Microcirculatory and Mitochondrial PO2 in different (Patho-)Physiological states of the rat heart

Handling and availability issues of oxygen are relevant processes fueling evolution of several diseases. Measuring oxygen in organs, at cellular and subcellular level bears several challenges. Earlier our group had developed dual-wavelength phosphorimeter allowing measurements of microcirculatory PO2 at two depths. Then, adaptation of this technique made the measurement of mitochondrial pO2 possible. The next logic step accomplished in this thesis was to combine both techniques. The aim of the thesis was therefore to further develop and characterize this phosphorimetric method of near-simultaneous measurements of microcirculatory and mitochondrial oxygenation in the heart in vivo. Then in two animal models, namely endotoxemia and right ventricular pressure overload, we measured the oxygenation level in the microcirculation and mitochondria and investigated the changes induced by therapeutic interventions. We hypothesized that in sepsis hypoxia would be found in non-resuscitated animals but no oxygen shortage would be found with supportive therapy indicating oxygen management issues arising from mitochondrial dysfunction. In pressure overload induced right heart failure we expected a switch increased anaerobic glycolysis without occurrence of hypoxia.<br/

Monitoring mitochondrial PO2: the next step

PURPOSE OF REVIEW: To fully exploit the concept of hemodynamic coherence in resuscitating critically ill one should preferably take into account information about the state of parenchymal cells. Monitoring of mitochondrial oxygen tension (mitoPO2) has emerged as a clinical means to assess information of oxygen delivery and oxygen utilization at the mitochondrial level. This review will outline the basics of the technique, summarize its development and describe the rationale of measuring oxygen at the mitochondrial level. RECENT FINDINGS: Mitochondrial oxygen tension can be measured by means of the protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT). After validation and use in preclinical animal models, the technique has recently become commercially available in the form of a clinical measuring system. This system has now been used in a number of healthy volunteer studies and is currently being evaluated in studies in perioperative and intensive care patients in several European university hospitals. SUMMARY: PpIX-TSLT is a noninvasive and well tolerated method to assess aspects of mitochondrial functio

Staphylococcus aureus Endocarditis as a Complication of Toxocariasis-Associated Endomyocarditis With Fibrosis: A Case Report

Complications associated with Toxocara canis infection are rare. We present a case of a patient with Staphylococcus aureus endocarditis as a complication of an endomyocardial fibrosis caused by T canis. The epidemiological, pathological, and clinical features of this rare complication are described here

Thyroid Hemorrhage Causing Airway Obstruction After Intravenous Thrombolysis for Acute Ischemic Stroke

Background: There are several life-threatening complications associated with intravenous thrombolysis after acute ischemic stroke such as symptomatic intracerebral hemorrhage, orolingual angioedema, or less frequent, bleedings of the mucosa or ecchymosis. Aside from these known critical incidents, rare and unfamiliar complications may be even more challenging, as they are unexpected and may mimic events that appear more frequently. We report a rare and unusual acute complication of intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) (0.9mg/kg) administered for acute ischemic stroke. Methods: Medical records, radiologic imaging, and pathologic specimens were reviewed. Results: A 86-year-old woman developed acute respiratory failure 20h after thrombolysis with suspected angioedema triggered by intravenous rt-PA. The inspiratory stridor and dyspnea were unresponsive to bronchodilators, corticosteroids, and inhaled adrenaline. After endotracheal intubation, laryngoscopy showed no significant supraglottic narrowing. Thyroidal sonography and cervical computed tomography revealed a thyroidal mass causing a tracheal and vascular compression compatible with thyroidal hemorrhage. Sonography showed a nodular goiter of the right thyroid gland. A total thyroidectomy was performed and histologic analysis confirmed a hemorrhage of the right thyroidal lobe. Conclusions: Acute airway obstruction with respiratory failure due to thyroidal hemorrhage after intravenous thrombolysis is an important life-threatening complication, mimicking an anaphylactic reaction or a more frequent orolingual angioedem

Prolonged administration of beta-lactam antibiotics - a comprehensive review and critical appraisal

Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care

縫い合わされる物語 : E.T.A. ホフマン『ブランビラ王女』におけるNadelとFiletzeug

Measurement of tissue oxygenation is a complex task and various techniques have led to a wide range of tissue PO 2 values and contradictory results. Tissue is compartmentalized in microcirculation, interstitium and intracellular space and current techniques are biased towards a certain compartment. Simultaneous oxygen measurements in various compartments might be of great benefit for our understanding of determinants of tissue oxygenation. Here we report simultaneous measurement of microvascular PO 2 (μPO 2) and mitochondrial PO 2 (mitoPO 2) in rats. The μPO 2 measurements are based on oxygen-dependent quenching of phosphorescence of the near-infrared phosphor Oxyphor G2. The mitoPO 2 measurements are based on oxygen-dependent quenching of delayed fluorescence of protoporphyrin IX (PpIX). Favorable spectral properties of these porphyrins allow simultaneous measurement of the delayed luminescence lifetimes. A dedicated fiber-based time-domain setup consisting of a tunable pulsed laser, 2 red-sensi

Improvement of Sidestream Dark Field Imaging with an Image Acquisition Stabilizer

Background: In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging.Methods: The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared.Results: Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 ± 0.15 N without vs. 0.62 ± 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 ± 2 s without vs. 42 ± 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 ± 5 s without vs. 67 ± 14 s with the IAS, p = 0.006).Conclusions: The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS improved both axial and lateral SDF image stability and thereby increased the critical force required to induce pressure artifacts. The IAS ensured a significantly increased duration of maintaining a stable image sequence

Microcirculatory and Mitochondrial PO2 in different (Patho-)Physiological states of the rat heart

Handling and availability issues of oxygen are relevant processes fueling evolution of several diseases. Measuring oxygen in organs, at cellular and subcellular level bears several challenges. Earlier our group had developed dual-wavelength phosphorimeter allowing measurements of microcirculatory PO2 at two depths. Then, adaptation of this technique made the measurement of mitochondrial pO2 possible. The next logic step accomplished in this thesis was to combine both techniques. The aim of the thesis was therefore to further develop and characterize this phosphorimetric method of near-simultaneous measurements of microcirculatory and mitochondrial oxygenation in the heart in vivo. Then in two animal models, namely endotoxemia and right ventricular pressure overload, we measured the oxygenation level in the microcirculation and mitochondria and investigated the changes induced by therapeutic interventions. We hypothesized that in sepsis hypoxia would be found in non-resuscitated animals but no oxygen shortage would be found with supportive therapy indicating oxygen management issues arising from mitochondrial dysfunction. In pressure overload induced right heart failure we expected a switch increased anaerobic glycolysis without occurrence of hypoxia.<br/