12, RPB≥4, 37±7 years, 34±4 kg/m(2)) and -DOE (n=10, RPB≤2, 32±6 years, 33±3 kg/m(2)). No significant differences between the groups in body composition, pulmonary function, or cardiorespiratory fitness were observed pre-training. Post-training,peak was improved significantly in both groups (+DOE: 12±7, -DOE: 14±8%). RPB was significantly decreased in the +DOE (4.7±1.0-2.5±1.0) and remained low in the -DOE group (1.2±0.6-1.3±1.0) (interaction p<0.001). The reduction in RPB was not significantly correlated with the improvement in cardiorespiratory fitness. Aerobic exercise training improved cardiorespiratory fitness and DOE and thus appears to be an effective treatment for DOE in obese women.

Exertional dyspnoea in obesity

The purpose of cardiopulmonary exercise testing (CPET) in the obese person, as in any cardiopulmonary exercise test, is to determine the patients exercise tolerance, and to help identify and/or distinguish between the various physiological factors that could contribute to exercise intolerance. Unexplained dyspnoea on exertion is a common reason for CPET, but it is an extremely complex symptom to explain. Sometimes obesity is the simple answer by elimination of other possibilities. Thus, distinguishing among multiple clinical causes for exertional dyspnoea depends on the ability to eliminate possibilities while recognising response patterns that are unique to the obese patient. This includes the otherwise healthy obese patient, as well as the obese patient with potentially multiple cardiopulmonary limitations. Despite obvious limitations in lung function, metabolic disease and/or cardiovascular dysfunction, obesity may be the most likely reason for exertional dyspnoea. In this article, we will review the more common cardiopulmonary responses to exercise in the otherwise healthy obese adult with special emphasis on dyspnoea on exertion. Obesity alone and/or as a confounding factor may contribute to DOE requiring careful assessment during CPET http://ow.ly/Secp305mId2

Short-term modulation of the ventilatory response to exercise is preserved in obstructive sleep apnea.

BACKGROUND The ventilatory response to exercise can be transiently adjusted in response to environmentally (e.g., breathing apparatus) or physiologically altered conditions (e.g., respiratory disease), maintaining constant relative arterial PCO2 regulation from rest to exercise (Mitchell and Babb, 2006); this augmentation is called short-term modulation (STM) of the exercise ventilatory response. Obesity and/or obstructive sleep apnea could affect the exercise ventilatory response and the capacity for STM due to chronically increased mechanical and/or ventilatory loads on the respiratory system, and/or recurrent (chronic) intermittent hypoxia experienced during sleep. We hypothesized that: (1) the exercise ventilatory response is augmented in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is diminished in obese OSA patients. METHODS Nine obese adults with OSA (age: 39±6 yr, BMI: 40±5kg/m2, AHI: 25±24 events/h [range 6-73], mean±SD) and 8 obese adults without OSA (age: 38±10 yr, BMI: 37±6kg/m2, AHI: 1±2) completed three, 20-min bouts of constant-load submaximal cycling exercise (8min rest, 6min at 10 and 30W) with or without added external dead space (200 or 400mL; 20min rest between bouts). Steady-state measurements were made of ventilation (V˙E), oxygen consumption V˙O2), carbon dioxide production (V˙CO2), and end-tidal PCO2 (PETCO2). The exercise ventilatory response was defined as the slope of the V˙E-V˙CO2 relationship (ΔV˙E/ΔV˙CO2). RESULTS In control (i.e. no added dead space), the exercise ventilatory response was not significantly different between non-OSA and OSA groups (ΔV˙E/ΔV˙CO2 slope: 30.5±4.2 vs 30.5±3.8, p>0.05); PETCO2 regulation from rest to exercise did not differ between groups (p>0.05). In trials with added external dead space, ΔV˙E/ΔV˙CO2 increased with increased dead space (p < 0.05) and the PETCO2 change from rest to exercise remained small (<2mmHg) in both groups, demonstrating STM. There were no significant differences between groups. CONCLUSIONS Contrary to our hypotheses: (1) the exercise ventilatory response is not increased in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is preserved in obese OSA and non-OSA adults.