BackgroundMitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro.MethodsMale Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 μM) was administered over 10 min before the beginning of ischemia. The mBKCa channel inhibitor paxilline (1 μM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 μM). Myocardial cGMP concentration was measured by ELISA. Data (mean±SD) were analysed with a one and two-way analysis of variance as appropriate.ResultsIn control animals infarct size was 52±8%. Sildenafil increased cGMP concentration and reduced infarct size to 35±6% (P<0.05 vs. control). Paxilline and KT5823 completely blocked sildenafil-induced cardioprotection (paxilline+sildenafil: 50±8%, KT5823+sildenafil: 45±8%; both P<0.05 vs. sildenafil). Functional heart parameters and coronary flow were not different between the study groups.ConclusionThis study shows that in male rats protein kinase G-dependent opening of mBKCa channels plays a pivotal role in sildenafil-induced cardioprotection.

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Purpose Analysis of patients with pre-operative 3 T multiparametric prostate MRI (mpMRI) to determine reliable MRI-based risk predictors of patients at risk for positive surgical margins (PSM) in robotic assisted radical prostatectomy (RPE). Methods Consecutive patients with 3 T mpMRI and subsequent RPE from 01/2015 to 12/2018 were retrospectively included. Patients were compared regarding clinical and MRI related parameters such as length of capsular tumor contact (LCC) and distance to the membranous urethra (UD). Results Forty-nine of 179 patients (27%) had PSM in 70 different localizations, with the majority located at the capsule (57%, 40/70), mostly apical and/or posterior. The second most often PSM occurred at the apical urethra (22%, 15/70). PCA was visible on mpMRI at the localization of PSM in 93% at the capsule and in 80% at the urethra. PSA, PI-RADS classification, extraprostatic extension (EPE), and seminal vesicles infiltration (SVI) on MRI were significantly higher / more frequent in patients with PSM. LCC (AUC 0.710), EPE (AUC 0.693), and UD (1-AUC 0.673) predicted PSM (overall). An UD of ≤ 3.5 mm showed the highest accuracy of 95% (J = 0.946) for PSM at the urethra and a LCC of ≥ 22.5 mm with 77% (J = 0.378) for PSM at the capsule. Conclusion PSM occurred mostly in the apex and/or posteriorly at the capsule or at the apical urethra. LCC was the best MRI predictor for PSM at the capsule and UD for tumors with PSM at the apical urethra. Using these MRI parameters readers might pre-operatively determine PCA localizations at risk for PSM.

Objectives The aim of this study was to investigate 3 Tesla multiparametric magnetic resonance imaging (mpMRI)-based predictors for the pretherapeutic T staging of prostate cancer and their accuracy. Methods Consecutive patients with 3 Tesla mpMRI, positive systematic and MR-targeted biopsy, and subsequent radical prostatectomy (RPE) between 01/2016 and 12/2017 were included. MRI parameters such as measurable extraprostatic extension (EPE) (≥ 3 mm), length of (pseudo)capsular contact (LCC), invasion of neurovascular bundle (NVBI), and/or seminal vesicles lesion contact (SVC) or infiltration (SVI) were assessed and correlated to clinical and histopathological results. Results 136 men were included. In 76 cases, a pT2 stage was determined, in 29 cases a pT3a, and in 31 a pT3b stage. The positive and negative predictive values (PPV, NPV) for the detection of T3 by measurable EPE on MRI was 98% (CI 0.88–1) and 81% (CI 0.72–0.87). No visible NVBI was found in pT2 patients (NPV 100%; CI 0.95–1). ROC analysis for T3a prediction with LCC (AUC 0.81) showed a sensitivity of 87% and a specificity of 62% at a threshold of 12.5 mm (J = 0.485) and 93% and 58% at 11 mm (Jmax = 0.512). All patients with pT3a had a LCC > 5 mm. In case of pT3b, 29/31 patients showed a SVC (PPV 76%, CI 0.61–0.87; NPV 98%, CI 0.93–0.99), and 23/31 patients showed a SVI (PPV 100%, CI 0.86–1; NPV 93%, CI 0.87–0.96). EPE (p < 0.01), LCC (p = 0.05), and SVC (p = 0.01) were independent predictors of pT3. Conclusions MRI-measurable EPE, LCC, and SVC were reliable, independent, preoperative predictors for a histopathological T3 stage. A LCC ≥ 11 mm indicated a pT3a stage, whereas a LCC < 5 mm excluded it. On MRI, visible SVI or even SVC of the PCa lesion was reliable preoperative predictors for a pT3b stage.