Clopidogrel treatment in patients with coronary artery disease not only inhibits platelet activation but also improves endothelial function and nitric oxide (NO) bioavailability. Congestive heart failure (CHF) is associated with endothelial dysfunction and increased platelet activation. In rats with CHF following myocardial infarction (MI), we investigated whether treatment with clopidogrel modifies endothelial function. Eight weeks after coronary artery ligation, rats with CHF were randomized to placebo or the P2Y(12) receptor antagonist clopidogrel (5 mg/kg twice daily, given by gavage) for another 2 weeks. Afterwards, endothelial function was assessed in isolated aortic rings in organ bath experiments. Acetylcholine-induced, endothelium-dependent, nitric oxide-mediated vasorelaxation was significantly attenuated in CHF rats compared to sham-operated animals, and was significantly improved by treatment with clopidogrel. Adenosine-induced vasorelaxation via adenylyl cyclase stimulation was attenuated in CHF and significantly improved by clopidogrel. Increased vasoconstriction to phenylephrine was observed in CHF, particularly evident under cyclooxygenase inhibition, but prevented by clopidogrel treatment. Vasoconstriction by the P2Y(12) activator 2MeS-ADP was increased in CHF. Clopidogrel-treated CHF animals displayed enhanced phosphorylation of AKT and eNOS. In conclusion, clopidogrel improved endothelial function and NO bioavailability in heart failure. During CHF, sensitivity to P2Y(12) signaling was increased leading to impaired adenylyl cyclase-mediated signaling. Chronic P2Y(12)-blockade with clopidogrel improved adenylyl cyclase-mediated signaling including increased AKT- and eNOS-phosphorylation contributing to improved NO-mediated vasorelaxation.

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Background Surgical resection of pulmonary metastases leads to prolonged survival if strictly indicated. Usually, thoracotomy with manual palpation of the entire lung with lymph node dissection or sampling is performed. The aim of this study was to evaluate the role of video-assisted thoracoscopic surgery (VATS) in pulmonary metastectomy with curative intent. Methods In this study, all patients with suspected pulmonary metastasis (n = 483) who visited the Center for Thoracic Surgery in Regensburg, between January 2009 and December 2017 were analysed retrospectively. Results A total of 251 patients underwent metastectomy with curative intent. VATS was performed in 63 (25.1%) patients, 54 (85.7%) of whom had a solitary metastasis. Wedge resection was the most performed procedure in patients treated with VATS (82.5%, n = 52) and thoracotomy (72.3%, n = 136). Postoperative revisions were necessary in nine patients (4.8%), and one patient died of pulmonary embolism after thoracotomy (0.5%). Patients were discharged significantly faster after VATS than after thoracotomy (p < 0.001). Complete (R0) resection was achieved in 89% of patients. The median recurrence-free survival was 11 months (95% confidence interval 7.9–14.1). During follow-up, eight (12.7%) patients in the VATS group and 42 (22.3%) patients in the thoracotomy group experienced recurrence (p = 0.98). The median overall survival was 61 months (95% confidence interval 46.1–75.9), and there was no significant difference with regard to the surgical method used (p = 0.34). Conclusions VATS metastasectomy can be considered in patients with a solitary lung metastasis. An open surgical approach with palpation of the lung showed no advantage in terms of surgical outcome or survival.

Background: Hyperthermic perfusion of the pleural cavity with cisplatin after pleurectomy/decortication is an additional therapeutic option to reduce local relapse of malignant pleural tumours. Although there are data on the clinical effect, only little is known about the local impact on human lung tissue by cisplatin.The objective of this experimental study is to evaluate both the concentration and the penetration depth of cisplatin in human lung tissue after normothermic and hyperthermic exposure under ex-vivo-in-vitro conditions.Methods: This study was approved by the local ethics committee. In total, 46 patients underwent elective lobectomy and wedge resections were taken from the resected lobes. A decortication of the visceral pleura was performed under ex-vivo conditions, and the tissue samples were incubated with cisplatin (c =0.05 mg/mL) at 37, 42 or 45 ℃ for 60 minutes. Then the mass concentration of platinum was measured with flameless atomic absorption spectroscopy and then converted into cisplatin concentration. In addition, the current data were compared with previous data of our working group (42 ℃, without decortication).Results: The overall maximum penetration depth was 7.5 mm due to limitations of our methods. The functional maximum penetration depth did not vary with temperature (P=0.243) but by decortication (P<0.001). The cisplatin concentration decreased with increasing penetration depth (P<0.001). An increase of temperature showed no effect on the cisplatin concentration in decorticated tissue samples (P=0.985).However, decortication at 42 ℃ significantly increased the cisplatin concentration in comparison to not decorticated tissue samples (P=0.005).Conclusions: Decortication of the visceral pleura increases the cisplatin concentration in the lung tissue.Therefore, it possibly reduces the likelihood of a local relapse. An increase of temperature did not show any effect.