Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.     

Effects of inspiratory resistance loading on lung fluid balance in awake sheep

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.     

Determinants of gas flow through a bronchopleural fistula

To assess the determinants of bronchopleural fistula (BPF) flow, we used a surgically created BPF to study 15 anesthetized intubated mechanically ventilated New Zealand White rabbits. Mean airway pressure and intrathoracic pressure were evaluated independently. Mean airway pressure was varied (8, 10, or 12 cmH2O) by independent manipulations of either peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Intrathoracic pressure was varied from 0 to -40 cmH2O. BPF flow varied directly with mean airway pressure (P less than 0.001). However, at constant mean airway pressure, BPF flow was not influenced independently by changes in peak inspiratory pressure, positive end-expiratory pressure, or inspiratory time. Resistance of the BPF increased as intrathoracic pressure became more negative. Despite increased resistance, BPF flow also increased. BPF resistance was constant over the range of mean airway (P less than 0.01) pressures investigated. Our data document the influence of mean airway pressure and intrathoracic pressure on BPF flow and suggest that manipulations which reduce transpulmonary pressure will decrease BPF flow.     

Expiratory threshold loading impairs cardiovascular function in health and chronic heart failure during submaximal exercise.

We determined the effects of augmented expiratory intrathoracic pressure (P(ITP)) production on cardiac output (Q(TOT)) and blood flow distribution in healthy dogs and dogs with chronic heart failure (CHF). From a control expiratory P(ITP) excursion of 7 +/- 2 cmH2O, the application of 5, 10, or 15 cmH2O expiratory threshold loads increased the expiratory P(ITP) excursion by 47 +/- 23, 67 +/- 32, and 118 +/- 18% (P < 0.05 for all). Stroke volume (SV) rapidly decreased (onset <10 s) with increases in the expiratory P(ITP) excursion (-2.1 +/- 0.5%, -2.4 +/- 0.9%, and -3.6 +/- 0.7%, P < 0.05), with slightly smaller reductions in Q(TOT) (0.8 +/- 0.6, 1.0 +/- 1.1, and 1.8 +/- 0.8%, P < 0.05) owing to small increases in heart rate. Both Q(TOT) and SV were restored to control levels when the inspiratory P(ITP) excursion was augmented by the addition of an inspiratory resistive load during 15 cmH2O expiratory threshold loading. The highest level of expiratory loading significantly reduced hindlimb blood flow by -5 +/- 2% owing to significant reductions in vascular conductance (-7 +/- 2%). After the induction of CHF by 6 wk of rapid cardiac pacing at 210 beats/min, the expiratory P(ITP) excursions during nonloaded breathing were not significantly changed (8 +/- 2 cmH2O), and the application of 5, 10, and 15 cmH2O expiratory threshold loads increased the expiratory P(ITP) excursion by 15 +/- 7, 23 +/- 7, and 31 +/- 7%, respectively (P < 0.05 for all). Both 10 and 15 cmH2O expiratory threshold loads significantly reduced SV (-3.5 +/- 0.7 and -4.2 +/- 0.7%, respectively) and Q(TOT) (-1.7 +/- 0.4 and -2.5 +/- 0.4%, P < 0.05) after the induction of CHF, with the reductions in SV predominantly occurring during inspiration. However, the augmentation of the inspiratory P(ITP) excursion now elicited further decreases in SV and Q(TOT). Only the highest level of expiratory loading significantly reduced hindlimb blood flow (-4 +/- 2%) as a result of significant reductions in vascular conductance (-5 +/- 2%). We conclude that increases in expiratory P(ITP) production-similar to those observed during severe expiratory flow limitation-reduce cardiac output and hindlimb blood flow during submaximal exercise in health and CHF.     

Head-down bed rest alters sympathetic and cardiovascular responses to mental stress

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.     

Effects of lung inflation and blood flow on capillary transit time in isolated rabbit lungs.

In a previous study, direct measurements of pulmonary capillary transit time by fluorescence video microscopy in anesthetized rabbits showed that chest inflation increased capillary transit time and decreased cardiac output. In isolated perfused rabbit lungs we measured the effect of lung volume, left atrial pressure (Pla), and blood flow on capillary transit time. At constant blood flow and constant transpulmonary pressure, a bolus of fluorescent dye was injected into the pulmonary artery and the passage of the dye through the subpleural microcirculation was recorded via the video microscope on videotape. During playback of the video signals, the light emitted from an arteriole and adjacent venule was measured using a video photoanalyzer. Capillary transit time was the difference between the mean time values of the arteriolar and venular dye dilution curves. We measured capillary transit time in three groups of lungs. In group 1, with airway pressure (Paw) at 5 cmH2O, transit time was measured at blood flow of approximately 80, approximately 40, and approximately 20 ml.min-1.kg-1. At each blood flow level, Pla was varied from 0 (Pla less than Paw, zone 2) to 11 cmH2O (Pla greater than Paw, zone 3). In group 2, at constant Paw of 15 cmH2O, Pla was varied from 0 (zone 2) to 22 cmH2O (zone 3) at the same three blood flow levels. In group 3, at each of the three blood flow levels, Paw was varied from 5 to 15 cmH2O while Pla was maintained at 0 cmH2O (zone 2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep

We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/- 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml-1.min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of encouraged water drinking on thermoregulatory responses after 20 days of head-down bed rest in humans

We tested the hypothesis that encouraged water drinking according to urine output for 20 days could ameliorate impaired thermoregulatory function under microgravity conditions. Twelve healthy men, aged 24 ± 1.5 years (mean ± SE), underwent −6° head-down bed rest (HDBR) for 20 days. During bed rest, subjects were encouraged to drink the same amount of water as the 24-h urine output volume of the previous day. A heat exposure test consisting of water immersion up to the knees at 42°C for 45 min after a 10 min rest (baseline) in the sitting position was performed 2 days before the 20-day HDBR (PRE), and 2 days after the 20-day HDBR (POST). Core temperature (tympanic), skin temperature, skin blood flow and sweat rate were recorded continuously. We found that the −6° HDBR did not increase the threshold temperature for onset of sweating under the encouraged water drinking regime. We conclude that encouraged water drinking could prevent impaired thermoregulatory responses after HDBR.     

Effect of dehydration on interstitial pressures in the isolated dog lung

We have determined the effect of dehydration on regional lung interstitial pressures. We stopped blood flow in the isolated blood-perfused lobe of dog lung at vascular pressure of approximately 4 cmH2O. Then we recorded interstitial pressures by micropuncture at alveolar junctions (Pjct), in perimicrovascular adventitia (Padv), and at the hilum (Phil). After base-line measurements, we ventilated the lobes with dry gas to decrease extravascular lung water content by 14 +/- 5%. In one group (n = 10), at constant inflation pressure of 7 cmH2O, Pjct was 0.2 +/- 0.8 and Padv was -1.5 +/- 0.6 cmH2O. After dehydration the pressures fell to -5.0 +/- 1.0 and -5.3 +/- 1.3 cmH2O, respectively (P less than 0.01), and the junction-to-advential gradient (Pjct-Padv) was abolished. In a second group (n = 6) a combination of dehydration and lung expansion with inflation pressure of 15 cmH2O further decreased Pjct and Padv to -7.3 +/- 0.7 and -7.1 +/- 0.7 cmH2O, respectively. Phil followed changes in Padv. Interstitial compliance was 0.6 at the junctions, 0.8 in adventitia, and 0.9 ml.cmH2O-1.100 g-1 wet lung at the hilum. We conclude, that perialveolar interstitial pressures may provide an important mechanism for prevention of lung dehydration.     

Pressure-flow behavior of pulmonary interstitium

A method to measure the pressure-flow behavior of the interstitium around large pulmonary vessels is presented. Isolated rabbit lungs were degassed, and the air spaces and vasculature were inflated with a silicon rubber compound. After the rubber had hardened the caudal lobes were sliced into 1-cm-thick slabs. Two chambers were bonded to opposite sides of a slab enclosing a large blood vessel and were filled with saline containing 3 g/dl albumin. The flow through the interstitium surrounding the vessel was measured at a constant driving pressure of 5 cmH2O and at various mean interstitial pressures. Flow decreased with a reduction of mean interstitial pressure and reached a limiting minimum value at approximately -9 cmH2O. The pressure-flow behavior was analyzed under the assumptions that the interstitium is a porous material described by a single permeability constant that increases with hydration and that the expansion of the interstitium with interstitial pressure was due to the elastic response of the surrounding rubber compound. This resulted in an interstitial resistance (reciprocal of permeability constant) of 1.31 +/- 1.03 (SD) cmH2O.h.cm-2 and a ratio of interstitial cuff thickness to vessel radius of 0.022 +/- 0.007 (SD), n = 11. The phenomenon of flow limitation was demonstrated by holding the upstream pressure constant at 15 cmH2O and measuring the flow while the downstream pressure was reduced. The flow was limited at downstream pressures below -10 cmH2O.     

Effects of simulated natural air movement on thermoregulatory response during head-down bed rest

Spaceflight and its bed rest analog impair thermoregulatory responses, including elevated core temperature observed at rest and during exercise. Natural air flow has been found to increase cold sensation significantly compared to artificial constant air flow (CAF). The present study tested the hypothesis that simulated natural air flow (SNAF) ventilation would ameliorate impaired thermoregulatory function to a greater extent than CAF under simulated microgravity conditions. Seven healthy males underwent 30 days of −6° head-down bed rest (HDBR). During pre-HDBR and the day 29 of HDBR (HDBR 29), the subjects were exposed to three air flow patterns at 23 °C while in a supine posture: a still air flow control (CON), CAF, and SNAF. The mean air velocity of the latter two patterns was 0.2 m/s. Subjective perception of the thermal environment was recorded by thermal sensation vote (TSV), and rectal temperature (T_re), skin temperature (T_sk), and cutaneous vascular conductance (CVC) were also measured during the sessions. T_re was significantly elevated after 29 days of HDBR and decreased to a greater extent in SNAF than in CAF on HDBR 29. However, there was no significant difference between T_re in SNAF on HDBR 29 and that in CON on pre-HDBR. Mean T_sk, CVC, and TSV in SNAF were also significantly lower than those in CAF on HDBR 29. Moreover, TSV was close to ‘neutral’ under SNAF on HDBR 29. These data indicate that simulated natural air movement might be more effective than constant air movement at preserving core temperature at a thermoneutral ambient temperature during HDBR.     

Changes in tracheal cross-sectional area during Mueller and Valsalva maneuvers in humans

Pressure-area behavior of the excised trachea is well documented, but little is known of tracheal compliance in vivo. Extratracheal tissue pressures are not directly measurable, but transmural pressure for the intrathoracic trachea is inferred from intra-airway and pleural pressure differences. Extramural pressure of the cervical trachea is assumed to be atmospheric. The difference in transmural pressure between the intra- and extrathoracic tracheal segments should be exaggerated during Mueller and Valsalva maneuvers. We used the acoustic reflection technique to measure tracheal areas above and below the thoracic inlet during these isovolume-pressure maneuvers. We found that 10 cmH2O positive pressure increased tracheal area in the extrathoracic segment by 34 +/- 16% (mean +/- SD) and in the intrathoracic segment by 35 +/- 15%. There was a reduction in area of 27 +/- 16 and 24 +/- 14%, respectively, for the extra- and intrathoracic segments with 10 cmH2O negative pressure. We conclude that the effective transmural pressure gradients do not vary significantly between intra- and extrathoracic tracheal segments.     

Differential effect of recruitment maneuvres on pulmonary blood flow and oxygenation during HFOV in preterm lambs.

The effects of lung volume recruitment manouvres on pulmonary blood flow (PBF) during high-frequency oscillatory ventilation (HFOV) in preterm neonates are unknown. Since increased airway pressure adversely affects PBF, we compared the effects of two HFOV recruitment strategies on PBF and oxygenation index (OI). Preterm lambs (128+/-1 day gestation; term approximately 150 days) were anesthetized and ventilated using HFOV (10 Hz, 33% tI) with a mean airway pressure (Pao) of 15 cmH2O. Lung volume was recruited by either increasing Pao to 25 cmH2O for 1 min, repeated five times at 5-min intervals (Sigh group; n=5) or stepwise (5 cmH2O) changes in Pao at 5-min intervals incrementing up to 30 cmH2O then decrementing back to 15 cmH2O (Ramp group; n=6). Controls (n=5) received constant HFOV at 15 cmH2O. PBF progressively decreased (by 45+/-4%) and OI increased (by 15+/-6%, indicating reduced oxygenation) in controls during HFOV, which was similar to the changes observed in the Sigh group of lambs. In the Ramp group, PBF fell (by 54+/-10%) as airway pressure increased (r2=0.99), although the PBF did not increase again as the Pao was subsequently reduced. The OI decreased (by 47+/-9%), reflecting improved oxygenation at high Pao levels during HFOV in the Ramp group. However, high Pao restored retrograde PBF during diastole in four of six lambs, indicating the restoration of right-to-left shunting through the ductus arteriosus. Thus the choice of volume recruitment maneuvre influences the magnitude of change in OI and PBF that occurs during HFOV. Despite significantly improving OI, the ramp recruitment approach causes sustained changes in PBF.     

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans.

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.     

Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90-110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of airway and left atrial pressures on microcirculation of newborn lungs

To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular-interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions.     

Flow characteristics of open vessels in zone 1 rabbit lungs

To describe the flow characteristics of vessels open in zone 1, we perfused isolated rabbit lungs with Tyrode's solution containing 1% albumin, 4% dextran, and papaverine (0.05 mg/ml). Lungs were expanded by negative pleural pressure (Ppl) of -10, -15, -20, and -25 cmH2O. Pulmonary arterial (Ppa) and venous (Ppv) pressures were varied relative to alveolar pressure (PA = 0) and measured 5-10 mm inside the pleura (i) and outside (o) of the lungs. With Ppa(o) at -2.5 cmH2O, we constructed pressure-flow (P-Q) curves at each Ppl by lowering Ppv(o) until Q reached a maximum, indicating fully developed zone 1 choke flow. Maximum flows were negligible until Ppl fell below -10 cmH2O, then increased rapidly at Ppl of -15 and -20 cmH2O, and at Ppl of -25 cmH2O reached about 15 ml.min-1.kg body wt-1. The Ppv(o) at which flow became nearly constant depended on degree of lung inflation and was 5-8 cmH2O more positive than Ppl. As Ppv(o) was lowered below Ppa(o), Ppv(i) remained equal to Ppv(o) until Ppv(i) became fixed at a pressure 2-3 cmH2O more positive than Ppl. At this point the choke flow was therefore located in veins near the pleural boundary. No evidence of choke flow (only ohmic resistance) was seen in the intrapulmonary segment of the vessels remaining open in zone 1. With Ppv(o) held roughly at Ppl, Q could be stopped by lowering Ppa(o), at which time Ppa(i) was several cmH2O above Ppv(i), showing that intrapulmonary vessel closure had occurred.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Lung expansion and the perialveolar interstitial pressure gradient

We have determined the combined effects of lung expansion and increased extravascular lung water (EVLW) on the perialveolar interstitial pressure gradient. In the isolated perfused lobe of dog lung, we measured interstitial pressures by micropuncture at alveolar junctions (Pjct) and in adventitia of 30- to 50-microns microvessels (Padv) with stopped blood flow at vascular pressure of 3-5 cmH2O. We induced edema by raising vascular pressures. In nonedematous lobes (n = 6, EVLW = 3.1 +/- 0.3 g/g dry wt) at alveolar pressure of 7 cmH2O, Pjct averaged 0.5 +/- 0.8 (SD) cmH2O and the Pjct-Padv gradient averaged 0.9 +/- 0.5 cmH2O. After increase of alveolar pressure to 23 cmH2O the gradient was abolished in nonedematous lobes, did not change in moderately edematous lobes (n = 9, EVLW = 4.9 +/- 0.6 g/g dry wt), and increased in severely edematous lobes (n = 6, EVLW = 7.6 +/- 1.4 g/g dry wt). Perialveolar interstitial compliance decreased with increase of alveolar pressure. We conclude that increase of lung volume may reduce perialveolar interstitial liquid clearance by abolishing the Pjct-Padv gradient in nonedematous lungs and by compressing interstitial liquid channels in edematous lungs.     

Lung overexpansion increases pulmonary microvascular protein permeability in young lambs

To study the effects of inflation pressure and tidal volume (VT) on protein permeability in the neonatal pulmonary microcirculation, we measured lung vascular pressures, blood flow, lymph flow (QL), and concentrations of protein in lymph (L) and plasma (P) of 22 chronically catheterized lambs that received mechanical ventilation at various peak inflation pressures (PIP) and VT. Nine lambs were ventilated initially with a PIP of 19 +/- 1 cmH2O and a VT of 10 +/- 1 ml/kg for 2-4 h (base line), after which we overexpanded their lungs with a PIP of 58 +/- 3 cmH2O and a VT of 48 +/- 4 ml/kg for 4-8 h. QL increased from 2.1 +/- 0.4 to 13.9 +/- 5.0 ml/h. L/P did not change, but the ratio of albumin to globulin in lymph relative to the same ratio in plasma decreased, indicating altered protein sieving in the pulmonary microcirculation. Seven other lambs were mechanically ventilated for 2-4 h at a PIP of 34 +/- 1 cmH2O and a VT of 23 +/- 2 ml/kg (base line), after which their chest and abdomen were bound so that PIP increased to 54 +/- 1 cmH2O for 4-6 h without a change in VT. QL decreased on average from 2.8 +/- 0.6 to 1.9 +/- 0.3 ml/h (P = 0.08), and L/P was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)