Respiratory mechanical effects of surgical pneumoperitoneum in humans.

Pneumoperitoneum for laparoscopic surgery is known to stiffen the chest wall and respiratory system, but its effects on resting pleural pressure in humans are unknown. We hypothesized that pneumoperitoneum would raise abdominal pressure, push the diaphragm into the thorax, raise pleural pressure, and squeeze the lung, which would become stiffer at low volumes as in severe obesity. Nineteen predominantly obese laparoscopic patients without pulmonary disease were studied supine (level), under neuromuscular blockade, before and after insufflation of CO2 to a gas pressure of 20 cmH2O. Esophageal pressure (Pes) and airway pressure (Pao) were measured to estimate pleural pressure and transpulmonary pressure (Pl = Pao - Pes). Changes in relaxation volume (Vrel, at Pao = 0) were estimated from changes in expiratory reserve volume, the volume extracted between Vrel, and the volume at Pao = -25 cmH2O. Inflation pressure-volume (Pao-Vl) curves from Vrel were assessed for evidence of lung compression due to high Pl. Respiratory mechanics were measured during ventilation with a positive end-expiratory pressure of 0 and 7 cmH2O. Pneumoperitoneum stiffened the chest wall and the respiratory system (increased elastance), but did not stiffen the lung, and positive end-expiratory pressure reduced Ecw during pneumoperitoneum. Contrary to our expectations, pneumoperitoneum at Vrel did not significantly change Pes [8.7 (3.4) to 7.6 (3.2) cmH2O; means (SD)] or expiratory reserve volume [183 (142) to 155 (114) ml]. The inflation Pao-Vl curve above Vrel did not show evidence of increased lung compression with pneumoperitoneum. These results in predominantly obese subjects can be explained by the inspiratory effects of abdominal pressure on the rib cage.

Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity.

To explore mechanisms of restrictive respiratory physiology and high pleural pressure (P(Pl)) in severe obesity, we studied 51 obese subjects (body mass index = 38-80.7 kg/m(2)) and 10 nonobese subjects, both groups without lung disease, anesthetized, and paralyzed for surgery. We measured esophageal and gastric pressures (P(Es), P(Ga)) using a balloon-catheter, airway pressure (P(AO)), flow, and volume. We compared P(Es) to another estimate of P(Pl) based on P(AO) and flow. Reasoning that the lungs would not inflate until P(AO) exceeded alveolar and pleural pressures (P(AO) > P(Alv) > P(Pl)), we disconnected subjects from the ventilator for 10-15 s to allow them to reach relaxation volume (V(Rel)) and then slowly raised P(AO) until lung volume increased by 10 ml, indicating the "threshold P(AO)" (P(AO-Thr)) for inflation, which we took to be an estimate of the lowest P(Alv) or P(Pl) to be found in the chest at V(Rel). P(AO-Thr) ranged from 0.6 to 14.0 cmH2O in obese and 0.2 to 0.9 cmH2O in control subjects. P(Es) at V(Rel) was higher in obese than control subjects (12.5 +/- 3.9 vs. 6.9 +/- 3.1 cmH2O, means +/- SD; P = 0.0002) and correlated with P(AO-Thr) (R(2) = 0.16, P = 0.0015). Respiratory system compliance (C(RS)) was lower in obese than control (0.032 +/- 0.008 vs. 0.053 +/- 0.007 l/cmH2O) due principally to lower lung compliance (0.043 +/- 0.016 vs. 0.084 +/- 0.029 l/cmH2O) rather than chest wall compliance (obese 0.195 +/- 0.109, control 0.223 +/- 0.132 l/cmH2O). We conclude that many severely obese supine subjects at relaxation volume have positive P(pl) throughout the chest. High P(Es) suggests high P(Pl) in such individuals. Lung and respiratory system compliances are low because of breathing at abnormally low lung volumes.

Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress?

Acute lung injury can be worsened by inappropriate mechanical ventilation, and numerous experimental studies suggest that ventilator-induced lung injury is increased by excessive lung inflation at end inspiration or inadequate lung inflation at end expiration. Lung inflation depends not only on airway pressures from the ventilator but, also, pleural pressure within the chest wall. Although esophageal pressure (Pes) measurements are often used to estimate pleural pressures in healthy subjects and patients, they are widely mistrusted and rarely used in critical illness. To assess the credibility of Pes as an estimate of pleural pressure in critically ill patients, we compared Pes measurements in 48 patients with acute lung injury with simultaneously measured gastric and bladder pressures (Pga and P(blad)). End-expiratory Pes, Pga, and P(blad) were high and varied widely among patients, averaging 18.6 +/- 4.7, 18.4 +/- 5.6, and 19.3 +/- 7.8 cmH(2)O, respectively (mean +/- SD). End-expiratory Pes was correlated with Pga (P = 0.0004) and P(blad) (P = 0.0104) and unrelated to chest wall compliance. Pes-Pga differences were consistent with expected gravitational pressure gradients and transdiaphragmatic pressures. Transpulmonary pressure (airway pressure - Pes) was -2.8 +/- 4.9 cmH(2)O at end exhalation and 8.3 +/- 6.2 cmH(2)O at end inflation, values consistent with effects of mediastinal weight, gravitational gradients in pleural pressure, and airway closure at end exhalation. Lung parenchymal stress measured directly as end-inspiratory transpulmonary pressure was much less than stress inferred from the plateau airway pressures and lung and chest wall compliances. We suggest that Pes can be used to estimate transpulmonary pressures that are consistent with known physiology and can provide meaningful information, otherwise unavailable, in critically ill patients.

Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival.

Dendritic cells (DCs) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DCs (dDCs and rDCs, respectively) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDCs to recipient lymphoid tissues as early as 3 h post-islet allotransplantation. Compared with rDCs, dDCs express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDCs undergo during islet cell preparation and engraftment. Intriguingly, we detected dDCs in the spleen of recipients long after rejection of islet allografts. Given that dDCs express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDCs from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDCs and rDCs as two distinct types of DCs and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival.