TY  - JOUR
A1  - Frantz, Stefan
A1  - Klaiber, Michael
A1  - Baba, Hideo A.
A1  - Oberwinkler, Heinz
A1  - Völker, Katharina
A1  - Gaßner, Birgit
A1  - Bayer, Barbara
A1  - Abeßer, Marco
A1  - Schuh, Kai
A1  - Feil, Robert
A1  - Hofmann, Franz
A1  - Kuhn, Michaela
T1  - Stress-dependent dilated cardiomyopathy in mice with cardiomyocyte-restricted inactivation of cyclic GMP-dependent protein kinase I
JF  - European Heart Journal
N2  - Aims: Cardiac hypertrophy is a common and often lethal complication of arterial hypertension. Elevation of myocyte cyclic GMP levels by local actions of endogenous atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) or by pharmacological inhibition of phosphodiesterase-5 was shown to counter-regulate pathological hypertrophy. It was suggested that cGMP-dependent protein kinase I (cGKI) mediates this protective effect, although the role in vivo is under debate. Here, we investigated whether cGKI modulates myocyte growth and/or function in the intact organism.

Methods and results: To circumvent the systemic phenotype associated with germline ablation of cGKI, we inactivated the murine cGKI gene selectively in cardiomyocytes by Cre/loxP-mediated recombination. Mice with cardiomyocyte-restricted cGKI deletion exhibited unaltered cardiac morphology and function under resting conditions. Also, cardiac hypertrophic and contractile responses to β-adrenoreceptor stimulation by isoprenaline (at 40 mg/kg/day during 1 week) were unaltered. However, angiotensin II (Ang II, at 1000 ng/kg/min for 2 weeks) or transverse aortic constriction (for 3 weeks) provoked dilated cardiomyopathy with marked deterioration of cardiac function. This was accompanied by diminished expression of the \([Ca^{2+}]_i\)-regulating proteins SERCA2a and phospholamban (PLB) and a reduction in PLB phosphorylation at Ser16, the specific target site for cGKI, resulting in altered myocyte \(Ca^{2+}_i\) homeostasis. In isolated adult myocytes, CNP, but not ANP, stimulated PLB phosphorylation, \(Ca^{2+}_i\)-handling, and contractility via cGKI.

Conclusion: These results indicate that the loss of cGKI in cardiac myocytes compromises the hypertrophic program to pathological stimulation, rendering the heart more susceptible to dysfunction. In particular, cGKI mediates stimulatory effects of CNP on myocyte \(Ca^{2+}_i\) handling and contractility.
KW  - cyclic
KW  - GMPcGMP-dependent protein kinase I
KW  - cardiac hypertrophy
KW  - natriuretic peptide
KW  - Ca2+i handling
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134693
VL  - 34
ER  - 
TY  - JOUR
A1  - Herzberg, Moritz
A1  - Scherling, Korbinian
A1  - Stahl, Robert
A1  - Tiedt, Steffen
A1  - Wollenweber, Frank A.
A1  - Küpper, Clemens
A1  - Feil, Katharina
A1  - Forbrig, Robert
A1  - Patzig, Maximilian
A1  - Kellert, Lars
A1  - Kunz, Wolfgang G.
A1  - Reidler, Paul
A1  - Zimmermann, Hanna
A1  - Liebig, Thomas
A1  - Dieterich, Marianne
A1  - Dorn, Franziska
T1  - Late Thrombectomy in Clinical Practice: Retrospective Application of DAWN/DEFUSE3 Criteria within the German Stroke Registry
JF  - Clinical Neuroradiology
N2  - Background and Purpose
To provide real-world data on outcome and procedural factors of late thrombectomy patients.

Methods
We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2).

Results
Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes.

Conclusion
In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.
KW  - late thrombectomy
KW  - stroke
KW  - endovascular therapy
KW  - outcome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264765
VL  - 31
IS  - 3
ER  - 
TY  - JOUR
A1  - Herzberg, Moriz
A1  - Dorn, Franziska
A1  - Trumm, Christoph
A1  - Kellert, Lars
A1  - Tiedt, Steffen
A1  - Feil, Katharina
A1  - Küpper, Clemens
A1  - Wollenweber, Frank
A1  - Liebig, Thomas
A1  - Zimmermann, Hanna
T1  - Middle cerebral artery M2 thrombectomy: safety and technical considerations in the German Stroke Registry (GSR)
JF  - Journal of Clinical Medicine
N2  - There is ongoing debate concerning the safety and efficacy of various mechanical thrombectomy (MT) approaches for M2 occlusions. We compared these for MT in M2 versus M1 occlusions. Subgroup analyses of different technical approaches within the M2 MT cohort were also performed. Patients were included from the German Stroke Registry (GSR), a multicenter registry of consecutive MT patients. Primary outcomes were reperfusion success events. Secondary outcomes were early clinical improvement (improvement in NIHSS score > 4) and independent survival at 90 days (mRS 0–2). Out of 3804 patients, 2689 presented with M1 (71%) and 1115 with isolated M2 occlusions (29%). The mean age was 76 (CI 65–82) and 77 (CI 66–83) years, respectively. Except for baseline NIHSS (15 (CI 10–18) vs. 11 (CI 6–16), p < 0.001) and ASPECTS (9 (CI 7–10) vs. 9 (CI 8–10, p < 0.001), baseline demographics were balanced. Apart from a more frequent use of dedicated small vessel stent retrievers (svSR) in M2 (17.4% vs. 3.0; p < 0.001), intraprocedural aspects were balanced. There was no difference in ICH at 24 h (11%; p = 1.0), adverse events (14.4% vs. 18.1%; p = 0.63), clinical improvement (62.5% vs. 61.4 %; p = 0.57), mortality (26.9% vs. 22.9%; p = 0.23). In M2 MT, conventional stent retriever (cSR) achieved higher rates of mTICI3 (54.0% vs. 37.7–42.0%; p < 0.001), requiring more MT-maneuvers (7, CI 2–8) vs. 2 (CI 2–7)/(CI 2–2); p < 0.001) and without impact on efficacy and outcome. Real-life MT in M2 can be performed with equal safety and efficacy as in M1 occlusions. Different recanalization techniques including the use of svSR did not result in significant differences regarding safety, efficacy and outcome.
KW  - mechanical thrombectomy
KW  - M2
KW  - distal occlusion
KW  - endovascular therapy
KW  - aspiration
KW  - stent retriever
KW  - outcome
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286052
SN  - 2077-0383
VL  - 11
IS  - 15
ER  -