Johnson, Bruce D.

Patients with heart failure with preserved ejection fraction (HFpEF) experience symptoms of exertional dyspnea that may be related to lung fluid accumulation during exercise. A computed tomography (CT)-based method was used to measure exercise-induced changes in extravascular lung fluid content and thoracic blood volumes and to determine the effect of lung fluid on lung diffusing capacity for carbon monoxide (DLCO) in stable subjects with HFpEF and healthy controls. Nine subjects with HFpEF (age = 68 ± 8 yr; body mass index = 32.1 ± 2.6 kg/m2) and eight healthy controls (62 ± 9 yr, 23.8 ± 2.4 kg/m2) performed triplicate rebreathe DLCO/DLNO (lung diffusing capacity for nitric oxide) tests in a supine position at rest and duplicate measurements during two 5-min submaximal exercise stages (15W and 35W) and recovery. Subjects subsequently performed a 5-min exercise bout (35W) inside a CT scanner, and extravascular lung fluid content and thoracic blood volumes were quantified at rest and immediately following exercise from thoracic and contrast perfusion scans, respectively. Subjects with HFpEF had a higher lung fluid content at rest compared with controls (means ± SD, HFpEF: 14.4 ± 1.7%, control: 12.8 ± 1.7%, P = 0.043) and a higher lung fluid content following exercise (15.2 ± 2.0% vs. 12.6 ± 1.5%, P = 0.009). Higher lung fluid content was associated with a lower DLCO and alveolar-capillary membrane conductance (Dm) in subjects with HFpEF (DLCO: R = −0.57, P = 0.022, Dm: R = −0.61, P = 0.012) but not in controls. Pulmonary blood volume was not altered by exercise and was similar between groups. Submaximal exercise elicited a greater accumulation of lung fluid in subjects with HFpEF compared with in controls, and lung fluid content was negatively correlated with lung diffusing capacity and alveolar-capillary membrane conductance in subjects with HFpEF.

The steadily growing elderly population calls for efficient, reliable and preferably ambulant health supervision. Since cardiovascular risk factors interact with psychosocial strain (e.g., depression), we investigated the potential contribution of psychosocial factors in discriminating generally healthy elderly from those with a cardiovascular condition, on and above routinely applied physiological assessments. Fifteen elderly (aged 60 to 88) with a cardiovascular diagnosis were compared to fifteen age and gender matched healthy peers. Six sequential standardized lab assessments were conducted (one every two weeks), including an autonomic test battery, a 6-min step test and questionnaires covering perceived psychological state and experiences over the previous two weeks. Specific combinations of physiological and psychological factors (most prominently symptoms of depression) effectively predicted (clinical) cardiovascular markers. Additionally, a highly significant prognostic model was found, including depressive symptoms, recently experienced negative events and social isolation. It appeared slightly superior in identifying elderly with or without a cardiovascular condition compared to a model that only included physiological parameters. Adding psychosocial parameters to cardiovascular assessments in elderly may consequently provide protocols that are significantly more efficient, relatively comfortable and technologically feasible in ambulant settings, without necessarily compromising prognostic accuracy.

AbstractThe present study investigated the impact of 12 weeks of pulsed electromagnetic field (PEMF) therapy on peripheral vascular function, blood pressure (BP), and nitric oxide in hypertensive individuals. Thirty hypertensive individuals (SBP > 130 mm Hg and/or MAP > 100 mm Hg) were assigned to either PEMF group (n = 15) or control group (n = 15). During pre‐assessment, participants underwent measures of flow‐mediated dilation (FMD), BP, and blood draw for nitric oxide (NO). Subsequently, they received PEMF therapy 3x/day for 12 weeks and, at conclusion, returned to the laboratory for post‐assessment. Fifteen participants from the PEMF group and 11 participants from the control group successfully completed the study protocol. After therapy, the PEMF group demonstrated significant improvements in FMD and FMDNOR (normalized to hyperemia), but the control group did not (P = .05 and P = .04, respectively). Moreover, SBP, DBP, and MAP were reduced, but the control group did not (P = .04, .04, and .03, respectively). There were no significant alterations in NO in both groups (P > .05). Twelve weeks of PEMF therapy may improve BP and vascular function in hypertensive individuals. Additional studies are needed to identify the mechanisms by which PEMF affects endothelial function.

Background Previous studies have demonstrated that the near‐infrared spectroscopy venous occlusion technique (NIRS‐VOT) provides a valid assessment of regional forearm muscle blood flow; however, day‐to‐day reproducibility of hemodynamic variables derived from the NIRS‐VOT remains to be determined, particularly across the range of physiological blood flows observed during handgrip exercise. Purpose The purpose of this study was to evaluate the day‐to‐day reproducibility of forearm hemodynamics assessed via the NIRS‐VOT. Methods Near‐infrared spectroscopy (NIRS) data were obtained from the flexor digitorum superficialis muscle on the right arm of 14 young, healthy adults (age: 27 ± 6 yrs; BMI: 24.6 ± 2.8 kg·m −2 ). The NIRS‐VOT was performed via rapid inflation of a pneumatic cuff placed on the upper arm for approximately 10 s. The NIRS‐VOT was performed at rest, and immediately after a 15 s isometric handgrip contraction at 20%, 40% and 60% of the subject’s maximum voluntary contraction. Measurements were repeated 3–5 times. Participants returned to the laboratory for a second visit on a separate day, and repeated the same number of measurements. Forearm blood flow (FBF), and blood pressure were measured on a beat‐by‐beat basis, and forearm vascular conductance (FVC) was calculated. FBF and FVC were subsequently compared for day‐to‐day reproducibility. Results FBF and FVC significantly increased with the intensity of handgrip exercise ( P < 0.05); however, these measures of forearm hemodynamics were not significantly different ( P >0.05) between Day 1 and Day 2 at each exercise‐intensity (Table ). Conclusion The findings of the present study indicate that the NIRS‐VOT provides a reliable assessment of regional forearm muscle hemodynamics across a physiological range of blood flows incurred by isometric handgrip exercise. Support or Funding Information MJJ is funded by the NIH (R‐35‐HL139854) and the Mayo Foundation. CCW is supported by the NIH training grant (5T32DK007352‐39), JRS is supported by AHA (18POST3990251), and TJC is funded by AFAR Postdoctoral Transition Award (DIAMOND18161). FBF and FVC on experimental days Day 1 Day 2 P ‐value FBF , mL · min − 1 · 100mL − 1 (tissue) Rest 2.0 ± 0.5 0.8 ± 0.2 0.001 20% MVC 14.4 ± 2.65 15.4 ± 2.4 0.679 40% MVC 26.0 ± 5.19 28.0 ± 4.3 0.606 60% MVC 39.4 ± 6.39 47.4 ± 7.7 0.858 FVC , mL · min − 1 · 100 mmHg − 1 Rest 170 ± 47.3 72 ± 16.4 0.001 20% MVC 1297 ± 227.8 1454 ± 209.6 0.380 40% MVC 2496 ± 492.8 2656 ± 434.0 0.912 60% MVC 3820 ± 659.1 4542 ± 744.7 0.535 MVC , kg 49.4 ± 3.0 47.9 ± 2.6 0.721 Abbreviations: FBF, forearm blood flow; FVC, forearm vascular conductance; MVC, maximal voluntary contraction. Values are presented as means ± SE. P values indicate comparison between days 1 and 2.

The Beta‐2 adrenergic receptors (β 2 ARs) are located on alveolar cells and the pulmonary lymphatics and regulate lung fluid clearance through activation of epithelial sodium channels on the alveolar cells and through the relaxation of the lymphatic vessels. We sought to determine the influence of an inhaled β 2 ‐selective agonist on alveolar‐capillary conductance (DM) and pulmonary capillary blood volume (Vc) in healthy humans. To determine this, we assessed the diffusing capacity of the lungs for carbon monoxide (DLCO) and nitric oxide before and every 15 minutes for one‐hour following the administration of nebulized albuterol (2.5mg, diluted to 3ml) in 28 healthy subjects (age=28±5yrs, ht=171±14cm, wt=75±17kg, BMI=26±8kg/m 2 , values are mean±SD). Cardiac output (Q, determined via acetylene wash‐in), heart rate (HR), stroke volume (SV), systemic vascular resistance (SVR), blood pressure (BP), and oxygen saturation (SaO2) were also assessed at baseline and following the administration of albuterol. Albuterol resulted in elevations in HR, Q, and SV as well as a drop in SVR (% change from baseline, HR=4±11, 4±8, 4±8, and 4±8%; Q=15±17, 12±17, 9±19, and 4±17%; SV= 24±32, 16±27, 11±28, and 14±23%; and SVR= −15±12, −12±16, −7±20, and −4±17, at 15, 30, 45, and 60 minutes post‐albuterol, respectively, P‐ANOVA<0.05), but no change in BP. There was no change in DLCO, a decrease in Vc and an increase in DM when assessed alone or when corrected for Vc (%change from baseline, Vc=5±37, −5±30, −12±35, and −20±26%, DM= 0±18, 1±18, 6±22, and 5±19%; DM/Vc=10±44, 17±48, 47±70, and 48±70%, at 15, 30, 45, and 60 minutes post‐nebulization, respectively, p<0.05). These data suggest that the administration of albuterol improves alveolar‐capillary conductance in healthy humans, despite a small decrease in pulmonary capillary blood volume.

Assessments of electrocardiographic (ECG) responses during swimming activities are impossible without mobile waterproof recording units and rarely completed. This preliminary study characterized changes in the ventricular diastolic, PR‐, QT‐, and RR‐intervals that occurred during a 1 km indoor swim in 78°F water with a waterproof Actiwave ECG recording system (CamNtech Inc., Boerne, TX) and the .epf data files were analyzed with software from ADInstruments Inc. (Colorado Springs CO). Values within times expressed as mean ± SE with significance evaluated using ANOVA and repeated measures. Competitive club swimmers (3 male, 1 female) with an age, height, and weight of 51 ± 3 years, 175 ± 4 cm, and 83 ± 8 kg, with a BMI of 27 ± 2 completed the 1 km swim (44 laps × 75 foot laps) using a standard crawl in 17.9 ± 1.3 minutes using 10.5 ± 0.50 arm cycles/second. A continuous ECG with waveform was obtained and measurements were performed 120 and 30 seconds before swim, during the swim (at end of lap‐1, ‐22 and ‐43), and at 30 and 300 seconds post‐completion. Heart rate (from RR‐interval) −120, and −30 seconds prior to the swim, at end of swim lap 1, 22 and 43, and during recovery 30 and 300 seconds post swim was 68 ± 5, 73 ± 6, 107 ± 3, 142 ± 4, 147 ± 5, 132 ± 8 and 89 ± 3 beats/minute (P<0.0001). Respective QT‐intervals were 392 ± 14, 374 ± 13, 307 ± 38, 259 ± 15, 254 ± 2, 255 ± 14, and 338 ± 6 msec (n = 2 at lap‐1, and n = 3 at lap‐22) (P<0.0001). Respective ventricular diastole time was 509 ± 61, 468 ± 61, 253 ± 45, 166 ± 10, 166 ± 7, 204 ± 25 and 339 ± 26 msec (P<0.0001). Respective PR‐Intervals were 130 ± 12, 127 ± 12, 111 ± 18, 111 ± 2, 105 ± 14, 107 ± 15 and 125 ± 18 msec (P<0.094). Heart rate increased and duration of ventricular diastole decreased between lap 1 and 22, and was relatively stable between lap 22 and the end of lap 43. This study determined that with appropriate waterproof equipment a continuous ECG record can be collected from swimming athletes and used to provide an accurate assessment swim‐associated changes in cardiac function. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Abstract Aims Lung congestion in patients with heart failure (HF) has traditionally been treated using interventions that reduce pulmonary capillary hydrostatic pressure. The transient receptor potential vanilloid 4 (TRPV4) channel regulates fluid transit across the pulmonary capillary-interface, and represents a novel target to reduce lung water, independent of pulmonary capillary hypertension. This pilot study examined the safety and potential efficacy of TRPV4 blockade as a novel treatment for HF. Methods and results In this randomized, double-blind, placebo-controlled crossover pilot trial, 11 subjects with chronic, compensated HF were treated with a novel TRPV4 antagonist (GSK2798745) or placebo. The primary endpoint was lung diffusing capacity for carbon monoxide (DLCO) after 7 days of treatment with GSK2798745 as compared to placebo. Secondary endpoints included additional diffusion parameters, spirometry and safety assessments. Compared to placebo, treatment with GSK2798745 resulted in a trend to improvement in DLCO (placebo: −0.336 mL/mmHg/min; GSK2798745: +0.458 mL/mmHg/min; treatment difference: +0.793 mL/mmHg/min; 95% confidence interval: −0.925 to 2.512) that was not statistically significant. GSK2798745 was well-tolerated with no serious adverse events. Conclusion In this pilot trial, GSK2798745 was found to be safe and well-tolerated, with a trend toward improved gas transfer. Further investigation is warranted in larger studies to determine whether treatment with TRPV4 antagonists or alternative treatments targeting capillary permeability might be effective to improve lung congestion, pulmonary gas transfer and clinical status in patients with acute or chronic HF.