Amorphous nano-selenium quantum dots improve endothelial dysfunction in rats and prevent atherosclerosis in mice through Na+/H+ exchanger 1 inhibition.

AIM: Selenium, a trace element involved in important enzymatic activities inside the body, has protective effects against cardiovascular diseases including atherosclerosis. The safe dose of selenium in the organism is very narrow, limiting the supplementation of selenium in diet. The aim of this study is to explore whether selenium quantum dots (SeQDs) prevent atherosclerosis and to investigate the potential mechanisms. METHODS: An amorphous form of SeQDs (A-SeQDs) and a crystalline form of SeQDs (C-SeQDs) were prepared through self-redox decomposition of selenosulfate precursor. Endothelial dysfunction was induced by balloon injury plus high fat diet (HFD) in rats. Atherosclerotic model was established by feeding Apoe-/- mice with HFD. RESULTS: Administrations of A-SeQDs but not C-SeQDs dramatically improved endothelium-dependent relaxation, and accelerated would healing in primary endothelial cells isolated from rats, which was comprised by co-treatment of LiCl. Lentivirus-mediated knockdown of Na+/H+ exchanger 1 (NHE1) abolished LiCl-induced endothelial dysfunction in rats. In cultured endothelial cells, A-SeQDs, as well as cariporide, inhibited NHE1 activities, decreased intracellular pH value and Ca2+ concentration, and reduced calpain activity increased by ox-LDL. These protective effects of A-SeQDs were reversed by LiCl treatment in endothelial cells. In Apoe-/- mice feeding with HFD, A-SeQDs prevented endothelial dysfunction and reduced the size of atherosclerotic plaque in aortic arteries. Further, lentivirus-mediated NHE1 gene overexpression abolished the protective effects of A-SeQDs against endothelial dysfunction and atherosclerosis in Apoe-/- mice. CONCLUSION: A-SeQDs prevents endothelial dysfunction and the growth of atherosclerotic plaque through NHE1 inhibition and subsequent inactivation of Ca2+/calpain signaling. Clinically, the administration of A-SeQDs is an effective approach to treat atherosclerosis.

Targeting Phosphodiesterase-5 by Vardenafil Improves Vascular Graft Function.

OBJECTIVES: Ischaemia reperfusion (IR) injury occurs during vascular graft harvesting and implantation during vascular/cardiac surgery. Elevated intracellular cyclic guanosine monophosphate (cGMP) levels contribute to an effective endothelial protection in different pathophysiological conditions. The hypothesis that the phosphodiesterase-5 inhibitor vardenafil would protect vascular grafts against IR injury by upregulating the nitric oxide-cGMP pathway in the vessel wall of the bypass graft was investigated. METHODS: Lewis rats (n = 6-7/group) were divided into Group 1, control; Group 2, donor rats received intravenous saline; Group 3, received intravenous vardenafil (30 µg/kg) 2 h before explantation. Whereas aortic arches of Group 1 were immediately mounted in an organ bath, aortic segments of Groups 2 and 3 were stored for 2 h in saline and transplanted into the abdominal aorta of the recipient. Two hours after transplantation, the implanted grafts were harvested. Endothelium dependent and independent vasorelaxations were investigated. TUNEL, CD-31, ICAM-1, VCAM-1, α-SMA, nitrotyrosine, dihydroethidium and cGMP immunochemistry were also performed. RESULTS: Compared with the control, the saline group showed significantly attenuated endothelium dependent maximal relaxation (Rmax) 2 h after reperfusion, which was significantly improved by vardenafil supplementation (Rmax control, 91 ± 2%; saline 22 ± 2% vs. vardenafil 39 ± 4%, p < .001). Vardenafil pre-treatment significantly reduced DNA fragmentation (control 9 ± 1%, saline 66 ± 8% vs. vardenafil 13 ± 1%, p < .001), nitro-oxidative stress (control 0.8 ± 0.3, saline 7.6 ± 1.3 vs. vardenafil 3.8 ± 1, p = .036), reactive oxygen species level (vardenafil 36 ± 4, control 34 ± 2 vs. saline 43 ± 2, p = .049), prevented vascular smooth muscle cell damage (control 8.5 ± 0.7, saline 4.3 ± 0.6 vs. vardenafil 6.7 ± 0.6, p = .013), decreased ICAM-1 (control 4.1 ± 0.5, saline 7.0 ± 0.9 vs. vardenafil 4.4 ± 0.6, p = .031), and VCAM-1 score (control 4.4 ± 0.4, saline 7.3 ± 1.0 vs. vardenafil 5.2 ± 0.4, p = .046) and increased cGMP score in the aortic wall (control 11.2 ± 0.8, saline 6.5 ± 0.8 vs. vardenafil 8.9 ± 0.6, p = .016). The marker for endothelial integrity (CD-31) was also higher in the vardenafil group (control 74 ± 4%, saline 22 ± 2% vs. vardenafil 40 ± 3%, p = .008). CONCLUSIONS: The results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction of an arterial graft after bypass surgery, which can effectively be prevented by vardenafil. Its clinical use as preconditioning drug could be a novel approach in vascular/cardiac surgery.

Upper Limb Ischemia by Subclavian Artery Dissection after Osteopathic Manipulation.

We report the case of a young woman who experienced ischemia of upper limb after osteopathic manipulation. Duplex and computed tomography scan showed wall hematoma of the ostium of subclavian artery. The patient spontaneously recovered so that no surgery was necessary. Dissection of vertebral and carotid arteries has been reported after osteopathic manipulations. We report ischemia of upper limb secondary to dissection of subclavian artery. Arterial dissections associated with manipulation should be recorded in a register in order to assess more carefully the vascular risk that this method carries.

Traumatic Anterior Knee Dislocation with Popliteal Artery Injury: The Importance of a Prompt Diagnosis and Treatment to Obtain Lower Limb Salvage.

We report a case of traumatic anterior dislocation of the left knee in association with disruption of the soft tissues including knee ligaments, popliteal artery, and common peroneal nerve, resulting in lower limb acute ischemia. All components of this complex trauma were recognized and treated promptly. First, he was submitted to closed reduction of the dislocated knee under general anesthesia; right after he underwent superficial femoro-tibioperoneal trunk bypass using a reversed saphenous contralateral vein recurring to a posterior approach through a popliteal S-shaped incision; rehabilitation program was initiated early; a second and final reconstructive orthopedic operation was carried out in a different center. The present case is important in 2 aspects. First, it reports a very rare occurrence of simultaneous anterior dislocation of the knee associated with vascular insult and common peroneal nerve injury, which was rarely reported in the current literature; second, it highlights that with timely intervention and a team approach, excellent results could be achieved.

Management of Vascular Trauma during the Paris Terrorist Attack of November 13, 2015.

BACKGROUND: On November 13, 2015, Paris and Saint-Denis were the targets of terrorist attacks. The Public Hospitals of Paris Organization and the Percy Armed Forces Instruction Hospitals were mobilized to face the mass casualty situation. The objective of this study is to analyze the management of the victims presenting with a nonthoracic vascular trauma (NTVT). METHODS: All the data relating to the victims of NTVT who required a specific vascular open or endovascular treatment were analyzed retrospectively. A 6-month follow-up was obtained for all the patients. RESULTS: Among the 351 wounded, 20 (5.7%) patients had an NTVT and were dispatched in 8 hospitals (11 men of average age 32). NTVTs were gunshots in 17 cases (85%) or due to a handmade bomb in 3 cases (15%). Twelve patients (60%) received cardiopulmonary resuscitation during prehospital care. NTVT affected the limbs (14 cases, 70%) and the abdomen or the small pelvis (6 cases, 30%). All the patients were operated in emergency. Arterial lesions were treated with greater saphenous vein bypasses, by ligation, and/or embolization. Eleven venous lesions were treated by direct repair or ligation. Associated lesions requiring a specific treatment were present in 19 patients (95%) and were primarily osseous, nervous, and abdomino-pelvic. Severe postoperative complications were observed in 9 patients (45%). Fourteen patients (70%) required blood transfusion (6.4 U of packed red blood cells on average, range 0-48). There were no deaths or amputation and all vascular reconstructions were patent at 6 months. CONCLUSIONS: The effectiveness of the prehospital emergency services and a multisite and multidisciplinary management made it possible to obtain satisfactory results for NTVT casualties. All the departments of vascular surgery must be prepared to receive many wounded victims in the event of terrorist attacks.

Platelet activation and microvascular injury in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dual antiplatelet therapy reduces the risk of thrombotic complications after primary percutaneous coronary intervention (PCI). AIM: To assess whether inhibition of platelet function attenuates microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 83 STEMI patients treated with primary PCI. Platelet aggregation was measured on admission (ADM) and 4 days later (D4) by light transmission aggregometry after stimulation with 0.5 mM of arachidonic acid and after stimulation with 5 and 20 µM of adenosine diphosphate (ADP) on treatment with dual antiplatelet therapy with aspirin and clopidogrel. Platelet-neutrophil aggregate (PNA) and platelet-monocyte aggregate (PMA) were analysed by flow cytometry. Contrast-enhanced magnetic resonance imaging was performed 2-4 days after STEMI to detect the area of perfusion defect at rest and to determine the size of microvascular obstruction. Microvascular obstruction was expressed as a percentage of infarct area. RESULTS: Perfusion defect at rest was found in 56 (67.5%) patients whereas microvascular obstruction in 63 (75.9%) patients. Patients with perfusion defect at rest had on admission a significantly higher level of both PMA (7.0 vs. 4.5%, p = 0.004) and PNA (4.1 vs. 2.2%, p = 0.016), however there were no significant differences at D4. Platelet aggregation after stimulation with 5 µM of ADP on ADM was correlated (r = 0.37, p = 0.004) with microvascular obstruction area. Moreover, the higher the concentration of PMA(ADM) (r = 0.31, p = 0.016), PNA(ADM) (r = 0.34, p = 0.006) and PM(AD4) (r = 0.35, p = 0.005) the larger the size of microvascular obstruction. Infarct size (ß = 0.43, 95% CI 0.19 to 0.67, p 〈 0.0001), TIMI < 3 after PCI (ß = -0.27, 95% CI -1.90 to -0.11, p = 0.015) and PMA(D4) (ß = 0.21, 95% CI 0.13 to 1.86, p = 0.032) independently influenced the size of microvascular obstruction (R2 = 0.60, p 〈 0.0001). CONCLUSIONS: Excessive platelet activation during reperfusion in STEMI patients despite dual antiplatelet therapy is associated with greater microvascular impairment.

Critical role for Syk in responses to vascular injury.

Although current antiplatelet therapies provide potent antithrombotic effects, their efficacy is limited by a heightened risk of bleeding and failure to affect vascular remodeling after injury. New lines of research suggest that thrombosis and hemorrhage may be uncoupled at the interface of pathways controlling thrombosis and inflammation. Here, as one remarkable example, studies using a novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5-carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition ameliorates both the acute and chronic responses to vascular injury without affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras) attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly inhibited arterial thrombosis in vivo in multiple animal species while having minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses to vascular injury, including inflammatory cell recruitment and neointima formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and long-term responses to arterial vascular injury. The therapeutic potential of Syk may be exemplary of a new class of antiatherothrombotic agents that target the interface between thrombosis and inflammation.