Background: Intraplaque hemorrhage promotes atherosclerosis progression, and erythrocytes may contribute to this process. In this study we examined the effects of red blood cells on smooth muscle cell mineralization and vascular calcification and the possible mechanisms involved. Methods: Erythrocytes were isolated from human and murine whole blood. Intact and lysed erythrocytes and their membrane fraction or specific erythrocyte components were examined in vitro using diverse calcification assays, ex vivo by using the murine aortic ring calcification model, and in vivo after murine erythrocyte membrane injection into neointimal lesions of hypercholesterolemic apolipoprotein E–deficient mice. Vascular tissues (aortic valves, atherosclerotic carotid artery specimens, abdominal aortic aneurysms) were obtained from patients undergoing surgery. Results: The membrane fraction of lysed, but not intact human erythrocytes promoted mineralization of human arterial smooth muscle cells in culture, as shown by Alizarin red and van Kossa stain and increased alkaline phosphatase activity, and by increased expression of osteoblast-specific transcription factors (eg, runt-related transcription factor 2, osterix) and differentiation markers (eg, osteopontin, osteocalcin, and osterix). Erythrocyte membranes dose-dependently enhanced calcification in murine aortic rings, and extravasated CD235a-positive erythrocytes or Perl iron-positive signals colocalized with calcified areas or osteoblast-like cells in human vascular lesions. Mechanistically, the osteoinductive activity of lysed erythrocytes was localized to their membrane fraction, did not involve membrane lipids, heme, or iron, and was enhanced after removal of the nitric oxide (NO) scavenger hemoglobin. Lysed erythrocyte membranes enhanced calcification to a similar extent as the NO donor diethylenetriamine-NO, and their osteoinductive effects could be further augmented by arginase-1 inhibition (indirectly increasing NO bioavailability). However, the osteoinductive effects of erythrocyte membranes were reduced in human arterial smooth muscle cells treated with the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide or following inhibition of NO synthase or the NO receptor soluble guanylate cyclase. Erythrocytes isolated from endothelial NO synthase–deficient mice exhibited a reduced potency to promote calcification in the aortic ring assay and after injection into murine vascular lesions. Conclusions: Our findings in cells, genetically modified mice, and human vascular specimens suggest that intraplaque hemorrhage with erythrocyte extravasation and lysis promotes osteoblastic differentiation of smooth muscle cells and vascular lesion calcification, and also support a role for erythrocyte-derived NO.

A higher degree of local tissue hypoxia and up-regulation of leptin expression in the perivascular adipose tissue, along with increased vascularization, inflammation, and fibrosis, may contribute to the increased atherosclerotic plaque burden in the coronary arteries compared to the IMA.

In this work we studied the frequency dependence of the dynamic mechanical characteristic s of saphenous vein (SV) and internal mammary artery (IMA) grafts. Rectangular longitudinal strips from 14 patients were tested under cyclic uniaxial tensile loading in the frequency range of 0.1–20 Hz, at 37°C in wet conditions. The dynamic mechanical parameters (the storage modulus ES and the hysteresis ratio h (loading/loop area)) together with the collagen phase modulus EH were computed as a function of frequency. The results showed that in all graft types ES and EH varied with frequency in the range 0.5–10 Hz, presenting a maximum in the neighboring of 1 Hz. The hysteresis ratio h was increased in the frequency range 1–20 Hz. It seems from the results that the physical resonance frequency of the components of the tissue responsible for their elastic behavior may lay in the range around 1 Hz, while that for the viscous behavior in the range of 20 Hz or more. Early clinical outcomes of both grafting were studied in parallel. In a one-year postoperative period the follow-up (clinical examination, electrocardiography, echocardiography and stress test) did not reveal any sign of graft occlusion or severe stenosis except one perioperative infraction but without any correlation to the graft quality.

The present paper is an interesting and rare complication of implantation of a permanent pacemaker lead. The rarity of the case is based upon that ventricular perforation is usually present during implantation, whereas in our case, it was presented late--1 month after implantation. Furthermore, in our case, the pacemaker lead had migrated through the left hemidiaphragm into the peritoneal cavity.

Background: The diagnosis of peribronchial pulmonary lesions located in the tertiary bronchi, also known as segmental bronchi, as well as, the 4th order and 5th order segmental bronchi is very difficult. Histopathological specimens cannot be easily obtained by endobronchial biopsies (EBBX) due to the patent but small segmental bronchial lumen. The aim of the present study was to evaluate the diagnostic accuracy and safety of the novel technique with radial probe endobronchial ultrasound (R-EBUS) assisted conventional transbronchial needle aspiration (C-TBNA) in the diagnosis of solitary peribronchial pulmonary lesions located in segmental bronchi from 3th to 5th order.Methods: From December 2014 to December 2015, 16 patients with solitary peribronchial pulmonary lesions in the segmental bronchi from 3th to 5th order confirmed by computed tomography (CT) were enrolled. The lesions were located using radial probe endobronchial ultrasound (R-EBUS) to determine the sites of conventional transbronchial needle aspiration (C-TBNA), then, histopathological specimens were obtained using the technique of C-TBNA. The final pathological diagnosis was made based on the findings from the surgical specimens. Statistical analyses were performed for specimen results and complications.Results: On pathological evaluation, 14 of the 16 specimens were malignant, including 8 adenocarcinomas, 4 squamous cell carcinomas, and 2 small cell carcinomas, while 2 were non-malignant diseases. The diagnostic accuracy rate, sensitivity and missed diagnosis rates were 87.5%, 87.5% and 12.5%, respectively. When Combined the results of cytology with histologic samples obtained from C-TBNA the total diagnostic accuracy rate, sensitivity and missed diagnosis rate were 93.75%, 93.75% and 6.25%, respectively. There were 2 cases of bleeding complications >5 mL after C-TBNA, and both were resolved with endobronchial management.Conclusions: The combination of R-EBUS with C-TBNA was advantageous and safe for the diagnosis of solitary peribronchial pulmonary lesions located in the segmental bronchi. However, possible bleeding complications should be anticipated with needle aspiration. Further verification of this combined application should be investigated in larger clinical trials.