Implantable Sensors Based on Gold Nanoparticles for Continuous Long-Term Concentration Monitoring in the Body.

Implantable sensors continuously transmit information on vital values or biomarker concentrations in bodily fluids, enabling physicians to survey disease progression and monitor therapeutic success. However, currently available technologies still face difficulties with long-term operation and transferability to different analytes. We show the potential of a generalizable platform based on gold nanoparticles embedded in a hydrogel for long-term implanted biosensing. Using optical imaging and an intelligent sensor/reference-design, we assess the tissue concentration of kanamycin in anesthetized rats by interrogating our implanted sensor noninvasively through the skin. Combining a tissue-integrating matrix, robust aptamer receptors, and photostable gold nanoparticles, our technology has strong potential to extend the lifetime of implanted sensors. Because of the easy adaptability of gold nanoparticles toward different analytes, our concept will find versatile applications in personalized medicine or pharmaceutical development.

Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.

AIM OF THE STUDY: To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. CLINICAL RATIONALE FOR THE STUDY: G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. MATERIAL AND METHODS: A controlled traumatic right sciatic nerve lesion was set using a waterjet device. Three treatment groups were created. In the first group, G-CSF was administered after sciatic nerve injury. The second group received G-CSF before and after trauma, while the third group was treated with glucose 5%-solution. Sciatic nerve function was assessed clinically and electrophysiologically at day 1, and after weeks 1, 2, 4 and 6. Additionally, α-motoneurons of the spinal cord and sciatic nerve fibres were counted at week 6. RESULTS: Clinically, rats in both G-CSF groups improved faster compared to the control group. Additionally, animals treated with G-CSF had a significantly better improvement of motor potential amplitude and motor nerve conduction velocity at week 6 (p < 0.05). Histologically, G-CSF treatment resulted in a significantly higher number of α-motoneurons and small myelinated nerve fibres compared to placebo treatment (p < 0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: Under G-CSF treatment, the recovery of motor nerve conduction velocity and amplitude was enhanced. Further, signs of nerve regeneration and preservation of α-motoneurons were observed. These results indicate that G-CSF might accelerate and intensify the recovery of injured nerves. Thus, treatment with G-CSF may be beneficial for patients with peripheral nerve damage, and should be explored in further clinical studies.

Comparing Aachen Minipigs and Pietrain Piglets as Models of Experimental Pediatric Urology to Human Reference Data.

INTRODUCTION: Swine had special roles in the development of minimally invasive procedures to treat vesicoureteral reflux, and minipigs have been gaining ground in recent years in experimental pediatric urology as they combine small size with less vulnerable adult physiology, but their suitability as a model has never been assessed. We therefore compared a landrace piglet with a juvenile minipig to elucidate comparability. METHODS: We evaluated five 3-week old Pietrain piglets and five 3-month old Aachen Minipigs as representatives of landrace and minipig models based on their expected bodyweight being similar to a newborn human. We compared renal weight, volume - via the ellipsoid formula - and ureteral length. In addition, we calculated porcine renal function via Gasthuys' formula. In order to compare the groups with previously published values for infants, we used resampling techniques to allow comparison to humans. RESULTS: Renal weight was higher in humans than in Pietrain piglets (ΔL = 7.6 g; ΔR = 5.4 g) and Aachen Minipigs (ΔL = 11 g; ΔR = 9.4 g). Renal volumes in humans were higher than in both Pietrain piglets (ΔL = 5.6 mL, p < 0.001; ΔR = 3.7 mL, p = 0.004) and Aachen Minipigs (ΔL = 8.1 mL; ΔR = 6.6 mL; both p < 0.001). Ureteral lengths in humans and both pig breeds were comparable as were estimated renal functions between both pig breeds. DISCUSSION AND CONCLUSION: Both landrace piglets and juvenile minipigs are suitable models for experimental pediatric urology as parameters did not differ between them. In addition, the anatomic parameters are comparable or smaller than in infants. This might facilitate translational research as technical failure is less likely in larger organs. Additional research is necessary to cover higher age ranges than those included in the present pilot study.

Comparative analysis of fibrinolytic properties of Alteplase, Tenecteplase and Urokinase in an in vitro clot model of intracerebral haemorrhage.

OBJECTIVE: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral and intraventricular haemorrhage (ICH and IVH). However, the MISTIE III and CLEAR III trial failed to show significant improvement of favourable outcomes. Besides experimental and clinical trials revealed neurotoxic effects of rtPA. The demand for optimization of fibrinolytic therapy persists. Herein, we used our recently devised clot model of ICH to systematically analyse fibrinolytic properties of rtPA, tenecteplase and urokinase. METHODS: In vitro clots of human blood (size: 25 ml and 50 ml; age: 1.5 tenecteplase, 24 tenecteplase and 48 tenecteplase) were produced and equipped with a catheter into the clot core for drug delivery and drainage. Various doses of tenecteplase and urokinase with different treatment periods were examined (overall 117 clots), assessing the optimal dose and treatment time of these fibrinolytics. Clots were weighed before and at the end of treatment. These results were compared with clots treated with 1 mg rtPA or with 0.9% sodium chloride solution. RESULTS: The optimal treatment scheme of tenecteplase was found to be 100 IU with an incubation time of 30 min, for urokinase it was 50 000 IU with an incubation time of 20 min. The relative clot end weight of tenecteplase and urokinase (31.3±11.9%, 34.8 ±7.7%) was comparable to rtPA (36.7±10.7%). Larger clots were more effectively treated with tenecteplase compared to the control group (P=0.0013). urokinase and tenecteplase had similar lysis rates in aged clots and 90 min clots. One and two repetitive treatments with tenecteplase were as effective as two and three cycles of urokinase. CONCLUSIONS: In our in vitro clot model we could determine optimal treatment regimens of tenecteplase (100 IU, 30 min) and urokinase (50 000 IU, 20 min). Urokinase and tenecteplase were comparable in their fibrinolytic potential compared to 1mg rtPA in small clots and showed an effective lysis in aged clots. tenecteplase was more effective in larger clots.

Using simple interrupted suture anastomoses may impair translatability of experimental rodent oesophageal surgery.

Background/purpose: Irreproducibility and missing translatability are major drawbacks in experimental animal studies. Hand-sewn anastomoses in oesophageal surgery are usually continuous, whereas those in experimental oesophageal surgery are widely performed using the simple interrupted technique. It has been implicated to be inferior in tolerating anastomotic tension, which we aimed to test in rats due to their importance as an animal model in oesophageal surgery.Methods: We determined linear breaking strengths for the native oesophagus (n = 10), the simple interrupted suture anastomosis (n = 11), and the simple stitch (n = 9) in 8-week old Sprague-Dawley rats. Experiments were powered to a margin of error of 10% around the results of exploratory investigations. The comparison of anastomotic resilience between native organ and simple interrupted suture anastomosis was a priori powered to 99%.Results: Native oesophagi sustained traction forces of 4.25 N (95% CI: 4.03-4.58 N), but the simple interrupted suture anastomosis had only 38.6% (Δ= -2.78 N, 95% CI: -2.46 to -3.11 N, p < .0001) of the resilience of native oesophagi.Conclusions: Oesophageal division and re-anastomosis markedly decreases resilience to traction forces compared to the native organ. This effect is even more pronounced in rats compared to other species and might impair transferability of results.

Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation.

Aims: Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results: C57BL/6j and Nox2-/- (gp91phox-/-) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effects of around-the-clock noise on the vasculature and brain were mostly prevented by Nox2 deficiency. Around-the-clock aircraft noise of the mice caused the most pronounced vascular effects and dysregulation of Foxo3/circadian clock as revealed by next generation sequencing (NGS), suggesting impaired sleep quality in exposed mice. Accordingly, sleep but not awake phase noise caused increased blood pressure, endothelial dysfunction, increased markers of vascular/systemic oxidative stress, and inflammation. Noise also caused cerebral oxidative stress and inflammation, endothelial and neuronal nitric oxide synthase (e/nNOS) uncoupling, nNOS mRNA and protein down-regulation, and Nox2 activation. NGS revealed similarities in adverse gene regulation between around-the-clock and sleep phase noise. In patients with established coronary artery disease, night-time aircraft noise increased oxidative stress, and inflammation biomarkers in serum. Conclusion: Aircraft noise increases vascular and cerebral oxidative stress via Nox2. Sleep deprivation and/or fragmentation caused by noise triggers vascular dysfunction. Thus, preventive measures that reduce night-time aircraft noise are warranted.

Evaluation of a New Multiparameter Brain Probe for Simultaneous Measurement of Brain Tissue Oxygenation, Cerebral Blood Flow, Intracranial Pressure, and Brain Temperature in a Porcine Model.

BACKGROUND: A novel multiparameter brain sensor (MPBS) allows the simultaneous measurement of brain tissue oxygenation (ptiO2), cerebral blood flow (CBF), intracranial pressure (ICP), and brain temperature with a single catheter. This laboratory investigation evaluates the MPBS in an animal model in relation to established reference probes. METHODS: The study group consisted of 17 juvenile male pigs. Four MPBS and four reference probes were implanted per pig and compared simultaneously. The measured parameters were challenged by standardized provocations such as hyperoxia, dobutamine, and norepinephrine application, hypercapnia and hypoxia in combination with and without a controlled cortical impact (CCI) injury. Mean values over 2 min were collected for predefined time points and were analyzed using Bland-Altman plots. RESULTS: The protocol was successfully conducted in 15 pigs of which seven received CCI. ICP and ptiO2 were significantly influenced by the provocations. Subtraction of MPBS from reference values revealed a mean difference (limits of agreement) of 3.7 (- 20.5 to 27.9) mm Hg, - 2.9 (- 7.9 to 2.1) mm Hg, and 5.1 (- 134.7 to 145.0) % for ptiO2, ICP, and relative CBF, respectively. CONCLUSIONS: The MPBS is a promising measurement tool for multiparameter neuromonitoring. The conducted study demonstrates the in vivo functionality of the probe. Comparison with standard probes revealed a deviation which is mostly analogous to other multiparameter devices. However, further evaluation of the device is necessary before it can reliably be used for clinical decision making.

Pringle maneuver increases the risk of anastomotic leakage after colonic resection in rats.

BACKGROUND: Many centers use the Pringle's maneuver during liver resections. Since this maneuver might impair healing of bowel anastomoses, we evaluated its influence on the healing of colonic anastomosis in rats. METHODS: Male Wistar rats underwent median laparotomy and sigmoid resection with end-to-end anastomosis under inhalation anesthesia. Thereafter, rats received a 25 minutes Pringle's maneuver (PM, group 1) or were kept under anesthesia for the same period of time (group 2). The anastomotic bursting pressure (BP) was measured on postoperative days (POD) 3, 6 and 9. Hematoxylin and Eosin (H&E) staining was used for histopathological evaluation of the anastomosis. The Mann-Whitney U and χ2 -tests were used, p<0.05 values were considered significant. RESULTS: All animals (n=48) lost body weight (BW) until POD3 (95.2% vs. 85.7%, p=0.003), and BW remained lower after PM (106.2% vs. 92.8%, p=0.001). The anastomotic BP was lower in group 1 compared to group 2 on POD 3 (116mmHg vs. 176.28mmHg, p=0.001), POD 6 (182.8mmHg vs. 213mmHg, p=0.029) and POD 9 (197.2mmHg vs. 251.7mmHg, p=0.009), and mortality was higher in group 1 (1 vs. 7, p=0.022). CONCLUSIONS: Pringle's maneuver increases anastomotic complications in rats. Therefore, a Pringle's maneuver should be avoided during simultaneous liver and colorectal surgery.

Surface Electromyography Reliably Records Electrophysiologically Evoked Internal Anal Sphincter Activity: A More Minimally Invasive Approach for Monitoring Extrinsic Innervation.

BACKGROUND: Even in the case of minimally invasive pelvic surgery, sparing of the autonomic nerve supply is a prerequisite for maintaining anal sphincter function. Internal anal sphincter (IAS) innervation could be electrophysiologically identified based on processed electromyographic (EMG) recordings with conventional bipolar needle electrodes (NE). This experimental study aimed for the development of a minimally invasive approach via intra-anal surface EMG for recordings of evoked IAS activity. METHODS: Six male pigs underwent nerve-sparing low anterior rectal resection. Electric autonomic nerve stimulations were performed under online-processed EMG of the IAS. EMG recordings were simultaneously carried out with conventional bipolar NE as the reference method and newly developed intra-anal surface electrodes (SE) in different designs. RESULTS: In all experiments, the IAS activity could be continuously visualized via EMG recordings based on NE and SE. The median number of bipolar electric stimulations per animal was 27 (range 5-52). The neurostimulations resulted in significant EMG amplitude increases for both recording types [NE: median 3.0 µV (interquartile range, IQR 2.8-3.5) before stimulation vs. 7.1 µV (IQR 3.9-13.8) during stimulation, p < 0.001; SE: median 3.6 µV (IQR 3.1-4.3) before stimulation vs. 6.8 µV (IQR 4.8-10.3) during stimulation, p < 0.001]. CONCLUSIONS: Intra-anal SE enabled reliable EMG of electrophysiologically evoked IAS activity similar to the conventional recording via NE. The transfer of the method to access platforms for transanal total mesorectal excision or robotics may offer a practical more minimally invasive approach for monitoring extrinsic innervation.

Towards a glioma model for surgical technique evaluation in the rat.

INTRODUCTION: Evaluation of new surgical techniques in animal models is frequently challenging. This article describes the pitfalls, peculiarities and the final best applicable model for evaluating surgical techniques for glioma resection. METHODS: The C6 glioma cell line and the Sprague-Dawley rat strain were selected. Fifty-thousand glioma cells were stereotactically transplanted in the left hemisphere of 137 male adult rats. Evaluation of solid tumour formation, tumour growth and scheduling of surgical resection was performed by MR scanning at 1, 2, and 4 weeks after transplantation and 3 and 6 months after tumour resection. Microsurgical tumour resection was performed with conventional techniques or with the waterjet dissector at a pressure of 6 bar. One subgroup of each surgical technique was sacrificed directly after surgery for histological analysis. The other subgroup was followed up for long-term analysis. RESULTS: The transplantation site was of great importance. After transplantation of tumour cells posterior to the bregma, intra-ventricular tumour growth with spreading occurred. Homogenous and reproducible tumour growth was achieved after grafting cells lateral - 3 mm, anterior + 1 mm, and - 2.5 mm ventral to the bregma. After development of solid tumours on MR imaging, animals were subjected to surgery. MR and intra-operative findings corresponded well. However, MRI and intra-operative none-detectable perivascular tumour spreading was histologically observed in the majority of cases. CONCLUSIONS: The presented glioma rat model consisting of the C6 cell line and Sprague-Dawley rats as recipients is a well-suited model to investigate surgical techniques and their impact on tumour therapy. However, the site of transplantation, the preparation of cell grafts and the technique of tumour growth evaluation is of utmost importance to achieve reliable results.

In vitro testing of a funnel-tip catheter with different clot types to decrease clot migration in mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy is the standard treatment for acute ischemic stroke in patients with large vessel occlusion and can be performed up to 24h after symptom onset. Despite high recanalization rates, embolism in new territories has been reported in 8.6% of the cases. Causes for this could be clot abruption during stent retrieval into the smaller opening of a standard distal access catheter, and antegrade blood flow via collaterals despite proximal balloon protection. A funnel-shaped tip with a larger internal diameter was developed to increase the rate of first-pass recanalization and to improve the safety and efficacy of mechanical thrombectomy. METHODS: This in vitro study compared the efficacy of a funnel-shaped tip with a standard tip in combination with different clot compositions. Mechanical thrombectomy was performed 80 times for each tip, using two stent retrievers (Trevo XP ProVue 3/20 mm, 4/20 mm) and four different clot types (hard vs. soft clots, 0-24h vs. 72h aged clots). RESULTS: Significantly higher first-pass recanalization rates (mTICI 3) were observed for the funnel-shaped tip, 70.0% versus 30.0% for the standard tip (absolute difference, 32; relative difference 57.1%; P < .001), regardless of the clot type and stent retriever. Recanalization could be increased using harder Chandler loop clots versus softer statically generated clots, as well as 0-24h versus 72h aged clots, respectively. CONCLUSION: The funnel-shaped tip achieved higher first-pass recanalization rates than the smaller standard tip and lower rates of clot abruption at the tip. Clot compositions and aging times impacted recanalization rates.

Sub-cellular tumor identification and markerless differentiation in the rat brain in vivo by multiphoton microscopy.

OBJECTIVE/BACKGROUND: Aim of the current study was to localize and differentiate between tumor (glioma) and healthy tissue in rat brains on a cellular level. Near-infrared multiphoton microscopy takes advantage of the simultaneous absorption of two or more photons to analyze various materials such as cell and tissue components via the observation of endogenous fluorophores such as NAD(P)H, FAD, porphyrins, melanin, elastin, and collagen, with a very high resolution, without inducing the problems of photo-bleaching on out-of-focus areas. METHODS: In vitro and in vivo studies on healthy rat brains as well as C6 glioma cell line allografts have been performed. Near-infrared laser pulses (λ = 690-1060 nm, τ ~140 fs) generated by an ultrafast Ti:Sapphire tunable laser system (Chameleon, Coherent GmbH, Santa Clara, CA) were coupled into a laser scanning microscope (LSM 510 META, Carl Zeiss, Germany) to observe high quality images. RESULTS: Several image acquisitions have been performed by varying the zoom scale of the multiphoton microscope, image acquisition time and the wavelength (765, 840 nm) to detect various tissue components. With a penetration depth of ~200 µm in vitro and about 30-60 µm in vivo into the brain tissue it was possible to differentiate between tumor and healthy brain tissue even through thin layers of blood. CONCLUSION: Near-infrared multiphoton microscopy allows the observation and possibly differentiation between tumor (glioma) and healthy tissue in rat brains on a cellular level. Our findings suggest that a further miniaturization of this technology might be very useful for scientific and clinical applications in neurosurgery.

Spontaneous cortical spreading depression and intracranial pressure following acute subdural hematoma in a rat.

Acute subdural hemorrhage (ASDH) is a frequent and devastating consequence of traumatic brain injury. Tissue damage develops rapidly and makes treatment even more difficult. Management of increased intracranial pressure (ICP) due to extravasated blood volume and brain swelling is often insufficient to control all adverse effects of ASDH. In addition to sheer volume, spontaneously triggered cortical spreading depression (CSD) that leads to cell death following ischemia or trauma may contribute to injury development after ASDH. Therefore, we explored the occurrence of CSD by tissue impedance (IMP) measurement in a rat model subjected to ASDH. IMP and intraventricular and mean arterial pressure were monitored before (baseline), during (blood infusion), and after ASDH for 3 h.Tissue impedance increased by around 203% of baseline during subdural infusion of 300 µl of autologous, venous blood and dropped back to baseline within 22 min. Fifty-six minutes after the start of ASDH a cluster of four short-lasting (3-3.5 min; 140-160% of baseline) IMP increases started that reflected spontaneous CSDs. This pattern presumes that CSD occurs early after ASDH and therefore may contribute to the rapid lesion development in this disease.

Multiparametric Monitoring of Early Pathophysiological Changes in a Porcine Model of Sequential Focal and Global Cerebral Ischemia.

OBJECTIVE: Large animal models of cerebral ischemia have the potential to increase the translational value of stroke research. This study aims to measure early changes of brain tissue oxygen pressure (ptiO2) and cerebral blood flow (CBF) to characterize a porcine model of sequential middle cerebral artery occlusion (MCAO) and common carotid artery occlusion (CCAO). METHODS: Eight juvenile German Landrace pigs received unilateral MCAO via a frontotemporal approach under continuous intraparenchymal multiparametric monitoring. Insufficient reduction (i.e., <50% in both ptiO2 and CBF) was followed by additional bilateral CCAO. Neurodegenerative changes were detected by Fluoro-Jade B (FJB) staining. RESULTS: Only 1 of 8 animals demonstrated a decrease of >50% in both ptiO2 and CBF after MCAO. Additional CCAO in 7 pigs led to a significant reduction of both ipsilateral and contralateral ptiO2 (P < 0.01) but not of CBF. There was no difference in ptiO2 and FJB positive area between hemispheres in this group. Measurement of ptiO2 correlated negatively with the FJB positive area (P < 0.05). CONCLUSIONS: Intraparenchymal multiparametric measurements of acute changes in ptiO2 and CBF were variable after MCAO. Bilateral CCAO led to a consistent decrease in ptiO2 and correlated with early degenerative histologic changes, but CBF did not. Real-time procedural ptiO2 monitoring could provide useful guidance in large animal ischemia models. Feasibility in the context of global cerebral hypoperfusion is demonstrated.

An experimental study on long term outcomes after magnetic esophageal compression anastomosis in piglets.

BACKGROUND/PURPOSE: Previous studies have shown that a patent, watertight esophageal anastomosis can be accomplished safely using specially-shaped magnets in piglets. However, it is unclear whether such a magnetic esophageal compression anastomosis (MECA) remains patent in the long-term. The purpose of this study was to evaluate the long-term outcome of MECA in an experimental pig model over an observation period of 2 months. METHODS: Ten piglets underwent creation of an MECA with custom-made 8 mm magnets and a U-shaped esophageal bypass loop to allow peroral nutrition at eight weeks of life. Two weeks later, the bypass loop was closed surgically, requiring the pigs to swallow via the newly created magnetic compression anastomosis. The pigs were fed soft chow for 2 months. They were monitored for weight gain and signs of dysphagia. At the endpoint of two months, esophagoscopy and contrast esophagography was performed. After removal of the esophagus, the tissues were macroscopiocally and histologically assessed. RESULTS: Six piglets survived until the endpoint. In two pigs, closure of the bypass loop failed, these demonstrated mean weight gain of 792 gs/day [95% Confidence interval 575 to 1009 gs/day]. Weight gain in four pigs that exclusively fed via the magnetic anastomosis averaged 577 gs/day [95% confidence interval 434 to 719 gs/day (p = 0.18)]. There were no signs of dysphagia. All magnets passed with the stool within 16 days. After 2 months, a well-formed magnetic compression anastomosis was visible and easily negotiated with a 6.5 mm endoscope. Esophogram and macroscopic findings confirmed patentency of the esophageal anastomoses. Histopathology showed a circular anastomosis lined with contiguous epithelium. CONCLUSION: MECA creates a long-term functional and patent anastomosis in pigs. This concept may facilitate minimally-invasive esophageal atresia repair by obviating a technically challenging and time-consuming hand-sewn anastomosis.

A Continuous Suture Anastomosis Outperforms a Simple Interrupted Suture Anastomosis in Esophageal Elongation.

INTRODUCTION: Long-gap esophageal atresia represents a distinct entity among the esophageal atresia spectrum. In many patients, achieving a reasonable anastomosis depends on some millimeters of tissue. We aimed to determine what effect the suturing technique would have on esophageal ex vivo elongation as it may determine the strength of a primary anastomosis. MATERIALS AND METHODS: In an analysis of porcine esophagi from animals for slaughter (100-120 days old with a weight of 100-120 kg), we determined esophageal length gain of simple continuous and simple interrupted suture anastomoses subjected to linear traction until linear breaking strength was reached. Statistical power of 80% was ensured based on an a priori power analysis using five specimens per group in a separate exploratory experiment. RESULTS: The simple continuous suture anastomosis in 15 porcine esophagi ( = 4.47 cm, 95% confidence interval: 4.08-4.74 cm) outperformed the simple interrupted suture anastomosis in another 15 esophagi ( = 3.03 cm, 95% confidence interval: 2.59-3.43 cm) in length gain (Δ = 1.44 cm, 95% confidence interval: 0.87-2.01 cm, p < 0.0001). CONCLUSION: Simple continuous anastomoses achieved higher length gain compared with simple interrupted suture anastomoses. This effect warrants an experimental assessment in vivo to assess its potential merits for clinical applicability.

Intrahematomal Ultrasound Enhances RtPA-Fibrinolysis in a Porcine Model of Intracerebral Hemorrhage.

Catheter-based ultrasound-thrombolysis has been successfully used in a small clinical trial in order to enhance recombinant tissue plasminogen activator (rtPA)-fibrinolysis, for the treatment of spontaneous intracerebral hemorrhages (ICHs). The aim of this study was to investigate the ultra-early effects of ultrasound on hematoma and the surrounding brain tissue in a porcine ICH-model. To achieve this, 21 pigs with a right frontal ICH were randomly assigned to four groups: (1) drainage (n = 3), (2) drainage + rtPA (n = 6), (3) drainage + ultrasound (n = 6), and (4) drainage + ultrasound + rtPA (n = 6). The hematoma volume assessment was performed using cranial MRI before and after the treatments. Subsequently, the brain sections were analyzed using HE-staining and immunohistochemistry. The combined treatment using rtPA and ultrasound led to a significantly higher hematoma reduction (62 ± 5%) compared to the other groups (Group 1: 2 ± 1%; Group 2: 30 ± 12%; Group 3: 18 ± 8% (p < 0.0001)). In all groups, the MRI revealed an increase in diffusion restriction but neither hyper- or hypoperfusion, nor perihematomal edema. HE stains showed perihematomal microhemorrhages were equally distributed in each group, while edema was more pronounced within the control group. Immunohistochemistry did not reveal any ultra-early side effects. The combined therapy of drainage, rtPA and ultrasound is a safe and effective technique for hematoma-reduction and protection of the perihematomal tissue in regard to ultra-early effects.

Levosimendan increases brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion.

Prompt reperfusion is important to rescue ischemic tissue; however, the process itself presents a key pathomechanism that contributes to a poor outcome following cardiac arrest. Experimental data have suggested the use of levosimendan to limit ischemia-reperfusion injury by improving cerebral microcirculation. However, recent studies have questioned this effect. The present study aimed to investigate the influence on hemodynamic parameters, cerebral perfusion and oxygenation following cardiac arrest by ventricular fibrillation in juvenile male pigs. Following the return of spontaneous circulation (ROSC), animals were randomly assigned to levosimendan (12 µg/kg, followed by 0.3 µg/kg/min) or vehicle treatment for 6 h. Levosimendan-treated animals showed significantly higher brain PbtO2 levels. This effect was not accompanied by changes in cardiac output, preload and afterload, arterial blood pressure, or cerebral microcirculation indicating a local effect. Cerebral oxygenation is key to minimizing damage, and thus, current concepts are aimed at improving impaired cardiac output or cerebral perfusion. In the present study, we showed that NIRS does not reliably detect low PbtO2 levels and that levosimendan increases brain oxygen content. Thus, levosimendan may present a promising therapeutic approach to rescue brain tissue at risk following cardiac arrest or ischemic events such as stroke or traumatic brain injury.