The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.

In vivo radioactive tracer and microsphere studies have differing conclusions as to the magnitude of the gravitational effect on the distribution of pulmonary blood flow. We hypothesized that some of the apparent vertical perfusion gradient in vivo is due to compression of dependent lung increasing local lung density and therefore perfusion/volume. To test this, six normal subjects underwent functional magnetic resonance imaging with arterial spin labeling during breath holding at functional residual capacity, and perfusion quantified in nonoverlapping 15 mm sagittal slices covering most of the right lung. Lung proton density was measured in the same slices using a short echo 2D-Fast Low-Angle SHot (FLASH) sequence. Mean perfusion was 1.7 +/- 0.6 ml x min(-1) x cm(-3) and was related to vertical height above the dependent lung (slope = -3%/cm, P < 0.0001). Lung density averaged 0.34 +/- 0.08 g/cm3 and was also related to vertical height (slope = -4.9%/cm, P < 0.0001). By contrast, when perfusion was normalized for regional lung density, the slope of the height-perfusion relationship was not significantly different from zero (P = 0.2). This suggests that in vivo variations in regional lung density affect the interpretation of vertical gradients in pulmonary blood flow and is consistent with a simple conceptual model: the lung behaves like a Slinky (Slinky is a registered trademark of Poof-Slinky Incorporated), a deformable spring distorting under its own weight. The greater density of lung tissue in the dependent regions of the lung is analogous to a greater number of coils in the dependent portion of the vertically oriented spring. This implies that measurements of perfusion in vivo will be influenced by density distributions and will differ from excised lungs where density gradients are reduced by processing.

To minimize transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus responsible for coronavirus disease (COVID-19), the U.S. Centers for Disease Control and Prevention and the World Health Organization recommend wearing face masks in public. Some have expressed concern that these may affect the cardiopulmonary system by increasing the work of breathing, altering pulmonary gas exchange and increasing dyspnea, especially during physical activity. These concerns have been derived largely from studies evaluating devices intentionally designed to severely affect respiratory mechanics and gas exchange. We review the literature on the effects of various face masks and respirators on the respiratory system during physical activity using data from several models: cloth face coverings and surgical masks, N95 respirators, industrial respirators, and applied highly resistive or high–dead space respiratory loads. Overall, the available data suggest that although dyspnea may be increased and alter perceived effort with activity, the effects on work of breathing, blood gases, and other physiological parameters imposed by face masks during physical activity are small, often too small to be detected, even during very heavy exercise. There is no current evidence to support sex-based or age-based differences in the physiological responses to exercise while wearing a face mask. Although the available data suggest that negative effects of using cloth or surgical face masks during physical activity in healthy individuals are negligible and unlikely to impact exercise tolerance significantly, for some individuals with severe cardiopulmonary disease, any added resistance and/or minor changes in blood gases may evoke considerably more dyspnea and, thus, affect exercise capacity.

The blood-gas barrier must be very thin to allow gas exchange and it is therefore subjected to high mechanical stresses when the capillary pressure rises. In some animals, such as the thoroughbred race-horse during intense exercise, the stresses are so large that the capillaries fail and bleeding occurs. We tested the hypothesis that, in elite human athletes, the high capillary pressure that occurs during severe exercise alters the structure and function of the blood-gas barrier. We performed bronchoalveolar lavage (BAL) in six healthy athletes, who had a history suggestive of lung bleeding, 1 h after a 7-min cycling race simulation and four normal sedentary control subjects who did not exercise before BAL. The athletes had higher (p < 0.05) concentrations of red blood cells (0.51 x 10(5) versus 0.01 x 10(5).ml-1), total protein (128.0 versus 94.1 micrograms/ml), albumin (65.6 versus 53.0 micrograms/ml), and leukotriene B4 (LTB4) (243 versus 0 pg/ml) in BAL fluid than control subjects. The proportion of neutrophils was similar in athletes and control subjects but the proportion of lymphocytes in BAL fluid was reduced (p < 0.05). There were no differences in levels of surfactant apoprotein A, tumor necrosis factor bioactivity, lipopolysaccharide, or interleukin-8 (IL-8) between groups. These results show that brief intense exercise in athletes with a history suggestive of lung bleeding alters blood-gas barrier function resulting in higher concentrations of red cells and protein in BAL fluid. The lack of activation of proinflammatory pathways (except LTB4) in the airspaces supports the hypothesis that the mechanism for altered blood-gas barrier function is mechanical stress.

Uneven hypoxic pulmonary vasoconstriction has been proposed to expose parts of the pulmonary capillary bed to high pressure and vascular injury in high-altitude pulmonary edema (HAPE). We hypothesized that subjects with a history of HAPE would demonstrate increased heterogeneity of pulmonary blood flow during hypoxia. A functional magnetic resonance imaging technique (arterial spin labeling) was used to quantify spatial pulmonary blood flow heterogeneity in three subject groups: (1) HAPE-susceptible (n = 5), individuals with a history of physician-documented HAPE; (2) HAPE-resistant (n = 6), individuals with repeated high-altitude exposure without illness; and (3) unselected (n = 6), individuals with a minimal history of altitude exposure. Data were collected in normoxia and after 5, 10, 20, and 30 minutes of normobaric hypoxia FI(O(2)) = 0.125. Relative dispersion (SD/mean) of the signal intensity was used as an index of perfusion heterogeneity. Oxygen saturation was not different between groups during hypoxia. Relative dispersion was not different between groups (HAPE-susceptible 0.94 +/- 0.05, HAPE-resistant 0.94 +/- 0.05, unselected 0.87 +/- 0.06; means +/- SEM) during normoxia, but it was increased by hypoxia in HAPE-susceptible (to 1.10 +/- 0.05 after 30 minutes, p < 0.0001) but not in HAPE-resistant (0.91 +/- 0.05) or unselected subjects (0.87 +/- 0.05). HAPE-susceptible individuals have increased pulmonary blood flow heterogeneity in acute hypoxia, consistent with uneven hypoxic pulmonary vasoconstriction.

Purpose:To evaluate lung water density at three different levels of lung inflation in normal lungs using a fast gradient echo sequence developed for rapid imaging. Materials and Methods:Ten healthy volunteers were imaged with a fast gradient echo sequence that collects 12 images alternating between two closely spaced echoes in a single 9-s breathhold. Data were fit to a single exponential to determine lung water density and T* 2 . Data were evaluated in a single imaging slice at total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV). Analysis of variance for repeated measures was used to statistically evaluate changes in T* 2 and lung water density across lung volumes, imaging plane, and spatial locations in the lung. Results:In normal subjects (n ϭ 10), T* 2 (and [lung density/ water density]) was 1.2 Ϯ 0.1 msec (0.10 Ϯ 0.02), 1.8 Ϯ 0.2 ms (0.25 Ϯ 0.04), and 2.0 Ϯ 0.2 msec (0.27 Ϯ 0.03) at TLC, FRC, and RV, respectively. Results also show that there is a considerable intersubject variability in the values of T* 2 .Conclusion: Data show that T* 2 in the lung is very short, and varies considerably with lung volume. Thus, if quantitative assessment of lung density within a breathhold is to be measured accurately, then it is necessary to also determine T* 2 .

Henderson AC, Sá RC, Theilmann RJ, Buxton RB, Prisk GK, Hopkins SR. The gravitational distribution of ventilation-perfusion ratio is more uniform in prone than supine posture in the normal human lung. J Appl Physiol 115: 313-324, 2013. First published April 25, 2013 doi:10.1152/japplphysiol.01531.2012.-The gravitational gradient of intrapleural pressure is suggested to be less in prone posture than supine. Thus the gravitational distribution of ventilation is expected to be more uniform prone, potentially affecting regional ventilation-perfusion (V A/Q ) ratio. Using a novel functional lung magnetic resonance imaging technique to measure regional V A/Q ratio, the gravitational gradients in proton density, ventilation, perfusion, and V A/Q ratio were measured in prone and supine posture. Data were acquired in seven healthy subjects in a single sagittal slice of the right lung at functional residual capacity. Regional specific ventilation images quantified using specific ventilation imaging and proton density images obtained using a fast gradient-echo sequence were registered and smoothed to calculate regional alveolar ventilation. Perfusion was measured using arterial spin labeling. Ventilation (ml·min Ϫ1 ·ml Ϫ1 ) images were combined on a voxel-by-voxel basis with smoothed perfusion (ml·min Ϫ1 ·ml Ϫ1 ) images to obtain regional V A/Q ratio. Data were averaged for voxels within 1-cm gravitational planes, starting from the most gravitationally dependent lung. The slope of the relationship between alveolar ventilation and vertical height was less prone than supine (Ϫ0.17 Ϯ 0.10 ml·min, P ϭ 0.02) as was the slope of the perfusion-height relationship (Ϫ0.14 Ϯ 0.05 ml·min, P ϭ 0.02). There was a significant gravitational gradient in V A/Q ratio in both postures (P Ͻ 0.05) that was less in prone (0.09 Ϯ 0.08 cm Ϫ1 supine, 0.04 Ϯ 0.03 cm Ϫ1 prone, P ϭ 0.04). The gravitational gradients in ventilation, perfusion, and regional V A/Q ratio were greater supine than prone, suggesting an interplay between thoracic cavity configuration, airway and vascular tree anatomy, and the effects of gravity on V A/Q matching. magnetic resonance imaging; arterial spin labeling; specific ventilation imaging; ventilation-perfusion ratio; gravity WHILE THE LUNG HAS A NUMBER of functions, it is primarily a gas exchange organ. 1 Ventilation-perfusion (V A/Q ) matching, such that regions of the lung that receive fresh gas also receive deoxygenated capillary blood, is the most important mechanism determining gas exchange efficiency (53). Although several mechanisms are thought to accomplish V A/Q matching in the healthy lung (see Ref. 18 for review), it is thought that passive mechanisms dominate under normal conditions. Such passive mechanisms include vascular branching structure and the effect of gravity on ventilation and perfusion (53).Modeling studies suggest that, because of the shape of the lungs within the thorax, the gradient of intrapleural pressures is more uniform in prone posture compared with supine (48). This predicts that the g...

When freed from central cardiorespiratory limitations, healthy human skeletal muscle has exhibited a significant metabolic reserve. We studied the existence of this reserve in 10 severely compromised (FEV1 = 0.97 +/- SE 0.01) patients with chronic obstructive pulmonary disease (COPD). To manipulate O2 supply and O2 demand in locomotor and respiratory muscles, subjects performed both maximal conventional two-legged cycle ergometry (large muscle mass) and single-leg knee extensor exercise (KE, small muscle mass) while breathing room air (RA), 100% O2, and 79% helium + 21% O2 (HeO2). With each gas mixture, peak ventilation, peak heart rate, and perceived breathlessness were lower in KE than cycle exercise (p < 0. 05). Arterial O2 saturation and maximal work capacity increased in both exercise modalities while subjects breathed 100% O2 (work: +10% bike, +25% KE, p < 0.05). HeO2 increased maximal work capacity on the cycle (+14%, p < 0.05) but had no effect on KE. HeO2 resulted in the greatest maximum minute ventilation in both bike and KE (p < 0. 05) but had no effect on arterial O2 saturation. Thus, a skeletal muscle metabolic reserve in these patients with COPD is evidenced by: (1) greater muscle mass specific work in KE; (2) greater work rates with higher fraction of inspired oxygen (FIO2); (3) an even greater effect of FIO2 during KE (i.e., when the lungs are less challenged); and (4) the positive effect of HeO2 on bicycle work rate. This skeletal muscle metabolic reserve suggests that reduced whole body exercise capacity in COPD is the result of central restraints rather than peripheral skeletal muscle dysfunction, while the beneficial effect of 100% O2 (with no change in maximum ventilation) suggests that the respiratory system is not the sole constraint to oxygen consumption.