Johnson, Bruce D.

Abstract Background: Doppler ultrasound of the common carotid artery is used to infer central hemodynamics. For example, change in the common carotid artery corrected flow time (ccFT) and velocity time integral (VTI) are proposed surrogates of changing stroke volume. However, conflicting data exist which may be due to inadequate beat sample size and measurement variability – both intrinsic to handheld systems. In this brief communication, we determined the correlation between changing ccFT and carotid VTI during progressively severe central blood volume loss and resuscitation. Methods: Measurements were obtained through a novel, wireless, wearable Doppler ultrasound system. Sixteen participants (ages of 18–40 years with no previous medical history) were studied across 25 lower body-negative pressure protocols. Relationships were assessed using repeated-measures correlation regression models. Results: In total, 33,110 cardiac cycles comprise this analysis; repeated-measures correlation showed a strong, linear relationship between ccFT and VTI. The strength of the ccFT-VTI relationship was dependent on the number of consecutively averaged cardiac cycles (R 1 cycle = 0.70, R 2 cycles = 0.74, and R 10 cycles = 0.81). Conclusions: These results positively support future clinical investigations employing common carotid artery Doppler as a surrogate for central hemodynamics.

Activation of group III/IV skeletal muscle afferents (ergoreflex) and hypoxia (chemoreflex) are two potent stimuli of the sympathetic nervous system during exercise. Venous distention by graded sub‐systolic occlusion contributes to the ergoreflex during exercise. Although the ergoreflex causes greater increases in blood pressure (BP) compared with the chemoreflex, the interaction of the ergoreflex and hypoxia during lower extremity dynamic exercise is unknown. Objective To determine the effect of hypoxia and graded cuff occlusion on hemodynamic responses during low‐intensity cycling exercise. Methods 19 healthy adults (9 men, 25±5 yr) completed two sessions. Session 1 included a maximal cycle ergometry exercise test. Session 2 included two randomized bouts (hypoxia: 12.5% FiO 2 and normoxia: 21% FiO 2 ) of constant‐load cycling at 30% peak workload for 3 min (control, CTL) followed by randomized inflation of bilateral thigh pressure tourniquets to 20, 40, 60, 80, 100 mmHg for 2 min with 2 min of deflation between occlusions. The bouts were separated by 30 minutes of rest. Blood pressure, heart rate and cardiac output (CO) were measured continuously. Results During hypoxia, the average SPO 2 was 80%. Venous occlusion and hypoxia had differential effects on mean arterial pressure (MAP, occlusion × hypoxia, p=0.02). Significant increases of MAP from CTL occurred at 60 (Δ9 ± 6mmHg), 80 (Δ15 ± 8mmHg), and 100mmHg (Δ17 ± 9mmHg) under normoxia (p<0.05). MAP only increased at 100mmHg (Δ14 ± 9mmHg) under hypoxia (p<0.05). Under hypoxia, MAP was much greater at CTL and 20mmHg as compared to normoxia (p<0.05). SBP exhibited responses similar to MAP under hypoxia (100mmHg increase, p<0.001, occlusion × hypoxia interaction, p=0.02). CO was greater with venous occlusion as mediated by increases in HR (p<0.001). In addition, CO increased under hypoxia (p=0.007) but had no interaction with venous occlusion. Conclusion During low pressure venous occlusion, hypoxia had a greater effect on BP, but as pressure increased (60–100mmHg), there were no significant differences in BP between normoxia and hypoxia. Therefore, sympathetically mediated increases of BP during exercise attributed to hypoxia may negate any responses mediated by the ergoreflex when elicited by venous occlusion at low pressures.

Parks, Jordan K, Courtney M. Wheatley-Guy, Glenn M. Stewart, Caitlin C. Fermoyle, Bryan J. Taylor, Jesse Schwartz, Briana Ziegler, Kay Johnson, Alice Gavet, Loïc Chabridon, Paul Robach, and Bruce D. Johnson. Lung “Comet Tails” in healthy individuals: accumulation or clearance of extravascular lung water? High Alt Med Biol. 24:230–233, 2023—Ultrasound lung comet tails (or B-lines) tend to be limited in number (<5) or absent under ultrasound examination, and the appearance of diffuse B-lines with lung sliding has been suggested to identify pulmonary edema. Clinical evaluation of B-lines has been utilized as a bedside test to assess pulmonary congestion in patients with heart failure. Exposure to altitude or prolonged exercise can alter fluid regulation and can lead to pulmonary congestion or edema. As such, B-lines have been utilized in the field to monitor for pathological lung fluid accumulation. However, ultrasound lung comet lines might not be as reliable for identifying extravascular lung water (EVLW) as previously thought in healthy individuals exercising at altitude where an increase in the number of ultrasound lung comets would reflect fluid buildup in the interstitial space of the alveoli and pulmonary capillaries. This report will focus on reviewing the literature and our data from a group of ultraendurance runners that completed the Ultra Trail Mont Blanc race that demonstrates that lung comet tails may not always be evidence of pathological fluid accumulation in healthy individuals and as such should be used to assess EVLW in concert with other diagnostic testing.

Background: Heart failure patients with preserved ejection fraction (HFpEF) exhibit exercise intolerance and exertional dyspnea. The underlying pathophysiology is complex and involves multiple physiological systems. To this point, HFpEF patients exhibit pulmonary abnormalities at rest and during exercise. For example, HFpEF patients have higher work of breathing during exercise due to greater inspiratory and expiratory resistive work of breathing. Importantly, this greater resistive work of breathing is not associated with higher inspiratory and expiratory flow rates suggesting pulmonary resistance is elevated in HFpEF patients. One potential explanation for the increase in resistive work of breathing during exercise in HFpEF patients is smaller luminal area of the airways. Purpose: The purpose of this study was to determine if differences exist in the luminal area of the large conducting airways in HFpEF patients compared to controls. We hypothesized that HFpEF patients will exhibit smaller luminal areas of the large conducting airways compared to controls. Methods: HFpEF patients (n=9; 67±7 yrs; 30±3 kg/m2) and controls (n=8; 62±9 yrs; 24±3 kg/m2) were enrolled. All participants performed pulmonary function testing and a thoracic computerized tomographic (CT) scan (assessed at total lung capacity). The airway luminal area was quantified from three-dimensional reconstructions from the high-resolution CT scans. The luminal areas of the large conducting airways were measured at three discreet points (corresponding to the beginning, middle, and end of the airway), averaged, and indexed to height. Results: The luminal area of the trachea was not different between groups (p=0.95). HFpEF patients had smaller luminal area of the right main bronchus (control: 1.38±0.21 vs. HFpEF: 1.18±0.13 mm2/cm) and left main bronchus (control: 0.98±0.20 vs. HFpEF: 0.79±0.15 mm2/cm) (both, p<0.04) than controls. HFpEF patients also had smaller luminal area of the bronchus intermedius (control: 0.82±0.14 vs. HFpEF: 0.67±0.15 mm2/cm) and left lower lobe bronchus (control: 0.48±0.13 vs. HFpEF: 0.36±0.07 mm2/cm) compared to controls (both, p<0.04). No differences were present between groups in the right and left upper lobe bronchi (both, p>0.40). Conclusion: HFpEF patients have smaller luminal areas of some, but not all large conducting airways compared to controls. These findings provide support for smaller large conducting airways in HFpEF contributing to the pulmonary abnormalities during exercise in these patients. This is the full abstract presented at the American Physiology Summit 2023 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.

The diaphragm muscle is important in both sustaining ventilation and performing higher-force behaviors necessary for maintaining airway patency. Ventilatory behaviors (i.e., eupnea and response to hypoxia-hypercapnia) require only ~20% of maximal force generation, whereas coughing requires forces ~60% of maximal. Existing techniques to measure the full range of forces generated by respiratory muscles are limited by their invasiveness (e.g., balloon manometry for transdiaphragmatic pressure (Pdi) measurements), requirements for training, supervision and subjectivity (e.g., maximal inspiratory and expiratory pressures). Ultrasound-based shear-wave elastography (SWE) assesses muscle stiffness and has shown promising results in being used as a surrogate for Pdi to evaluate diaphragm muscle force. Previous literature has demonstrated a correlation between diaphragm SWE and Pdi at lower force behaviors and the goal of the present study was to evaluate the efficacy of SWE-based measurements of the diaphragm in correlating with Pdi measurements across the range of forces generated by the diaphragm. In this pilot study, we recruited 6 male and 5 female healthy volunteers. Subjects were positioned in a seated position with their torso unsupported. Pdi was measured during graded inspiratory threshold loading trials using a POWERbreathe Plus commercial inspiratory loading device, as well as during maximal inspiratory pressure (MIP). Simultaneously, SWE was performed at the zone of apposition in the right anterior axillary line, and diaphragm Young’s modulus and shear wave speed were subsequently measured. The average Pdi during MIP testing was 149 ± 66 cm H2O. Pdi during inspiratory loading at a low resistance was 39 ± 14 cm H2O and at a high resistance was 78 ± 29 cm H2O. Subjects were able to generate an average Pdi range of 39 ± 19 cm H2O across the graded resistance levels, and the average percent of MIP obtained was 54 ± 13%. Average Young’s modulus as measured with SWE during inspiratory loading at a low resistance was 46 ± 19 kPa and at a high resistance was 104 ± 19 kPa. From low to high resistance, Pdi, Young’s modulus, and shear wave speed increased by an average of 100%, 126%, and 59%, respectively. Taken together, SWE is a promising method of non-invasive assessment of diaphragm muscle forces across a range of voluntary behaviors. Support from NIH grant R21 DA055848 and the Mayo Clinic. This is the full abstract presented at the American Physiology Summit 2023 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.

A wireless, wearable Doppler ultrasound offers a new paradigm for linking physiology to resuscitation medicine. To this end, the image analysis of simultaneously-acquired venous and arterial Doppler spectrograms attained by wearable ultrasound represents a new source of hemodynamic data. Previous investigators have reported a direct relationship between the central venous pressure (CVP) and the ratio of the internal jugular-to-common carotid artery diameters. Because Doppler power is directly related to the number of red cell scatterers within a vessel, we hypothesized that (1) the ratio of internal jugular-to-carotid artery Doppler power (V/APOWER) would be a surrogate for the ratio of the vascular areas of these two vessels and (2) the V/APOWER would track the anticipated CVP change during simulated hemorrhage and resuscitation. To illustrate this proof-of-principle, we compared the change in V/APOWER obtained via a wireless, wearable Doppler ultrasound to B-mode ultrasound images during a head-down tilt. Additionally, we elucidated the change in the V/APOWER during simulated hemorrhage and transfusion via lower body negative pressure (LBNP) and release. With these Interesting Images, we show that the Doppler V/APOWER ratio qualitatively tracks anticipated changes in CVP (e.g., cardiac preload) which is promising for both diagnosis and management of hemodynamic unrest.

Importance Reduced heart rate during exercise is common and associated with impaired aerobic capacity in heart failure with preserved ejection fraction (HFpEF), but it remains unknown if restoring exertional heart rate through atrial pacing would be beneficial. Objective To determine if implanting and programming a pacemaker for rate-adaptive atrial pacing would improve exercise performance in patients with HFpEF and chronotropic incompetence. Design, Setting, and Participants Single-center, double-blind, randomized, crossover trial testing the effects of rate-adaptive atrial pacing in patients with symptomatic HFpEF and chronotropic incompetence at a tertiary referral center (Mayo Clinic) in Rochester, Minnesota. Patients were recruited between 2014 and 2022 with 16-week follow-up (last date of follow-up, May 9, 2022). Cardiac output during exercise was measured by the acetylene rebreathe technique. Interventions A total of 32 patients were recruited; of these, 29 underwent pacemaker implantation and were randomized to atrial rate responsive pacing or no pacing first for 4 weeks, followed by a 4-week washout period and then crossover for an additional 4 weeks. Main Outcomes and Measures The primary end point was oxygen consumption (V̇ o 2 ) at anaerobic threshold (V̇ o 2,AT ); secondary end points were peak V̇ o 2 , ventilatory efficiency (V̇ e /V̇ co 2 slope), patient-reported health status by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Results Of the 29 patients randomized, the mean age was 66 years (SD, 9.7) and 13 (45%) were women. In the absence of pacing, peak V̇ o 2 and V̇ o 2 at anaerobic threshold (V̇ o 2,AT ) were both correlated with peak exercise heart rate ( r = 0.46-0.51, P &amp;lt; .02 for both). Pacing increased heart rate during low-level and peak exercise (16/min [95% CI, 10 to 23], P &amp;lt; .001; 14/min [95% CI, 7 to 21], P &amp;lt; .001), but there was no significant change in V̇ o 2,AT (pacing off, 10.4 [SD, 2.9] mL/kg/min; pacing on, 10.7 [SD, 2.6] mL/kg/min; absolute difference, 0.3 [95% CI, −0.5 to 1.0] mL/kg/min; P = .46), peak V̇ o 2 , minute ventilation (V̇ e) /carbon dioxide production (V̇ co 2 ) slope, KCCQ-OSS, or NT-proBNP level. Despite the increase in heart rate, atrial pacing had no significant effect on cardiac output with exercise, owing to a decrease in stroke volume (−24 mL [95% CI, −43 to −5 mL]; P = .02). Adverse events judged to be related to the pacemaker device were observed in 6 of 29 participants (21%). Conclusions and Relevance In patients with HFpEF and chronotropic incompetence, implantation of a pacemaker to enhance exercise heart rate did not result in an improvement in exercise capacity and was associated with increased adverse events. Trial Registration ClinicalTrials.gov Identifier: NCT02145351

Adults with cardiovascular disease and heart failure are at higher risk of cognitive decline. Cerebral hypoperfusion appears to be a significant contributor, which can result from vascular dysfunction and impairment of cerebral blood flow regulation. In contrast, higher cardiorespiratory fitness shows protection against brain atrophy, reductions in cerebral blood flow, and cognitive decline. Given that high intensity interval training (HIIT) has been shown to be a potent stimulus for improving cardiorespiratory fitness and peripheral vascular function, its utility for improving cognitive aging is an important area of research. This article will review the physiology related to cerebral blood flow regulation and cognitive decline in adults with cardiovascular disease and heart failure, and how HIIT may provide a more optimal stimulus for improving cognitive aging in this population.

Czech physiologist Penaz tried to overcome limitations of invasive pulse-contour methods (PCM) in clinical applications by a non-invasive method (finger mounted BP cuff) for continuous arterial waveform detection and beat-to-beat analysis. This discovery resulted in significant interest in human physiology and non-invasive examination of hemodynamic parameters, however has limitations because of the distal BP recording using a volume-clamp method. Thus, we propose a validation of beat-to-beat signal analysis acquired by novel a brachial occlusion-cuff (suprasystolic) principle and signal obtained from Finapres during a forced expiratory effort against an obstructed airway (Valsalva maneuver). Twelve healthy adult subjects [2 females, age = (27.2 ± 5.1) years] were in the upright siting position, breathe through the mouthpiece (simultaneously acquisition by brachial blood pressure monitor and Finapres) and at a defined time were asked to generate positive mouth pressure for 20 s (Valsalva). For the purpose of signal analysis, we proposed parameter a “Occlusion Cuff Index” (OCCI). The assumption about similarities between measured signals (suprasystolic brachial pulse waves amplitudes and Finapres’s MAP) were proved by averaged Pearson’s correlation coefficient (r- = 0.60, p < 0.001). The averaged Pearson’s correlation coefficient for the comparative analysis of OCCI between methods was r- = 0.88, p < 0.001. The average percent change of OCCI during maneuver: 8% increase, 19% decrease and percent change of max/min ratio is 35%. The investigation of brachial pulse waves measured by novel brachial blood pressure monitor shows positive correlation with Finapres and the parameter OCCI shows promise as an index, which could describe changes during beat-to-beat cardiac cycles.