Potential of dietary nitrate in angiogenesis

Endothelial dysfunction with impaired bioavailability of nitric oxide(NO) is the hallmark in the development of cardiovascular disease. Endothelial dysfunction leads to atherosclerosis, characterized by chronic inflammation of the arterial wall and stepwise narrowing of the vessel lumen. Atherosclerosis causes deprivation of adequate tissue blood flow with compromised oxygen supply. To overcome this undersupply, remodeling of the vascular network is necessary to reconstitute and sustain tissue viability. This physiological response is often not sufficient and therapeutic angiogenesis remains an unmet medical need in critical limb ischemia or coronary artery disease. Feasible approaches to promote blood vessel formation are sparse. Administration of pro-angiogenic factors, gene therapy, or targeting of micro RNAs has not yet entered the daily practice. Nitric oxide is an important mediator of angiogenesis that becomes limited under ischemic conditions and the maintenance of NO availability might constitute an attractive therapeutic target. Until recently it was unknown how the organism provides NO under ischemia. In recent years it could be demonstrated that NO can be formed independently of its enzymatic synthesis in the endothelium by reduction of inorganic nitrite under hypoxic conditions. Circulating nitrite derives from oxidation of NO or reduction of inorganic nitrate by commensal bacteria in the oral cavity. Intriguingly, nitrate is a common constituent of our everyday diet and particularly high concentrations are found in leafy green vegetables such as spinach, lettuce, or beetroot. Evidence suggests that dietary nitrate supplementation increases the regenerative capacity of ischemic tissue and that this effect may offer an attractive nutrition-based strategy to improve ischemia-induced revascularization. We here summarize and discuss the regenerative capacity of dietary nitrate on the vascular system.

Concepts of hypoxic NO signaling in remote ischemic preconditioning

Acute coronary syndromes remain a leading single cause of death worldwide. Therapeutic strategies to treat cardiomyocyte threatening ischemia/reperfusion injury are urgently needed. Remote ischemic preconditioning(r IPC) applied by brief ischemic episodes to heartdistant organs has been tested in several clinical studies, and the major body of evidence points to beneficial effects of r IPC for patients. The underlying signaling, however, remains incompletely understood. This relates particularly to the mechanism by which the protective signal is transferred from the remote site to the target organ. Many pathways have been forwarded but none can explain the protective effects completely. In light of recent experimental studies, we here outline the current knowledge relating to the generation of the protective signal in the remote organ, the signal transfer to the target organ and the transduction of the transferred signal into cardioprotection. The majority of studies favors a humoral factor that activates cardiomyocyte downstream signaling- receptor-dependent and independently. Cellular targets include deleterious calcium(Ca2+) signaling, reactive oxygen species, mitochondrial function and structure, and cellular apoptosis and necrosis. Following an outline of the existing evidence, we will furthermore characterize the existing knowledge and discuss future perspectives with particular emphasis on the interaction between the recently discovered hypoxic nitrite-nitric oxide signaling in r IPC. This refers to the protective role of nitrite, which can be activated endogenously using r IPC and which then contributes to cardioprotection by rIPC.

Red cell distribution width in anemic patients undergoing transcatheter aortic valve implantation

AIM: To determine the impact of red blood cell distribution width on outcome in anemic patients undergoing transcatheter aortic valve implantation(TAVI).METHODS: In a retrospective single center cohort study we determined the impact of baseline red cell distribution width(RDW) and anemia on outcome in 376 patients with aortic stenosis undergoing TAVI. All patients were discussed in the institutional heart team and declined for surgical aortic valve replacement due to high operative risk. Collected data included patient characteristics, imaging findings, periprocedural in hospital data, laboratory results and follow up data. Blood samples for hematology and biochemistry analysis were taken from every patient before and at fixed intervals up to 72 h after TAVI including blood count and creatinine. Descriptive statistics were used for patient's characteristics. KaplanMeier survival curves were used for time to event outcomes. A recursive partitioning regression and classification was used to investigate the association between potential risk factors and outcome variables.RESULTS: Mean age in our study population was 81 ± 6.1 years. Anemia was prevalent in 63.6%(n = 239) of our patients. Age and creatinine were identified as risk factors for anemia. In our study population, anemia per se did influence 30-d mortality but did not predict longterm mortality. In contrast, a RDW > 14% showed to be highly predictable for a reduced short- and longterm survival in patients with aortic valve disease after TAVI procedure.CONCLUSION: Age and kidney function determine the degree of anemia. The anisocytosis of red blood cells in anemic patients supplements prognostic information in addition to that derived from the WHO-based definition of anemia.

Initial clinical experience using the Echo Navigator~-system during structural heart disease interventions

AIM: To present our initial clinical experience using this innovative software solution for guidance of percutaneous structural heart disease interventions.METHODS: Left atrial appendage, atrial septal defect and paravalvular leak closure, transaortic valve repair and Mitra Clip procedures were performed in the catheter laboratory under fluoroscopic and echocardiographic guidance. The two-dimensional and three-dimensional images generated by the transesophageal echocardiography probe were interfaced with the fluoroscopic images in real-time using the Echo Navigator-system.RESULTS:The application of the novel image fusion technology was safe and led to a better appreciation of multimodality imaging guidance due to improved visualization of the complex relationship between catheter devices and anatomical structures.CONCLUSION:The Echo Navigator-system is a feasible and safe tool for guidance of interventional procedures in structural heart disease.This innovative technology may improve confidence of interventional cardiologists in targeting and positioning interventional devices in order to increase safety,accuracy,and efficacy of percutaneous interventions in the catheter laboratory.