Preload-adjusted left ventricular dP/dtmax: a sensitive, continuous, load-independent contractility index.

The classical indicators of left ventricular (LV) performances have been derived from pressure-volume (PV) and stroke work-volume plots obtained during various loading or pharmacological interventions. More recently, the preload-adjusted maximal change in pressure over time (PAdP/dtmax), derived from single beat PV analysis, has been shown to reflect the LV systolic performance accurately in varying conditions of inotropy and afterload. The objective of this study was to address whether PAdP/dtmax is a valid indicator of LV function in the setting of large preload variations, compared with the classical dP/dtmax-end-diastolic volume (EDV) and stroke work-EDV (preload recruitable stroke work) relationships. Nine anaesthetized and mechanically ventilated rats were instrumented with a ventricular conductance catheter. Stepwise preload reduction was achieved by repeated blood withdrawals (up to a total of 5 ml). Steady-state and dynamic PV loops were recorded during brief occlusion of the inferior vena cava, and LV function parameters were derived from these recordings. Our results demonstrate that PAdP/dtmax behaved in a similar manner to preload recruitable stroke work, reflecting well-maintained LV contractility during controlled haemorrhage until mean arterial pressure decreased below 40 mmHg. In contrast, dP/dtmax-EDV increased significantly and exhibited a curvilinear response that was associated with a large inter- and intra-animal variability. In a model of acute preload reduction, PAdP/dtmax was found to be the best indicator of systolic LV function. Given its simplicity, this real-time index derived from single beat analysis should be tested further in clinical settings.

Effects of isoflurane anesthesia on aortic compliance and systemic hemodynamics in compliant and noncompliant aortas.

OBJECTIVES: To investigate the effect of general anesthesia on aortic compliance and other cardiovascular hemodynamics in chronically instrumented pigs with compliant and noncompliant (stiff) aortas. DESIGN: Experimental study. SETTING: University animal laboratory. PARTICIPANTS: Twelve adult Yucatan miniature pigs. INTERVENTIONS: Chronic instrumentation of a compliant (control; n = 7) and noncompliant (n = 5) group to measure pressure and flow in the ascending aorta. A Teflon prosthesis was wrapped around the aorta (noncompliant group) to limit wall compliance. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded on the 15th postoperative day, both awake and after general anesthesia. Banding the aorta caused a significant decrease in arterial compliance (-49%, p<0.001) and increases in systolic blood pressure (SBP: +38%, p = 0.001) and pulse pressure (+107%, p< 0.01). Induction of anesthesia in the control group produced a 15% increase in arterial compliance (p<0.05), resulting in a subtle decrease in SBP (-12%), diastolic blood pressure (DBP; -13%) and mean blood pressure (MBP; -12%). Induction of anesthesia in the noncompliant group also caused a significant increase in arterial compliance (17%, p<0.001), but caused significant decreases in SBP (21%, p<0.01), DBP (23%, p<0.01) and MBP (22%, p<0.01) as compared with controls. CONCLUSIONS: Induction of general anesthesia caused a similar increase in total arterial compliance and was associated with a decrease in SBP that was more pronounced in animals with noncompliant aortas. These results indicated that anesthesia caused a greater hemodynamic effect on noncompliant (stiff) aortas and may explain the extensive hemodynamic fluctuation and instability often observed in atherosclerotic, elderly patients with stiff aortas.

Respiratory change in ECG-wave amplitude is a reliable parameter to estimate intravascular volume status.

Electrocardiogram (ECG) is a standard type of monitoring in intensive care medicine. Several studies suggest that changes in ECG morphology may reflect changes in volume status. The "Brody effect", a theoretical analysis of left ventricular (LV) chamber size influence on QRS-wave amplitude, is the key element of this phenomenon. It is characterised by an increase in QRS-wave amplitude that is induced by an increase in ventricular preload. This study investigated the influence of changes in intravascular volume status on respiratory variations of QRS-wave amplitudes (ΔECG) compared with respiratory pulse pressure variations (ΔPP), considered as a reference standard. In 17 pigs, ECG and arterial pressure were recorded. QRS-wave amplitude was measured from the Biopac recording to ensure that in all animals ECG electrodes were always at the same location. Maximal QRS amplitude (ECGmax) and minimal QRS amplitude (ECGmin) were determined over one respiratory cycle. ΔECG was calculated as 100 × [(ECGmax - ECGmin)/(ECGmax + ECGmin)/2]. ΔECG and ΔPP were simultaneously recorded. Measurements were performed at different time points: during normovolemic conditions, after haemorrhage (25 mL/kg), and following re-transfusion (25 mL/kg) with constant tidal volume (10 mL/kg) and respiration rate (15 breath/min). At baseline, ΔPP and ΔECG were both <12 %. ΔPP were significantly correlated with ΔECG (r(2) = 0.89, p < 0.001). Volume loss induced by haemorrhage increased significantly ΔPP and ΔECG. Moreover, during this state, ΔPP were significantly correlated with ΔECG (r(2) = 0.86, p < 0.001). Re-transfusion significantly decreased ΔPP and ΔECG, and ΔPP were significantly correlated with ΔECG (r(2) = 0.90, p < 0.001). The observed correlations between ΔPP and ΔECG at each time point of the study suggest that ΔECG is a reliable parameter to estimate the changes in intravascular volume status and provide experimental confirmation of the "Brody effect."

ARFI-prepared MRgHIFU in liver: simultaneous mapping of ARFI-displacement and temperature elevation, using a fast GRE-EPI sequence.

MR acoustic radiation force imaging (ARFI) is an elegant adjunct to MR-guided high intensity focused ultrasound for treatment planning and optimization, permitting in situ assessment of the focusing and targeting quality. The thermal effect of high intensity focused ultrasound pulses associated with ARFI measurements is recommended to be monitored on line, in particular when the beam crosses highly absorbent structures or interfaces (e.g., bones or air-filled cavities). A dedicated MR sequence is proposed here, derived from a segmented gradient echo-echo planar imaging kernel by adding a bipolar motion encoding gradient with interleaved alternating polarities. Temporal resolution was reduced to 2.1 s, with in-plane spatial resolution of 1 mm. MR-ARFI measurements were executed during controlled animal breathing, with trans-costal successively steered foci, to investigate the spatial modulation of the focus intensity and the targeting offset. ARFI-induced tissue displacement measurements enabled the accurate localization, in vivo, of the high intensity focused ultrasound focal point in sheep liver, with simultaneous monitoring of the temperature elevation. ARFI-based precalibration of the focal point position was immediately followed by trans-costal MR-guided high intensity focused ultrasound ablation, monitored with a conventional proton resonance frequency shift MR thermometry sequence. The latter MR thermometry sequence had spatial resolution and geometrical distortion identical with the ARFI maps, hence no coregistration was required.

Superiority of desflurane over sevoflurane and isoflurane in the presence of pressure-overload right ventricle hypertrophy in rats.

BACKGROUND: Pulmonary hypertension and associated pressure-overload right ventricular (RV) hypertrophy represent a tremendous challenge for the anesthesiologist, as optimal perioperative management is mandatory. However, the ideal anesthetic agent remains unknown because scientific evidence is lacking. METHODS: Twenty-eight rats were randomly assigned to a control or a monocrotaline group (60 mg kg). Four weeks later, animals were anesthetized, instrumented with a RV conductance catheter, and underwent well-controlled dose-responses to isoflurane, desflurane, and sevoflurane inhalation (minimum alveolar concentrations 0.5, 1.0, 1.5). RESULTS: Compared with controls, rats injected with monocrotaline presented with RV hypertrophy, increased afterload, and contractility, without change in cardiac output. The ratio of pressures in the right over the left circulation increased. The halogenated volatiles differently altered hemodynamics. Sevoflurane reduced RV contractility (more than 50%) and the right over left pressures ratio increased (from 0.41 ± 0.08 [SD] to 0.82 ± 0.14; P < 0.0001) secondary to profound concomitant systemic vasodilation, demonstrating a critical pressure gradient between right and left circulations. Despite significantly higher RV systolic pressures and afterload, desflurane decreased RV contractility much less (<10%; P < 0.0001 vs. sevoflurane) and maintained the right over left pressures ratio at more favorable values (0.47 ± 0.07; P < 0.0001 vs. sevoflurane). Isoflurane presented intermediate effects. CONCLUSION: In the presence of pressure-overload RV hypertrophy, hemodynamics are better preserved under desflurane inhalation, whereas sevoflurane-and to a lesser extent isoflurane-cause large discrepancies on the left and right circulations, raising the right over left pressures ratio to critical levels despite a conserved cardiac output.

Relevance of the volume-axis intercept, V0, compared with the slope of end-systolic pressure-volume relationship in response to large variations in inotropy and afterload in rats.

The end-systolic pressure-volume relationship (ESPVR) is proposed and used as a reliable index of left ventricular (LV) contractility despite the fact that its afterload independence has been challenged. Furthermore, the physiological relevance of its volume-axis intercept, V(0), remains unclear. Systemic haemodynamics and pressure-volume loops obtained by inferior vena cava occlusion were recorded in 21 rats anaesthetized by isoflurane inhalation and instrumented with a conductance pressure-volume catheter in response to incremental I.V. doses of adrenaline, dobutamine, phenylephrine, metoprolol, papaverine and isoflurane inhalation. In conditions with large variations (± 100%) of both inotropy and afterload, infusion of negative inotropic drugs was associated with a dose-dependent rightward shift of ESPVR accompanied by a decrease in its slope (end-systolic elastance, E(es)), whereas positive inotropic agents produced an isolated decrease in V(0). With the predominant vasoactive drugs, there was a dose-dependent change in E(es) without major horizontal shifts, demonstrating that this slope mainly represents LV afterload rather than inotropy. When contractility was altered, V(0) was negatively correlated to the preload-adjusted contractility index, PAdP/dt(max), demonstrating that a reduced V(0) provides a good reflection of increased LV contractility. From these results, we computed a logarithmically adjusted E(es)/V(0) ratio, which resulted in reasonably strong concordance with PAdP/dt(max), including all the investigated drugs and dosages [n = 288; bias, 0.8 ± 16.2% (SD)]. Concordance with E(es) (bias, 7.2 ± 58.7%) or V(0) (bias, -0.6 ± 33.4%), used alone or with other commonly used contractility indices, was far less significant. In contrast to E(es), V(0) provides a relatively good LV contractility index because it is much less sensitive to afterload.

Pre-ejection period to estimate cardiac preload dependency in mechanically ventilated pigs submitted to severe hemorrhagic shock.

BACKGROUND: Respiratory change in pre-ejection period (ΔPEP) has been described as a potential parameter for monitoring cardiac preload dependency in critically ill patients. This study was designed to describe the relationship between ΔPEP and pulse pressure variation (PPV) in pigs submitted to severe hemorrhagic shock. METHODS: In 17 paralyzed, anesthetized mechanically ventilated pigs, electrocardiography, arterial pressure, and cardiac output derived from pulmonary artery catheter were recorded. Hemorrhagic shock was induced by removal of blood volume followed by restoration. PEP was defined as the time interval between the beginning of the Q wave on the electrocardiogram and the upstroke of the invasive radial arterial pressure curve. RESULTS: At baseline, ΔPEP and PPVs were both <12% with PPV significantly correlated with ΔPEP (r = 0.96, p < 0.001). Volume loss induced by hemorrhage significantly increased PPV and ΔPEP values (p < 0.05). During severe hemorrhage, PPV correlated well with ΔPEP (r = 0.88, p < 0.001) with PPV values significantly higher than ΔPEP (p < 0.05). However, the reproducibility of ΔPEP measurements was significantly better than PPV during this step (p < 0.05). Retransfusion significantly decreased PPV and ΔPEP (p < 0.05) with PPV significantly correlated to ΔPEP (r = 0.94, p < 0.001). CONCLUSION: Available correlations between PPV and ΔPEP at each time of the study were observed, meaning that ΔPEP is a reliable parameter to estimate and track the changes in cardiac preload dependency. Moreover, during the severe hemorrhagic shock period, ΔPEP measurements were more reproducible than PPV values.

In vivo labelling of resting monocytes in the reticuloendothelial system with fluorescent iron oxide nanoparticles prior to injury reveals that they are mobilized to infarcted myocardium.

AIMS: To evaluate the feasibility of loading resting monocytes/macrophages by intravenous (i.v.) injection of fluorescent iron oxide nanoparticles prior to injury and tracking of these cells in the very same animal to myocardial infarction (MI) by magnetic resonance imaging (MRI) and optical imaging. METHODS AND RESULTS: Rats were injected with fluorescent iron oxide nanoparticles (10 mg/kg) (n = 15) prior to injury. After disappearance of the nanoparticles from the blood, MI was induced. Monocytes/macrophages were then tracked in the very same animal by MRI and optical imaging. Control groups were (i) non-injected animals (n = 15), (ii) injected animals associated with a sham operation (n = 8), and (iii) animals treated with an anti-inflammatory agent (n = 6). The presence of iron-loaded cells can be detected by MRI in vivo in the infarcted myocardium. Here, we showed that the detection of inflammatory cells in vivo correlated well with ex vivo imaging (MRI and reflectance fluorescence) and histology. We also showed that the method is robust enough to depict changes in the inflammatory response. CONCLUSION: This study demonstrates that resting monocytes/macrophages can be loaded in vivo by a simple i.v. injection of fluorescent superparamagnetic iron oxide nanoparticles prior to injury and then tracked, in the same animal, in a model of ischaemia-reperfusion leading to myocardial infarct. Although previous studies of macrophages infiltration following MI have labelled the macrophages after injury, this study, for the first time, has pre-load the resting monocytes with fluorescent iron oxide nanoparticles.

Delayed production of IL-18 in lungs and pancreas of rats with acute pancreatitis.

BACKGROUND/AIMS: During acute pancreatitis, tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 play a pivotal role in promoting injury in the pancreas and remote organs. IL- 18 is a more recently discovered proinflammatory cytokine whose expression is also increased in serum. However, the profile of IL-18 expression in the pancreas and lung is unknown, and the aim of our study was to investigate such expression in rats with pancreatitis. METHODS: Acute pancreatitis was induced by taurocholic acid and endotoxin. Pulmonary and pancreatic injury was measured by biological and histological parameters. Lung injury was also evaluated in ex vivo lung preparations. RESULTS: Pancreatic and pulmonary injury appeared within 2 h after pancreatitis induction and persisted until the end of the protocol (18 h). TNF-α, IL-1 and IL-6 expression increased early in the lungs and pancreas, with a partial recovery by the end of the study. In contrast, IL-18 increased mostly by the end of the protocol (18 h after pancreatitis induction). CONCLUSION: IL-18 may serve as an additional marker to monitor the severity of inflammation during pancreatitis since its tissue production is delayed and appears after that of more commonly investigated cytokines. and IAP.

Influence of tidal volume on pulse pressure variations in hypovolemic ventilated pigs with acute respiratory distress-like syndrome.

BACKGROUND: Sensitivity and specificity of respiratory change in pulse pressure (DeltaPP) to predict preload dependency has been questioned at small tidal volumes (VT) in critically ill patients suffering from acute respiratory distress syndrome (ARDS). We studied DeltaPP in pigs with ARDS-like syndrome during reversible hemorrhagic shock. METHODS: Prospective, observational animal study in a Laboratory Investigation Unit. Sixteen deeply sedated mechanically ventilated pigs were successively ventilated with VT of 10 ml/kg at a respiratory rate of 15 breaths/min (RR15) and VT of 6 ml/kg at RR15 and RR25. ARDS-like syndrome was produced by lung lavage in eight pigs (ARDS group). Severe hemorrhagic shock was induced by removal of 40% of total blood volume followed by restoration. RESULTS: After bleeding, in the control group ventilated with a VT of 10 ml/kg, DeltaPP increased from 8.5 (95% confidence interval [CI], 7.1 to 9.9%) to 18.5% (CI, 15.3 to 21.7%; P<0.05). In the ARDS group, this index increased similarly, from 7.1% (95% CI, 5.3 to 9.0%) to 20.1% (CI, 15.3 to 24.9%; P<0.05). In control lungs, reduction in VT from 10 to 6 ml/kg reduced the DeltaPP reaction by 40%, although it remained a statistically valid indicator of hypovolemia regardless of the RR value. In contrast, in the ARDS group, DeltaPP was an unreliable hypovolemia marker at low VT ventilation, regardless of the RR value (p=not statistically significant). CONCLUSIONS: The present study suggests that DeltaPP is a reliable indicator of severe hypovolemia in pigs with healthy lungs regardless of VT or RR. In contrast, in pigs with ARDS-like syndrome ventilated with small VT, DeltaPP is not a good indicator of severe hemorrhage. However, in this setting, indexing DeltaPP to respiratory changes in transpulmonary pressure allows this marker to significantly indicate the occurrence of hypovolemia.

Left ventricular hypertrophy induced by reduced aortic compliance.

AIM: It was the aim of this study to investigate the long- term effects of reduced aortic compliance on cardiovascular hemodynamics and cardiac remodeling. METHOD: Sixteen swine, divided into 2 groups, a control and a banding group, were instrumented for pressure and flow measurement in the ascending aorta. Teflon prosthesis was wrapped around the aortic arch in order to limit wall compliance in the banding group. Hemodynamic parameters were recorded throughout a 60-day period. After sacrifice, the mean cell surface of the left ventricle was documented. RESULTS: Banding decreased aortic compliance by 49 +/- 9, 44 +/- 16 and 42 +/- 7% on the 2nd, 30th and 60th postoperative day, respectively (p < 0.05), while systolic pressure increased by 41 +/- 11, 30 +/- 11 and 35 +/- 12% (p < 0.05), and pulse pressure by 86 +/- 27, 76 +/- 21 and 88 +/- 23%, respectively (p < 0.01). Aortic characteristic impedance increased significantly in the banding group. Diastolic pressure, cardiac output and peripheral resistance remained unaltered. The mean left ventricular cell surface area increased significantly in the banding group. CONCLUSIONS: Acute reduction in aortic compliance results in a significant increase in characteristic and input impedance, a significant decrease in systemic arterial compliance and a subsequent increase in systolic and pulse pressures leading to left ventricular hypertrophy.

Lung mechanical and vascular changes during positive- and negative-pressure lung inflations: importance of reference pressures in the pulmonary vasculature.

The continuous changes in lung mechanics were related to those in pulmonary vascular resistance (Rv) during lung inflations to clarify the mechanical changes in the bronchoalveolar system and the pulmonary vasculature. Rv and low-frequency lung impedance data (Zl) were measured continuously in isolated, perfused rat lungs during 2-min inflation-deflation maneuvers between transpulmonary pressures of 2.5 and 22 cmH(2)O, both by applying positive pressure at the trachea and by generating negative pressure around the lungs in a closed box. ZL was averaged and evaluated for 2-s time windows; airway resistance (Raw), parenchymal damping and elastance (H) were determined in each window. Lung inflation with positive and negative pressures led to very similar changes in lung mechanics, with maximum decreases in Raw [-68 +/- 4 (SE) vs. -64 +/- 18%] and maximum increases in H (379 +/- 36 vs. 348 +/- 37%). Rv, however, increased with positive inflation pressure (15 +/- 1%), whereas it exhibited mild decreases during negative-pressure expansions (-3 +/- 0.3%). These results demonstrate that pulmonary mechanical changes are not affected by the opposing modes of lung inflations and confirm the importance of relating the pulmonary vascular pressures in interpreting changes in Rv.

Adverse effects of methylene blue on the central nervous system.

BACKGROUND: An increasing number of clinical observations suggest adverse neurologic outcome after methylene blue (MB) infusion in the setting of parathyroid surgery. Hence, the aim of the current study was to investigate the potentially neurotoxic effects of MB using a combination of in vivo and in vitro experimental approaches. METHODS: Isoflurane-anesthetized adult rats were used to evaluate the impact of a single bolus intravascular administration of MB on systemic hemodynamic responses and on the minimum alveolar concentration (MAC) of isoflurane using the tail clamp test. In vivo, MB-induced cell death was evaluated 24 h after MB administration using Fluoro-Jade B staining and activated caspase-3 immunohistochemistry. In vitro, neurotoxic effects of MB were examined in hippocampal slice cultures by measuring excitatory field potentials as well as propidium iodide incorporation after MB exposure. The impact of MB on dendritic arbor was evaluated in differentiated single cell neuronal cultures. RESULTS: Bolus injections of MB significantly reduced isoflurane MAC and initiated widespread neuronal apoptosis. Electrophysiologic recordings in hippocampal slices revealed a rapid suppression of evoked excitatory field potentials by MB, and this was associated with a dose-dependent effect of this drug on cell death. Dose-response experiments in single cell neuronal cultures revealed that a 2-h-long exposure to MB at non-cell-death-inducing concentrations could still induce significant retraction of dendritic arbor. CONCLUSIONS: These results suggest that MB exerts neurotoxic effects on the central nervous system and raise questions regarding the safety of using this drug at high doses during parathyroid gland surgery.

Improved visualization of vessels and hepatic tumors by micro-computed tomography (CT) using iodinated liposomes.

OBJECTIVE: The goal of this study was to determine whether iodinated liposomes are a suitable tracer for mice microvessel and liver imaging by preclinical computed tomography (CT). MATERIALS AND METHODS: Iodinated liposomes were evaluated for vessel and liver imaging. A first group of nude mice was imaged by micro-CT after i.v. injection of liposomes at 1 or 2 gI/kg body weight (b.w.) for intervals up to 24 hours. A second group of mice bearing liver micrometastases was imaged after injection of liposomes at 2 gI/kg b.w. for intervals up to 24 hours. RESULTS: Vascular enhancements of 120 +/- 8 and 322 +/- 20 Hounsfield unit (HU) were obtained after injection of liposomes at 1 or 2 gI/kg b.w., respectively. This enhancement decreased with a blood half-life of 135 +/- 10 and 86 +/- 9 minutes, respectively. Liver enhancement of 157 +/- 5 and 235 +/- 23 HU were obtained after injection of iodinated liposomes at 1 and 2 gI/kg b.w., respectively. Liver micrometastases (250 microm) were detectable after injection of iodinated liposomes at 2 gI/kg b.w. CONCLUSIONS: Iodinated liposomes are a suitable contrast agent for vessels and liver imaging by micro-CT allowing clear vascular enhancement and detection of small liver metastases.

High-resolution complementary spatial modulation of magnetization (CSPAMM) rat heart tagging on a 1.5 Tesla Clinical Magnetic Resonance System: a preliminary feasibility study.

The purpose of this study was to assess the feasibility of cardiac magnetic resonance (MR) tagging in rats on a standard clinical 1.5T MR system. Small animal models have been largely used as an experimental model in cardiovascular disease studies but mainly on high field systems (>4T) dedicated to research. Given the larger availability of routine clinical MR systems in centers with active cardiac research programs, it is of great interest to perform small animal imaging on whole-body MR systems of moderate field strength. The feasibility study was performed on 7 rats within 6 to 8 hours after myocardial infarction and 3 normal control rats. Myocardial strain was measured successfully in normal rats using the harmonic phase (ie, HARP) method, and a transmural gradient was demonstrated. In a rat model of acute occlusion/reperfusion, the myocardial circumferential strains were decreased, but the transmural strain gradient was preserved. This study demonstrated the feasibility of cardiac MR tagging in rats with a subendocardial resolution using a clinical 1.5T system.

Volume-targeted modes of modern neonatal ventilators: how stable is the delivered tidal volume?

OBJECTIVE: Volume-targeted modes are designed to deliver a constant tidal volume (V(t)) at lowest possible pressure independently of changes in compliance, resistance, and leak of the respiratory system. We examined whether these volume-targeted modes respond rapidly enough to sudden changes in respiratory mechanics (e.g., selective intubation, surfactant administration, endotracheal tube kinking, de-kinking, obstruction), resulting in insufficient or excessive V(t) delivery. DESIGN AND SETTING: Bench study of six neonatal ventilators in the volume-targeted mode simulating preterm and full-term infant settings on a test lung. MEASUREMENTS AND RESULTS: Breath-to-breath expiratory V(t) were measured after rapid compliance, resistance, and leak changes. Under our test settings all ventilators showed important volume overshooting following rapid increase in compliance or decrease in resistance. Between one and 16 inflations were required to return to the set V(t). Some ventilators delivered inaccurate V(t) under steady state condition while others showed considerable breath-to-breath V(t) variability. CONCLUSIONS: We observed inaccurate V(t) delivery under specific conditions as well as immediate and sometimes prolonged volume overshooting after a rapid respiratory system compliance increase or resistance decrease in volume-targeted modes of modern neonatal ventilators. Similar discrepancies between the set V(t) and the delivered inflations can be harmful in clinical situations, especially in newborns. Their clinical relevance needs to be clarified with safety studies in the neonatal population and we encourage manufacturers to further improve the ventilators algorithms.

The contribution of the pulmonary microvascular pressure in the maintenance of an open lung during mechanical ventilation.

Changes in pulmonary hemodynamics modify the mechanical properties of the lungs. The effects of alterations in pulmonary capillary pressure (Pc) were investigated on the airway and lung tissue mechanics during positive-pressure ventilation and following lung recruitment maneuvers. Isolated, mechanically normoventilated (PEEP 2.5 cmH(2)O) rat lungs were perfused with Pc set to 0 (unperfused), 5, 10 or 15 mmHg, in random sequence. The pulmonary input impedance (ZL) was measured at end-expiration before and after a 10-min long ventilation. After inflation of the lung to 30 cmH(2)O during P-V curve recordings, another set of ZL was measured to evaluate the degree of recruitment. The PEEP was then decreased to 0.5 cmH(2)O and the sequence was repeated. Airway resistance and parenchymal damping and elastance (H) were estimated from ZL by model fitting. From the P-V curves, elastance (E) and hysteresis indices were determined. Mechanical ventilation at both PEEP levels resulted primarily in elevations in the tissue parameters, with the greatest increases at the 0 Pc level (H changes of 27.8+/-4.2 and 61.3+/-3.7% at 2.5 and 0.5 cmH(2)O PEEP, respectively). The maintenance of physiological Pc (10 mmHg) led to a significantly lower elevation in H (11.6+/-1.5% versus 31.4+/-3.6%). The changes in the oscillatory mechanics were also reflected in E and the hysteresis of the P-V curves. These findings indicate that pulmonary hypoperfusion during mechanical ventilation forecasts a parenchymal mechanical deterioration. Physiological pressure in the pulmonary capillaries is therefore an important mechanical factor promoting maintenance of the stability of the alveolar architecture during positive-pressure mechanical ventilation.

Time course of lung injury in rat acute pancreatitis.

OBJECTIVE: Lung injury is a severe complication of acute pancreatitis that increases the mortality rate of the disease. The pathophysiology of acute pancreatitis has been studied in several experimental models, but the kinetics of pulmonary complications in relation to the pancreatic disease is not completely understood. We then studied the severity of acute pancreatitis-associated lung injury over 18h in rats that had taurocholic acid injection in the pancreatic duct and determined whether blood collected from rats with pancreatitis is toxic enough to induce injury in normal lungs. DESIGN AND SETTING: Prospective, randomized, and controlled animal study in an animal research laboratory in a university hospital. INTERVENTIONS: We isolated lungs from rats with acute pancreatitis 2, 6, and 18h after taurocholic acid injection in the biliopancreatic duct and perfused them with blood collected from the same rats. Additionally, blood collected from rats with acute pancreatitis (time-points: 2 and 6h) was perfused in normal lungs. MEASUREMENTS AND RESULTS: Taurocholic acid injection induced a severe pancreatic injury that started as early as 2h after the injection and persisted without recovery over the 18-h study period. In contrast, the pulmonary injury was transient, appearing at the 6-h time point with recovery by the end of the study. Pulmonary injury was moderate and evidenced mostly during lung reperfusion. Interestingly, blood collected at the 2-h time point in pancreatic rats induced pulmonary injury in normal lungs while blood collected at the 6-h time-point was not toxic. CONCLUSIONS: While pancreatic injury persists over the full experimental period, pulmonary injury is transient in our experimental model. The recovery of lung injury by 18h might be explained by a decrease in the overall toxicity of pancreatic blood over time.

Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.

In this study, we have found that dipeptidylpeptidase IV (DPPIV) plays in vivo an active role in the modulation of the inflammatory response of chronic rhinosinusitis. Human nasal mucosa expresses DPPIV-like immunoreactivity in submucosal seromucus glands, leukocytes, and endothelial cells of blood vessels. DPPIV enzymatic activity in nasal tissue biopsies taken from patients suffering from chronic rhinosinusitis was correlated inversely with the density of inflammatory cells in the nasal mucosa, and the DPPIV activity rose when chronic rhinosinusitis was treated. By using a pig animal model, we have shown that the intranasal administration of recombinant DPPIV decreased the vasodilatation induced by exogenous substance P (SP), a proinflammatory peptide released by sensory nerves. In contrast, an inhibitor of DPPIV enhanced the vasodilatatory effect at low doses of SP. SP5-11 was 100- to 1000-fold less potent than SP as a vasodilator of the nasal mucosa. The vasodilatatory effect of SP was abolished by a NK1 receptor antagonist. In conclusion, these results suggest a new pathophysiological pathway for rhinitis based on clinical observations in humans, indicating the involvement of an enzyme to modulate non-adrenergic and non-cholinergic substrate that occurred during nasal dysfunctions.

Effects of pulmonary vascular pressures and flow on airway and parenchymal mechanics in isolated rat lungs.

Changes in pulmonary hemodynamics have been shown to alter the mechanical properties of the lungs, but the exact mechanisms are not clear. We therefore investigated the effects of alterations in pulmonary vascular pressure and flow (Q(p)) on the mechanical properties of the airways and the parenchyma by varying these parameters independently in three groups of isolated perfused normal rat lungs. The pulmonary capillary pressure (Pc(est)), estimated from the pulmonary arterial (Ppa) and left atrial pressure (Pla), was increased at constant Q(p) (n = 7), or Q(p) was changed at Pc(est) = 10 mmHg (n = 7) and at Pc(est) = 20 mmHg (n = 6). In each condition, the airway resistance (Raw) and parenchymal damping (G) and elastance (H) were identified from the low-frequency pulmonary input impedance spectra. The results of measurements made under isogravimetric conditions were analyzed. The changes observed in the mechanical parameters were consistent with an altered Pla: monotonous increases in Raw were observed with increasing Pla, whereas G and H were minimal at Pla of approximately 7-10 mmHg and increased at lower and higher Pla. The results indicate that Pla, and not Ppa or Q(p), is the primary determinant of the mechanical condition of the lungs after acute changes in pulmonary hemodynamics: the parenchymal mechanics are impaired if Pla is lower or higher than physiological, whereas airway narrowing occurs at high Pla.