Double Indicator Dilution Research Articles

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS

BackgroundLung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS.MethodsTwelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH2O and limited peak inspiratory pressure (17 ± 4 cmH2O) versus increased peak inspiratory pressure (23 ± 6 cmH2O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t–test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively.ResultsMechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p < 0.001, respectively), increased cardiac output (140 ± 32 vs. 110 ± 22 ml/min/kg, p<0.05) and regional blood flow in the myocardium, brain and spinal cord, adrenal and thyroid glands, the mucosal layers of the esophagus and jejunum, the muscularis layers of the esophagus and duodenum, and the gall and urinary bladders. Perfusion of kidneys, pancreas, spleen, hepatic arterial bed, and the mucosal and muscularis blood flow to the other evaluated intestinal regions remained unchanged.ConclusionsIn this porcine model of ARDS mechanical ventilation with limited peak inspiratory pressure resulting in moderate respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Validation of Extravascular Lung Water Measurement by Transpulmonary Thermodilution in a Pediatric Animal Model

The measurement of extravascular lung water using the transpulmonary thermodilution technique enables the bedside quantification of the amount of pulmonary edema. Children have higher indexed to body weight values of extravascular lung water compared with adults. Transpulmonary thermodilution measurements of extravascular lung water in children have not yet been validated. The purpose of this study was to validate the extravascular lung water measurements with the transpulmonary thermodilution method over a wide range of lung water values in a pediatric animal model. Experimental animal intervention study. Animal laboratory at the Radboud University Nijmegen, The Netherlands. Eleven lambs. Pulmonary edema was induced using a surfactant washout model. Between the lavages, extravascular lung water index was estimated using transpulmonary single and double indicator dilution. Two additional lambs were used to estimate extravascular lung water index in lungs without pulmonary edema. The final extravascular lung water index results were compared with the extravascular lung water index estimations by postmortem gravimetry (EVLWIG). The results were analyzed using both correlation and Bland-Altman statistics. Extravascular lung water index by transpulmonary thermodilution (EVLWITPTD) correlated significantly with either EVLWIG (r = 0.88) or with extravascular lung water index by transpulmonary double indicator dilution (EVLWITPDD) (r = 0.98). The mean bias with EVLWIG was 12.2 mL/kg (limits of agreement ± 10.9 mL/kg) and with EVLWITPDD 2.4 mL/kg (limits of agreement ± 3.8 mL/kg). The percentage errors were 41% and 14%, respectively. The bias became more positive when the mean of EVLWITPTD and EVLWIG increased (r = 0.72; p = 0.003). EVLWITPTD was significantly correlated to the postmortem gravimetric gold standard, although a significant overestimation was demonstrated with increasing pulmonary edema.

The role of amiloride‐insensitive sodium transport in alveolar fluid homeostasis (695.2)

Under both normal and pathological conditions, the lung fluid balance across the alveolar epithelial barrier is mainly regulated by active sodium transporters. Previous work has largely focused on the critical role of ENaC, yet ~60% of alveolar fluid clearance in rats or humans is amiloride insensitive. We decided to explore the role of the amiloride‐insensitive sodium cotransporters SGLT1 (Na+‐glucose co‐transporter 1) and SNATs (Na+‐coupled neutral amino acid transporters) in the intact lung. In isolated perfused rat lungs, we determined alveolar fluid clearance (AFC) using a double indicator dilution technique and probed for the role of SGLT1 and SNATs by addition of appropriate cotransporter substrates or inhibitors. While addition of the SNAT substrate L‐alanine did not affect basal AFC, it rescued AFC in lungs pre‐treated with amiloride, and this response was blocked by the SNAT inhibitor HgCl2. Analysis of bronchoalveolar lavage fluid revealed &gt; 2‐fold of L‐alanine in the epithelial lining fluid compared to plasma level. RT‐PCR identified mRNAs for all 6 SNAT isoforms in whole lung, yet in alveolar epithelial cells, only SNAT 2 and 5 mRNA and protein were detected. In contrast, no functional involvement of SGLT1 in AFC was detected. These results indicate a new role for SNATs in AFC which becomes unmasked when ENaC is inhibited. SNAT2 and SNAT5 may represent novel targets for the resolution of pulmonary edema.Grant Funding Source: Funded by CIHR MOP # 245251

13 Validation of Extravascular Lungwater Measurement by Transpulmonary Thermodilution in Severe Pulmonary Edema in a Newborn Animal Model

IntroductionExtravascular lungwater (EVLW) can be measured at the bedside using the transpulmonary thermodilution method (TPTD), which quantifies the amount of pulmonary edema. This technique has never been validated in conditions...

Active transepithelial Cl−‐secretion promotes hydrostatic lung edema

Hydrostatic lung edema evolves from increased fluid filtration and inhibition of epithelial Na+ channels (ENaC) that facilitate alveolar fluid clearance. Recently, we identified alveolar fluid secretion (AFS) as new key component in edema formation. Here, we tested whether Cl− secretion via cystic fibrosis transmemberane conductance regulator (CFTR) and Na+‐K+‐Cl− cotransporter 1 (NKCC1) may mediate AFS at elevated left atrial pressure (PLA) and may be induced by inhibition of ENaC.In isolated lungs, we quantified AFS by a double indicator dilution technique, and transepithelial Cl− flux by radionuclide tracing and alveolar Cl− imaging. PLA elevation induced lung edema and AFS that coincided with transepithelial Cl− secretion and alveolar Cl− influx. These effects were blocked by inhibitors of CFTR, NKCC or Na+‐K+‐ATPase, and CFTR−/− mice were protected from hydrostatic edema. Inhibition of ENaC by amiloride at physiologicalPLA induced AFS and Cl− secretion that were again CFTR‐, NKCC‐ and Na+‐K+‐ ATPase dependent.We conclude that transepithelial Cl− and fluid flux reverse from absorptive to secretory mode at hydrostatic stress as a result of ENaC inhibition, and are mediated by NKCC and CFTR.

Effects of Spontaneous Breathing During Airway Pressure Release Ventilation on Cerebral and Spinal Cord Perfusion in Experimental Acute Lung Injury

Systemic-blood flow, cerebral-blood flow, and spinal cord blood flow can be affected by mechanical ventilation. We investigated the effect of spontaneous breathing on cerebral and spinal blood flow during airway pressure release ventilation (APRV) with and without spontaneous breathing. Twelve pigs with oleic-acid-induced lung injury were ventilated with APRV with or without spontaneous breathing in random order. Without spontaneous breathing, either the upper airway pressure limit of mechanical ventilation or the ventilator rate was increased to maintain pH and PaCO2 constant. Systemic hemodynamic parameters were determined by the double indicator dilution method, cerebral and spinal cord blood flow was measured with colored microspheres. ANOVA+Newmann-Keuls-test. As compared with APRV without spontaneous breathing and high tidal volume (V(T)) spontaneous breathing during APRV showed higher systemic blood flow and perfusion of the basal ganglia, frontal lobe, hippocampus, brain stem, temporal lobe, thalamus (all P<0.001), cerebellum, spinal cord (all P<0.01), and the central cortical region (P<0.05). During APRV without spontaneous breathing and low V(T) blood flow was lower in the basal ganglia, frontal lobe, hippocampus (all P<0.01), and temporal lobe (P<0.05) whereas perfusion of the thalamus, central cortical region, brain stem, cerebellum, and spinal cord were not different compared with APRV with spontaneous breathing. In parallel with higher systemic blood flow regional cerebral and spinal cord blood flow were also higher when spontaneous breathing was maintained during APRV. The higher regional blood flow by maintaining spontaneous breathing was more pronounced when compared with full ventilatory support using high V(T).

Simultaneous Bedside Assessment of Global Cerebral Blood Flow and Effective Cerebral Perfusion Pressure in Patients with Intracranial Hypertension

We examined a bedside technique transcerebral double-indicator dilution (TCID) for global cerebral blood flow (CBF) as well as the concept of effective cerebral perfusion pressure (CPP(eff)) during different treatment options for intracranial hypertension, and compared global CBF and CPP(eff) with simultaneously obtained conventional parameters. Twenty-six patients developing intracranial hypertension in the course of traumatic brain injury or subarachnoid hemorrhage were prospectively analyzed using a combined assessment during elevated ventilation (n = 15) or osmotherapy (hypertonic saline or mannitol). For calculation of global CBF, injections of ice-cold indocyanine green boluses were performed and temperature and dye concentration changes were monitored in the thoracic aorta and the jugular bulb. CBF was then calculated according to the mean transit time principle. Estimation of CCP, the arterial pressure at which cerebral blood flow becomes zero, was performed by synchronized registration of corresponding values of blood flow velocity in the middle cerebral artery and arterial pressure and extrapolation to zero-flow velocity. CPP(eff) was calculated as mean arterial pressure minus critical closing pressure (CPP(eff) = MAP(c) - CCP). Elevated ventilation causes a decrease in both ICP (P < 0.001) and CBF (P < 0.001). While CPP(conv) increased (P < 0.001), CPP(eff) decreased during this observation (P = 0.002). Administration of osmotherapeutic agents resulted in a decrease of ICP (P < 0.001) and a temporary increase of CBF (P = 0.052). CPP(conv) and CPP(eff) showed no striking difference under osmotherapy. TCID allows repeated measurements of global CBF at the bedside. Elevated ventilation lowered and osmotherapy temporarily raised global CBF. In situations of increased vasotonus, CPP(eff) is a better indicator of blood flow changes than conventional CPP.

Extravascular lung water measurement using transpulmonary thermodilution in children

Measurement of extravascular lung water (EVLW) may be useful in the treatment of critically ill children and can be performed at the bedside using the transpulmonary thermodilution technique (TPTD). There are currently no data to verify the accuracy of these measurements in (small) children. We compared the results of TPTD measurement with the clinical gold standard transpulmonary double indicator dilution (TPDD) measurement in young children. Prospective clinical study in children. Catheterization laboratory of a university hospital. Twelve children (<2 yrs or <12 kg) under general anesthesia. None. Measurements were performed using injections of ice-cold indicator (saline or dye) through a central venous catheter. Mean cardiac index was 3.91 L/min/m, mean intrathoracic blood volume index (ITBVITPDD) was 614.9 mL/m, and mean extravascular lung water index (EVLWITPDD) was 11.7 mL/kg. The correlation coefficient between EVLWITPDD and EVLWITPTD is 0.96 (95% confidence interval: 0.87-0.99; p < 0.0001). Bland-Altman analysis for EVLW measurements showed a mean bias of 2.34 mL/kg (18.13%) and limits of agreement +/-2.97 mL/kg (19.78%). The difference between measurements via the right atrium compared with the femoral vein was 2.8% for cardiac output, 8.2% for global end-diastolic volume, and 0.1% for EVLW. Clinical measurement of EVLW in young children can be performed using the TPTD with the injection catheter inserted in the femoral vein. Further studies are needed to clarify the clinical value of these measurements.

Extravascular lung water volume measurement by a novel lithium-thermal indicator dilution method: comparison of three techniques to post-mortem gravimetry

To compare the lithium-thermal double indicator dilution (Li-thermal), indocyanine green-thermal double indicator dilution (ICG-thermal), single thermal indicator dilution (single-thermal) and gravimetric techniques of extravascular lung water volume (EVLW) measurement in porcine models of acute lung injury. Two animal models designed to invoke a systemic inflammatory response. Laboratory study. A total of 12 immature Deutsches Landschwein pigs. Extravascular lung water volume was measured at four time points using Li-thermal, ICG-thermal and single-thermal techniques. Measurements were performed using existing technology according to manufacturer's instructions. Post-mortem gravimetric EVLW measurements were performed by measuring wet and dry mass of lung tissue. Measurements were compared using the Bland-Altman method. Data are presented as mean (SD). Data were collected in 12 animals and comparison between all 4 techniques was possible in 10 animals. EVLW measured by gravimetry was 9.2 (+/-3.0)ml kg(-1). When compared to gravimetry, both Li-thermal and ICG-thermal techniques showed minimal bias but wide limits of agreement (LOA) [Li-thermal: bias -1.8 ml kg(-1) (LOA +/- 13.1); ICG-thermal bias -1.0 ml kg(-1) (LOA +/- 6.6)]. Comparison between the single-thermal and gravimetric methods identified both considerable bias and wide LOA [+8.5 ml kg(-1) (LOA +/- 14.5)]. Clinically significant differences between EVLW measurements obtained with the gravimetric method and three in vivo indicator dilution techniques were identified. While none of the techniques could be considered ideal, the ICG-thermal method appeared more reliable than either the Li-thermal or single thermal techniques. Further research is required to determine whether the accuracy of the prototype Li-thermal technique can be improved.

Measurement of extravascular lung water in patients with pulmonary edema

measurement of extravascular lung water has been a topic of major interest for more than two decades ([1][1], [5][2], [19][3]). In the recent article by Effros et al. ([2][4]), they provide a review of current and past efforts to measure extravascular lung water with thermal and osmotic dilution

Spontaneous breathing during airway pressure release ventilation in experimental lung injury: effects on hepatic blood flow

Positive pressure ventilation can affect systemic haemodynamics and regional blood flow distribution with negative effects on hepatic blood flow. We hypothesized that spontaneous breathing (SB) with airway pressure release ventilation (APRV) provides better systemic and hepatic blood flow than APRV without SB. Animal study with a randomized cross-over design. Animal laboratory of Bonn University Hospital. Twelve pigs with oleic-acid-induced lung injury. APRV with or without SB in random order. Without SB, either the upper airway pressure limit or the ventilator rate was increased to maintain constant pH and PaCO2. Systemic haemodynamics were determined by double-indicator dilution, organ blood flow by coloured microspheres. Systemic blood flow was best during APRV with SB. During APRV with SB blood flow (ml g(-1) min(-1)) was 0.91+/-0.26 (hepatic arterial), 0.29+/-0.05 (stomach), 0.64+/-0.08 (duodenum), 0.62+/-0.10 (jejunum), 0.53+/-0.07 (ileum), 0.53+/-0.07 (colon), 0.46+/-0.09 (pancreas) and 3.59+/-0.55 (spleen). During APRV without SB applying high P(aw) it decreased to 0.13+/-0.01 (stomach), 0.37+/-0.03 (duodenum), 0.29+/-0.03 (jejunum), 0.31+/-0.05 (ileum), 0.32+/-0.03 (colon) and 0.23+/-0.04 (pancreas) p<0.01, respectively. During APRV without SB applying same Paw limits it decreased to 0.18+/-0.03 (stomach, p<0.01), 0.47+/-0.06 (duodenum, p<0.05), 0.38+/-0.05 (jejunum, p<0.01), 0.36+/-0.03 (ileum, p<0.05), 0.39+/-0.05 (colon, p<0.05), and 0.27+/-0.04 (pancreas, p<0.01). Arterial liver blood flow did not change significantly when SB was abolished (0.55+/-0.11 and 0.63+/-0.11, respectively). Maintaining SB during APRV was associated with better systemic and pre-portal organ blood flow. Improvement in hepatic arterial blood flow was not significant.

Respiratory system inertance corresponds to extravascular lung water in surfactant-deficient piglets

In various cardio-pulmonary diseases lung mass is considerably increased due to intrapulmonary fluid accumulation, i.e. extravascular lung water (EVLW). Generally, inertance is a physical system parameter that is mass-dependent. We hypothesized that changes in lung mass influence the inertive behavior of the respiratory system. EVLW and intrathoracic blood volume (ITBV) were compared with respiratory system inertance (I(rs)) in four piglets before and after broncho-alveolar lavage (BAL) that induced surfactant deficiency with interstitial edema. EVLW and ITBV were determined using the double-indicator dilution technique, I(rs) by multiple linear regression analysis. Measurements were taken before, and 1 and 2 h after BAL. EVLW increased threefold (from 6.2+/-0.8 mL/kg at baseline to 17.7+/-0.9 mL/kg (p < 0.001) after BAL). I(rs) increased by 35% (from 0.17+/-0.02 to 0.23+/-0.04 cmH(2)O s(2)/L (p = 0.036) after BAL) and was tightly correlated to EVLW (r(2) = 0.95, p < 0.023). ITBV did not change significantly after BAL. We conclude that I(rs) reflects actual changes in lung mass and thus hints at fluid accumulation within the lung.

Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature

POINT-COUNTERPOINT COMMENTSChronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculatureJohn T. BergJohn T. BergPublished Online:01 Oct 2007https://doi.org/10.1152/japplphysiol.00739.2007MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat The following letter is in response to Point:Counterpoint: “Chronic hypoxia-induced pulmonary hypertension does/does not lead to loss of pulmonary vasculature” that appears in this issue.To the Editor: In their initial statement supporting the hypothesized loss of precapillary arteries in chronic hypoxia Rabinovitch, Chesler, and Molthen (6) provide evidence derived from perfusion studies using contrast dyes and other markers. In reply, McLoughlin and McMurtry (5) introduce the problem of artifactual measurements resulting from hypoxic pulmonary vasoconstriction (HPV) of pulmonary arteries. I believe that clarification of how HPV may cause the proposed loss of vessels to occur may contribute to the debate. One way this could happen is through uneven HPV where flow in some vascular channels may become entirely blocked and downstream vessels would appear to be lost through a lack of perfusion. Hultgren (4) initially introduced the concept of uneven HPV in pulmonary arteries to explain the observed patchy distribution of high-altitude pulmonary edema in humans. Anatomically, pulmonary arteries in the adult human lung have a highly variable distribution of smooth muscle (2) consistent with the observed variability of HPV response between individuals. Studies by Dawson et al. (1), using the double-indicator dilution method, showed that hypoxia causes more than a doubling of transit times for infused indicator agents in dog lungs, suggesting that flow rates through parallel channels become more variable with hypoxia. More recently, Hopkins et al. (3), using functional magnetic resonance imaging techniques, provide additional evidence for uneven HPV. It is therefore likely that at least some of the data presented in defense of vessel loss as a cause of pulmonary hypertension may be the result of uneven HPV and artifactual inclusion of HPV-blocked vessels.REFERENCES1 Dawson CA, Bronikowski TA, Linehan JH, Hakim TS. Influence of pulmonary vasoconstriction on lung water and perfusion heterogeneity. J Appl Physiol 54: 654–660, 1983.Link | ISI | Google Scholar2 deMello D, Reid LM. Arteries and veins. In: The Lung: Scientific Foundations, edited by Crystal RG and West JB. New York: Raven, 1991, p. 767–777.Google Scholar3 Hopkins SR, Garg J, Bolar DS, Balouch J, Levin DL. Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema. Am J Respir Crit Care Med 171: 83–87, 2005.Crossref | PubMed | ISI | Google Scholar4 Hultgren HN. High altitude pulmonary edema. In: Biomedicine of High Terrestrial Altitude, edited by Hegnauer AH. New York: Springer-Verlag, 1969, p. 131–141.Google Scholar5 McLoughlin P, McMurtry I. Counterpoint: Chronic hypoxia-induced pulmonary hypertension does not lead to loss of pulmonary vasculature. J Appl Physiol; doi:10.1152/japplphysiol.00274a.2007.Google Scholar6 Rabinovitch M, Chesler N, Molthen RC. Point: Chronic hypoxia-induced pulmonary hypertension does lead to loss of pulmonary vasculature. J Appl Physiol; doi:10.1152/japplphysiol.00274.2007.Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByCellular Pathways Promoting Pulmonary Vascular Remodeling by HypoxiaLarissa A. Shimoda3 June 2020 | Physiology, Vol. 35, No. 4Lung Circulation15 March 2016Vascular remodeling in pulmonary hypertension19 January 2013 | Journal of Molecular Medicine, Vol. 91, No. 3Chronic hypoxia-induced pulmonary hypertension in rat: the best animal model for studying pulmonary vasoconstriction and vascular medial hypertrophyDrug Discovery Today: Disease Models, Vol. 7, No. 3-4 More from this issue > Volume 103Issue 4October 2007Pages 1455-1455 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00739.2007PubMed17916681History Published online 1 October 2007 Published in print 1 October 2007 Metrics

Measurement of Extravascular Lung Water in Critically Ill Patients

In critically ill patients, capillary leakage often occurs which in the lungs may lead to pulmonary edema by increased microvascular pressure and permeability. However, clinical assessment of the extent of pulmonary capillary leakage and pulmonary edema is difficult. Several decades ago, the transpulmonary double indicator (thermo-dye) dilution technique has been introduced for quantification of extravasastion of fluids in the lungs by determination of the extravascular lung water (EVLW). The thermo-dye is based on simultaneous central venous injection of a freely diffusible indicator (‘cold’) and a plasma-bound indicator (indocyanine green). This technique has been extensively validated in animal experiments using post-mortem gravimetry and in humans using radionuclide techniques. However, the thermo-dye dilution technique is relatively expensive and time consuming therefore assessment of EVLW is increasingly performed by single transpulmonary thermodilution, which according to animal experimental and clinical studies is sufficiently accurate for estimation of EVLW. Using EVLW to guide the management of patients with both cardiac and non-cardiac pulmonary edema (ARDS) has been shown to reduce the duration of mechanical ventilation, length of stay in the intensive care unit and potentially intensive care costs. EVLW-guided therapy also reduced mortality in those patients with congestive heart failure and ARDS. Recent clinical studies have shown that in critically ill patients EVLW correlates with the severity of lung injury and that it does have a prognostic value. Thus, monitoring EVLW can be a useful additional tool in the goaldirected therapy of critically ill patients, especially those with severe sepsis and sepsis-induced acute lung injury. Keywords: Pulmonary edema, extravascular lung water, acute lung injury, critically ill patients

Nitric oxide-dependent inhibition of alveolar fluid clearance in hydrostatic lung edema

Formation of cardiogenic pulmonary edema in acute left heart failure is traditionally attributed to increased fluid filtration from pulmonary capillaries and subsequent alveolar flooding. Here, we demonstrate that hydrostatic edema formation at moderately elevated vascular pressures is predominantly caused by an inhibition of alveolar fluid reabsorption, which is mediated by endothelial-derived nitric oxide (NO). In isolated rat lungs, we quantified fluid fluxes into and out of the alveolar space and endothelial NO production by a two-compartmental double-indicator dilution technique and in situ fluorescence imaging, respectively. Elevation of hydrostatic pressure induced Ca(2+)-dependent endothelial NO production and caused a net fluid shift into the alveolar space, which was predominantly attributable to impaired fluid reabsorption. Inhibition of NO production or soluble guanylate cyclase reconstituted alveolar fluid reabsorption, whereas fluid clearance was blocked by exogenous NO donors or cGMP analogs. In isolated mouse lungs, hydrostatic edema formation was attenuated by NO synthase inhibition. Similarly, edema formation was decreased in isolated mouse lungs of endothelial NO synthase-deficient mice. Chronic heart failure results in endothelial dysfunction and preservation of alveolar fluid reabsorption. These findings identify impaired alveolar fluid clearance as an important mechanism in the pathogenesis of hydrostatic lung edema. This effect is mediated by endothelial-derived NO acting as an intercompartmental signaling molecule at the alveolo-capillary barrier.

Effect of a miniaturized extracorporeal circulation (MECC™System) on liver function

To evaluate the effect of a miniaturized extracorporeal circulation system (MECC System) compared to conventional extracorporeal circulation (ECC) regarding liver function in cardiac surgical patients. Double indicator dilution measurements were achieved by bolus injection of indocyanine green (ICG) for assessment of cardiac index (CI) and plasma disappearance rate of ICG (PDRig). Measurements were simultaneously performed preoperatively after induction of anaesthesia (T1), following admission on the ICU (T2) and 6 h postoperatively (T3). CI and PDRig were markedly increased after cardiac surgery without significant differences between groups. The percentage increase in CI was significantly correlated to the percentage increase in PDRig in both groups. Liver function improved after cardiac surgery in both groups of patients, which may partly be explained by an increase in CI under mild inotrope support. Differences between the extracorporeal circuits with respect to PDRig appear to be minimal in a group of patients without pre-existing liver injury.

Bedside assessment of extravascular lung water by dilution methods: Temptations and pitfalls

To review the advantages and limitations of dilution methods to assess extravascular lung water (EVLW) at the bedside and to discuss the clinical value of EVLW measurements. Experimental and clinical studies were searched in PUBMED by using "extravascular lung water" and "dilution method" as keywords and further selected as studies investigating either the reliability or the clinical usefulness of dilution methods to assess EVLW. Related articles and the reference lists of selected studies were scanned for additional relevant references. Both the double-indicator (thermo-dye) dilution and the single-indicator (cold saline) dilution methods showed close agreement with gravimetric measurement of EVLW (the reference ex vivo method) and have the advantage of being available at the bedside. Most limitations of dilution methods have been described in experimental conditions and lead to an underestimation of EVLW. These limitations include large pulmonary vascular obstruction, focal lung injury, and lung resection. Dilution methods provide an easy and clinically acceptable estimation of EVLW in most critically ill patients, including those with acute respiratory distress syndrome (ARDS). Assessing EVLW may be useful to predict outcome, to diagnose pulmonary edema, to better characterize patients with ARDS, to guide fluid therapy, and to assess the value of new treatments or ventilatory strategies in patients with pulmonary edema.

Inhaled nitric oxide does not prevent postpneumonectomy pulmonary edema in pigs

Increase in lung permeability is an inevitable consequence of pneumonectomy in relation to inflammatory injury and increased perfusion flow. We tested whether inhaled nitric oxide, a potent vasodilatator and anti-inflammatory agent, prevents postpneumonectomy edema in the first 24 hours after pneumonectomy in pigs. We assessed hemodynamics, gas exchange, extravascular lung water estimated with the double-indicator dilution method, and lung neutrophil sequestration measured on the basis of lung myeloperoxidase activity at 1 and 24 hours after left pneumonectomy in 14 pigs randomly assigned to inhaled nitric oxide (10 ppm) or control groups. Extravascular lung water content markedly increased at 1 and 24 hours after pneumonectomy, with no difference between the 2 groups. Hemodynamics did not differ between the 2 groups. Myeloperoxidase activity was higher and PaO2 values were lower in the nitric oxide group compared with in the control group. Over the 24 hours after pneumonectomy, intraoperative inhaled nitric oxide levels neither improved gas exchange nor attenuated accumulation of lung water. On the contrary, they were associated with an increase in lung neutrophil sequestration and deterioration of arterial oxygenation, suggesting the occurrence of an early and toxic effect of nitric oxide.

Transpulmonary lithium indicator dilution: a new method of intrathoracic blood volume measurement

Extravascular lung water (EVLW) measurement may improve outcome. Double indicator dilution, which is the most accurate method of EVLW measurement, is no longer commercially available. Lithium indicator dilution could be used to measure the intrathoracic blood volume index (ITBVI) and therefore EVLW.

Changes of jugular venous blood temperature associated with measurements of cerebral blood flow using the transcerebral double-indicator dilution technique

Changes of jugular venous blood temperature associated with measurements of cerebral blood flow using the transcerebral double-indicator dilution technique