Search

Acute pulmonary embolism (PE) is the third most common cardiovascular cause of death after acute myocardial infarction and stroke. Patients are, however, often under-treated due to the risks associated with systemic thrombolysis and surgical embolectomy. Novel pharmacological and catheter-based treatment strategies show promise, but the data supporting their use in patients are sparse. We therefore aimed to develop an in vivo model of acute PE enabling controlled evaluations of efficacy and safety of novel therapies. Danish Landrace pigs (n = 8) were anaesthetized and mechanically ventilated. Two pre-formed autologous PEs (PE1, PE2, 20 × 1 cm) were administered consecutively via the right external jugular vein. The intact nature and central location were visualized in situ by magnetic resonance imaging (MRI). The hemodynamic and biochemical responses were evaluated at baseline (BL) and after each PE by invasive pressure measurements, MRI, plus arterial and venous blood analysis. Pulmonary arterial pressure increased after administration of the PEs (BL: 16.3 ± 1.2, PE1: 27.6 ± 2.9, PE2: 31.6 ± 3.1 mmHg, BL vs. PE1: P = 0.0027, PE1 vs. PE2: P = 0.22). Animals showed signs of right ventricular strain evident by increased end systolic volume (BL: 60.9 ± 5.1, PE1: 83.3 ± 5.0, PE2: 99.4 ± 6.5 mL, BL vs. PE1: P = 0.0005, PE1 vs. PE2: P = 0.0045) and increased plasma levels of Troponin T. Ejection fraction decreased (BL: 58.9 ± 2.4, PE1: 46.4 ± 2.9, PE2: 37.3 ± 3.5%, BL vs. PE1: p = 0.0008, PE1 vs. PE2: P = 0.009) with a compensatory increase in heart rate preserving cardiac output and systemic blood pressure. The hemodynamic and biochemical responses were comparable to that of patients suffering from intermediate-high-risk PE. This porcine model mirrors the anatomical and physiologic changes seen in human patients with intermediate-high-risk PE, and may enable testing of future therapies for this disease.

Objective: To investigate whether changes in muscle tissue perfusion measured with positron emission tomography would be reflected by parallel changes in muscle tissue oxygen saturation (StO 2 ) measured using near-infrared spectroscopy during high and low blood flow levels achieved using cardiopulmonary bypass (CPB) in an animal model., Design: A prospective, randomized study., Setting: Research laboratory, single institution., Participants: Eight pigs (69-71 kg)., Interventions: In anesthetized pigs, normothermic CPB was established with a blood flow of 60 mL/kg/min for 1 hour. Thereafter, a low blood flow of either 47.5 or 35 mL/kg/min was applied for 1 hour followed by a blood flow of 60 mL/kg/min for an additional hour. Regional StO 2 was measured continuously by placing a near-infrared spectroscopy electrode on the skin above the gracilis muscle of the noncannulated back leg. Muscle tissue perfusion was measured using positron emission tomography with 15 O-labeled water during spontaneous circulation and the different CPB blood flows. Systemic oxygen consumption was estimated by measurement of venous saturation and lactate levels., Measurements and Main Results: The results showed profound systemic ischemia during low CPB blood flow. StO 2 remained high until muscle tissue perfusion decreased to about 50%, after which StO 2 paralleled the linear decrease in muscle tissue perfusion., Conclusion: In an experimental CPB animal model, StO 2 was stable until muscle tissue perfusion was reduced by about 50%, and at lower blood flow levels, there was almost a linear relationship between StO 2 and muscle tissue perfusion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: The aim of the present study was to assess the ability of the biomarkers neuron-specific enolase (NSE) and S100 calcium-binding protein b (S100b) to predict mortality and poor neurologic outcome after 30days in patients admitted with severe accidental hypothermia., Methods: Consecutive patients with severe accidental hypothermia, defined as a core temperature <32°C, were included. Patients were treated with active rewarming and/or extracorporeal life support (ECLS) using extra corporeal circulation (ECC) and/or extra corporeal membrane oxygenation (ECMO). The day following admission blood was analyzed for NSE and S100b. Follow-up was conducted after 30days and poor neurologic outcome was defined as a Cerebral Performance Category (CPC) score of 3-5. The predictive value of NSE and S100b was assessed as the area under the receiver-operating characteristics curve (AUC)., Results: A total of 34 patients were admitted with a diagnosis of severe accidental hypothermia and 29 (85%) were resuscitated from cardiac arrest. ECLS was initiated in 27 (79%) of patients. The day following admission three (9%) patients had died and one (3%) patient was awake, and accordingly, NSE and S100b were analyzed in 30 unconscious and/or sedated patients. NSE and S100b achieved AUCs of 0.93 and 0.88, respectively, for prediction of 30day mortality and AUCs of 0.88 and 0.87, respectively, for prediction of poor neurologic outcome., Conclusions: In patients remaining unconscious the day following admission for severe accidental hypothermia, the biomarkers NSE and S100b appear to be solid predictors of mortality and poor neurologic outcome after 30days., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Tracheostomy decannulation is accompanied by several clinical concerns due to air leakage. In this study, we introduced a novel tracheostoma closure device that facilitates the use of noninvasive ventilation, improvement of pulmonary function, and vocalization in the newly decannulated patient. The biosafety and feasibility of the device were evaluated in an animal model., Methods: Five Danish Landrace pigs were subjected to tracheostomy followed by decannulation and insertion of the tracheostoma closure device. Correct placement of the device was ensured by flexible tracheoscopy. The device consisted of an intratracheal silicone seal disc fixated by a cord through the stoma to an external part. At day 14, computed tomography (CT) was performed before the device was extracted. With the pulling of a cord, the disc unraveled into a thin thread and was extracted through the stoma. At day 21, CT was repeated before euthanasia. The trachea and epidermis were excised en bloc for histopathological evaluation., Results: Insertion and correct placement of the disc was unproblematic in all animals. CT at day 14 confirmed a clear airway, appropriate placement of the disc, and full closure of the tracheostoma. Extraction was successful in one animal but complicated in the remaining animals. There was histological evidence of healing after the foreign body placement., Conclusions: The study demonstrated that the tracheostoma closure device is feasible and biosafe in a porcine animal model, but the design and quality of the materials need to be improved before clinical trials., (Copyright © 2017 by Daedalus Enterprises.)

Background: Muscle tissue saturation (StO 2 ) measured with near-infrared spectroscopy has generally been considered a measurement of the tissue microcirculatory condition. However, we hypothesized that StO 2 could be more regarded as a fast and reliable measure of global than of regional circulatory adequacy and tested this with muscle, intestinal and brain metabolomics at normal and two levels of low cardiopulmonary bypass blood flow rates in a porcine model., Methods: Twelve 80 kg pigs were connected to normothermic cardiopulmonary bypass with a blood flow of 60 mL/kg/min for one hour, reduced randomly to 47.5 mL/kg/min (Group I) or 35 mL/kg/min (Group II) for one hour followed by one hour of 60 mL/kg/min in both groups. Regional StO 2 was measured continuously above the musculus gracilis (non-cannulated leg). Metabolomics were obtained by brain tissue oxygen monitoring system (Licox) measurements of the brain and microdialysis perfusate from the muscle, intestinal mucosa and brain. A non-parametric statistical method was used., Results: The systemic parameters showed profound systemic ischaemia during low CPB blood flow. StO 2 did not change markedly in Group I, but in Group II, StO 2 decreased immediately when blood flow was reduced and, furthermore, was not restored despite blood flow being normalized. Changes in the metabolomics from the muscle, colon and brain followed the changes in StO 2 ., Conclusion: We found, in this experimental cardiopulmonary bypass model, that StO 2 reacted rapidly when the systemic circulation became inadequate and, furthermore, reliably indicate insufficient global tissue perfusion even when the systemic circulation was restored after a period of systemic hypoperfusion.

Objectives: Surviving long lasting cardiac arrest following accidental hypothermia has been reported after treatment with extra corporeal life support (ECLS), but there is a risk of neurologic injury. Most surviving hypothermia patients have a prolonged stay in the intensive care unit, where most patients experience polyneuropathy. Theoretically, accidental hypothermic cardiac arrest may in itself contribute to polyneuropathy. This study was designed to examine the impact of three hours of cardiac arrest at a core temperature of 20°C followed by reanimation of peripheral nerve function., Methods: Seven pigs were cannulated for ECLS and cooled to a core temperature of 20°C followed by three hours of circulatory arrest where the extremities were packed with ice. After three hours, ECLS was started and rewarming was performed. During the process, neural testing of the ulnar nerve (a somatic nerve) and of the vagus nerve (an autonomic nerve) were performed and blood was drawn for analysis of p-potassium, serum-neuron-specific enolase, and S100b protein., Results: The ulnar nerve was cooled from 34.9±1.6°C to 12.8±3.8°C and the vagus nerve from 36.2±1.2°C to 15.4±1.4°C. Physiologic function of both somatic and autonomic nerves were strongly affected by cooling, but recovered to almost normal levels during rewarming, even after three hours of hypothermic cardiac arrest. P-potassium rose from 3.9 (3.6-4.6)mmol/l to 8.1 (7.2-9.1)mmol/l after three hours of cardiac arrest, but normalized after recirculation. There was no rise in serum-neuron-specific enolase, but a slight rise in S100b protein during three hours of hypothermic cardiac arrest was observed. All pigs obtained return of spontaneous circulation (ROSC)., Conclusions: Reanimation after three hours of hypothermic cardiac arrest using ECLS was possible with no or, if present, minor damage to the two nerves tested., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: (177)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of (177)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications., Results: (177)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq (177)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of (177)Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels., Conclusions: The (177)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range.

Background: The optimal method for out-of-hospital ventilation during cardiopulmonary rescue (CPR) is controversial. The aim of this study was to test different modes of ventilation during CPR for a prolonged period of 60 min., Methods: Pigs were randomized to four groups after the induction of ventricular fibrillation, which was followed by one hour of mechanical cardiac compressions. The study comprised five pigs treated with free airways, five pigs treated with ventilators, six pigs treated with a constant oxygen flow into the tube, and six pigs treated with apnoeic oxygenation., Results: The free airway group was tested for 1 h, but in the first 15 min, the median PaO2 had already dropped to 5.1 kPa. The ventilator group was tested for 1 h and still had an acceptable median PaO2 of 10.3 kPa in the last 15 min. The group was slightly hyperventilated, with PaCO2 at 3.8 kPa, even though the ventilator volumes were unchanged from those before induction of cardiac arrest. In the group with constant oxygen flowing into the tube, one pig was excluded after 47 min due to blood pressure below 25 mmHg. For the remaining 5 pigs, the median PaO2 in the last 15 min was still 14.3 kPa, and the median PaCO2 was 6.2 kPa. The group with apnoeic oxygenation for 1 h had a resulting median PaO2 of 10.2 kPa and a median PaCO2 of 12.3 kPa in the last 15 min., Discussion: Except for the free airway group, the other methods resulted in PaO2 above 10 kPa and PaCO2 between 3.8 and 12.3 kPa after one hour., Conclusion: Constant oxgen flow and apnoeic oxygenation seemed to be useable alternatives to ventilator treatment.

Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 10(9) CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

Background: The fusing of the epicardium and sternum due to adhesion is a common problem during repeated cardiac surgery and carries with it an increased risk of bleeding. The use of barriers and patches has been tested to prevent the formation of adhesions, but the very presence of a patch can provoke adhesion formation. The objective of this study was, therefore, to investigate both biodegradable and bioresorbable polylactone patches [(polycaprolactone-poly(ethylene oxide)-polycaprolactone tri-block copolymer (PCE)]. The patches were also tested with a controlled release of rapamycin, which prevents cell migration and extracellular matrix deposition. The clinical effectiveness of rapamycin in pericardial patches has not previously been examined., Materials and Methods: Three groups of 6 female Danish Landrace pigs underwent sternotomy and abrasion of the epicardium, before being randomized to either group 1--the control group (with no patch), group 2--PCE patch implanted between the sternum and epicardium, or group 3--PCE patch and slow-release 1.6-mg rapamycin. After a median time period of 26 days, the pigs were euthanized and their hearts removed en bloc with the sternum, for macroscopic, histological and pathological examination., Results: Upon macroscopic examination, a significantly lower degree of adhesion in group 2, as compared to group 1 (p < 0.05), was found. Histological analysis of the tissues showed significantly more fibrosis, inflammation and foreign body granulomas (p < 0.05) in both group 2 and group 3, when compared to group 1., Conclusion: A PCE patch following sternotomy in animal subjects reduces postoperative macroscopic adhesions without reducing microscopic fibrosis or inflammation. Loading the patch with rapamycin was found not to increase the antifibrotic effect., (© 2016 S. Karger AG, Basel.)

Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma levels of high-sensitive troponin T were assessed repeatedly. The experimenters were blinded with regard to treatment regimen. Melatonin did not significantly increase myocardial salvage index compared with placebo [melatonin 21.8% (16.1; 24.8) vs. placebo 20.2% (16.9; 27.0), p = 1.00]. The extent of microvascular obstruction was similar between the groups [melatonin 3.8% (2.7; 7.1) vs. placebo 3.7% (1.3; 7.7), p = 0.96]. The area under the curve for high-sensitive troponin T release was insignificantly reduced by 32% in the melatonin group [AUC melatonin 12,343.9 (6,889.2; 20,147.4) ng h/L vs. AUC placebo 18,285.3 (5,180.4; 23,716.8) ng h/L, p = 0.82]. Combined intracoronary and intravenous treatment with melatonin did not reduce myocardial reperfusion injury. The lack of a positive effect could be due to an ineffective dose of melatonin, a type II error or the timing of administration.

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background and Purpose: It has been suggested that off-label use of transdermal nitroglycerine patches to prevent frostbite may lead to severe acute mountain sickness and ataxia. The aim of this study was to investigate the effect of nitroglycerine on brain vascular permeability by using dynamic contrast-enhanced MR imaging in a swine model., Materials and Methods: Eight Danish Landrace-Yorkshire-Danish Landrace pigs of approximately 20-25 kg were scanned with a dynamic contrast-enhanced MR perfusion protocol with and without nitroglycerine intravenous infusion. Compartmental analysis was performed on the basis of the Tofts model, and voxel-based quantitative values of the volume transfer constants from the vascular to the extracellular space were determined., Results: The scan with nitroglycerine infusion resulted in significantly higher volume transfer constant values than values derived from the first scan without nitroglycerine infusion. Increased volume transfer constant values were observed in 6 of 8 animals., Conclusions: Infusion of nitroglycerine increases the vascular permeability of the swine brain on the basis of the transfer constant estimated from dynamic contrast-enhanced MR imaging., (© 2015 by American Journal of Neuroradiology.)

Introduction: The treatment of massive pulmonary embolisms with an associated cardiac arrest is controversial; however, surgical thrombectomy with extracorporeal circulation (ECC) is an option for treatment. It is difficult to remove all thromboembolic material. Theoretically, retrograde blood perfusion through the lungs may be beneficial., Objectives: To investigate whether retrograde blood perfusion through the lungs during a thrombectomy is beneficial., Methods: Twelve pigs were prepared for ECC. Repetitive injections of preformed blood thrombi into the right atrium resulted in cardiac arrests. ECC was established after 10 minutes of cardiac arrest, and after a sternotomy, the main pulmonary artery was incised and as much thrombotic material as possible was removed from the pulmonary arteries. The pigs were randomised to ECC for one hour either with or without retrograde perfusion in the pulmonary circulation. After one hour, the released material was removed from the pulmonary arteries, and the incision was sutured. The pigs were weaned from the ECC. After sacrificing the pigs, they were autopsied with special attention to the amount of remaining thrombi. Additional histological analyses were performed with special attention to microembolisms, atelectases, and signs of tissue damage., Results: All of the pigs were weaned from the ECC. The amount of the embolic material removed varied considerably, as did the amount removed after the retrograde or antegrade perfusion, and there was no significant difference between the two treatment modalities. There were no signs of tissue damage in the lungs., Conclusions: Retrograde lung perfusion was not generally beneficial in the treatment of massive pulmonary embolism in this setup; however, it may be an option if only a modest amount of material is accessible in the pulmonary artery., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

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.

Background: Since 2005, ST-elevation myocardial infarction (STEMI) patients from the island of Bornholm in the Baltic Sea have been transferred for primary percutaneous coronary intervention (pPCI) by an airborne service. We describe the result of pPCI as part of the Danish national reperfusion strategy offered to a remote island population., Methods: In this observational study, patients from Bornholm (n=101) were compared with patients from the mainland (Zealand) (n=2495), who were grouped according to time intervals (<120, 121-180, >180 min). The primary endpoint was all-cause 30-day mortality. Individual-level data from the Central Population Registry provided outcome that was linked to our inhospital PCI database., Results: Treatment delay was longer in patients from Bornholm (349 min (IQR 267-446)) vs Zealand (211 (IQR 150-315)) (p<0.001). In patients from Zealand, 30-day mortality did not increase with time intervals (p=0.176), whereas, long-term mortality did (∼3 years) (p=0.007). Thirty-day mortality was similar for Bornholm and the overall Zealand group (5.9% vs 6.2% p=0.955). Early presenters (<180 min) from Zealand (37%) had similar 30-day (5.3% vs 5.9% p=0.789), but numerically reduced long-term mortality compared with Bornholm (12.8% vs 15.8% p=0.387). Age, female gender, diabetes, Killipclass >2 and preprocedural thrombolysis in myocardial infarction (TIMI) flow 0/1 independently predicted 30-day mortality, however, treatment delay did not. Postprocedural TIMI flow 3 predicted improved survival., Conclusions: In this small population of STEMI patients from a remote island, airborne transfer appears feasible and safe, and their 30-day mortality after pPCI comparable with that of the mainland population despite inherent reperfusion delay exceeding guidelines., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To test whether melatonin reduces oxidative and inflammatory biomarkers in a closed-chest porcine model of acute myocardial infarction., Materials and Methods: Twenty pigs were randomized to receive a total dosage of 200 mg (0.4 mg/ml) of melatonin, or placebo immediately prior to reperfusion of a coronary artery balloon occlusion in a randomized, observer-blinded, placebo-controlled trial. We assessed high-sensitivity troponin T (hs-TnT), malondialdehyde and interleukin-1b, -6 and -10 at baseline, 30 min and 1, 2, 3 and 4 h after the start of reperfusion., Results: Seventeen pigs completed the trial. There was an increase in hs-TnT, but no significant difference between the melatonin-treated and placebo-treated groups. There were no significant differences in development of any of the circulating plasma markers between the two groups., Conclusion: Melatonin treatment did not result in reduction of inflammatory or oxidative stress markers after experimental myocardial infarction compared to placebo., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The treatment of accidental hypothermia is still controversial and is missing detailed evidence-based guidelines. Current knowledge suggests that advanced trauma life support principles must be prioritized ahead of rewarming. In case of cardiac arrest, initiation of extracorporeal circulation before rewarming and prolongation of hypothermia at 33 °C to reduce reperfusion injury and cerebral hyperthermia is recommended but is not as yet implemented as standard treatment. We propose a simplified clinical approach to on-site triage of hypothermia: 1. Awake below 35 °C (Glasgow Coma Scale > 8). 2. Unconscious below 32 °C. 3. Absent respiration and circulation below 32 °C.

Introduction: Although the effects of radiotherapy (RT) on implantable cardioverter defibrillators (ICDs) have been studied in vitro, and some information has been gathered from case reports and series, no in vivo experiments have previously been performed., Methods: In vivo effects of photon RT applied directly to five modern ICD generators from different manufacturers implanted in pigs were studied. The devices were interrogated between and after increasing doses of ionizing radiation. Afterwards, the shock function was tested., Results: All ICDs withstood fractionated irradiations with a cumulative dose of 18.5 gray (Gy) of 6 megavolt (MV) photons and 18.5 Gy of 18 MV photons and were still fully functional. Especially, no oversense was recorded. Induced ventricular fibrillation was detected and treated properly by shock therapy in all cases. However, one of the ICDs converted to back-up mode later the same night., Conclusion: The animal model is feasible for investigating RT effects on implanted cardiac devices. During irradiations with 37 Gy, one recoverable malfunction was present in the tested devices. Additional animal studies could provide supplementary evidence for treating ICD patients, including recommendations for reprogramming of the ICD during RT and avoidance of relocating the device., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Introduction: Treatment of massive pulmonary embolism leading to cardiac arrest is controversial but restitution of circulation within a shorter time is crucial. Cardiopulmonary support and therapeutic hypothermia is an option for cardiac arrest and could be used to treat massive PE. However, hypothermia may influence the effect of the ongoing intrinsic fibrinolysis., Objectives: To establish a porcine model of massive pulmonary embolism, to show that cardiopulmonary support can rescue pigs with massive pulmonary embolism and to examine the effect of hypothermia on fibrinolysis., Methods: Pigs ~80 kg were anesthetised and prepared for cardiopulmonary support. Repetitive injections of preformed blood thrombi into the right atrium were done until cardiac arrest. Cardiopulmonary support was established and eighteen pigs were randomised into 3 groups: Normothermia (38-39 °C); hypothermia (33-34 °C); or medication with recombinant tissue plasminogen activator. After three hours the pigs were weaned from cardiopulmonary support, and after 15 minutes with spontaneous circulation assassinated and autopsied. Remaining thrombi in the lungs were weighed., Results: The development of fatal pulmonary embolism was highly reproducible. All 18 pigs could be weaned from cardiopulmonary support and survived more than 15 minutes. The amount of remaining thromboemboli was substantial in all groups and not significantly different between groups. Normothermic group 20.0 ± 2.2 g, Hypothermic group 17.0 ± 3.7 g, and rt-PA group 14.3 ± 3.2 g., Conclusions: Cardiopulmonary support could rescue pigs with massive pulmonary embolism. Hypothermia did not reduce the emboli but may for other reasons be beneficial. The optimal additional treatment is still unknown but treatment modalities can be tested in this model., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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 beam's 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The aim of the present study was to test the feasibility of a Nickel-Titanium (Ni-Ti) stent technique (Memocore™) in a porcine model. The stent is intended as a new fiducial for gated image guided radiotherapy in the lung. The study included test of an improved insertion system and respiratory gated treatments with this new technique., Methods and Materials: Tests were carried out in a porcine model using Göttingen mini-pigs. The study included 10 animals. Planning CT was performed as 4 dimensional CT (4DCT) using the Varian RPM system. Respiratory gated radiotherapy treatments were simulated using the Brainlab ExacTrac system. Reproducibility of stent position during treatment was analyzed off-line using an experimental version of the ExacTrac software. The experimental version has a dedicated algorithm for segmentation of the stent in the planning CT and subsequent registration to X-ray position images., Results: A total of 23 stents were inserted in the 10 animals. Stents could be placed in all parts of the lungs. No stent migrated within the four weeks the experiment lasted. Stent trajectories in the lung were not reproducible, even though respiration was highly standardized using a respirator. The best accuracy of stent position in the gating window was obtained using gating at the half&#95;max amplitude as reference level. The smallest stent movement within the gating window was observed in the exhale phase. Further success of human application will depend on the possibility to insert the stent within or close to lung tumors., Conclusions: This new technique based on the Memocore™ lung stent used in connection with respiratory gated radiotherapy was demonstrated to be feasible in a porcine model. The study demonstrated lack of reproducibility in lung trajectories of inserted stents. The technique gave the best accuracy when applied to the exhale phase of respiration., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objectives: In accidental hypothermia, normal signs of death are unreliable. It is generally accepted that a lifeless person is beyond the limits of rescue if plasma potassium (P-potassium) is higher than10 mmol/l. However, the rate of increase in potassium or in other markers after cardiac arrest has not been carefully studied in hypothermic individuals. The aim of this animal study was to assess biochemical changes after anoxic circulatory arrest at hypothermia and at normothermia followed by external cooling., Methods: Five pigs were treated with heparin and extracorporeal circulation and cooled to 20 degrees C (primary hypothermia group). The animals were weaned from extracorporeal circulation, suffered cardiac arrest, and were cooled externally with ice to mimic victims found in a cold environment. With the use of intermittent external cardiac compressions mixing the blood, arterial P-potassium was followed after cardiac arrest until the level exceeded 10 mmol/l. Another group of five pigs (anoxic cardiac arrest group) were treated with heparin and killed by anoxia at normothermia and were thereafter treated and followed similarly to the primary hypothermia group., Results: In primary hypothermia P-potassium exceeded 10 mmol/l after median 3.5 h, whereas in anoxic cardiac arrest P-potassium exceeded 10 mmol/l after median 1 h., Conclusion: This study shows that if cardiac arrest occurs before hypothermia is established, P-potassium increases quickly in contrast to the situation when hypothermia induces cardiac arrest. Thus, a low P-potassium in a hypothermic individual with cardiac arrest indicates that cardiac arrest occurred recently or was secondary to the hypothermic event.

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.

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.

Background: It has been claimed that needle electrodes can be a useful means to detect weak ECG signals in cases of accidental hypothermia., Methods: Four pigs were cooled by immersion in ice water, followed by direct cooling of the blood through an extracorporeal circulation system until the core temperature was lowered to 12 degrees C and surface-measured ECG indicated asystole. Following cooling, the pigs were rewarmed and weaned from extracorporeal circulation if possible. ECG and interelectrode impedance were measured between surface electrodes, needle electrodes and electrodes sewn to the epicardium during the cooling and rewarming procedure., Results: Needle and surface electrodes showed exactly the same ECG whatever the temperature of the skin or the core was. The impedance varied only slightly with temperature and could not explain the disappearance of surface ECG. The QRS wave amplitude showed the greatest sensitivity to temperature, disappearing completely before the P-wave disappeared. The P-wave showed the least sensitivity, and was the last wave to disappear, indicating that the sinus node is the most resistant part of the heart to cooling. Between 19 and 17 degrees C, a commercial monitor indicated asystole although P-waves could be seen in the ECG and atrial contractions could be visually observed on the heart., Conclusion: Surface electrodes had a similar high accuracy to indicate electric activity as needle electrodes. Higher amplification and reduction of the timebase made it possible to detect ECG in a situation where asystole was indicated by commercial monitors.

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.

Treatment of the hypothermic patient depends more on the clinical condition than on the core temperature. Unconscious patients need thorough investigation, and they can often be rewarmed with warm water in the pleural cavities. Cardiac arrest requires cardio pulmonary rescue until rewarming can be established by extra corporeal circulation unless the patient is dead. The diagnosis of death can be difficult in the hypothermic patient. A rescue team is available to assist in rewarming at local hospitals.

Objective: Acute respiratory failure can make long distance transport by air extremely difficult. Despite pressurised cabins, the pressure will fall to about three quarters of one atmosphere, and the oxygen partial pressure will fall proportionally. Interventional lung assist (iLA) is a well documented treatment in the critical care unit, but has not been evaluated scientifically in long range aero-medical evacuation. The present animal study was performed to test the feasibility of treating lung failure with iLA during intercontinental air evacuation in a military setting., Methods: Eight adult female pigs were cannulated in the right axillary artery and the right jugular vein. An arterio-venous iLA device (Novalung) was connected. The ventilator was adjusted to below half of the needed minute volume before the use of iLA. The animals went through different modalities of transportation in ambulances, helicopters and aircraft. Two of the pigs were tested in a hypobaric chamber, and the remaining two animals underwent a 7.5 h intercontinental transportation from Denmark to Greenland in a Hercules C130J transport airplane., Results: It was possible to maintain physiological PaCO(2) and PaO(2) in normal flight altitudes with iLA. Compared to pump-driven ECMO systems iLA is safer and more efficient. The current study demonstrates the feasibility of iLA during military aero-medical evacuation.

In all, five patients with accidental hypothermia below 32 degrees C are described. All were unconscious and in mortal danger, but with an intact circulation. The youngest was 11 years and the oldest 85 years of age. The two oldest patients suffered from critical hypothermia only, while the other cases were complicated by other trauma and drug poisoning. All were warmed using pleural lavage with warm saline. All were discharged to their own homes neurologically intact.

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.

During periods of five weeks before and five weeks after distribution of a pamphlet entitled "Before you go to your doctor or to the casualty department" which was distributed to all households, the patterns of attendance at a casualty department were investigated with subdivision into degrees of indication for attendance. A significant decrease in the number of attendances was observed after distribution of the pamphlet. Patients with lesser indications remained away. It was estimated that at least 56% of the cases could have been treated in the primary sector. 37% of the attendances outside normal working hours were considered as being postponable until daytime.

Twenty-three postmenopausal women with recurrent cystitis were allorted at random to treatment for five months with local oestrogen in the vagina or placebo treatment with the object of assessing the local effect on the vaginal epithelium and on the tendency to recurrent cystitis. The therapeutic group and the placebo group were entirely comparable prior to treatment. In the therapeutic group, the oestrogen index in vaginal scrapings was significantly higher after treatment than in the placebo group (p less than 0.01). The number of positive urine cultures and the patients/satisfaction with treatment wee not significantly different in the two groups.

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.

An oral electronic thermometer was compared with Hg-thermometer used rectally in the daily clinical routine. The rectal temperatures were, on an average, 0.7 degrees C higher than the oral temperatures. In 27% of the cases, the difference between rectal and oral measurement was more than 1 degree C. The variations between the differences of oral and rectal temperature measurement were unacceptable. It is concluded that the precision of oral electronic thermometers was not found to be satisfactory, and employment of this apparatus can not be recommended in daily clinical work.

85 women undergoing vacuum aspiration following miscarriage were studied. At the time of vacuum aspiration, immunofluorescent stainings for detection of C. trachomatis proved positive in 5.9% of the patients. Group B streptococci were isolated in 7.5%, coliforms in 3.5%, and Gardnerella vaginalis in 51% of the patients. The overall frequency of postabortal pelvic inflammatory disease (PID) was 3.5%, whereas 40% of chlamydia-positive women contracted postabortal PID (p less than 0.05). No significant relation between other microorganisms and postabortal PID was observed. The duration of postabortal bleeding was unrelated to the genital microbiologic flora. Based on anamnestic information about previous pregnancies and duration of preoperative bleeding it was possible to define subgroups at risk of harboring C. trachomatis and coliforms. The clinical significance of this is unknown.

Sixty-four patients with obstruction or lesions of the ureter were, on 115 therapeutic sessions, submitted to internal diversion of urine employing JJ-catheters. Prior to the first treatment, 53% of the patients had been treated with nephrostomy catheters on account of postrenal obstruction. In 12% of the therapeutic sessions, the patients developed pyrexia of over 38.5 degrees C (101.3 degrees F) in the 24 hours immediately after introduction of the catheter. Only few patients had complications in the form of macroscopic haematuria, migration of the catheter, incrustations and perforation of the ureter. It is concluded that JJ-catheters provide a good and gentle method of relieving obstruction in the upper urinary passages. Bacteriological investigation and treatment of urinary infection is recommended prior to introduction of the catheter.

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.

Examination for the presence of C. Trachomatis in the cervix and urethra and bacteriological examination of the cervix were performed in a material of 224 patients for legal abortion in the first trimester of pregnancy. Chlamydia was demonstrated in 8.9% of the patients, Neisseria gonorrhoeae in 0.5% and, in 41%, growth of Gardnerella vaginalis predominated. It proved possible to define a group at risk for the presence of Chlamydia consisting of all the patients under the age of 25 years and nulliparae aged 25-29 years. 17% in this group had positive Chlamydia tests as compared with 1.7% in the patients in other groups. Patients in the above mentioned risk group should be examined for C. trachomatis in cases of legal termination of pregnancy so that appropriate treatment can be administered prior to evacuation.

Fifty women with recurrent symptoms of cystitis (urgent onset of painful and frequent voiding) were extensively examined bacteriologically. All were submitted to intravenous urography, cystoscopy, gynaecological and urodynamic examination and the urine was examined cytologically and by culture. A control group of 10 healthy women were submitted to the same bacteriologic examinations. Only in a few cases did the investigations give an explanation of the condition but, generally, the examination programme did not contribute to the etiology. Chlamydia trachomatis was found in 6%, which was comparable to the normal population. Gardnerella vaginalis must be considered as part of the normal flora. The extensive examination programme cannot be recommended as a routine.