Benedict Kjærgaard

Apneic oxygenation combined with extracorporeal arteriovenous carbon dioxide removal provides sufficient gas exchange in experimental lung injury.

We hypothesized that apneic oxygenation, using an open lung approach, combined with extracorporeal CO2 removal, would provide adequate gas exchange in acute lung injury. We tested this hypothesis in nine anesthetized and mechanically ventilated pigs (85–95 kg), in which surfactant was depleted from the lungs by repeated lung lavage. After a lung recruitment maneuver, the tracheal tube was connected to 20 cm H2O continuous pressure (100% O2) for oxygenation of the blood. A pumpless membrane ventilator (interventional lung assist by Novalung) was connected in an arteriovenous shunt for CO2 removal. PaO2 and PaCO2 were recorded for 3.5 hours. PaO2 was 464 (403, 502) mm Hg (median and interquartile range) throughout the experiment. The O2 uptake through the lungs was 185 (164, 212) ml/min. PaCO2 increased asymptotic towards 60 mm Hg. The CO2 removal through the membrane ventilator was 180 (150, 180) ml/min. Thus, the method provided adequate gas exchange in this experimental model, suggesting that it might have potential as an alternative treatment modality in acute lung injury.

MEGAVOLTAGE IMAGE-BASED DYNAMIC MULTILEAF COLLIMATOR TRACKING OF A NITI STENT IN PORCINE LUNGS ON A LINEAR ACCELERATOR

PURPOSE To investigate the accuracy and potential limitations of MV image-based dynamic multileaf collimator (DMLC) tracking in a porcine model on a linear accelerator. METHODS AND MATERIALS A thermo-expandable NiTi stent designed for kilovoltage (kV) X-ray visualization of lung lesions was inserted into the bronchia of three anaesthetized Göttingen minipigs. A four-dimensional computed tomography scan was used for planning a five-field conformal treatment with circular multileaf collimator (MLC) apertures. A 22.5 Gy single fraction treatment was delivered to the pigs. The peak-to-peak stent motion was 3 to 8 mm, with breathing periods of 1.2 to 4 s. Before treatment, X-ray images were used for image-guided setup based on the stent. During treatment delivery, continuous megavoltage (MV) portal images were acquired at 7.5 Hz. The stent was segmented in the images and used for continuous adaptation of the MLC aperture. Offline, the tracking error in beams eye view of the treatment beam was calculated for each MV image as the difference between the MLC aperture center and the segmented stent position. The standard deviations of the systematic error Σ and the random error σ were determined and compared with the would-be errors for a nontracking treatment with pretreatment image-guided setup. RESULTS Reliable stent segmentation was obtained for 11 of 15 fields. Segmentation failures occurred when image contrast was dominated by overlapping anatomical structures (ribs, diaphragm) rather than by the stent, which was designed for kV rather than MV X-ray visibility. For the 11 fields with reliable segmentation, Σ was 0.5 mm/0.4 mm in the two imager directions, whereas σ was 0.5 mm/1.1 mm. Without tracking, Σ and σ would have been 1.7 mm/1.4 mm and 0.8 mm/1.4 mm, respectively. CONCLUSION For the first time, in vivo DMLC tracking has been demonstrated on a linear accelerator showing the potential for improved targeting accuracy. The study mimicked the envisioned patient workflow of future patient treatments. Clinical implementation of MV image-based tracking would require markers designed for MV visibility.

A porcine model of massive, totally occlusive, pulmonary embolism

BACKGROUND A reliable, animal model of massive, totally occlusive, pulmonary embolism (PE) is lacking. OBJECTIVES To design an animal model of totally occlusive PE and to challenge the model by a plasminogen activator. METHODS In eight anaesthetized pigs (approximately 90 kg) a massive preformed autologous thrombus was injected into the caval vein. One animal was autopsied to assess the extent of injected clot, whereas in the other animals extracorporeal life support (ECLS) was initiated and continued for three hours. These animals received 100 mg rt-PA. Blood gases, coagulation tests, creatine kinase (CK), lactate dehydrogenase (LDH), end-tidal CO2, systemic and pulmonary artery blood pressures and flow were registered. RESULTS All animals went into circulatory arrest within 2 minutes after injection of the thrombus. In the animal where ECLS was not started, autopsy relieved a totally occlusive embolus of the pulmonary artery. The ECLS maintained a systemic blood flow of 6-8 L/min with adequate oxygenation and CO2-removal. However, lactate increased and base-excess became negative. Ddimer increased, fibrinogen decreased, and CK and LDH increased. All seven animals were weaned from ECLS. Despite the rt-PA treatment, the animals had at that time low end tidal CO2/PaCO2 ratio and increased mean pulmonary arterial pressure, suggesting a significant amount of embolic material remaining in the pulmonary artery. CONCLUSION This model of massive, totally occlusive, pulmonary embolism mimics well fatal PE seen in the clinic, and has the potential for use in testing of new therapeutic interventions.

Extra corporeal life support makes advanced radiologic examinations and cardiac interventions possible in patients with cardiac arrest

OBJECTIVES Extra corporeal life support (ECLS) with a mobile system is an option in the treatment of cardiac arrest often of unknown reason. After commencing ECLS the search for a provoking origin may include advanced radiologic examinations before deciding further treatment. METHODS Fifty-eight patients with circulatory arrest were treated with ECLS. In 15 cases the patient went through CT scans of the cerebrum, thorax and abdomen, pulmonary angiography, and or invasive cardiologic examinations. Two patients were transported in ambulance and helicopter on ECLS before the examinations. RESULTS The underlying diagnosis in the 15 patients were: lung embolism (n = 6), accidental hypothermia (n = 2), myocardial infarction (n = 2), WPW syndrome (n = 1), sepsis (n = 1), disseminated intravascular coagulation (n = 2), high voltage accident (n = 1). Only in the last mentioned patient the CT scan was indicative of major brain damage, and further treatment was stopped. Five of the 15 examined patients survived. The diagnoses in the survivors were lung embolism (n = 2), myocardial infarction (n = 1), WPW syndrome (n = 1), and accidental hypothermia (n = 1). The results of the radiologic examinations had great influence on all treatments. CONCLUSIONS It is possible to make radiological examinations i.e., CT scans, pulmonary and coronary angiography in patients suffering heart arrest of unknown origin with the use of ECLS in order to improve patient treatment in this very high-risk population.

A mobile system for the treatment of accidental hypothermia with extracorporeal circulation

When deep accidental hypothermia causes circulatory failure, the best chance of survival is treatment with extracorporeal circulation (ECC) and warming of the blood. This may be difficult to achieve if the patient is first admitted to a hospital without a department of thoracic surgery. Our aim was to test a lightweight mobile system for ECC. The equipment could be transported almost anywhere, making it possible to start ECC on the spot and during transfer. The system was tested on six hypothermic pigs, two of the pigs at the institute laboratory, two of the pigs in a normal ambulance, and two of the pigs in an air force rescue helicopter. All of the pigs were transported back to the institute for warming to normal temperature. After warming, and the ECC stopped, all the pigs were in sinus rhythm and had an obviously satisfactory circulation. It is possible to bring a lightweight ECC system to the unstable patient. Treatment is possible in any hospital, ambulance or helicopter.

Dye-Free Porcine Model of Experimental Branch Retinal Vein Occlusion: A Suitable Approach for Retinal Proteomics

Branch retinal vein occlusion induces complex biological processes in the retina that are generated by a multitude of interacting proteins. These proteins and their posttranslational modifications can effectively be studied using modern proteomic techniques. However, no method for studying large-scale protein changes following branch retinal vein occlusion has been available until now. Obtainment of retinal tissue exposed to branch retinal vein occlusion is only available through experimental animal models. Traditional models of experimental branch retinal vein occlusion require the use of Rose Bengal dye combined with argon laser photocoagulation. The use of Rose Bengal dye is problematic in proteomic studies as the dye can induce multiple protein modifications when irradiated. This paper presents a novel technique for proteomic analysis of porcine retinal tissue with branch retinal vein occlusion combining a dye-free experimental model with label-free liquid chromatography mass spectrometry based proteomics.

Prophylactic One-Dose Treatment with Clindamycin and Gentamicin in Transurethral Prostatic Resection

One hundred and sixty-eight patients scheduled for transurethral prostatic resection were randomly assigned to treatment either with a combination of clindamycin and gentamycin or with placebo, administered preoperatively as a single bolus infusion. The patients were stratified into a group of 35 with preoperative bacteriuria, and a group of 133 with preoperative sterile urine. Postoperatively the frequency of bacteriuria and bacteriaemia, the maximum body temperature measured, the number of patients with antibiotic therapy instituted, and the duration of hospitalization were significantly lower in the treated than in the placebo group. This applied both to the group with preoperative sterile urine and to the group with preoperative bacteriuria.

Prazosin, an adrenergic blocking agent inadequate as male contraceptive pill

The purpose of this study was to investigate the efficacy and the acceptability of Prazosin as a male contraceptive pill. Acceptable antifertility drugs for men are proving difficult to produce, and the possibility of using pharmacological agents to block selectively or to inhibit normal sperm transport through the male genital tract is an interesting approach. Prazosin administered in doses up to 10 mg/day did not cause azoospermia following ejaculation. In conclusion, we have not been able to confirm either the efficacy or the acceptability of the alpha 1-adrenoceptor antagonist Prazosin as a male contraceptive drug. Homonnai et al. confirmed the fact that phenoxybenzamine blocks ejaculation, but it should be noted that although both drugs are alpha 1-adrenoceptor blocking agents, they are not chemically identical.

Alveolar Accumulation/concentration of Nitrogen During Apneic Oxygenation With Arteriovenous Carbon Dioxide Removal

In a model of acute lung injury (ALI), previously, we have shown that apneic oxygenation, using an inspiratory O2 fraction (FiO2) of 1.0 combined with extracorporeal arteriovenous CO2 removal (AO-AVCR) maintains adequate arterial O2 and CO2 levels for a prolonged period. However, it is important that FiO2 lower than 1.0 can be used to avoid possible pulmonary oxygen toxicity. In preliminary studies, arterial oxygenation decreased to extreme low levels, when FiO2 <1 was used in apneic oxygenation. We assumed that this was caused either by alveolar accumulation/concentration of N2 or by absorption atelectasis. In four anesthetized and mechanically ventilated pigs, mild lung injury was induced. After a lung recruitment maneuver, we initiated two 20-minute periods of AO-AVCR with FiO2 of 1 and 0.5, respectively. By using FiO2 = 1, PaO2 remained above 300 mm Hg. At the end of the period, the alveolar O2 fraction (FAO2) was 0.89 (0.88–0.89; median and ranges). With FiO2 = 0.5, PaO2 decreased 90% compared with baseline values and FAO2 decreased to 0.07 (0.06–0.07). No atelectasis was visible on computed tomography after either period, and we, therefore, conclude that the alveolar hypoxia was caused by the alveolar N2 accumulation/concentration and subsequently by the O2 depletion.

Proteins Involved in Focal Adhesion Signaling Pathways are Differentially Regulated in Experimental Branch Retinal Vein Occlusion

Branch retinal vein occlusion (BRVO) is a common retinal vascular disease, but global protein changes following the condition remain largely unelucidated. To bring new insights into pathological processes and identify potential therapeutic targets, large-scale retinal protein changes following BRVO were studied by combining a porcine model of experimental BRVO with proteomic analysis by label-free liquid chromatography mass spectrometry. Among a total set of 1974 proteins, 52 significantly upregulated proteins and 10 significantly downregulated proteins were identified in retinas with BRVO after 15 days. Significantly upregulated proteins were involved in signaling pathways of focal adhesion via integrin and blood coagulation. Proteins involved in focal adhesion signaling included collagen α-2 chain, laminin subunit β-2, laminin subunit γ-1, lipocalin-7, nidogen-2, osteopontin, integrin-β, α-actinin-1, isoform 2 of α-actinin-1, talin-2 and filamin C. The identified proteins indicate that BRVO was associated with extracellular matrix remodeling processes. The present study identified focal adhesion signaling and ECM remodeling as important biological mechanisms to evaluate in the search for signaling pathways that promote neovascularisation and macular edema following BRVO.