@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Erg{\"u}n, S{\"u}leyman and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Kunz, Andreas Steven and Pannenbecker, Pauline and Kuhl, Philipp Josef and Augustin, Anne Marie and Bley, Thorsten Alexander and Petritsch, Bernhard and Grunz, Jan-Peter},
  title     = {Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-39063-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357912},
  year      = {2023},
  abstract  = {This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall's concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.},
  language  = {en}
}
@article{HennesHuflageGrunzetal.2023,
  author    = {Hennes, Jan-Lucca and Huflage, Henner and Grunz, Jan-Peter and Hartung, Viktor and Augustin, Anne Marie and Patzer, Theresa Sophie and Pannenbecker, Pauline and Petritsch, Bernhard and Bley, Thorsten Alexander and Gruschwitz, Philipp},
  title     = {An intra-individual comparison of low-keV photon-counting CT versus energy-integrating-detector CT angiography of the aorta},
  series = {Diagnostics},
  volume    = {13},
  journal   = {Diagnostics},
  number    = {24},
  issn      = {2075-4418},
  doi       = {10.3390/diagnostics13243645},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-355568},
  year      = {2023},
  abstract  = {This retrospective study aims to provide an intra-individual comparison of aortic CT angiographies (CTAs) using first-generation photon-counting-detector CT (PCD-CT) and third-generation energy-integrating-detector CT (EID-CT). High-pitch CTAs were performed with both scanners and equal contrast-agent protocols. EID-CT employed automatic tube voltage selection (90/100 kVp) with reference tube current of 434/350 mAs, whereas multi-energy PCD-CT scans were generated with fixed tube voltage (120 kVp), image quality level of 64, and reconstructed as 55 keV monoenergetic images. For image quality assessment, contrast-to-noise ratios (CNRs) were calculated, and subjective evaluation (overall quality, luminal contrast, vessel sharpness, blooming, and beam hardening) was performed independently by three radiologists. Fifty-seven patients (12 women, 45 men) were included with a median interval between examinations of 12.7 months (interquartile range 11.1 months). Using manufacturer-recommended scan protocols resulted in a substantially lower radiation dose in PCD-CT (size-specific dose estimate: 4.88 ± 0.48 versus 6.28 ± 0.50 mGy, p < 0.001), while CNR was approximately 50\% higher (41.11 ± 8.68 versus 27.05 ± 6.73, p < 0.001). Overall image quality and luminal contrast were deemed superior in PCD-CT (p < 0.001). Notably, EID-CT allowed for comparable vessel sharpness (p = 0.439) and less pronounced blooming and beam hardening (p < 0.001). Inter-rater agreement was good to excellent (0.58-0.87). Concluding, aortic PCD-CTAs facilitate increased image quality with significantly lower radiation dose compared to EID-CTAs},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Peter, Dominik and Lichthardt, Sven and Huflage, Henner and Grunz, Jan-Peter and Augustin, Anne Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Petritsch, Bernhard},
  title     = {Continuous extracorporeal femoral perfusion model for intravascular ultrasound, computed tomography and digital subtraction angiography},
  series = {PLoS One},
  volume    = {18},
  journal   = {PLoS One},
  number    = {5},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0285810},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350136},
  year      = {2023},
  abstract  = {Objectives We developed a novel human cadaveric perfusion model with continuous extracorporeal femoral perfusion suitable for performing intra-individual comparison studies, training of interventional procedures and preclinical testing of endovascular devices. Objective of this study was to introduce the techniques and evaluate the feasibility for realistic computed tomography angiography (CTA), digital subtraction angiography (DSA) including vascular interventions, and intravascular ultrasound (IVUS). Methods The establishment of the extracorporeal perfusion was attempted using one formalin-fixed and five fresh-frozen human cadavers. In all specimens, the common femoral and popliteal arteries were prepared, introducer sheaths inserted, and perfusion established by a peristaltic pump. Subsequently, we performed CTA and bilateral DSA in five cadavers and IVUS on both legs of four donors. Examination time without unintentional interruption was measured both with and without non-contrast planning CT. Percutaneous transluminal angioplasty and stenting was performed by two interventional radiologists on nine extremities (five donors) using a broad spectrum of different intravascular devices. Results The perfusion of the upper leg arteries was successfully established in all fresh-frozen but not in the formalin-fixed cadaver. The experimental setup generated a stable circulation in each procedure (ten upper legs) for a period of more than six hours. Images acquired with CT, DSA and IVUS offered a realistic impression and enabled the sufficient visualization of all examined vessel segments. Arterial cannulating, percutaneous transluminal angioplasty as well as stent deployment were feasible in a way that is comparable to a vascular intervention in vivo. The perfusion model allowed for introduction and testing of previously not used devices. Conclusions The continuous femoral perfusion model can be established with moderate effort, works stable, and is utilizable for medical imaging of the peripheral arterial system using CTA, DSA and IVUS. Therefore, it appears suitable for research studies, developing skills in interventional procedures and testing of new or unfamiliar vascular devices.},
  language  = {en}
}
@article{GruschwitzHartungErguenetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Erg{\"u}n, S{\"u}leyman and Peter, Dominik and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Pannenbecker, Pauline and Augustin, Anne Marie and Kunz, Andreas Steven and Feldle, Philipp and Bley, Thorsten Alexander and Grunz, Jan-Peter},
  title     = {Comparison of ultrahigh and standard resolution photon-counting CT angiography of the femoral arteries in a continuously perfused in vitro model},
  series = {European Radiology Experimental},
  volume    = {7},
  journal   = {European Radiology Experimental},
  doi       = {10.1186/s41747-023-00398-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357905},
  year      = {2023},
  abstract  = {Background With the emergence of photon-counting CT, ultrahigh-resolution (UHR) imaging can be performed without dose penalty. This study aims to directly compare the image quality of UHR and standard resolution (SR) scan mode in femoral artery angiographies. Methods After establishing continuous extracorporeal perfusion in four fresh-frozen cadaveric specimens, photon-counting CT angiographies were performed with a radiation dose of 5 mGy and tube voltage of 120 kV in both SR and UHR mode. Images were reconstructed with dedicated convolution kernels (soft: Body-vascular (Bv)48; sharp: Bv60; ultrasharp: Bv76). Six radiologists evaluated the image quality by means of a pairwise forced-choice comparison tool. Kendall's concordance coefficient (W) was calculated to quantify interrater agreement. Image quality was further assessed by measuring intraluminal attenuation and image noise as well as by calculating signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR). Results UHR yielded lower noise than SR for identical reconstructions with kernels ≥ Bv60 (p < 0.001). UHR scans exhibited lower intraluminal attenuation compared to SR (Bv60: 406.4 ± 25.1 versus 418.1 ± 30.1 HU; p < 0.001). Irrespective of scan mode, SNR and CNR decreased while noise increased with sharper kernels but UHR scans were objectively superior to SR nonetheless (Bv60: SNR 25.9 ± 6.4 versus 20.9 ± 5.3; CNR 22.7 ± 5.8 versus 18.4 ± 4.8; p < 0.001). Notably, UHR scans were preferred in subjective assessment when images were reconstructed with the ultrasharp Bv76 kernel, whereas SR was rated superior for Bv60. Interrater agreement was high (W = 0.935). Conclusions Combinations of UHR scan mode and ultrasharp convolution kernel are able to exploit the full image quality potential in photon-counting CT angiography of the femoral arteries. Relevance statement The UHR scan mode offers improved image quality and may increase diagnostic accuracy in CT angiography of the peripheral arterial runoff when optimized reconstruction parameters are chosen. Key points • UHR photon-counting CT improves image quality in combination with ultrasharp convolution kernels. • UHR datasets display lower image noise compared with identically reconstructed standard resolution scans. • Scans in UHR mode show decreased intraluminal attenuation compared with standard resolution imaging.},
  language  = {en}
}
@article{ThurnerAugustinBleyetal.2022,
  author    = {Thurner, Annette and Augustin, Anne Marie and Bley, Thorsten Alexander and Kickuth, Ralph},
  title     = {2D-perfusion angiography for intra-procedural endovascular treatment response assessment in chronic mesenteric ischemia: a feasibility study},
  series = {BMC Medical Imaging},
  volume    = {22},
  journal   = {BMC Medical Imaging},
  doi       = {10.1186/s12880-022-00820-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301131},
  year      = {2022},
  abstract  = {Background Endovascular revascularization has become the first-line treatment of chronic mesenteric ischemia (CMI). The qualitative visual analysis of digital subtraction angiography (DSA) is dependent on observer experience and prone to interpretation errors. We evaluate the feasibility of 2D-Perfusion Angiography (2D-PA) for objective, quantitative treatment response assessment in CMI. Methods 49 revascularizations in 39 patients with imaging based evidence of mesenteric vascular occlusive disease and clinical signs of CMI were included in this retrospective study. To assess perfusion changes by 2D-PA, DSA-series were post-processed using a dedicated, commercially available software. Regions of interest (ROI) were placed in the pre- and post-stenotic artery segment. In aorto-ostial disease, the inflow ROI was positioned at the mesenteric artery orifice. The ratios outflow to inflow ROI for peak density (PD), time to peak and area-under-the-curve (AUC) were computed and compared pre- and post-interventionally. We graded motion artifacts by means of a four-point scale. Feasibility of 2D-PA and changes of flow parameters were evaluated. Results Motion artifacts due to a mobile vessel location beneath the diaphragm or within the mesenteric root, branch vessel superimposition and inadequate contrast enhancement at the inflow ROI during manually conducted DSA-series via selective catheters owing to steep vessel angulation, necessitated exclusion of 26 measurements from quantitative flow evaluation. The feasibility rate was 47\%. In 23 technically feasible assessments, PD\(_{outflow}\)/PD\(_{inflow}\) increased by 65\% (p < 0.001) and AUC\(_{outflow}\)/AUC\(_{inflow}\) increased by 85\% (p < 0.001). The time to peak density values in the outflow ROI accelerated only minimally without reaching statistical significance. Age, BMI, target vessel (celiac trunk, SMA or IMA), stenosis location (ostial or truncal), calcification severity, plaque composition or the presence of a complex stenosis did not reach statistical significance in their distribution among the feasible and non-feasible group (p > 0.05). Conclusions Compared to other vascular territories and indications, the feasibility of 2D-PA in mesenteric revascularization for CMI was limited. Unfavorable anatomic conditions contributed to a high rate of inconclusive 2D-PA results.},
  language  = {en}
}
@article{AugustinWolfschmidtElsaesseretal.2022,
  author    = {Augustin, Anne Marie and Wolfschmidt, Franziska and Els{\"a}sser, Thilo and Sauer, Alexander and Dierks, Alexander and Bley, Thorsten Alexander and Kickuth, Ralph},
  title     = {Color-coded summation images for the evaluation of blood flow in endovascular aortic dissection fenestration},
  series = {BMC Medical Imaging},
  volume    = {22},
  journal   = {BMC Medical Imaging},
  number    = {1},
  doi       = {10.1186/s12880-022-00744-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301107},
  year      = {2022},
  abstract  = {Background To analyze the benefit of color-coded summation images in the assessment of target lumen perfusion in patients with aortic dissection and malperfusion syndrome before and after fluoroscopy-guided aortic fenestration. Methods Between December 2011 and April 2020 25 patients with Stanford type A (n = 13) or type B dissection (n = 12) and malperfusion syndromes were treated with fluoroscopy-guided fenestration of the dissection flap using a re-entry catheter. The procedure was technically successful in 100\% of the cases and included additional iliofemoral stent implantation in four patients. Intraprocedural systolic blood pressure measurements for gradient evaluation were performed in 19 cases. Post-processed color-coded DSA images were obtained from all DSA series before and following fenestration. Differences in time to peak (dTTP) values in the compromised aortic lumen and transluminal systolic blood pressure gradients were analyzed retrospectively. Correlation analysis between dTTP and changes in blood pressure gradients was performed. Results Mean TTP prior to dissection flap fenestration was 6.85 ± 1.35 s. After fenestration, mean TTP decreased significantly to 4.96 ± 0.94 s (p < 0.001). Available systolic blood pressure gradients between the true and the false lumen were reduced by a median of 4.0 mmHg following fenestration (p = 0.031), with significant reductions in Stanford type B dissections (p = 0.013) and minor reductions in type A dissections (p = 0.530). A moderate correlation with no statistical significance was found between dTTP and the difference in systolic blood pressure (r = 0.226; p = 0.351). Conclusions Hemodynamic parameters obtained from color-coded DSA confirmed a significant reduction of TTP values in the aortic target lumen in terms of an improved perfusion in the compromised aortic region. Color-coded DSA might thus be a suitable complementary tool in the assessment of complex vascular patterns prevailing in aortic dissections, especially when blood pressure measurements are not conclusive or feasible.},
  language  = {en}
}
@article{AugustinLuciusThurneretal.2022,
  author    = {Augustin, Anne Marie and Lucius, Leonie Johanna and Thurner, Annette and Kickuth, Ralph},
  title     = {Malignant obstruction of the inferior vena cava: clinical experience with the self-expanding Sinus-XL stent system},
  series = {Abdominal Radiology},
  volume    = {47},
  journal   = {Abdominal Radiology},
  number    = {10},
  doi       = {10.1007/s00261-022-03587-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324951},
  pages     = {3604-3614},
  year      = {2022},
  abstract  = {Purpose To evaluate the technical and clinical outcome of Sinus-XL stent placement in patients with malignant obstruction syndrome of the inferior vena cava. Methods Between October 2010 and January 2021, 21 patients with different malignant primary disease causing inferior vena cava obstruction were treated with Sinus-XL stent implantation. Procedural data, technical and clinical outcome parameters were retrospectively analyzed. Results Technical success was 100\%. Analysis of available manometry data revealed a significant reduction of the mean translesional pressure gradient following the procedure (p = 0.008). Reintervention rate was 4.8\% (1/21). The available follow-up imaging studies showed primary and primary-assisted stent patency rates of 93\% (13/14) and 100\% (14/14), respectively. Major complications did not occur. The clinical success regarding lower extremity edema was 82.4\% (14/17) for the first and 85.7\% (18/21) for the last follow-up. Longer lengths of IVC obstruction were associated with reduced clinical improvement after the procedure (p = 0.025). Improvement of intraprocedural manometry results and lower extremity edema revealed only minor correlation. Ascites and anasarca were not significantly positively affected by the procedure. Conclusion Sinus-XL stent placement in patients with malignant inferior vena cava obstruction showed high technical success and low complication rates. Regarding the clinical outcome, significant symptom improvement could be achieved in lower extremity edema, whereas ascites and anasarca lacked satisfying symptom relief. Based on our results, this procedure should be considered as a suitable therapy in a palliative care setting for patients with advanced malignant disease.},
  language  = {en}
}
@article{AugustinKertelsWiegeringetal.2022,
  author    = {Augustin, Anne Marie and Kertels, Olivia and Wiegering, Verena and Thurner, Annette and Kickuth, Ralph},
  title     = {Percutaneous implantation of peripherally inserted totally implantable venous access systems in the forearm in adolescent patients},
  series = {Pediatric Radiology},
  volume    = {52},
  journal   = {Pediatric Radiology},
  number    = {8},
  doi       = {10.1007/s00247-022-05321-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324947},
  pages     = {1550-1558},
  year      = {2022},
  abstract  = {Background Children with different underlying malignant diseases require long-term central venous access. As for port systems in a pectoral position, peripherally implanted port systems in the forearm revealed high levels of technical and clinical success in adult cohorts. Objective To investigate the technical and clinical outcomes of percutaneous central venous port implantation in the forearm in adolescents. Materials and methods Between April 2010 and August 2020, 32 children ages 9 to 17 years with underlying malignancy received 35 totally implantable venous access ports (TIVAPs) in the forearm. All venous port systems were peripherally inserted under ultrasound guidance. Correct catheter placement was controlled by fluoroscopy. As primary endpoints, the technical success, rate of complications and catheter maintenance were analyzed. Secondary endpoints were the side of implantation, vein of catheter access, laboratory results on the day of the procedure, procedural radiation exposure, amount of contrast agent and reasons for port device removal. Results Percutaneous TIVAP placement under sonographic guidance was technically successful in 34 of 35 procedures (97.1\%). Procedure-related complications did not occur. During the follow-up, 13,684 catheter days were analyzed, revealing 11 complications (0.8 per 1,000 catheter-duration days), Of these 11 complications, 7 were major and 10 occurred late. In seven cases, the port device had to be removed; removal-related complications did not occur. Conclusion Peripheral TIVAP placement in the forearms of children is a feasible, effective and safe technique with good midterm outcome. As results are comparable with standard access routes, this technique may be offered as an alternative when intermittent venous access is required.},
  language  = {en}
}
@article{AugustinWelschBleyetal.2021,
  author    = {Augustin, Anne Marie and Welsch, Stefan and Bley, Thorsten Alexander and Lopau, Kai and Kickuth, Ralph},
  title     = {Color-coded summation images in the evaluation of renal artery stenosis before and after percutaneous transluminal angioplasty},
  series = {BMC Medical Imaging},
  volume    = {21},
  journal   = {BMC Medical Imaging},
  number    = {1},
  doi       = {10.1186/s12880-020-00540-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259086},
  pages     = {21},
  year      = {2021},
  abstract  = {Background: Endovascular therapy is the gold standard in patients with hemodynamic relevant renal artery stenosis (RAS) resistant to medical therapy. The severity grading of the stenosis as well as the result assessment after endovascular approach is predominantly based on visible estimations of the anatomic appearance. We aim to investigate the application of color-coded DSA parameters to gain hemodynamic information during endovascular renal artery interventions and for the assessment of the procedures technical success. Methods: We retrospectively evaluated 32 patients who underwent endovascular renal artery revascularization and applied color-coded summation imaging on selected monochromatic DSA images. The differences in time to peak (dTTP) of contrast enhancement in predefined anatomical measuring points were analyzed. Furthermore, differences in systolic blood pressure values (SBP) and serum creatinine were obtained. The value of underlying diabetes mellitus as a predictor for clinical outcome was assessed. Correlation analysis between the patients gender as well as the presence of diabetes mellitus and dTTP was performed. Results: Endovascular revascularization resulted in statistically significant improvement in 4/7 regions of interest. Highly significant improvement of perfusion in terms of shortened TTP values could be found at the segmental artery level and in the intrastenotical segment (p<0.001), significant improvement prestenotical and in the apical renal parenchyma (p<0.05). In the other anatomic regions, differences revealed not to be significant. Differences between SBP and serum creatinine levels before and after the procedure were significant (p=0.004 and 0.0004). Patients ' gender as well as the presence of diabetes mellitus did not reveal to be predictors for the clinical success of the procedure. Furthermore, diabetes and gender did not show relevant correlation with dTTP in the parenchymal measuring points. Conclusions: The supplementary use of color-coding DSA and the data gained from parametric images may provide helpful information in the evaluation of the procedures ' technical success. The segmental artery might be a particularly suitable vascular territory for analyzing differences in blood flow characteristics. Further studies with larger cohorts are needed to further confirm the diagnostic value of this technique.},
  language  = {en}
}
@phdthesis{Augustin2018,
  author    = {Augustin, Anne Marie},
  title     = {Auswirkung der SPRED2-Defizienz auf die kardiale Funktion und Beeinflussung durch die Behandlung mit dem Aldosteronantagonisten Eplerenon},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166029},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {SPRED2 ist ein Inhibitor des Ras/ERK-MAPK-Signalwegs. Um die Folgen einer SPRED2-Defizienz zu erforschen, wurden im Rahmen vorheriger von Ullrich et al. durchgef{\"u}hrter Untersuchungen mittels Gene-Trap-Methode bereits mannigfaltige Auff{\"a}lligkeiten im Ph{\"a}notyp der SPRED2-M{\"a}use festgestellt. So zeigten die Tiere einen Hypochondroplasie-{\"a}hnlichen Zwergenwuchs, Verhaltensauff{\"a}lligkeiten, einen krankhaft gesteigerten Wasserkonsum und nicht zuletzt eine deutlich reduzierte Lebenserwartung im Vergleich mit den WT-Tieren. Des Weiteren fielen erh{\"o}hte Aldosteronspiegel auf, die bei n{\"a}heren Untersuchungen nicht einer erh{\"o}hten Aktivit{\"a}t des RAAS geschuldet zu sein schienen. Vielmehr zeigte sich eine deutlich erh{\"o}hte Aldosteron-Synthase-Expression in der Nebennierenrinde. Erste Hinweise darauf, dass die SPRED2-Defizienz auch Auswirkungen auf den kardiologischen Ph{\"a}notyp haben k{\"o}nnte, ergaben sich bereits bei initialen Untersuchungen von Ullrich et al. So konnte bei den SPRED2-KO-Tieren neben h{\"a}modynamischer Auff{\"a}lligkeiten eine gesteigerte Herz-K{\"o}rpergewicht-Ratio festgestellt werden. Die im Rahmen dieses Folgeprojekts durchgef{\"u}hrten Untersuchungen sollten die Frage kl{\"a}ren, ob die Defizienz des SPRED2-Gens Auswirkungen auf die Herzleistung hat und hier{\"u}ber die verk{\"u}rzte Lebenserwartung der KO-Tiere verschulden k{\"o}nnte. Hierf{\"u}r wurden zun{\"a}chst Untersuchungen der elektrischen kardialen Aktivit{\"a}t mittels EKG und Elektrophysiologischer Untersuchung durchgef{\"u}hrt. Die Ermittlung von Herzrhythmusst{\"o}rung und die Quantifizierung derselben spielte hierbei eine besondere Rolle. Des Weiteren sollte mit der Durchf{\"u}hrung von PSR-F{\"a}rbungen zur Bestimmung des kardialen Kollagengehaltes histologischen Fragestellungen Rechnung getragen werden. Aufgrund des bereits aus den vorherigen Studien bekannten Hyperaldosteronismus der KO-Tiere stellte sich dar{\"u}ber hinaus die Frage, ob die im Rahmen der Studie feststellbaren kardiologischen Auff{\"a}lligkeiten als Konsequenz der gesteigerten Aldosteronwerte, oder aber als direkte Folge des Genotyps gewertet werden m{\"u}ssen. Aus diesem Grund wurden alle oben genannten Untersuchungen mit Tieren, welche einer Behandlung mit dem Aldosteronantagonisten Eplerenon zugef{\"u}hrt worden waren, wiederholt. Bei der Auswertung der basalen Ruhe- und Stress-EKGs zeigten sich einige Parameter bei den KO-Tieren pathologisch ver{\"a}ndert. So war das QRS-Intervall, als Korrelat zur intraventrikul{\"a}ren {\"U}berleitungszeit, bei den KO-M{\"a}usen verl{\"a}ngert, im Stress-EKG waren dar{\"u}ber hinaus sowohl die Dauer der P-Welle als auch des PQ-Intervalls erh{\"o}ht. Durch die Behandlung mit Aldosteron waren diese Unterschiede zwischen WT- und KO-Gruppe teilweise nicht mehr feststellbar. Das die atrioventrikul{\"a}re {\"U}berleitungszeit abbildende PQ-Intervall war sowohl im Vergleich mit dem behandelten WT, als auch mit dem unbehandelten WT nicht mehr signifikant erh{\"o}ht. Auch die L{\"a}nge des QRS-Komplexes n{\"a}herte sich unter Eplerenon-Behandlung dem der unbehandelten WT-Tiere an und sank bei der Stress-EKG-Auswertung sogar unterhalb des Signifkanzniveaus. Bei der EKG-Analyse in Bezug auf Arrhythmien ergab sich bei Gegen{\"u}berstellung der basalen WT- und KO-Gruppe eine deutlich gesteigerte Vulnerabilit{\"a}t f{\"u}r Herzrhythmusst{\"o}rungen bei den KO-Tieren. Durch die Behandlung mit Eplerenon konnte hierbei ein deutlicher Erfolg erzielt werden mit signifikanter Reduktion der Arrhythmieereignisse. Die elektrophysiologische Untersuchung ergab neben unauff{\"a}lligen Parametern der Funktion des Sinusknotens und der AV-{\"U}berleitung ebenfalls Hinweise f{\"u}r eine gesteigerte Empfindlichkeit f{\"u}r Arrhythmien. Die durch EPU induzierten Arrhythmien zeigten sich durch Eplerenon-Behandlung gleichermaßen r{\"u}ckg{\"a}ngig. Mittels Kollagenf{\"a}rbung konnte der initiale Verdacht, dass die SPRED2-KO-Tiere zu einer vermehrten kardialen Fibrosierung neigen, best{\"a}tigt werden. Dabei zeigte sich durch die Behandlung mit Eplerenon eine deutliche Beeinflussung und Reduktion des kardialen Kollagengehaltes. Insgesamt l{\"a}sst sich schlussfolgern, dass die mannigfaltigen ph{\"a}notypischen Effekte, die die SPRED2-Defizienz bedingt, nur teilweise dem Hyperaldosteronismus der Tiere geschuldet sind und durch therapeutische Einflussnahme auf diesen auch nur partiell kompensiert werden k{\"o}nnen.},
  subject      = {Spred-Proteine},
  language  = {de}
}