Influence of respiratory loading on left-ventricular function in cervical spinal cord injury.

Cervical spinal cord injury (C-SCI) negatively impacts cardiac and respiratory function. As the heart and lungs are linked via the pulmonary circuit these systems are interdependent. Here, we utilized inspiratory and expiratory loading to assess whether augmenting the respiratory pump improves left-ventricular (LV) filling and output in individuals with motor-complete C-SCI. We hypothesized LV end-diastolic volume (LVEDV) would increase and decrease with inspiratory and expiratory loading, respectively. Participants (C-SCI: 7M/1F, 35 ± 7 years; able-bodied: 7M/1F, 32 ± 6 years) were assessed under five conditions during 45° head-up tilt; unloaded, inspiratory loading with -10 and -20 cmH2 O oesophageal pressure (Poes ) on inspiration, and expiratory loading with +10 and +20 cmH2 O Poes on expiration. An oesophageal balloon catheter monitored Poes , and LV structure and function were assessed by echocardiography. In C-SCI only, (1) +20 cmH2 O reduced LVEDV vs. unloaded (81 ± 15 vs. 88 ± 11 ml, P = 0.006); (2) heart rate was higher during +20 cmH2 O compared to unloaded (P = 0.001) and +10 cmH2 O (P = 0.002); (3) cardiac output was higher during +20 cmH2 O than unloaded (P = 0.002); and (4) end-expiratory lung volume was higher during +20 cmH2 O vs. unloaded (63 ± 10 vs. 55 ± 13% total lung capacity, P = 0.003) but was unaffected by inspiratory loading. In both groups, -10 and -20 cmH2 O had no significant effect on LVEDV. These findings suggest greater expiratory positive pressure acutely impairs LV filling in C-SCI, potentially via impaired venous return, mediastinal constraint and/or direct ventricular interaction subsequent to dynamic hyperinflation. Inspiratory loading did not significantly improve LV function in C-SCI and neither inspiratory nor expiratory loading affected cardiac function or lung volumes in able-bodied participants. KEY POINTS: Cervical spinal cord injury (C-SCI) alters both the cardiac and the respiratory system, but little is known about how these systems interact following injury. Here, we manipulated inspiratory or expiratory intrathoracic pressure (ITP) to mechanistically test the role of the respiratory pump in circulatory function in highly trained individuals with C-SCI and an able-bodied reference group. In individuals with C-SCI, greater ITP during expiratory loading caused dynamic hyperinflation that was associated with impaired left-ventricular filling. More negative ITP during inspiratory loading did not significantly alter left-ventricular volumes in either group. Interventions that prevent dynamic hyperinflation and/or enhance the ability to generate expiratory pressures may help preserve left-ventricular filling in individuals with C-SCI.

Near-infrared spectroscopy measures of sternocleidomastoid blood flow during exercise and hyperpnoea.

NEW FINDINGS: What is the central question of this study? How does sternocleidomastoid blood flow change in response to increasing ventilation and whole-body exercise intensity? What is the main finding and its importance? Sternocleidomastoid blood flow increased with increasing ventilation. For a given ventilation, sternocleidomastoid blood flow was lower during whole-body exercise compared to resting hyperpnoea. These findings suggest that locomotor muscle work exerts an effect on respiratory muscle blood flow that can be observed in the sternocleidomastoid. ABSTRACT: Respiratory muscle work influences the distribution of blood flow during exercise. Most studies have focused on blood flow to the locomotor musculature rather than the respiratory muscles, owing to the complex anatomical arrangement of respiratory muscles. The purpose of this study was to examine how accessory respiratory (i.e. sternocleidomastoid, and muscles in the intercostal space) muscle blood flow changes in response to locomotor muscle work. Seven men performed 5 min bouts of constant load cycling exercise trials at 30%, 60% and 90% of peak work rate in a randomized order, followed by 5 min bouts of voluntary hyperpnoea (VH) matching the ventilation achieved during each exercise (EX) trial. Blood-flow index (BFI) of the vastus lateralis, sternocleidomastoid (SCM) and seventh intercostal space (IC) were estimated using near-infrared spectroscopy and indocyanine green and expressed relative to resting levels. BFISCM was greater during VH compared to EX (P = 0.002) and increased with increasing exercise intensity (P = 0.036). BFISCM reached 493 ± 219% and 301 ± 215% rest during VH and EX at 90% peak work rate, respectively. BFIIC increased to 242 ± 178% and 210 ± 117% rest at 30% peak work rate during VH and EX, respectively. No statistically significant differences in BFIIC were observed with increased work rate during VH or EX (both P > 0.05). Moreover, there was no observed difference in BFIIC between conditions (P > 0.05). BFISCM was lower for a given minute ventilation during EX compared to VH, suggesting that accessory respiratory muscle blood flow is influenced by whole-body exercise.

Diaphragm fatigue and inspiratory muscle metaboreflex in men and women matched for absolute diaphragmatic work during pressure-threshold loading.

KEY POINTS: The female diaphragm fatigues at a slower rate compared to that of males, with blunted cardiovascular consequences (i.e. inspiratory muscle metaboreflex). It is unclear if these findings are a function of relative or absolute diaphragmatic work. We asked if sex differences in diaphragm fatigue and the inspiratory muscle metaboreflex persisted during inspiratory loading performed at equal absolute intensities. We found that matching men and women for absolute diaphragmatic work resulted in an equal degree of diaphragm fatigue, despite women performing significantly greater work relative to body mass. Metabolite-induced reflex influences in sympathetic outflow originating from the diaphragm are attenuated in women, with potential implications for blood flow distribution during exercise. ABSTRACT: In response to inspiratory pressure-threshold loading (PTL), women have greater inspiratory muscle endurance time, slower rate of diaphragm fatigue development, and a blunted pressor response compared to men. It is unclear if these differences are due to discrepancies in absolute diaphragm force output. We tested the hypothesis that following inspirations performed at equal absolute intensities, females would develop a similar level of diaphragm fatigue and an attenuated cardiovascular response relative to men. Healthy young men (n = 8, age = 24 ± 3 years) and women (n = 8, age = 23 ± 3 years) performed PTL whilst targeting a transdiaphragmatic pressure (Pdi ) of 92 cmH2 O for 5 min. Diaphragm fatigue was assessed via twitch Pdi (Pdi,tw ) using cervical magnetic stimulation. Heart rate (HR) and mean arterial blood pressure were monitored continuously. During PTL, the absolute amount of diaphragm work was not different between men (13,399 ± 2019 cmH2 O s) and women (12,986 ± 1846 cmH2 O s; P > 0.05); however, women performed the PTL task at a higher relative P¯di /Pdi,max . Following inspiratory PTL, the magnitude of reduction in Pdi,tw was similar between men (-27.1 ± 7.2%) and women (-23.8 ± 13.8%; P > 0.05). There were significant increases in HR over time (P < 0.05), but this did not differ on the basis of sex (P > 0.05). Mean arterial blood pressure increased significantly over time in both men and women (P < 0.05); however, the rate of change was higher in men (6.24 ± 2.54 mmHg min-1 ) than in women (4.15 ± 2.52 mmHg min-1 ) (P < 0.05). We conclude that the female diaphragm is protected against severe fatigue when inspiratory work is excessive and as a result does not evoke overt sympathoexcitation.

Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women.

KEY POINTS: The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly as a result of sex-differences in respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. ABSTRACT: We aimed to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. Eighteen healthy subjects (aged 60-80 years; nine men and nine women) completed two days of testing. On day 1, subjects were assessed for pulmonary function and performed a maximal incremental cycle exercise test. On day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: (i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); (ii) through an inspiratory resistance (RES) of ∼5 cmH2 O L-1  s-1 to increase Wb ; and (iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (category-ratio 10 Borg scale) were monitored throughout exercise. During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both P < 0.01). Moreover, if EFL was present during CON (four men and five women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both P < 0.01). There was no main effect of sex on Wb (P = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, P < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, the intensity of dyspnoea was unaffected, independent of sex (P = 0.46). When older men and women perform moderate intensity exercise, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea.

Analysis of maximal expiratory flow-volume curves in adult survivors of preterm birth.

Adult survivors of very preterm (≤32 wk gestational age) birth without (PRE) and with bronchopulmonary dysplasia (BPD) have variable degrees of airflow obstruction at rest. Assessment of the shape of the maximal expiratory flow-volume (MEFV) curve in PRE and BPD may provide information concerning their unique pattern of airflow obstruction. The purposes of the present study were to 1) quantitatively assess the shape of the MEFV curve in PRE, BPD, and healthy adults born at full-term (CON), 2) identify where along the MEFV curve differences in shape existed between groups, and 3) determine the association between an index of MEFV curve shape and characteristics of preterm birth (i.e., gestational age, mass at birth, duration of oxygen therapy) in PRE and BPD. To do so, we calculated the average slope ratio (SR) throughout the effort-independent portion of the MEFV curve and at increments of 5% of forced vital capacity (FVC) between 20 and 80% of FVC in PRE (n = 19), BPD (n = 25), and CON (n = 20). We found that average SR was significantly higher in PRE (1.34 ± 0.35) and BPD (1.33 ± 0.45) compared with CON (1.03 ± 0.22; both P < 0.05) but similar between PRE and BPD (P = 0.99). Differences in SR between groups occurred early in expiration (i.e., 20-30% of FVC). There was no association between SR and characteristics of preterm birth in PRE and BPD groups (all P > 0.05). The mechanism(s) of increased SR during early expiration in PRE/BPD relative to CON is unknown but may be due to differences in the structural and mechanical properties of the airways.

Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.

KEY POINTS: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. ABSTRACT: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.

Effects of respiratory muscle work on respiratory and locomotor blood flow during exercise.

NEW FINDINGS: What is the central question of this study? Does manipulation of the work of breathing during high-intensity exercise alter respiratory and locomotor muscle blood flow? What is the main finding and its importance? We found that when the work of breathing was reduced during exercise, respiratory muscle blood flow decreased, while locomotor muscle blood flow increased. Conversely, when the work of breathing was increased, respiratory muscle blood flow increased, while locomotor muscle blood flow decreased. Our findings support the theory of a competitive relationship between locomotor and respiratory muscles during intense exercise. Manipulation of the work of breathing (WOB) during near-maximal exercise influences leg blood flow, but the effects on respiratory muscle blood flow are equivocal. We sought to assess leg and respiratory muscle blood flow simultaneously during intense exercise while manipulating WOB. Our hypotheses were as follows: (i) increasing the WOB would increase respiratory muscle blood flow and decrease leg blood flow; and (ii) decreasing the WOB would decrease respiratory muscle blood flow and increase leg blood flow. Eight healthy subjects (n = 5 men, n = 3 women) performed a maximal cycle test (day 1) and a series of constant-load exercise trials at 90% of peak work rate (day 2). On day 2, WOB was assessed with oesophageal balloon catheters and was increased (via resistors), decreased (via proportional assist ventilation) or unchanged (control) during the trials. Blood flow was assessed using near-infrared spectroscopy optodes placed over quadriceps and the sternocleidomastoid muscles, coupled with a venous Indocyanine Green dye injection. Changes in WOB were significantly and positively related to changes in respiratory muscle blood flow (r = 0.73), whereby increasing the WOB increased blood flow. Conversely, changes in WOB were significantly and inversely related to changes in locomotor blood flow (r = 0.57), whereby decreasing the WOB increased locomotor blood flow. Oxygen uptake was not different during the control and resistor trials (3.8 ± 0.9 versus 3.7 ± 0.8 l min-1 , P > 0.05), but was lower on the proportional assist ventilator trial (3.4 ± 0.7 l min-1 , P < 0.05) compared with control. Our findings support the concept that respiratory muscle work significantly influences the distribution of blood flow to both respiratory and locomotor muscles.

Influence of inspiratory resistive loading on expiratory muscle fatigue in healthy humans.

NEW FINDINGS: What is the central question of this study? This study is the first to measure objectively both inspiratory and expiratory muscle fatigue after inspiratory resistive loading to determine whether the expiratory muscles are activated to the point of fatigue when specifically loading the inspiratory muscles. What is the main finding and its importance? The absence of abdominal muscle fatigue suggests that future studies attempting to understand the neural and circulatory consequences of diaphragm fatigue can use inspiratory resistive loading without considering the confounding effects of abdominal muscle fatigue. Expiratory resistive loading elicits inspiratory as well as expiratory muscle fatigue, suggesting parallel coactivation of the inspiratory muscles during expiration. It is unknown whether the expiratory muscles are likewise coactivated to the point of fatigue during inspiratory resistive loading (IRL). The purpose of this study was to determine whether IRL elicits expiratory as well as inspiratory muscle fatigue. Healthy male subjects (n = 9) underwent isocapnic IRL (60% maximal inspiratory pressure, 15 breaths min-1 , 0.7 inspiratory duty cycle) to task failure. Abdominal and diaphragm contractile function was assessed at baseline and at 3, 15 and 30 min post-IRL by measuring gastric twitch pressure (Pga,tw ) and transdiaphragmatic twitch pressure (Pdi,tw ) in response to potentiated magnetic stimulation of the thoracic and phrenic nerves, respectively. Fatigue was defined as a significant reduction from baseline in Pga,tw or Pdi,tw . Throughout IRL, there was a time-dependent increase in cardiac frequency and mean arterial blood pressure, suggesting activation of the respiratory muscle metaboreflex. The Pdi,tw was significantly lower than baseline (34.3 ± 9.6 cmH2 O) at 3 (23.2 ± 5.7 cmH2 O, P < 0.001), 15 (24.2 ± 5.1 cmH2 O, P < 0.001) and 30 min post-IRL (26.3 ± 6.0 cmH2 O, P < 0.001). The Pga,tw was not significantly different from baseline (37.6 ± 17.1 cmH2 O) at 3 (36.5 ± 14.6 cmH2 O), 15 (33.7 ± 12.4 cmH2 O) and 30 min post-IRL (32.9 ± 11.3 cmH2 O). Inspiratory resistive loading elicits objective evidence of diaphragm, but not abdominal, muscle fatigue. Agonist-antagonist interactions for the respiratory muscles appear to be more important during expiratory versus inspiratory loading.

Electrophysiologic features of fetal ventricular aneurysms and diverticula.

OBJECTIVE: Congenital ventricular wall defects are very rare and include congenital ventricular aneurysms (CVAs) and diverticula (CVDs). METHOD: We report a series of five fetuses: three with CVAs and two with CVDs referred due to fetal arrhythmia. In addition to routine fetal echocardiography, fetal magnetocardiography (fMCG) was used. The literature in CVA and CVD is reviewed. RESULTS: Incessant premature ventricular contractions (PVC), mainly bigeminy and trigeminy were found in three fetuses with CVAs and in one with CVD, who also had ventricular couplets. The other fetus with CVD, referred because of PVCs, had only sinus tachycardia. ST elevation was noted in two. Fetal movement had a variable impact on PVCs. Postnatal evaluation demonstrated two persistent left ventricular aneurysms and one persistent right CVD; one CVD resolved at 35-week gestation. Two neonates had incessant PVCs. Both arrhythmias resolved spontaneously while being treated with propranolol. CONCLUSION: FMCG is complementary to echocardiographic imaging. In fetuses with left ventricular wall defects, additional electrophysiological diagnosis can be made by fMCG, including the complexity of ventricular ectopy, arrhythmic response to fetal movement, presence of ST-T wave abnormalities, and atrial amplitude increases. Prenatal risk factor assessment using fMCG can additionally support post-natal treatment and follow-up.

Accuracy of symptoms and pulse checking for detecting atrial fibrillation following catheter ablation.

BACKGROUND: There is growing interest in the possibility of discontinuing oral anticoagulation following successful catheter ablation of atrial fibrillation (AF). However, it remains unknown whether patients can accurately detect arrhythmia recurrences following ablation. We therefore sought to characterize the accuracy of pulse checking and arrhythmia symptoms for the identification of AF following ablation. METHODS: This prospective cohort study included patients at the Hospital of the University of Pennsylvania with an insertable cardiac monitor (ICM) treated with catheter ablation for AF who recorded the results from minimum twice daily pulse checks and additionally with arrhythmia symptoms into a diary for 2 months following their procedure. Accuracy of this self-assessment protocol was determined by comparison to ICM-detected AF. RESULTS: A total of 55 patients (age 69 ± 8 years, 30 (55%) male, CHA2DS2VASc score 3.2 ± 1. 5) were included. Patients recorded a total of 5911 pulse checks, and there were 280 episodes of ICM-documented AF among 26 patients with an average duration of 2.5 ± 3.3 h. Among 362 episodes of patient-suspected AF, 134 correlated with ICM-identified AF (37% true positive rate). Of the 5549 pulse checks that did not identify AF, 196 correlated with ICM-identified AF (4% false negative rate). Twice daily pulse checking had a sensitivity of 47% and a specificity of 96% for identifying each episode of AF. CONCLUSIONS: Our data indicate that a strategy of pulse checks and symptom assessment is insufficient to identify all episodes of AF in many patients following catheter ablation.

Archaeological and molecular evidence for ancient chickens in Central Asia.

The origins and dispersal of the chicken across the ancient world remains one of the most enigmatic questions regarding Eurasian domesticated animals. The lack of agreement concerning timing and centers of origin is due to issues with morphological identifications, a lack of direct dating, and poor preservation of thin, brittle bird bones. Here we show that chickens were widely raised across southern Central Asia from the fourth century BC through medieval periods, likely dispersing along the ancient Silk Road. We present archaeological and molecular evidence for the raising of chickens for egg production, based on material from 12 different archaeological sites spanning a millennium and a half. These eggshells were recovered in high abundance at all of these sites, suggesting that chickens may have been an important part of the overall diet and that chickens may have lost seasonal egg-laying.

Is the Lung Built for Exercise? Advances and Unresolved Questions.

ABSTRACT: Nearly 40 yr ago, Professor Dempsey delivered the 1985 ACSM Joseph B. Wolffe Memorial Lecture titled: "Is the lung built for exercise?" Since then, much experimental work has been directed at enhancing our understanding of the functional capacity of the respiratory system by applying complex methodologies to the study of exercise. This review summarizes a symposium entitled: "Revisiting 'Is the lung built for exercise?'" presented at the 2022 American College of Sports Medicine annual meeting, highlighting the progress made in the last three-plus decades and acknowledging new research questions that have arisen. We have chosen to subdivide our topic into four areas of active study: (i) the adaptability of lung structure to exercise training, (ii) the utilization of airway imaging to better understand how airway anatomy relates to exercising lung mechanics, (iii) measurement techniques of pulmonary gas exchange and their importance, and (iv) the interactions of the respiratory and cardiovascular system during exercise. Each of the four sections highlights gaps in our knowledge of the exercising lung. Addressing these areas that would benefit from further study will help us comprehend the intricacies of the lung that allow it to meet and adapt to the acute and chronic demands of exercise in health, aging, and disease.

Characterization of the Lower Airways and Oral Microbiota in Healthy Young Persons in the Community.

Lower airway dysbiosis contributes to disease pathogenesis in respiratory diseases. However, little is known regarding the microbiota of lower airways or the oral cavity of healthy young persons. To address this gap, 25 healthy persons (24.3 ± 3.3 years; 52% females; no current smokers) underwent bronchoscopy during which bronchial brushing (BB) and bronchoalveolar lavage (BAL) fluid were collected. Prior to the procedure, an oral wash (OW) sample was also obtained. Microbiome analyses (16S rRNA locus) were performed (alpha- and beta-diversity, taxa annotations, and predicted functional metagenomic profiles) according to the airway compartment (BB, BAL, and OW). The greatest microbial richness was observed in OW and the lowest in BB (p < 0.001). Microbial communities differed significantly across compartments (p < 0.001), especially between BB and OW. Taxa analyses showed a significantly higher abundance of Firmicutes (BB: 32.7%; BAL: 31.4%) compared to OW (20.9%) (p < 0.001). Conversely, Proteobacteria predominated in OW (27.9%) as opposed to BB (7.0%) and BAL (12.5%) (p < 0.001), mostly due to a greater abundance of the bacteria in the Haemophilus genus in the OW (p < 0.001). The lower airway microbiota (BB and BAL) is significantly different from the OW microbiota in healthy young persons with respect to microbial diversity, taxa profiles, and predicted function.

Exercise-induced arterial hypoxemia in female masters athletes.

The purpose of the study was to characterize exercise induced arterial hypoxemia (EIAH) in female masters athletes (FMA). We hypothesized that FMA would experience EIAH during treadmill running. Eight FMA (48-57 years) completed pulmonary function testing and an incremental exercise test until exhaustion (V̇O2max⁡ = 45.7 ± 6.5, range:35-54 ml/kg/min). On a separate day, the participants were instrumented with a radial arterial catheter and an esophageal temperature probe. Participants performed three to four constant load exercise tests at 60-70 %, 75 %, 90 %, 95 %, and 100 % of maximal oxygen uptake while sampling arterial blood and recording esophageal temperature. We found that FMA decrease their partial pressure of oxygen (86.0 ± 7.6, range:73-108 mmHg), arterial saturation (96.2 ± 1.2, range:93-98 %), and widen their alveolar to arterial oxygen difference (23.2 ± 8.8, range:5-42 mmHg) during all exercise intensities however, with variability in terms of severity and pattern. Our findings suggest that FMA experience EIAH however aerobic fitness appears unrelated to occurrence or severity (r = 0.13, p = 0.756).

Durable Left Ventricular Assist Device Outflow Graft Obstructions: Clinical Characteristics and Outcomes.

PURPOSE: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center. METHODS: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported. RESULTS: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities. CONCLUSION: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting.

Chronotropic Incompetence after Heart Transplantation Is Associated with Increased Mortality and Decreased Functional Capacity.

INTRODUCTION: The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival. METHODS: We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan-Meier analysis. The optimal cut-off point for HRR was generated by Harrell's C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05. RESULTS: Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8-14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak VO2 and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96-0.99, p = 0.002). Using the optimal cut-off point generated by Harrell's C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012). CONCLUSION: In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

Leveraging palaeoproteomics to address conservation and restoration agendas.

Archaeological and paleontological records offer tremendous yet often untapped potential for examining long-term biodiversity trends and the impact of climate change and human activity on ecosystems. Yet, zooarchaeological and fossil remains suffer various limitations, including that they are often highly fragmented and morphologically unidentifiable, preventing them from being optimally leveraged for addressing fundamental research questions in archaeology, paleontology, and conservation paleobiology. Here, we explore the potential of palaeoproteomics-the study of ancient proteins-to serve as a critical tool for creating richer, more informative datasets about biodiversity change that can be leveraged to generate more realistic, constructive, and effective conservation and restoration strategies into the future.

Management of Type 2 Diabetes in Stage C Heart Failure with Reduced Ejection Fraction.

Type 2 diabetes is an increasingly common comorbidity of stage C heart failure with reduced ejection fraction (HFrEF). The two diseases are risk factors for each other and can bidirectionally independently worsen outcomes. The regulatory requirement of cardiovascular outcomes trials for antidiabetic agents has led to an emergence of novel therapies with robust benefits in heart failure, and clinicians must now ensure they are familiar with the management of patients with concurrent diabetes and stage C HFrEF. This review summarises the current evidence for the management of type 2 diabetes in stage C HFrEF, recapitulating data from landmark heart failure trials regarding the use of guideline-directed medical therapy for heart failure in patients with diabetes. It also provides a preview of upcoming clinical trials in these populations.