Systemic PaO2 oscillations cause mild brain injury in a pig model

OBJECTIVE: Systemic PaO2 oscillations occur during cyclic recruitment and derecruitment of atelectasis in acute respiratory failure and might harm brain tissue integrity. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult anesthetized pigs. INTERVENTIONS: Pigs were randomized to a control group (anesthesia and extracorporeal circulation for 20 hr with constant PaO2, n = 10) or an oscillation group (anesthesia and extracorporeal circulation for 20 hr with artificial PaO2 oscillations [3 cycles min⁻¹], n = 10). Five additional animals served as native group (n = 5). MEASUREMENTS AND MAIN RESULTS: Outcome following exposure to artificial PaO2 oscillations…

Multi frequency phase fluorimetry (MFPF) for oxygen partial pressure measurement: ex vivo validation by polarographic clark-type electrode.

BACKGROUND: Measurement of partial pressure of oxygen (PO2) at high temporal resolution remains a technological challenge. This study introduces a novel PO2 sensing technology based on Multi-Frequency Phase Fluorimetry (MFPF). The aim was to validate MFPF against polarographic Clark-type electrode (CTE) PO2 measurements. METHODOLOGY/PRINCIPAL FINDINGS: MFPF technology was first investigated in N = 8 anaesthetised pigs at FIO2 of 0.21, 0.4, 0.6, 0.8 and 1.0. At each FIO2 level, blood samples were withdrawn and PO2 was measured in vitro with MFPF using two FOXY-AL300 probes immediately followed by CTE measurement. Secondly, MFPF-PO2 readings were compared to CTE in an artificial circulatory s…

The effects of arterial carbon dioxide partial pressure and sevoflurane on capillary venous cerebral blood flow and oxygen saturation during craniotomy

Intraoperative routine monitoring of cerebral blood flow and oxygenation remains a technological challenge. Using the physiological principle of carbon dioxide reactivity of cerebral vasculature, we investigated a recently developed neuromonitoring device (oxygen-to-see, O2C device) for simultaneous measurements of regional cerebral blood flow (rvCBF), blood flow velocity (rvVelo), oxygen saturation (srvO2), and hemoglobin amount (rvHb) at the capillary venous level in patients subjected to craniotomy. METHODS: Twenty-six neurosurgical patients were randomly assigned to anesthesia with 1.4% or 2.0% sevoflurane end-tidal concentration. After craniotomy, a fiberoptic probe was applied on a ma…

Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment.

Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation.In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed …

An inhaled tumor necrosis factor-alpha-derived TIP peptide improves the pulmonary function in experimental lung injury: inhaled TIP peptide in experimental ALI

INTRODUCTION The lectin-like domain of TNF-α enhances the fluid clearance across the alveolar barrier. For experimental purposes, the lectin-like domain can be mimicked by a synthetic peptide representing the TIP-motif of TNF-α. The present study aims to assess the acute effect of TIP on the pulmonary function in a porcine model of acute respiratory distress syndrome (ARDS). METHODS Lung injury was induced in 16 pigs (25-27 kg) by bronchoalveolar lavage followed by injurious ventilation. Following randomisation, either nebulised TIP (1 mg/kg; AP301, APEPTICO, Vienna, Austria) or water for injection (control group) was administered. During 5 h of monitoring, the extravascular lung water inde…

Assessment of regional ventilation distribution: comparison of vibration response imaging (VRI) with electrical impedance tomography (EIT)

BACKGROUND: Vibration response imaging (VRI) is a bedside technology to monitor ventilation by detecting lung sound vibrations. It is currently unknown whether VRI is able to accurately monitor the local distribution of ventilation within the lungs. We therefore compared VRI to electrical impedance tomography (EIT), an established technique used for the assessment of regional ventilation. METHODOLOGY/PRINCIPAL FINDINGS: Simultaneous EIT and VRI measurements were performed in the healthy and injured lungs (ALI; induced by saline lavage) at different PEEP levels (0, 5, 10, 15 mbar) in nine piglets. Vibration energy amplitude (VEA) by VRI, and amplitudes of relative impedance changes (rel.ΔZ) …

Ventilation/perfusion ratios measured by multiple inert gas elimination during experimental cardiopulmonary resuscitation

Background During cardiopulmonary resuscitation (CPR) the ventilation/perfusion distribution (VA/Q) within the lung is difficult to assess. This experimental study examines the capability of multiple inert gas elimination (MIGET) to determine VA/Q under CPR conditions in a pig model. Methods Twenty-one anaesthetised pigs were randomised to three fractions of inspired oxygen (1.0, 0.7 or 0.21). VA/Q by micropore membrane inlet mass spectrometry-derived MIGET was determined at baseline and during CPR following induction of ventricular fibrillation. Haemodynamics, blood gases, ventilation distribution by electrical impedance tomography and return of spontaneous circulation were assessed. Inter…

Measurement of Cortical Microcirculation During Intracranial Aneurysm Surgery by Combined Laser-Doppler Flowmetry and Photospectrometry

Accidental vessel occlusion is one major risk of intracranial aneurysm surgery potentially causing cerebral ischemia. The intraoperative assessment of cerebral ischemia remains a technological challenge.As a novel approach, cortical tissue integrity was monitored using simultaneous measurements of regional capillary-venous cerebral blood flow (rvCBF), oxygen saturation (Srvo2), and hemoglobin amount (rvHb) during aneurysm surgery.Fifteen patients scheduled for aneurysm surgery of the anterior and posterior circulation were included. A fiber optic probe was placed on the cortex associated with the distal branch of the aneurysmatic vessel. Blinded measurements by combined laser-Doppler flowme…

Influence of respiratory rate and end-expiratory pressure variation on cyclic alveolar recruitment in an experimental lung injury model

Introduction Cyclic alveolar recruitment/derecruitment (R/D) is an important mechanism of ventilator-associated lung injury. In experimental models this process can be measured with high temporal resolution by detection of respiratory-dependent oscillations of the paO2 (ΔpaO2). A previous study showed that end-expiratory collapse can be prevented by an increased respiratory rate in saline-lavaged rabbits. The current study compares the effects of increased positive end-expiratory pressure (PEEP) versus an individually titrated respiratory rate (RRind) on intra-tidal amplitude of Δ paO2 and on average paO2 in saline-lavaged pigs. Methods Acute lung injury was induced by bronchoalveolar lavag…

Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium

Introduction Sepsis-associated delirium (SAD) increases morbidity in septic patients and, therefore, factors contributing to SAD should be further characterized. One possible mechanism might be the impairment of cerebrovascular autoregulation (AR) by sepsis, leading to cerebral hypo- or hyperperfusion in these haemodynamically unstable patients. Therefore, the present study investigates the relationship between the incidence of SAD and the status of AR during sepsis. Methods Cerebral blood flow velocity was measured using transcranial Doppler sonography and was correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx>0.3 indicates impaired AR). Mx was m…

Serial Measurement of Static and Dynamic Cerebrovascular Autoregulation After Brain Injury

In patients with neuronal injury, the knowledge of the status of cerebrovascular autoregulation can help to optimize the management of the cerebral perfusion pressure. This study characterizes dynamic and static cerebrovascular autoregulation during the first 7 days after severe traumatic brain injury or intracranial hemorrhage.After approval from the IRB, 16 patients were studied. Cerebral blood flow velocity (CBFV) was measured daily for the assessment of dynamic (10 patients) and static (16 patients) cerebrovascular autoregulation in both the middle cerebral arteries using the transcranial Doppler sonography. Dynamic cerebrovascular autoregulation (dAR) was measured using the cuff-deflat…

Intraoperative monitoring of cerebral microcirculation and oxygenation--a feasibility study using a novel photo-spectrometric laser-Doppler flowmetry.

The present study assesses the utility of a novel invasive device (O2C-, oxygen-to-see-device) for intraoperative measurement of the cerebral microcirculation. CO2 vasoreactivity during 2 different propofol concentrations was used to investigate changes of capillary venous cerebral blood flow (rvCBF), oxygen saturation (srvO2), and hemoglobin concentration (rvHb) during craniotomy.Thirty-four patients were randomly assigned to a low propofol (4 mg/kg/h) versus a high propofol (6 mg/kg/h) group. A fiberoptic probe was applied on the cortex next to the surgical site. Measurements were performed during lower (35 mm Hg) and higher (45 mm Hg) levels of partial pressure of carbon dioxide (paCO2).…

Human cerebral microcirculation and oxygen saturation during propofol-induced reduction of bispectral index †

† This study investigates the effects of propofol-induced changes in bispectral index (BIS) on cerebral microcirculation and oxygenation during craniotomies. † In 2 mm cerebral depth, an increase in propofol dosage resulted in increased oxygen saturation (srvO2 )w ithout reduction of capillary venous blood flow (rvCBF). † Difference in oxygen content (avDO2) and approximated cerebralmetabolicrateofoxygen (aCMRO2) decreased with an increase in propofol dosage in 2 mm cerebral depth. † Alterations in BIS showed no effect on rvCBF, srvO2 ,a nd haemoglobin amount (rvHb) or on avDO2 or aCMRO2 in 8 mm cerebral depth. † These findings suggest that the CBF/CMRO2 ratio is altered by propofol in a re…

PaO2oscillations caused by cyclic alveolar recruitment can be monitored in pig buccal mucosa microcirculation

BACKGROUND Cyclic alveolar recruitment and derecruitment play a role in the pathomechanism of acute lung injury and may lead to arterial partial pressure of oxygen (PaO(2) ) oscillations within the respiratory cycle. It remains unknown, however, if these PaO(2) oscillations are transmitted to the microcirculation. The present study investigates if PaO(2) oscillations can be detected in the pig buccal mucosa microcirculation. METHODS Respiratory failure was induced by surfactant depletion in seven pigs. PaO(2) oscillations caused by cyclic recruitment and derecruitment were measured in the thoracic aorta by fast fluorescence quenching of oxygen technology. Haemoglobin oxygen saturation, haem…

Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment.

Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …

Transcranial doppler and near infrared spectroscopy in the perioperative period

Maintenance of adequate blood flow and oxygen to the brain is one of the principal endpoints of all surgery and anesthesia. During operations in general anesthesia, however, the brain is at particular risk for silent ischemia. Despite this risk, the brain still remains one of the last monitored organs in clincial anesthesiology.Transcranial Doppler (TCD) sonography and near-infrared spectroscopy (NIRS) experience a revival as these noninvasive technologies help to detect silent cerebral ischemia. TCD allows for quantification of blood flow velocities in basal intracranial arteries. TCD-derived variables such as the pulsatility index might hint toward diminished cognitive reserve or raised i…

Influence of PEEP on cerebral blood flow and cerebrovascular autoregulation in patients with acute respiratory distress syndrome.

High levels of positive end-expiratory pressure (PEEP), as part of the treatment in patients with acute respiratory distress syndrome (ARDS), may prevent alveolar collapse and maintain oxygenation. PEEP potentially reduces cerebral venous return, increases intracranial blood volume, and may, therefore, affect cerebral blood flow (CBF) and cerebrovascular autoregulation (AR). This study investigates the effect of PEEP on CBF and AR in patients with respiratory failure.CBF velocity was measured using transcranial doppler and correlated with the invasive arterial blood pressure curve to calculate the index of AR Mx (Mx0.3 indicates impaired AR). Mx was measured at lower PEEP levels and after i…

Sevoflurane-induced reduction of bispectral index does not affect human cerebral microcirculation