Alveolar-arterial Oxygen Partial Pressure Difference Research Articles

Effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery

ObjectiveThis research aimed to ascertain the effect of dexmedetomidine on pulmonary function in obese patients undergoing laparoscopic surgery.MethodsObese patients undergoing laparoscopic surgery under general anesthesia were separated into the control group (group C) and the dexmedetomidine group (group D) (n = 30). Patients in group D were infused with dexmedetomidine (1 μg/kg) intravenously for 10 min and then at a rate of 0.5 mg/kg h until 30 min before the end of the surgery, and those in group C were infused with an equal volume of saline. The surgery time points were divided into: before anesthesia induction (T0), 5 min after intubation (T1), 30 min after pneumoperitoneum (T2), 10 min after pneumoperitoneum release (T3), at the time of extubation (T4), 3 min after extubation (T5), and 24 h after surgery (T6). Arterial blood was collected for blood gas analysis to record arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2). Dynamic lung compliance (Cdyn), oxygenation index (OI), alveolar-arterial oxygen partial pressure difference (A-aDO2), and respiratory index (RI) were calculated. The time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation were recorded. Plasma IL-8 and IL-10 levels were measured from T0 to T6.ResultsThe time of surgery, anesthesia, CO2 pneumoperitoneum, eye-opening, and time from the end of surgery to extubation in group D were not statistically significant when compared with those in group C. Versus at the T1 time point, A-aDO2 and RI were higher and Cdyn and OI were lower in both groups at T2 and T3 time points. Versus group C, group D had higher Cdyn and OI and lower A-aDO2 and RI at T2 and T3 time points. Versus at the T0 time point, at each time point from T1 to T6, IL-8 and IL-10 levels were higher in both groups. Versus group C, group D had lower IL-8 and higher IL-10 levels at each time point from T1 to T6.ConclusionIn obese patients undergoing laparoscopic surgery under general anesthesia, the use of dexmedetomidine can improve the lung compliance and OI of the patients, inhibit the inflammatory response of the lungs of the patients and thus have a certain protective effect on the lung function.

Parecoxib sodium alleviates ischemia reperfusion-induced pulmonary injury via inhibiting ERK/NF-κB and further activating the HIF-1α pathway.

IntroductionThe lungs are extremely vulnerable to ischemia/reperfusion (I/R), which is characterized by intense inflammation, oxidative stress, alveolar damage, and vascular permeability. Parecoxib sodium (Pare) has been shown to exert protective effects against multiple I/R‐induced tissue injuries. However, its role in I/R‐induced lung injury remains unknown. This study aimed to reveal the roles and mechanisms of Pare in pulmonary I/R injury.MethodsSixty‐six rats were randomly divided into three groups: The sham‐operated group, the pulmonary I/R group, and the Pare‐pretreated I/R group. Pare at 10 mg/kg or saline (vehicle control) were intraperitoneally administered to rats once per day for 5 consecutive days before ischemia. Serum and tissue samples were harvested following 2 h of reperfusion. The oxygenation index (OI) and alveolar‐arterial oxygen partial pressure difference (PA‐aO2) were analyzed. The levels or activities of malondialdehyde, superoxidase dismutase, catalase, glutathione peroxidase, intracellular reactive oxygen species, tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐8 were examined. The mitochondrial membrane potential was measured. The protein expression levels of the extracellular signal‐regulated kinase (ERK), nuclear factor‐κB (NF‐κB) and their phosphorylated forms, and hypoxia‐inducible factor‐1α (HIF‐1α) were detected. Histological changes were observed using hematoxylin and eosin staining. Moreover, the survival rate following pulmonary I/R injury was recorded daily.ResultsPare significantly increased the OI, decreased the PA‐aO2, increased the levels of antioxidants, while decreasing the levels of oxidants, and alleviated mitochondrial dysfunction and the histopathological damage induced by I/R. Furthermore, Pare inhibited the expression of proinflammatory cytokines, suppressed the activation of ERK and NF‐κB, further increased HIF‐1α expression, and significantly improved the rat survival rate.ConclusionsPare pretreatment attenuated lung I/R injury by inhibiting oxidative stress and the inflammatory response possibly via inhibiting the activation of the ERK/NF‐κB pathway and further activating the HIF‐1α pathway.

Parecoxib mitigates lung ischemia-reperfusion injury in rats by reducing oxidative stress and inflammation and up-regulating HO-1 expression.

ABSTRACTPurpose:To investigate the protective effect of parecoxib against lung ischemia-reperfusion injury (LIRI) in rats and the mechanism.Methods:Thirty rats were divided into sham-operated, LIRI and LIRI+parecoxib groups. LIRI model (ischemia for 60 min, followed by reperfusion for 120 min) was constructed in LIRI and LIRI+parecoxib groups. In LIRI+parecoxib group, 10 mg/kg parecoxib was given via femoral vein 15 min before ischemia beginning. At the end of the reperfusion, blood gas analysis, lung wet to dry mass ratio measurement, lung tissue biochemical determination and heme oxygenase-1 (HO-1) protein expression determination were performed.Results:Compared with LIRI group, in LIRI+parecoxib group the oxygenation index was significantly increased, the alveolar-arterial oxygen partial pressure difference was significantly decreased, the lung wet to dry mass ratio was significantly decreased, the lung tissue malondialdehyde content was significantly decreased, the lung tissue superoxide dismutase and myeloperoxidase activities were significantly increased, the lung tissue tumor necrosis factor α and interleukin 1β levels were significantly decreased, and the lung tissue HO-1 protein expression level was significantly increased (all P < 0.05).Conclusions:Parecoxib pretreatment can mitigate the LIRI in rats by reducing oxidative stress, inhibiting inflammatory response and up-regulating HO-1 expression in lung tissue.

Effect of Goal-Directed Fluid Therapy on Lung Function, Cognitive Function and Inflammatory Response in Patients Undergoing Radical Esophageal Cancer Surgery under One-Lung Ventilation

Objective: To explore the effects of goal-directed fluid therapy (GDFT) on lung function, cognitive function and inflammatory response in patients undergoing radical esophageal cancer surgery under one-lung ventilation. Methods: Sixty-seven patients undergoing radical esophageal cancer surgery were divided into GDFT group (GDFT therapy) and control group (conventional liquid therapy). The changes in patients’ pulmonary function, cognitive function and inflammatory response were evaluated. Results: Both alveolar-arterial oxygen partial pressure difference [P(A-a)O2] and respiratory index (RI) increased at one-lung ventilation for 30 minutes (T2) and decreased at one-lung ventilation for 60 minutes (T3), and after surgery (T4) in the two groups, and the GDFT group was lower than the control group (P 0.05); theoxygenation index (OI) of the two groups decreased at T2, T3, and T4 compared with that at T1 (before one-lung ventilation), and the GDFT group was higher than the control group (P 0.05). At T4 and T5, the tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), central nervous system specific protein (S100β), and neuron specific enolase (NSE) in the GDFT group were lower compared to the control group (P 0.05), while interleukin-10 (IL-10) was higher compared to the control group (P 0.05); the incidence of perioperative neurocognitive disorder (PND) in the GDFT group was lower than that in the control group (P 0.05). Conclusion: GDFT can help prevent lung injury during radical esophageal cancer surgery under one-lung ventilation, reduce the body’s inflammatory response, and reduce the incidence of perioperative cognitive disorder to a certain extent.

Effect of Dexmedetomidine on Postoperative Lung Injury during One-Lung Ventilation in Thoracoscopic Surgery.

Objective To investigate the effect of dexmedetomidine on postoperative lung injury in patients undergoing thoracoscopic surgery. Methods From March 2019 to October 2019, 40 patients were randomly divided into two groups: dexmedetomidine group (group D) and control group (group C). Except recording the general condition of the patients in both groups preoperatively and intraoperatively, the oxygenation index (OI) and alveolar-arterial oxygen partial pressure difference (A-aDO2) were monitored at admission (T0), immediately after one-lung ventilation (T1), 0.5 h after one-lung ventilation (T2), and 15 minutes after inhaling air before leaving the room (T3). The content of IL-8 in arterial blood was measured by enzyme-linked immunosorbent assay (ELISA) at T0 and T2, and the expression of AQP1 protein in isolated lung tissue was measured by immunohistochemistry and Western blot. The incidence of postoperative pulmonary complications (atelectasis, pneumonia, and acute respiratory distress syndrome) was used as the index of lung injury. Results There was no significant difference in the general condition before and during operation between the two groups. There was no significant difference in arterial blood IL-8 content between the two groups at the T0 time point, but the arterial blood IL-8 content at the T2 time point was significantly higher than that at the T0 time point, especially in group C. The results of immunohistochemistry and Western blot showed that the expression level of AQP1 protein in the isolated lung tissue of group D was significantly higher than that of group C (P < 0 05). At T3, the OI of group D was significantly higher than that of group C, and the A-aDO2 of group D was significantly lower than that of group C (P < 0.05). There was no significant difference in the incidence of postoperative PPCs between the two groups. Conclusion Dexmedetomidine can reduce the level of plasma IL-8 and upregulate the expression of AQP1 in the lung tissue of patients undergoing thoracoscopic surgery under one-lung ventilation, but it has no significant effect on the incidence of postoperative PPCs. Dexmedetomidine can be safely used in thoracoscopic surgery and has a certain protective effect on lung injury.

SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19

Background & AimsLiver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities.MethodsWe analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies.ResultsSixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed.ConclusionsSARS-CoV-2 infection in the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required.Lay summaryLiver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.

Effects of low tidal volume protective lung ventilation versus pressure controlled ventilation on oxygenation in patients un-dergoing gynecologic laparoscopic surgery

Objective To evaluate the effectiveness and safety of low tidal volume protective lung ventilation (PLV) and pressure controlled ventilation (PCV) in patients undergoing gynecologic laparoscopic surgery. Methods A total of 144 patients who were scheduled for gynecologic laparoscopic surgery in our hospital were enrolled. According to the random number table method, they were divided into two groups (n=72): a PLV group and a PCV group. The PLV group used a tidal volume of 6 ml/kg, an inspiration and expiration ratio of 1∶2, a respiratory rate of 16 breaths per minute, and a positive end expiratory pressure of 5 cmH2O (1 cmH2O=0.098 kPa). In the PCV group, the ventilation pressure was maintained at a tidal volume of 8 ml/kg, with an inspiration and expiration ratio of 1∶2, and a respiratory rate of 12-16 breaths per minute. Their airway peak pressure (Ppeak) and mean airway pressure (Pmean) were recorded 5 min after tracheal intubation (T1), 10 min after pneumoperitoneum (T2), 20 min af-ter pneumoperitoneum (T3), and 10 min after pneumonectomy (T4), while dynamic lung compliance (Cdyn) was calculated. Blood gas analysis was performed at T3 and T4 to record arterial oxygen partial pressure (PaO2), arterial CO2 partial pressure (PaCO2), and alveolar-arterial oxygen partial pressure difference (A-aDO2), while oxygenation index (OI) was calculated. Results At T3, the PLV group presented remarkably increased Ppeak and Pmean and decreased Cdyn, compared with the PCV group (P 0.05). There was no significant differ-ence in the incidence of respiratory complications and the length of hospitalization stay between the two groups (P>0.05). Conclusions For patients undergoing gynecologic laparoscopic surgery, PCV is helpful to maintain stable respiratory dynamics, while low tidal volume PLV is helpful to maintain oxygenation function during surgery. There is no significant difference in safety be-tween the two types of treatment. Key words: Gynaecology; Laparoscopy; Protective lung ventilation mode; Pressure controlled ventilation; Oxygenation function

Effects of Balanced Ultrafiltration During Extracorporeal Circulation for Children with Congenital Heart Disease on Postoperative Serum Inflammatory Response

Objectives: We studied inflammatory marker changes with ultrafiltration extracorporeal techniques and compared these levels to those occurring during conventional techniques. Methods: Seventy-four children undergoing extracorporeal circulation during congenital heart surgery were divided into two groups—conventional (control) and balanced ultrafiltrations (study). Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and soluble intercellular adhesion molecule-1 (sICAM-1), static lung compliance (Cstat), alveolar-arterial oxygen partial pressure difference (A-aDO2), and oxygenation index (OI) were measured. Results: Thirty minutes after extracorporeal circulation (T1), IL-6 and TNF-α levels significantly increased (p < .05), which plummeted 3 h after surgery (T2). The levels in the study group were lower (p < .05). sICAM-1 levels at T1 and T2 significantly exceeded those at T0, and study group had lower levels (p < .05). At T1, Cstat and OI dropped (p < .05), which increased at T2 (p < .05), and study group had less decreases (p < .05). A-aDO2 at T1 surpassed that before intervention (p < .05), and study group had less increase (p < .05). Conclusion: Balanced ultrafiltration exerts protective effects on children with congenital heart disease undergoing extracorporeal circulation.

Effect of dexmedetomidine on pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery

Objective To evaluate the effect of dexmedetomidine on pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery. Methods Sixty patients were included who underwent laparoseopic gallbladder surgery with general anesthesia. For the all subjects, the age ranged from 65 to 75 years old, the body mass index range was 18.5~23.9 kg/m2, and the ASA grade was Ⅱ or Ⅲ. In the subject selection, the gender was not limited, and the included subjects were diagnosed with mild obstructive ventilation dysfunction by preoperative pulmonary function tests. All the subjects were randomly divided into 2 groups (n=30), including dexmedetomidine group (group D) and control group (group C). In the group D, dexmedetomidine was intravenously infused at a dose of 1 μg/kg 10 min before and after the general anesthesia induction, and at a rate of 0.4 μg/(kg·h) after tracheal intubation until the end of operation. Group C was given an equal volume of normal saline. Airway peak pressure (Ppeak), mean airway pressure (Pmean), airway plateau pressure (Pplat), and positive end-expiratory pressure(PEEP) were measured at 5 min after intubation (before pneumoperitoneum) (T1), end of pneumoperjtoneum (T2), and 10 min after the end of pneumoperitoneum (T3). The driving pressure (DP) was calculated. The blood samples of the radial artery were collected for blood gas analysis, and PaO2 and PaCO2 were recorded. The oxygenation index (PaO2/FiO2), respiratory index (RI), dead space ventilation rate (VD/VT), and alveolar-arterial oxygen partial pressure difference (A-aDO2) were calculated. The time of removal of the tracheal tube and the occurrences of complications such as hypercapnia and hypoxemia within 48 hours after extubation were recorded. Results Compared with group C, Ppeak, Pmean, DP, RI, VD/VT and A-aDO2 at T1, T2, T3 were decreased in group D, PaO2/FiO2 was increased, postoperative extubation time was shortened, and the incidence of hypoxemia was reduced within 48 h after operation (P<0.05). Compared with T1, Ppeak, Pmean, DP, RI, VD/VT and A-aDO2 at T2 were increased, and PaO2/FiO2 was decreased(P<0.05). Conclusions Dexmedetomidine can improve the pulmonary function in elderly patients with mild obstructive ventilatory dysfunction under protective ventilation during laparoseopic gallbladder surgery. Key words: Dexmedetomidine; Laparoscopic surgery; Pulmonary function

Effect of ulinastatin on interleukins and pulmonary function in bypass patients: ameta-analysis of randomized controlled trials.

Our aim was to evaluate the effect of urinary trypsin inhibitors (UTI) on interleukin, tumor necrosis factor-α(TNF-α), and polymorphonuclear neutrophil elastase (PMNE) levels as well as on pulmonary function in patients undergoing cardiopulmonary bypass. We searched the following databases for relevant studies: PubMed, Medline (Ovid SP), Cochrane Library, Wanfang Data, China Biology Medicine Database, Chinese Periodical Database, China Knowledge Resource Integrated Database, and Chinese Clinical Trial Registry. Two investigators independently collected the data and assessed the quality of each study. RevMan5.3 was used for the meta-analysis. In total, 15 randomized controlled trials (646 patients) met the inclusion criteria. There was asignificant decrease in TNF-α, interleukin-6 (IL-6), IL-8, and PMNE levels at 6 h and 24 h after UTI treatment and an increase in IL-10 levels; additionally, there was adecrease in respiratory index and an improvement in the oxygenation index. Nevertheless, UTI treatment did not affect the length of intensive care unit stay, alveolar-arterial oxygen partial pressure difference, adverse lung events, or hospital mortality. Because of the high heterogeneity of the included trials, the results should be assessed carefully. UTI treatment can suppress proinflammatory cytokine elevation and upregulate the release of anti-inflammatory mediators, thereby reducing pulmonary injury and improving pulmonary function after cardiopulmonary bypass.

Effect of transcutaneous electric acupoint stimulation on prognosis in patients at high risk of postoperative pulmonary complications

Objective To evaluate the effect of transcutaneous electric acupoint stimulation(TEAS)on prognosis in the patients at high risk of postoperative pulmonary complications. Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes, aged 65-72 yr, with body mass index of 18-25 kg/m2, scheduled for elective thoracoscopic and laparoscopic radical resection of esophageal cancer, were divided into placebo control group(group C, n=30)and TEAS group(n=30). In group TEAS, bilateral Zusanli(ST36), Hegu(LI4)and Feishu(BL13)acupoints were stimulated for 30 min(disperse-dense waves, frequency 2/100 Hz, intensity of currents 8-12 mA)starting from 30 min before anesthesia induction.In group C, electrodes were placed on the same acupoints before anesthesia induction, but no current was given.General anesthesia was performed in two groups.Before one-lung ventilation, at 30 min and 2 h of one-lung ventilation and at 1 h after operation(T1-4), blood samples were drawn from the radial artery for blood gas analysis, and oxygenation index and alveolar-arterial oxygen partial pressure difference were calculated.Blood samples were collected from the internal jugular vein at T1-3 and 24 h after surgery(T5)for determination of plasma tumor necrosis factor-alpha, interleukin-6(IL-6)and IL-10 concentrations.The development of postoperative pulmonary complications, time for removal of drainage tube and length of hospital stay were recorded. Results Compared with group C, the oxygenation index at T2-4 and plasma IL-10 concentrations at T3 were significantly increased, the alveolar-arterial oxygen partial pressure difference at T2, 3, plasma tumor necrosis factor-alpha concentrations at T2, 3, plasma IL-10 concentrations at T3, 5 and incidence of postoperative pulmonary complications were decreased, and the time for removal of drainage tube and length of hospital stay were shortened in group TEAS(P<0.05). Conclusion TEAS can improve prognosis in the patients at high risk of postoperative pulmonary complications. Key words: Electric stimulation; Postoperative complications

Why Are High Altitude Natives So Strong at High Altitude? Nature vs. Nurture: Genetic Factors vs. Growth and Development.

Among high-altitude natives there is evidence of a general hypoxia tolerance leading to enhanced performance and/or increased capacity in several important domains. These domains likely include an enhanced physical work capacity, an enhanced reproductive capacity, and an ability to resist several common pathologies of chronic high-altitude exposure. The "strength" of the high-altitude native in this regard may have both a developmental and a genetic basis, although there is better evidence for the former (developmental effects) than for the latter. For example, early-life hypoxia exposure clearly results in lung growth and remodeling leading to an increased O2 diffusing capacity in adulthood. Genetic research has yet to reveal a population genetic basis for enhanced capacity in high-altitude natives, but several traits are clearly under genetic control in Andean and Tibetan populations e.g., resting and exercise arterial O2 saturation (SaO2). This chapter reviews the effects of nature and nurture on traits that are relevant to the process of gas exchange, including pulmonary volumes and diffusion capacity, the maximal oxygen consumption (VO2max), the SaO2, and the alveolar-arterial oxygen partial pressure difference (A-aDO2) during exercise.

Effects of sevoflurane and propofol on the inflammatory response and pulmonary function of perioperative patients with one-lung ventilation

This study compared the effects of sevoflurane and propofol on the inflammatory response and pulmonary function of patients with lung cancer during the perioperative period. Forty patients who underwent a selective resection of the inferior lobe of the left lung were randomly divided into two groups, with one group anesthetized with sevoflurane and the other with propofol (groups S and P, respectively). Radial arterial and mixed venous blood were extracted for blood gas analysis, in order to calculate the alveolar-arterial oxygen partial pressure difference (PA-aDO2), respiratory index (RI) and pulmonary shunt ratio (Qs/Qt) prior to the induction of anesthesia (T0), prior to one-lung ventilation (OLV) (T1), 1 h subsequent to the commencement of OLV (T2), 1 h following restoration of two-lung ventilation (T3), 2 h following restoration of two-lung ventilation (T4) and 24 h post-surgery (T5). In addition, blood was extracted from the radial artery at T0, T1, T2, T3, T4 and T5 in order to detect the presence of tumor necrosis factor-α (TNF-α), IL-6 and IL-10 in the blood serum. Between T1 and T4, the tidal volume, airway plateau pressure and end-expiratory positive airway pressure were recorded, in order to calculate the lung dynamic compliance (Cdyn). Heart rate, mean arterial pressure, central venous pressure, cardiac output and the duration of OLV (OLV-T) were recorded at T0–5. Compared with T0, the levels of TNF-α, IL-6 and IL-10 significantly increased during T2 to T4 in both groups (P<0.05). PA-aDO2 and RI increased during T1 to T4, and Qs/Qt increased at T2 (P<0.05). Compared with T1, Cdyn decreased during T2 to T4 in the S group, whereas Cdyn was reduced at T2 in the P group (P<0.05). Compared with the P group, TNF-α level increased and IL-10 decreased at T3 and T4 in the S group. PA-aDO2 and RI increased, but Cdyn decreased at T2 and T3 in the S group. Qs/Qt increased at T2 in the S group. The results of the present study demonstrated that, in comparison with propofol, sevoflurane exhibited an enhanced capacity to aggravate injury to pulmonary function during the perioperative stages. This occurred via the release of inflammatory factors, the aggravation of lung edema and the inhibition of hypoxic pulmonary vasoconstriction.

Dose-dependent effects of Chlamydia psittaci infection on pulmonary gas exchange, innate immunity and acute-phase reaction in a bovine respiratory model

The respiratory pathogen Chlamydia psittaci naturally occurs in bovine herds and was recently shown to impair calf health in a dose-dependent manner. The aim of this study was to determine whether the functional consequences and immunological reactions of infection were dose related by quantifying the consequences of acute respiratory chlamydial infection on respiratory signs, disturbances of pulmonary gas exchange, response of the innate immune system, and acute-phase reaction. Fourteen calves were challenged intrabronchially with different C. psittaci doses (from 106 to 109inclusion-forming units (ifu) per animal). Ten controls received either UV-inactivated chlamydiae or cell culture medium.Compared to the controls, all animals challenged with live C. psittaci developed hypoxaemia linked to reduced haemoglobin oxygen saturation, increased alveolar–arterial oxygen partial pressure difference (A-aO2) and pulmonary shunt, with symptoms following a dose-dependent pattern. Increases in lipopolysaccharide-binding protein (LBP) and leukocytes were also dose-dependent and accompanied by a regenerative left shift in neutrophil granulocytes. With the exception of LBP, which reflected the load of chlamydial cell components in the host, pathophysiological reactions were only detected in calves challenged with viable chlamydiae. These results indicate that the pathophysiological consequences of respiratory C. psittaci infections are strongly dependent on the challenge dose of chlamydiae. For further studies, challenge doses between 106 and 108ifu/calf are recommended.

Rapid intravenous infusion of 20 ml/kg saline does not impair resting pulmonary gas exchange in the healthy human lung

Rapid infusion of intravenous saline, a model of pulmonary interstitial edema, alters the distribution of pulmonary perfusion, raises pulmonary capillary blood volume, and increases bronchial wall thickness in humans. We hypothesized that infusion would disrupt pulmonary gas exchange by increasing ventilation/perfusion ((.)VA/(.)Q) inequality as opposed to a diffusive impairment in O2 exchange. Seven males (26 +/- 3 yr; FEV1: 110 +/- 16% predicted.) performed spirometry and had (.)VA/(.)Q mismatch measured using the multiple inert gas elimination technique, before and after 20 ml/kg iv of normal saline delivered in approximately 30 min. Infusion increased thoracic fluid content from transthoracic impedance by 12% (P < 0.0001) and left FVC unchanged but reduced expiratory flows (FEF(25-75) falling from 5.1 +/- 0.4 to 4.2 +/- 0.4 l/s, P < 0.05). However, (.)VA/(.)Q mismatch as measured by the log standard deviation of the ventilation (LogSD(.)V) and perfusion (LogSD(.)Q) distributions remained unchanged; LogSD(.)V: 0.40 +/- 0.03 pre, 0.38 +/- 0.04 post, NS; LogSD(.)Q: 0.38 +/- 0.03 pre, 0.37 +/- 0.03 post, NS. There was no significant change in arterial PO2 (99 +/- 2 pre, 99 +/- 3 mmHg post, NS) but arterial PCO2 was decreased (38.7 +/- 0.6 pre, 36.8 +/- 1.2 mmHg post, P < 0.05). Thus, infusion compressed small airways and caused a mild degree of hyperventilation. There was no evidence for a diffusive limitation to O2 exchange, with the measured-predicted alveolar-arterial oxygen partial pressure difference being unaltered by infusion at FIO2 = 0.125 (4.3 +/- 1.0 pre, 5.2 +/- 1.0 post, NS). After infusion, the fraction of perfusion going to areas with (.)VA/(.)Q < 1 was increased when a subject breathed a hyperoxic gas mixture [0.72 +/- 0.06 (FIO2 = 0.21), 0.80 +/- 0.06 (FIO2 = 0.30), P < 0.05] with similar effects on ventilation in the face of unchanged (.)VA and (.)Q. These results suggest active control of blood flow to regions of decreased ventilation during air breathing, thus minimizing the gas exchange consequences.

Le syndrome hépatopulmonaire

Hepatopulmonary syndrome is characterized by the presence of portal hypertension with or without cirrhosis, an increased alveolar-arterial oxygen partial pressure difference greater than or equal to 15 mm Hg, and dilated pulmonary capillaries. Hepatopulmonary syndrome is found in up to 20% of patients with cirrhosis and should be considered in any patient who develops dyspnea or hypoxemia. Contrast echocardiography is enough to make the diagnosis of hepatopulmonary syndrome. The exact pathophysiology of hepatopulmonary syndrome remains unknown but nitric oxide is an important factor underlying hepatopulmonary syndrome. Hypoxemia progressively deteriorates and worsens the prognosis of cirrhotic patients. Hypoxemic patients must be controlled regularly to optimise the timing of liver transplantation. Indeed, a preoperative PaO(2) of less than or equal to 50 mm Hg alone or in combination with an isotopic shunt fraction greater than or equal to 20% are the strongest predictors of postoperative mortality. There are currently no effective medical therapies for hepatopulmonary syndrome but garlic powder and iloprost inhalation demonstrate clinical improvements in the pre- and in the post-transplant period.

Do high-altitude natives have enhanced exercise performance at altitude?

Natives of high altitude (HA) may have enhanced physical work capacity in hypoxia due to growth and development at altitude or, in the case of indigenous Andean and Himalayan residents, due to population genetic factors that determine higher limits to exercise performance. There is a growing scientific literature in support of both hypotheses, although the specific developmental vs. genetic origins of putative population trait differences remain obscure. Considering whole-body measures of exercise performance, a review of the literature suggests that indigenous HA natives have higher mean maximal oxygen consumption (VO(2) (max)) in hypoxia and smaller VO(2) (max) decrement with increasing hypoxia. At present, there is insufficient information to conclude that HA natives have enhanced work economy or greater endurance capacity, although for the former a number of studies indicate that this may be the case for Tibetans. At the physiological level, supporting the hypothesis of enhanced pulmonary gas exchange efficiency, HA natives have smaller alveolar-arterial oxygen partial pressure difference ((A-a)DO(2)), lower pulmonary ventilation (VE), and likely higher arterial O(2) saturation (SaO(2)) during exercise. At the muscle level, a handful of studies show no differences in fiber-type distributions, capillarity, oxidative enzymes, or the muscle response to training. At the metabolic level, a few studies suggest differences in lactate production/removal and (or) lactate buffering capacity, but more work is needed in this area.

Acute Hypercapnia Improves Indices of Tissue Oxygenation More than Dobutamine in Septic Shock

Hypercapnia has similar hemodynamic effects to those of a dobutamine infusion and may have relevance in the management of septic shock. To compare the effects induced by hypercapnia with those of dobutamine in a clinically relevant model of septic shock. Fecal peritonitis was induced in 21 anesthetized, invasively monitored, mechanically ventilated female sheep. A combination of Ringer's lactate and 6% hydroxyethyl starch solution was titrated to maintain constant cardiac filling throughout the experiments. Two hours after feces spillage, animals were randomized to one of three groups (each, n = 7): (1) hypercapnia: carbon dioxide given to maintain partial pressure of carbon dioxide between 55 and 65 mm Hg throughout the experiment; (2) dobutamine: dobutamine infused intravenously (7 microg/kg/min); (3) control: no treatment. In the dobutamine and control groups, the partial pressure of carbon dioxide was kept between 35 and 45 mm Hg. All animals were monitored until spontaneous death. The animals in the hypercapnia group had significantly lower arterial pH than the other two groups (P < 0.05). Hypercapnic and dobutamine-treated animals developed significantly higher heart rate, cardiac index, and oxygen delivery, and lower lactate concentrations than control animals (P < 0.05). Hypercapnic animals had lower post mortem lung wet/dry ratio than the control animals (P < 0.05). The alveolar-arterial oxygen partial pressure difference and shunt fraction were significantly lower in hypercapnic animals than in the other groups (P < 0.05). In this clinically relevant ovine model of septic shock, hypercapnia had similar effects to dobutamine on hemodynamic variables and lactic acidosis. Hypercapnia improved tissue oxygenation and reduced lung edema formation more than dobutamine administration.

Continuous positive airway pressure does not improve lung function after cardiac surgery

Despite the well-documented impairment of pulmonary function after cardiopulmonary bypass, effective precautions and ideal management strategies for this problem are still under debate. This study aimed to evaluate the effects of continuous positive airway pressure (CPAP) applied during cardiopulmonary bypass on respiratory and hemodynamic variables. In this randomized, prospective, controlled trial, 120 male patients, aged 45 to 70 yr undergoing first-time elective bypass surgery, were randomly assigned to receive either 10 cm H2O of CPAP (Group I; n = 60) during cardiopulmonary bypass, or serve as control (Group II; n = 60), where the patient's lungs were vented to atmosphere during the bypass period. Alveolar-arterial oxygen partial pressure difference and shunt fraction were significantly higher in the control group compared with the CPAP group after cardiopulmonary bypass (T2) and after closure of sternum (T3), (P < 0.05). No differences between groups with respect to hemodynamic variables were observed at any time. Postoperative pulmonary function variables were lower in both groups compared to baseline values. Continuous positive airway pressure administered during cardiopulmonary bypass decreased shunt fraction and alveolar-arterial oxygen partial pressure difference during surgery, but had no sustained effect on either variable postoperatively. We conclude that, in patients with normal preoperative pulmonary function, application of 10 cm H2O CPAP does not improve lung function after cardiac surgery.

Pulmonary gas exchange during exercise in Fontan patients at a long‐term follow‐up

Desaturation during exercise in the Fontan type of circulation may be due to known right-to-left shunts in some patients, while in others there are no obvious signs of shunts. To evaluate the gas exchange and exercise capacity in patients with Fontan circulation. Twenty patients with the Fontan type of circulation, median age at operation 7.5 years (3.0-35 years), follow-up time 12.1 years (8.3-20.4 years), were included. The intrapulmonary gas mixing (N(2)-slope) and diffusion capacity for carbon monoxide (D(LCO)) was evaluated and determination of cardiac output was performed at rest and during exercise with measurements of ventilation, oxygen uptake, respiratory rate, carbon dioxide production and heart rate. Samples for blood gases (P(a)O(2), S(a)O(2)) were obtained at rest and at the end of each work load. The median exercise capacity was 1.47 l min(-1). During exercise, all the patients had an alveolar-arterial oxygen partial pressure difference (P(A-a)O(2)) above 2 SD. Patients with known right-to-left shunts had lower P(a)O(2) and S(a)O(2) values and higher P(A-a)O(2) values both at rest, median 7.5 kPa, 90%, and 7.2 kPa, respectively, and during exercise, median 5.8 kPa, 77% and 10.1 kPa, compared with those with no shunts, median 11.2 kPa, 97% and 4.1, respectively, at rest and 9.7 kPa, 94%, and 6.3 during exercise (P<0.01). No correlation was found between cardiac index, the N(2)-slope or the D(LCO) at rest and the P(a)O(2) and S(a)O(2) at rest or during exercise. In patients with the Fontan type of circulation, right-to-left shunts are the major cause of desaturation during exercise.