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Biomedical subjects

J B West

Publications and source records attributed to J B West.

At least 19 recordsLinked to original sources
PubMed1995

Vulnerability of pulmonary capillaries in heart disease.

The pulmonary blood-gas barrier presents a dilemma. It must be extremely thin for efficient gas exchange. However, it also needs to be immensely strong because the stresses in the pulmonary capillary wall become extremely high when the capillary pressure rises. Stress failure of the capillaries occurs in several pathological conditions. It causes high-permeability edema as in neurogenic pulmonary edema or high-altitude pulmonary edema; alveolar hemorrhage, which occurs in all galloping racehorses; or a combination of the two as in severe congestive heart failure. The vulnerability of the capillary wall to increased mechanical stress has not previously been sufficiently appreciated.

Animals↗
PubMed1995

Pulmonary microvascular permeability. Responses to high vascular pressure after induction of pacing-induced heart failure in dogs.

The pressure threshold for injury of pulmonary capillaries is approximately 50 to 55 cm H2O in the canine lung, as measured by changes in the filtration coefficient (Kf,c). Since the pulmonary endothelial basement membrane has been observed to thicken in patients with heart failure and pulmonary venous hypertension, we hypothesized that both baseline permeability and the threshold for high-vascular-pressure injury would be altered as a result. Dogs (n = 12) were chronically paced at 245 beats per minute for approximately 4 weeks, then were paced at 225 beats per minute for an additional 3 weeks. Lung lobes from anesthetized paced dogs and additional control dogs (n = 14) were then isolated, ventilated, and perfused with blood. Although vascular resistance was increased nearly threefold and vascular compliance reduced by 50% in the paced group, Kf,c referenced to 1 g blood-free dry weight was no different from control. Despite this lack of difference at normal pulmonary vascular pressures, several significant results were obtained. First, in the paced group there was a significant increase in the threshold for high-vascular-pressure injury: Kf,c measured at pulmonary vascular pressures commonly seen in heart failure (20 to 50 cm H2O) were significantly less in this group compared with control. Model predictions showed that in vivo, this difference in Kf,c would result in a 50% reduction in the amount of water and protein cleared across the pulmonary capillary endothelial barrier in the paced group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Pathogenesis of high-altitude pulmonary oedema: direct evidence of stress failure of pulmonary capillaries.

The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed. Recent reports show a strong correlation between the occurrence of HAPE and pulmonary artery pressure, and it is known that the oedema is of the high-permeability type. We have, therefore, proposed that HAPE is caused by ultrastructural damage to pulmonary capillaries as a result of stress failure of their walls. However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal models are difficult to find. Madison strain Sprague-Dawley rats show a brisk pulmonary pressure response to acute hypoxia and are susceptible to HAPE. We exposed 13 Madison rats to a pressure of 294 torr for up to 12.5 h, or 4 rats to 236 torr for up to 8 h. Pulmonary arterial or right ventricular systolic pressures measured with a catheter increased from 30.5 +/- 0.5 (SEM) in controls (n = 4) to 48 +/- 2 torr (n = 11). The lungs were fixed for electron microscopy with intravascular glutaraldehyde. Frothy bloodstained fluid was seen in the trachea of three animals. Ultrastructural examination showed evidence of stress failure of pulmonary capillaries, including disruption of the capillary endothelial layer, or all layers of the wall, swelling of the alveolar epithelial layer, red blood cells (RBCs) and oedematous fluid in the alveolar wall interstitium, proteinaceous fluid and RBCs in the alveolar spaces, and fluid-filled protrusions of the endothelium into the capillary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude Sickness↗
PubMed1992

Stress failure of pulmonary capillaries: role in lung and heart disease.

Pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently it has been shown that the wall stresses become very large when the capillary pressure is raised, and in anaesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mm Hg and above. The changes include breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. The strength of the thin part of the capillary wall can be attributed to the type IV collagen in the extracellular matrix. Stress failure of pulmonary capillaries results in a high-permeability form of oedema, or even frank haemorrhage, and is apparently the mechanism of neurogenic pulmonary oedema and high-altitude pulmonary oedema. It also explains the exercise-induced pulmonary haemorrhage that occurs in all racehorses. Several features of mitral stenosis are consistent with stress failure. Overinflation of the lung also leads to stress failure, a common cause of increased capillary permeability in the intensive care environment. Stress failure also occurs if the type IV collagen of the capillary wall is weakened by autoantibodies as in Goodpasture's syndrome. Neutrophil elastase degrades type IV collagen and this may be the starting point of the breakdown of alveolar walls that is characteristic of emphysema. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in lung and heart disease.

Animals↗
PubMed1992

Stress failure of pulmonary capillaries in the intensive care setting.

Recent work shows that when the pressure in pulmonary capillaries is raised to high levels, ultrastructural changes occur in their walls including disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. Since the calculated wall stresses are extremely high, this condition is referred to as stress failure, and it results in a high permeability type of pulmonary edema, or even frank hemorrhage. Stress failure is believed to play a part in diseases where the capillary pressure is abnormally high, such as neurogenic pulmonary edema, high altitude pulmonary edema, exercise-induced pulmonary hemorrhage in racehorses, and perhaps some cases of the adult respiratory distress syndrome. Stress failure also occurs if the blood-gas barrier is weakened as in Goodpasture's syndrome. Another important cause is overinflation of the lung as may occur with mechanical ventilation and high inflation pressures. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in the intensive care setting.

Altitude Sickness↗
PubMed1992

High altitude pulmonary edema is caused by stress failure of pulmonary capillaries.

The pathogenesis of high altitude pulmonary edema (HAPE) is disputed. We propose that the mechanism is stress failure of pulmonary capillaries. The main features to be accounted for are the strong association with pulmonary hypertension, the high permeability characteristics of the edema, and the presence of inflammatory markers in the lung lavage fluid. When the capillary pressure is raised to about 40 mmHg in anesthetized rabbits, ultrastructural damage to the capillary walls is seen including breaks in the capillary endothelial layer, alveolar epithelial layer, and sometimes all layers of the wall. This results in a high permeability form of edema with the escape of high molecular weight proteins and blood cells into the alveolar spaces. In addition the basement membrane of the endothelial layer is frequently exposed, and we suggest that this highly reactive surface attracts and activates platelets and neutrophils. The result is the formation of small thrombi which are frequently seen in HAPE, and the presence of inflammatory markers such as leukotriene B4 and the complement fragment C5a in the lung lavage fluid. Hypoxic pulmonary vasoconstriction raises the pressure in some capillaries because the constriction is uneven. Since HAPE has its origin in the high pulmonary artery pressure, the objective of treatment should be to reduce the pressure by descent, administering oxygen, or giving drugs such as calcium channel blockers (e.g. nifedipine) which relax pulmonary vasoconstriction. Stress failure of pulmonary capillaries satisfactorily accounts for the features of HAPE.

Altitude Sickness↗
PubMed1992

Effects of inspired CO2, hyperventilation, and time on VA/Q inequality in the dog.

In a recent study by Tsukimoto et al. (J. Appl. Physiol. 68: 2488-2493, 1990), CO2 inhalation appeared to reduce the size of the high ventilation-perfusion ratio (VA/Q) mode commonly observed in anesthetized mechanically air-ventilated dogs. In that study, large tidal volumes (VT) were used during CO2 inhalation to preserve normocapnia. To separate the influences of CO2 and high VT on the VA/Q distribution in the present study, we examined the effect of inspired CO2 on the high VA/Q mode using eight mechanically ventilated dogs (4 given CO2, 4 controls). The VA/Q distribution was measured first with normal VT and then with increased VT. In the CO2 group at high VT, data were collected before, during, and after CO2 inhalation. With normal VT, there was no difference in the size of the high VA/Q mode between groups [10.5 +/- 3.5% (SE) of ventilation in the CO2 group, 11.8 +/- 5.2% in the control group]. Unexpectedly, the size of the high VA/Q mode decreased similarly in both groups over time, independently of the inspired PCO2, at a rate similar to the fall in cardiac output over time. The reduction in the high VA/Q mode together with a simultaneous increase in alveolar dead space (estimated by the difference between inert gas dead space and Fowler dead space) suggests that poorly perfused high VA/Q areas became unperfused over time. A possible mechanism is that elevated alveolar pressure and decreased cardiac output eliminate blood flow from corner vessels in nondependent high VA/Q regions.

Animals↗
PubMed1992

Life in space.

Explore the source record for details and available documents.

Biological Science Disciplines↗
PubMed1992

High lung volume increases stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.

Air Pressure↗
PubMed1992

Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure.

We previously showed that when the pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to determine whether some of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. To test this, the Ptm was raised to 52.5 cmH2O for 1 min of blood perfusion and then reduced to 12.5 cmH2O for 3 min of saline-dextran perfusion, followed by intravascular fixation at the same pressure. In another group of animals, the pressure was elevated for 1 min of blood and 3 min of saline-dextran before being reduced. The results were compared with previous studies in which the capillary pressures were maintained elevated at 52.5 cmH2O during the entire procedure. Control studies were also done at sustained low pressures. The results showed that the number of endothelial and epithelial breaks per millimeter and the total fraction area of the breaks were reduced when the pressure was lowered. For example, the number of endothelial breaks per millimeter decreased from 7.1 +/- 2.1 to 2.4 +/- 0.7, and the number of epithelial breaks per millimeter fell from 11.4 +/- 3.7 to 3.4 +/- 0.7. There was evidence that the breaks that closed were those that were initially small and were associated with an intact basement membrane. The results suggest that cells can move along their underlying matrix by rapid disengagement and reattachment of cell adhesion molecules, causing breaks to open or close within minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Stress failure of alveolar epithelial cells studied by scanning electron microscopy.

Stress failure of capillary walls has previously been demonstrated in anesthetized rabbit lungs at high capillary transmural pressures, and the ultrastructural changes in the walls have been described with transmission electron microscopy. In the present study, the pattern of alveolar epithelial disruptions was studied using scanning electron microscopy (SEM). Lungs of anesthetized rabbits were perfused with autologous blood at capillary transmural pressures of 12.5, 32.5, 52.5, and 72.5 +/- 2.5 cm H2O and fixed by intravascular perfusion. Samples for SEM were processed by critical point-drying and freeze-drying, and the results of the two techniques agreed well. Out of a total of 433 alveolar epithelial breaks examined, 93% were elongated, with the remainder being roughly circular; 68% of the elongated breaks were oriented perpendicular to the capillary axis, suggesting that the surface tension of the alveolar lining layer played an important role in protecting the blood-gas barrier against stress failure. Most of the breaks involved the full blood-gas barrier, but 17% were limited to the epithelial cells. This finding is consistent with our earlier conclusion that the extracellular matrix, particularly the type IV collagen, is responsible for much of the strength of the blood-gas barrier. The dimensions of the elongated breaks of the epithelium were approximately 4 microns (length) and 1 micron (width). They varied little with pressure, suggesting that once the disruption had occurred the stresses were greatly relieved. Breaks affecting the complete blood-gas barrier tended to be larger than those confined to the epithelium, again consistent with the protective role of the extracellular matrix. Almost no breaks occurred at intercellular junctions although many were seen within 1 micron of the junctions. This finding suggests that the junctions themselves have considerable mechanical strength, but that their rigidity may make the cell in the vicinity of the junction more vulnerable to mechanical failure.

Animals↗
PubMed1992

Pulmonary function in microgravity.

We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non-gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS)

Gravitation↗
PubMed1991

Stress failure in pulmonary capillaries.

In the mammalian lung, alveolar gas and blood are separated by an extremely thin membrane, despite the fact that mechanical failure could be catastrophic for gas exchange. We raised the pulmonary capillary pressure in anesthetized rabbits until stress failure occurred. At capillary transmural pressures greater than or equal to 40 mmHg, disruption of the capillary endothelium and alveolar epithelium was seen in some locations. The three principal forces acting on the capillary wall were analyzed. 1) Circumferential wall tension caused by the transmural pressure. This is approximately 25 dyn/cm (25 mN/m) at failure where the radius of curvature of the capillary is 5 microns. This tension is small, being comparable with the tension in the alveolar wall associated with lung elastic recoil. 2) Surface tension of the alveolar lining layer. This contributes support to the capillaries that bulge into the alveolar spaces at these high pressures. When protein leakage into the alveolar spaces occurs because of stress failure, the increase in surface tension caused by surfactant inhibition could be a powerful force preventing further failure. 3) Tension of the tissue elements in the alveolar wall associated with lung inflation. This may be negligible at normal lung volumes but considerable at high volumes. Whereas circumferential wall tension is low, capillary wall stress at failure is very high at approximately 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2) where the thickness is only 0.3 microns. This is approximately the same as the wall stress of the normal aorta, which is predominantly composed of collagen and elastin. The strength of the thin part of the capillary wall is probably attributable to the collagen IV of the basement membranes. The safety factor is apparently small when the capillary pressure is raised during heavy exercise. Stress failure causes increased permeability with protein leakage, or frank hemorrhage, and probably has a role in several types of lung disease.

Animals↗
PubMed1991

Maximum expiratory flow-volume curves during short periods of microgravity.

To elucidate the effect of normal gravitation on the shape of the maximum expiratory flow-volume (MEFV) curve, we studied nine normal subjects in a National Aeronautics and Space Administration microgravity research aircraft. They performed multiple MEFV maneuvers at 0, 1, and approximately 2 G. The MEFV curves for each subject were filtered, aligned at residual volume, and ensemble averaged to produce an average MEFV curve for each state, allowing differences to be studied. Most subjects showed a decrease in the forced vital capacity at 0 G, which we attribute to an increased intrathoracic blood volume. In most of these subjects, the mean lung volume associated with a given flow was lower at 0 G over about the upper half of the vital capacity. This is similar to the change previously reported during headout immersion and is consistent with the known effect of engorgement of the lung with blood on elastic recoil. There were also consistent but highly individual changes in the position and magnitude of detailed features of the curve, the individual patterns being similar to those previously reported on transition from the erect to the supine position. This supports the idea that the location and motion of choke points that determine the detailed individual configuration of MEFV curves can be significantly influenced by gravitational forces, presumably via the effects of change in longitudinal tension on local airway pressure-diameter behavior and thus wave speed.

Adult↗
PubMed1991

Ultrastructural appearances of pulmonary capillaries at high transmural pressures.

Electronmicroscopic appearances of pulmonary capillaries were studied in rabbit lungs perfused in situ when the capillary transmural pressure (Ptm) was systematically raised from 12.5 to 72.5 +/- 2.5 cmH2O. The animals were anesthetized and exsanguinated, and after the chest was opened, the pulmonary artery and left atrium were cannulated and attached to reservoirs. The lungs were perfused with autologous blood for 1 min, and this was followed by saline-dextran and then buffered glutaraldehyde to fix the lungs for electron microscopy. Normal appearances were seen at 12.5 cmH2O Ptm. At 52.5 and 72.5 cmH2O Ptm, striking discontinuities of the capillary endothelium and alveolar epithelium were seen. A few disruptions were seen at 32.5 cmH2O Ptm (mostly in one animal), but the number of breaks per millimeter cell lining increased markedly up to 72.5 cmH20 Ptm, where the mean frequency was 27.8 +/- 8.6 and 13.6 +/- 1.4 (SE) breaks/mm for endothelium and epithelium, respectively. In some instances, all layers of the blood-gas barrier were disrupted and erythrocytes could be seen moving into the alveolar spaces. In about half the endothelial and epithelial breaks, the basement membranes remained intact. The average break lengths for both endothelium and epithelium did not change significantly with pressure. The width of the blood-gas barrier increased at 52.5 and 72.5 cmH2O Ptm as a result of widening of the interstitium caused by edema. The cause of the disruptions is believed to be stress failure of the capillary wall. The results show that high capillary hydrostatic pressures cause major changes in the ultrastructure of the walls of the capillaries, leading to a high-permeability form of edema.

Animals↗