Redistribution of blood flow and lung volume between lungs in lateral decubitus postures during unilateral atelectasis and PEEP

The effect of left lung atelectasis on the regional distribution of blood flow (Q), ventilation (V(A)) and gas exchange on the right lung ventilated with 100% O2 was studied in anesthetized dogs in the lateral decubitus posture. Q and V(A) were measured in 1.7 ml lung volume pieces using injected and aerosolized fluorescent microspheres, respectively. Hypoxic pulmonary vasoconstriction (HPV) in the atelectatic lung shifted flow to the ventilated lung. The increased flow in the ventilated lung ensured adequate gas exchange, compensating for the hypoxemia due to shunt contributed by the atelectatic lung. Left lung atelectasis caused a compensatory increase in the ventilated lung FRC that was smaller in the right (RLD) than left (LLD) lateral posture, the effect of lung compression by the atelectatic lung and mediastinal contents in the RLD posture. The O2 deficit measured by (A-a)DO2 increased with left lung atelectasis and was exacerbated in the LLD posture by 10 cm H2O PEEP, a result of increased shunt caused by a shift in Q from the ventilated to the atelectatic lung. The PEEP-induced O2 deficit was eliminated with inversion to the RLD posture.     

Effects of recruitment maneuvers with PEEP on lung volume distribution in canine models of direct and indirect lung injury

Lung recruitment maneuvers can help open collapsed lung units for sufficient oxygenation, and positive end expiratory pressure (PEEP) is used to keep the lung open after recruitment. However, the application of high PEEP levels may play a significant role in causing regional lung hyperinflation during mechanical ventilation. The authors sought to study the effects of PEEP targeting optimal oxygenation on regional lung volume distribution in a direct and an indirect acute respiratory distress syndrome (ARDS) model. ARDS was induced by either surfactant depletion or oleic acid injection in dogs. After lung recruitment, PEEP was decreased from 20 to 10 cmH₂O in 2 cmH₂O steps every 10 min to examine regional lung aeration by using computed tomography. Lung injury appeared to be localized in the model of surfactant depletion while it widely diffused after oleic acid infusion. At PEEP levels that achieved optimal oxygenation, nonaerated lung units decreased and normally aerated lung units enhanced, but hyperinflated areas increased significantly in both models (P < 0.05). Hyperinflated areas were greater in the surfactant depletion model than in the oleic acid model at PEEP levels applied (P < 0.05). Optimal oxygenation guided PEEP may cause hyperinflated in both focal lung injury and diffused lung injury post lung recruitment. Hyperinflation was more susceptible in focal lung injury than in diffused lung injury post lung recruitment.     

Spatial distribution of ventilation and perfusion in anesthetized dogs in lateral postures.

We aimed to assess the influence of lateral decubitus postures and positive end-expiratory pressure (PEEP) on the regional distribution of ventilation and perfusion. We measured regional ventilation (VA) and regional blood flow (Q) in six anesthetized, mechanically ventilated dogs in the left (LLD) and right lateral decubitus (RLD) postures with and without 10 cmH(2)O PEEP. Q was measured by use of intravenously injected 15-microm fluorescent microspheres, and VA was measured by aerosolized 1-microm fluorescent microspheres. Fluorescence was analyzed in lung pieces approximately 1.7 cm(3) in volume. Multiple linear regression analysis was used to evaluate three-dimensional spatial gradients of Q, VA, the ratio VA/Q, and regional PO(2) (Pr(O(2))) in both lungs. In the LLD posture, a gravity-dependent vertical gradient in Q was observed in both lungs in conjunction with a reduced blood flow and Pr(O(2)) to the dependent left lung. Change from the LLD to the RLD or 10 cmH(2)O PEEP increased local VA/Q and Pr(O(2)) in the left lung and minimized any role of hypoxia. The greatest reduction in individual lung volume occurred to the left lung in the LLD posture. We conclude that lung distortion caused by the weight of the heart and abdomen is greater in the LLD posture and influences both Q and VA, and ultimately gas exchange. In this respect, the smaller left lung was the most susceptible to impaired gas exchange in the LLD posture.     

Effects of body posture and tidal volume on inter- and intraregional ventilation distribution in healthy men.

The influences of body posture and tidal volume (VT) on inter- and intraregional ventilation inhomogeneity were assessed by normalized phase III slope (Sn(III)) analysis of multiple-breath washout recordings of SF(6) and He in 11 healthy men. Washouts with target VT of 750, 1,000, and 1,250 ml were performed standing and supine. A linear-fit method was used to establish the contributions of convection-dependent (interregional) (cdi) and diffusion-convection interaction-dependent (intraregional) inhomogeneity (dcdi). Overall inhomogeneity was defined as the sum of cdi and dcdi. The difference in first-breath Sn(III) for SF(6) vs. He, the (SF(6) - He)Sn(III), served as an index of intra-acinar inhomogeneity. Multiple-regression analysis revealed greater cdi supine vs. standing (P < 0.001) but no significant effects of posture on dcdi or overall inhomogeneity. Larger VT were associated with greater cdi (P < 0.001), particularly when supine, but reduced dcdi (P < 0.001), overall inhomogeneity (P < 0.001), and (SF(6) - He)Sn(III) (P = 0.031). In conclusion, during resting breathing overall and intraregional ventilation inhomogeneities remain unchanged when the supine posture is assumed and improve with larger VT, but supine posture and larger breaths result in greater interregional inhomogeneities.     

Marked differences between prone and supine sheep in effect of PEEP on perfusion distribution in zone II lung.

The classic four-zone model of lung blood flow distribution has been questioned. We asked whether the effect of positive end-expiratory pressure (PEEP) is different between the prone and supine position for lung tissue in the same zonal condition. Anesthetized and mechanically ventilated prone (n = 6) and supine (n = 5) sheep were studied at 0, 10, and 20 cm H2O PEEP. Perfusion was measured with intravenous infusion of radiolabeled 15-microm microspheres. The right lung was dried at total lung capacity and diced into pieces (approximately 1.5 cm3), keeping track of the spatial location of each piece. Radioactivity per unit weight was determined and normalized to the mean value for each condition and animal. In the supine posture, perfusion to nondependent lung regions decreased with little relative perfusion in nondependent horizontal lung planes at 10 and 20 cm H2O PEEP. In the prone position, the effect of PEEP was markedly different with substantial perfusion remaining in nondependent lung regions and even increasing in these regions with 20 cm H2O PEEP. Vertical blood flow gradients in zone II lung were large in supine, but surprisingly absent in prone, animals. Isogravitational perfusion heterogeneity was smaller in prone than in supine animals at all PEEP levels. Redistribution of pulmonary perfusion by PEEP ventilation in supine was largely as predicted by the zonal model in marked contrast to the findings in prone. The differences between postures in blood flow distribution within zone II strongly indicate that factors in addition to pulmonary arterial, venous, and alveolar pressure play important roles in determining perfusion distribution in the in situ lung. We suggest that regional variation in lung volume through the effect on vascular resistance is one such factor and that chest wall conformation and thoracic contents determine regional lung volume.     

High in comparison with low tidal volume ventilation aggravates oxidative stress-induced lung injury

Ventilator settings influence the development and outcome of acute lung injury. This study investigates the influence of low versus high tidal volume (V(t)) on oxidative stress-induced lung injury.Isolated rabbit lungs were subjected to one of three ventilation patterns (V(t)-positive end-expiratory pressure, PEEP): LVZP (6 ml/kg-0 cm H(2)O), HVZP (12 ml/kg-0 cm H(2)O), LV5P (6 ml/kg-5 cm H(2)O). These ventilation patterns allowed a comparison between low and high V(t) without dependence on peak inspiratory pressure (PIP). Infusion of hypochlorite (1000 nmol/min) or buffer (control) was started at t=0 min. Pulmonary artery pressure (PAP), PIP and weight were continuously recorded. Capillary filtration coefficient [K(f,c) (10(-4) ml s(-1) cm H(2)O(-1) g(-1))] was gravimetrically determined (-15/30/60/90/120 min).PIP averaged 5.8+/-0.6/13.9+/-0.6/13.9+/-0.4 cm H(2)O in the LVZP, HVZP and LV5P groups. PIP, K(f,c) or PAP did not change in control groups, indicating that none of the ventilation patterns caused lung injury by themselves. Hypochlorite-induced increase in K(f,c) but not hypochlorite-induced increase in PAP, was significantly attenuated in the LVZP-/LV5P- versus the HVZP-group (K(f,c,max.) 1.0+/-0.23/1.4+/-0.40 versus 3.2+/-1.0*). Experiments with hypochlorite were terminated due to excessive edema (>50 g) at 97+/-2.2/94.5+/-4.5 min in the LVZP-/LV5P-group versus 82+/-3.8* min in the HVZP-group (*: P<0.05).Low V(t) attenuated oxidative stress-induced increase in vascular permeability independently from PIP and PEEP.     

Ventilation in conscious dogs during acute and chronic hypercapnia.

Minute ventilation was measured in conscious dogs, at rest and during exercise (1 mph), over 60 min immediately following the acute inhalation of 5% carbon dioxide in air and at 2, 4, 7, and 14 days while breathing the same gas mixture in a chamber. The dogs were also studied in the immediate period of air recovery from chronic hypercapnia and 1 day later. Control studies were carried out with the dogs breathing air in the chamber under comparable conditions. A triphasic ventilation change was ovserved in dogs at rest over the 14 days of hypercapnia. After an initial marked increase in ventilation during acute hypercapnia, ventilation returned to control levels by 2 days and then appeared to be elevated above control studies from 4 to 14 days at a time when blood acid-base balance became compensated. When the same dogs were studied during exercise, ventilation was also not different from air control at 2 days of hypercapnia; however during exercise, unlike the resting studies, there was only a tendency for a secondary increase in ventilation at 7 and 14 days of hypercapnia. During the immediate recovery from chronic hypercapnia when the dogs breathed air there was no evidence of hypoventilation either at rest or exercise despite arterial alkalosis. At 24 h of recovery it appeared that dogs while at rest had a slightly reduced ventilatory response to 5% carbon dioxide relative to control studies. The findings provide suggestive evidence that other factors, in addition to acid-base balance, might contribute to the regulation of ventilation during chronic hypercapnia and the recovery from chronic hypercapnia.     

Accuracy of tidal volume, lung volume, and flow measurements by inductance vest in COPD patients

We analyzed the accuracy of the inductance vest in measuring several ventilatory parameters in five patients with chronic obstructive pulmonary disease (COPD). We assessed tidal volume (VT) accuracy at different respiratory frequencies in different lying body positions with different thoracic and abdominal contributions to breathing and the accuracy over a 4-h time span. Mean percent error was calculated without regard to direction of error. The mean error of vest VT estimation was 7.6% for all body positions studied and 5.6% for right and left lateral positions combined. Vest VT accuracy was unchanged after 4 h and with changes in thoracic and abdominal contributions to VT. The mean errors for inspiratory and expiratory times were 3.3 and 2.0%, respectively. Volume was differentiated to flow. For respiratory rates ranging from 12 to 30 breaths/min, the mean error of the vest and our differentiation circuit in duplicating peak flows measured at the mouth was 3.5%. The ability of the vest to estimate changes in end-expiratory position or functional residual capacity was not as good as with VT; the mean error was 30.7%. For estimation of VT, ventilatory timing, and airflow in COPD patients, the inductance vest performs well. For measurement of changes in lung volume, improvements in vest design need to be made.     

Relationship of central and peripheral airway resistance to lung volume in dogs

We could not reconcile reported relationships between lung resistance measurements and lung volume with bronchographic and anatomic studies showing that airway diameters change monotonically with lung volume and that small airways change diameter proportionately at least as much as large ones. Accordingly we measured central and peripheral airways resistances with a new technique. The relevant pressures were measured with a tracheal cannula, a wedged retrograde catheter, and two parenchymal needles in seven open-chested dogs while pleural pressure was oscillated at 1 Hz. In contrast to previous studies, the volume dependency of peripheral resistance was at least as great as that of central resistance with vagi intact, the volume dependencies of central and peripheral resistances were not abolished by vagotomy, and neither resistance increased systematically at high volumes. Volume dependency of central resistance resembled predictions for isotropic expansion of airways with vagi cut but increased with bronchomotor tone. These results fit generally with bronchographic data. Previous studies may have been affected by volume dependency due to "tissue resistance" and catheter phase lags.     

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.