Objectives To comprehensively examine cardiovascular reserve function with exercise in patients with heart failure and preserved ejection fraction (HFpEF). Background Optimal exercise performance requires an integrated physiologic response, with coordinated increases in heart rate, contractility, lusitropy, arterial vasodilatation, endothelial function and venous return. Cardiac and vascular responses are coupled, and abnormalities in several components may interact to promote exertional intolerance in HFpEF. Methods Subjects with HFpEF (n=21), hypertension without heart failure (n=19) and no cardiovascular disease (control, n=10) were studied before and during exercise with characterization of cardiovascular reserve function by Doppler echocardiography, peripheral arterial tonometry and gas exchange. Results Exercise capacity and tolerance were reduced in HFpEF compared with hypertensives and controls, with lower VO2 and cardiac index at peak, and more severe dyspnea and fatigue at matched low-level workloads. Endothelial function was impaired in HFpEF and in hypertensives as compared with controls. However, blunted exercise-induced increases in chronotropy, contractility and vasodilation were unique to HFpEF and resulted in impaired dynamic ventricular-arterial coupling responses during exercise. Exercise capacity and symptoms of exertional intolerance were correlated with abnormalities in each component of cardiovascular reserve function, and HFpEF subjects were more likely to display multiple abnormalities in reserve. Conclusion HFpEF is characterized by depressed reserve capacity involving multiple domains of cardiovascular function, which contribute in an integrated fashion to produce exercise limitation. Appreciation of the global nature of reserve dysfunction in HFpEF will better inform optimal design for future diagnostic and therapeutic strategies.

No abstract

SUMMARY1. Twelve healthy subjects (33 + 3 years) with a variety of fitness levels (maximal oxygen uptake (VO2 max) = 61+4 ml kg-1 min-', range , exercised at 95 and 85 % V02, max to exhaustion (mean time = 14 + 3 and 31+8 min, expired ventilation (VE) over final minute of exercise = 149+9 and 126 + 10 1 min-').2. Bilateral transcutaneous supramaximal phrenic nerve stimulation (BPNS) was performed before and immediately after exercise at four lung volumes, and 400 ms tetanic stimulations were performed at 10 and 20 Hz. The coefficients of variation of repeated measurements for the twitch transdiaphragm pressures (Pdi) were +7-10 % and for compound muscle action potentials (M wave) ± 10-15 %. 5. The fPdi min-' and the fP. min-' (PO, oesophageal pressure) rose together from rest through the fifth to tenth minute of exercise, after which fPdi min-' plateaued even though fPO min-', VE and inspiratory flow rate all continued to rise substantially until exercise terminated. Thus, the relative contribution of the diaphragm to total respiratory motor output was progressively reduced with exercise duration.6. We conclude that significant diaphragmatic fatigue is caused by the ventilatory requirements imposed by heavy endurance exercise in healthy persons with a variety of fitness levels. The magnitude of the fatigue and the likelihood of its occurrence increases as the relative intensity of the exercise exceeds 85 % of V02 max,

AimsExercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF), yet its mechanisms remain unclear. The current study sought to determine whether increases in cardiac output (CO) during exercise are appropriately matched to metabolic demands in HFpEF. Methods and resultsPatients with HFpEF (n ¼ 109) and controls (n ¼ 73) exercised to volitional fatigue with simultaneous invasive (n ¼ 96) or non-invasive (n ¼ 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO 2 ) during upright or supine exercise. At rest, HFpEF patients had higher LV filling pressures but similar heart rate, stroke volume, EF, and CO. During supine and upright exercise, HFpEF patients displayed lower peak VO 2 coupled with blunted increases in heart rate, stroke volume, EF, and CO compared with controls. LV filling pressures increased dramatically in HFpEF patients, with secondary elevation in pulmonary artery pressures. Reduced peak VO 2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO 2 was 20% lower in HFpEF patients (5.9 + 2.5 vs. 7.4 + 2.6 L blood/L O 2 , P ¼ 0.0005). While absolute increases in arterial -venous O 2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial-venous O 2 difference relative to VO 2 was greater in HFpEF patients (8.9 + 3.4 vs. 5.5 + 2.0 min/dL, P , 0.0001). These differences were observed in the total cohort and when upright and supine exercise modalities were examined individually. ConclusionWhile diastolic dysfunction promotes congestion and pulmonary hypertension with stress in HFpEF, reduction in exercise capacity is predominantly related to inadequate CO relative to metabolic needs.--

We addressed two questions concerned with the metabolic cost and performance of respiratory muscles in healthy young subjects during exercise: 1) does exercise hyperpnea ever attain a "critical useful level"? and 2) is the work of breathing (WV) at maximum O2 uptake (VO2max) fatiguing to the respiratory muscles? During progressive exercise to maximum, we measured tidal expiratory flow-volume and transpulmonary pressure- (Ptp) volume loops. At rest, subjects mimicked their maximum and moderate exercise Ptp-volume loops, and we measured the O2 cost of the hyperpnea (VO2RM) and the length of time subjects could maintain reproduction of their maximum exercise loop. At maximum exercise, the O2 cost of ventilation (VE) averaged 10 +/- 0.7% of the VO2max. In subjects who used most of their maximum reserve for expiratory flow and for inspiratory muscle pressure development during maximum exercise, the VO2RM required 13-15% of VO2max. The O2 cost of increasing VE from one work rate to the next rose from 8% of the increase in total body VO2 (VO2T) during moderate exercise to 39 +/- 10% in the transition from heavy to maximum exercise; but in only one case of extreme hyperventilation, combined with a plateauing of the VO2T, did the increase in VO2RM equal the increase in VO2T. All subjects were able to voluntarily mimic maximum exercise WV for 3-10 times longer than the duration of the maximum exercise. We conclude that the O2 cost of exercise hyperpnea is a significant fraction of the total VO2max but is not sufficient to cause a critical level of "useful" hyperpnea to be achieved in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing the burden, to Department of Defense, Washington Headquarters Services, Directorate for Information 14. ABSTRACT The mechanics of uncemented soft sediments during bubble growth are not widely understood and no rheological model has found wide acceptance. We offer definitive evidence on the mode of bubble formation in the form of X-ray computed tomographic images and comparison with theory. Natural and injected bubbles in muddy cohesive sediments are shown to be highly eccentric oblate spheroids (disks) that grow either by fracturing the sediment or by reopening preexisting fractures. In contrast, bubbles in soft sandy sediment tend to be spherical, suggesting that sand acts fluidly or plastically in response to growth stresses. We also present bubble-rise results from gelatin, a mechanically similar but transparent medium, that suggest that initial rise is also accomplished ABSTRACT idization, e.g., gravity flows, during some natThe mechanics of uncemented soft sediments during bubble growth are not widely ural disturbances have suggested that such understood and no rheological model has found wide acceptance. We offer definitive ev-sediments can act fluidly or plastically in reidence on the mode of bubble formation in the form of X-ray computed tomographic sponse to stress. Past mechanical models of images and comparison with theory. Natural and injected bubbles in muddy cohesive bubbles in these sediments have visualized the sediments are shown to be highly eccentric oblate spheroids (disks) that grow either by bubbles as essentially spherical (e.g., Wheeler, fracturing the sediment or by reopening preexisting fractures. In contrast, bubbles in soft 1988; Sills et al., 1991), with the implication, sandy sediment tend to be spherical, suggesting that sand acts fluidly or plastically in intentional or not, that the surrounding mediresponse to growth stresses. We also present bubble-rise results from gelatin, a mechan-um reacts fluidly or plastically to their growth ically similar but transparent medium, that suggest that initial rise is also accomplished and rise. Scientists and engineers have develby fracture. Given that muddy sediments are elastic and yield by fracture, it becomes oped an impressive understanding of bubble much easier to explain physically related phenomena such as seafloor pockmark forma-growth in fluids, and a vast literature covers tion, animal burrowing, and gas buildup during methane hydrate melting.the topic (e.g., Clift et al., 1978; Lohse, 2003). However, we show here that muddy sediment Keywords: bubbles, mud, fracture, methane.does not respond mechanically either a...

No abstract

An open-circuit (OpCirc) acetylene uptake cardiac output (QT) method was modified for use during exercise. Two computational techniques were used. OpCirc1 was based on the integrated uptake vs. end-tidal change in acetylene, and OpCirc2 was based on an iterative finite difference modeling method. Six subjects [28-44 yr, peak oxygen consumption (VO(2)) = 120% predicted] performed cycle ergometry exercise to compare QT using OpCirc and direct Fick methods. An incremental protocol was repeated twice, separated by a 10-min rest, and subsequently subjects exercised at 85-90% of their peak work rate. Coefficient of variation of the OpCirc methods and Fick were highest at rest (OpCirc1, 7%, OpCirc2, 12%, Fick, 10%) but were lower at moderate to high exercise intensities (OpCirc1, 3%, OpCirc2, 3%, Fick, 5%). OpCirc1 and OpCirc2 QT correlated highly with Fick QT (R(2) = 0.90 and 0.89, respectively). There were minimal differences between OpCirc1 and OpCirc2 compared with Fick up to moderate-intensity exercise (<70% peak VO(2)); however, both techniques tended to underestimate Fick at >70% peak VO(2). These differences became significant for OpCirc1 only. Part of the differences between Fick and OpCirc methods at the higher exercise intensities are likely related to inhomogeneities in ventilation and perfusion matching (R(2) = 0.36 for Fick - OpCirc1 vs. alveolar-to-arterial oxygen tension difference). In conclusion, both OpCirc methods provided reproducible, reliable measurements of QT during mild to moderate exercise. However, only OpCirc2 appeared to approximate Fick QT at the higher work intensities.