Lalande, Sophie

The aim of this study was to determine if left ventricular (LV) diastolic function influences pulmonary function (PF) in healthy subjects and to determine if they are independently related after accounting for age, gender, BMI and blood pressure (BP). Echocardiograms and PF tests were performed in 103 healthy subjects (22‐76 yr). The ratio of peak early (E) and late (A) mitral inflow velocities and the ratio of peak early (E') and late (A') mitral annular velocities were obtained by pulsed wave Doppler and tissue Doppler imaging. The first stage of diastolic dysfunction, often observed in healthy aging, is characterized by reduced E and E', and greater A and A' resulting in a reversal of E/A and E'/A'. PF measures included forced vital capacity (FVC), carbon monoxide diffusing capacity (DL CO ) and forced mid‐expiratory flow (FEF 25‐75 ). Age, gender and BMI accounted for >60% of the interindividual variation between diastolic function and PF. After accounting for age, gender, BMI and BP, E' was positively associated with FVC (additional R 2 =0.03 , P <0.01). A was negatively and A' positively associated with DL CO (additional R 2 =0.03, R 2 =0.01, P <0.05) and FVC (additional R 2 =0.03, R 2 =0.03, P <0.01). E/A was positively associated with DL CO (additional R 2 =0.02, P <0.01). In conclusion, LV diastolic function may influence PF in healthy subjects, with the greatest interactions being observed in older males. NIH HL71478

The ability to work efficiently at altitude is impaired by the reduced arterial oxygen tension. Acetazolamide may improve systemic saturation (SaO 2 ) by stimulating ventilation but increases the work of breathing. Efforts have focused on the potential role of sildenafil in improving exercise performance in high altitude environment. The purpose of this study was to determine the effects of acetazolamide and sildenafil on oxygen uptake (VO 2 ) and breathing efficiency during submaximal hypoxic exercise. Sixteen volunteers received sildenafil 40 mg (S), acetazolamide 125 mg (A) or matching placebo (P) tid × four doses in double‐blind fashion starting 8 hours prior to hypoxic exposure over 3 separate overnight stays in an altitude tent with an O 2 concentration of 12.5%, and then performed hypoxic submaximal exercise on a stationary bicycle for 10 min at a workload of 40% of VO 2 peak. SaO 2 decreased with exercise but there was no difference in exercising SaO 2 or VO 2 between conditions. As expected, acetazolamide increased ventilation compared to placebo and sildenafil. Breathing efficiency as measured by Ve/VCO 2 decreased with acetazolamide in comparison to placebo and sildenafil (P: 42.6±1.2, S: 41.9±1.6, A: 46.7±1.1, p<0.01). Sildenafil did not change breathing efficiency while acetazolamide reduced breathing efficiency during hypoxic exercise. This study was funded by Mayo Foundation and NIH Grant No. HL71478.

Maximal expiratory flows (MEF) are dependent on gas density, lung volume, subject effort and airway characteristics. Variable changes in MEF occur after ascent to altitude which may represent an interaction between gas density changes, catecholamine stimulation and mild interstitial edema. Hypoxia induced catecholamine up‐regulation has also been associated with acute mountain sickness (AMS). This study examined the association between MEF variability and AMS symptoms in United States Antarctic Program personnel (n=198, age 37±1 yrs, 3% asthma) rapidly transported to the South Pole (SP, 9302 ft). Spirometric parameters, epinephrine (Epi), norepinepherine (NE) and SaO2 levels were recorded at sea level (SL, McMurdo Station) and after the 2 nd night at SP. AMS was assessed using Lake Louise questionnaires (score ≥ 3). FVC, FEV 1 , FEF 25 , FEF 75 and FEF 25–75 increased by 0, 3, 17, 10 and 14% from SL to SP, respectively. On day 2, AMS incidence was 31% and Epi and NE increased by 44 and 71%. Changes in MEF ranged from −64 to +93% in FEF 25–75 and −63 to +70% in FEF 75 . Subjects with the greatest increase in MEF had higher incidence of AMS (24 vs 41%) and higher NE levels, while the subjects with the greatest decrease in MEF had lower SaO2 values (88 vs 90%). Subjects with increased MEF had increased AMS and bronchodilation while subjects with decreased MEF displayed values consistent with mild interstitial edema.

Currently, the effect of aging on sympathetic baroreflex control is equivocal, with some studies finding that integrated sympathetic baroreflex threshold gain is not affected by age, and others finding that it is blunted in older compared to young adults. While these studies evaluated the effect of aging on baroreflex control of integrated sympathetic burst frequency, it remains unclear how aging modulates the baroreflex control of postganglionic action potentials (AP). In young adults, the arterial baroreflex exerts non‐uniform control over varying‐sized APs spontaneously firing within bursts of muscle sympathetic nerve activity (MSNA), with the strongest control over medium sized AP clusters, and less control over the smallest and largest APs. Therefore, we tested the hypothesis that resting baroreflex control of AP subpopulations and integrated sympathetic bursts would be blunted in older compared to young adults. Baroreflex threshold relationships for integrated MSNA bursts and the underlying subpopulations of AP clusters (obtained using microneurography and a continuous wavelet transform) were assessed during 5 minutes of supine rest in eleven older (45‐75 years, 5 females) and eleven young (21‐30 years, 5 females) adults. Baroreflex threshold was quantified as the slope of the linear regression between AP probability (%) and MSNA burst probability (%) versus diastolic blood pressure (DBP, mmHg; Finger plethysmography). AP discharge was greater in older compared to young adults (Older: 614 ± 327 spikes/100 beats vs. Young: 211 ± 107 spikes/100 beats, P < 0.001), and the baroreflex control of AP subpopulations was reset towards greater firing probabilities in older adults (group‐by‐cluster effect: P < 0.001). Specifically, the arterial baroreflex threshold gain of medium AP clusters was greater in older compared to young adults (e.g. Cluster 4, Older: ‐7.8 ± 3.1 %/mmHg vs. Young: ‐4.1 ± 2.9 %/mmHg, P = 0.010), whereas the baroreflex threshold gains for the smallest (e.g. Cluster 1, Older: ‐1.2 ± 1.1 %/mmHg vs. Young: ‐0.7 ± 0.4 %/mmHg, P = 0.197) and largest (e.g. Cluster 10, Older: ‐0.5 ± 0.4 %/mmHg vs. Young: ‐0.6 ± 0.6 %/mmHg, P = 0.673) AP clusters were not modified by aging. Additionally, integrated sympathetic burst threshold gain was greater in older compared to young adults (Older: ‐7.9 ± 3.8 %/mmHg vs. Young: ‐3.9 ± 1.8 %/mmHg, P = 0.005), and the operating point was shifted rightward towards a higher DBP (Older: 76 ± 8 mmHg vs. Young: 68 ± 7 mmHg, P = 0.021). Contrary to our hypothesis, the strength of baroreflex control over medium sized AP clusters as well as integrated sympathetic baroreflex threshold gain was greater in this group of older adults compared to young adults.

Heart failure (HF) is a complex and multifaceted disease. The disease affects multiple organ systems, including the respiratory system. This review provides three unique examples illustrating how the cardiovascular and respiratory systems interrelate because of the pathology of HF. Specifically, these examples outline the impact of HF pathophysiology on 1) respiratory mechanics and the mechanical “cost” of breathing; 2) mechanical interactions of the heart and lungs; and on 3) abnormalities of pulmonary gas exchange during exercise, and how this may be applied to treatment. The goal of this review is to, therefore, raise the awareness that HF, though primarily a disease of the heart, is accompanied by marked pathology of the respiratory system.

We propose that abnormalities of the pulmonary system contribute significantly to the exertional dyspnea and exercise intolerance observed in patients with chronic heart failure. Interventions designed to address the deleterious pulmonary manifestations of heart failure may, therefore, yield promising improvements in exercise tolerance in this population.

Background Beta-2 adrenergic receptors (β 2 ARs) are located throughout the body including airway and alveolar cells. The β 2 ARs regulate lung fluid clearance through a variety of mechanisms including ion transport on alveolar cells and relaxation of the pulmonary lymphatics. We examined the effect of an inhaled β 2 -agonist (albuterol) on alveolar-capillary membrane conductance (DM) and pulmonary capillary blood volume ( V C ) in healthy humans. Methods We assessed the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide (DLNO) at baseline, 30 minutes, and 60 minutes following nebulized albuterol (2.5 mg, diluted in 3 mL normal saline) in 45 healthy subjects. Seventeen subjects repeated these measures following nebulized normal saline (age = 27 ± 9 years, height = 165 ± 21 cm, weight = 68 ± 12 kg, BMI = 26 ± 9 kg/m 2 ). Cardiac output (Q), heart rate, systemic vascular resistance (SVR), blood pressure, oxygen saturation, forced expiratory volume at one-second (FEV 1 ), and forced expiratory flow at 50% of forced vital capacity (FEF 50 ) were assessed at baseline, 30 minutes, and 60 minutes following the administration of albuterol or saline. Results Albuterol resulted in a decrease in SVR, and an increase in Q, FEV 1 , and FEF 50 compared to saline controls. Albuterol also resulted in a decrease in V C at 60 minutes post albuterol. Both albuterol and normal saline resulted in no change in DLCO or DM when assessed alone, but a significant increase was observed in DM when accounting for changes in V C . Conclusion These data suggest that nebulized albuterol improves pulmonary function in healthy humans, while nebulization of both albuterol and saline results in an increase in DM/ V C .

The purpose of this study is to examine the effects of a 3-month interval walking program on peak aerobic capacity and cardiovascular risk factors in middle-aged sedentary individuals. Participants were divided into 2 groups: a nontraining control group (n = 17) and an interval walking training group (n = 29). Participants in the interval walking training group were instructed to perform 5 or more sets of 3-min low-intensity walking interspersed by 3-min of moderate to high-intensity walking (>70% of peak aerobic capacity) on 4 or more days/week. Measurements of peak aerobic capacity, blood pressure, blood lipids, and glucose concentration were performed before and after training. Twenty-six individuals completed the interval walking program averaging 4 days/week for 34 min, of which 16 min were moderate to high-intensity walking, with a total energy expenditure of 776 kcal/week. Three months of interval walking increased peak aerobic capacity (from 20.4 ± 3.0 to 26.0 ± 5.2 mL/kg/min; P < .001) and reduced resting systolic blood pressure (127 ± 11 to 119 ± 11 mm Hg; P = .01). There was an inverse correlation between initial level and training-induced changes in glucose, HbA1c, high-density lipoprotein, and low-density lipoprotein. Conversely, 3 months of nontraining did not improve physical fitness or cardiovascular risk factors. Very modest amounts of aerobic exercise involving brief periods of interspersed higher intensity exercise can significantly increase peak aerobic capacity and reduce resting systolic blood pressure in middle-aged sedentary individuals and contribute to a normalization of cardiovascular risk factors in individuals with elevated initial values.