Suchergebnisse

Acute myocardial infarction (AMI) and the heart failure (HF) that often complicates this condition, are among the leading causes of death and disability worldwide. To reduce myocardial infarct (MI) size and prevent heart failure, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). In this regard, targeting cardiac innervation may provide a novel therapeutic strategy for cardioprotection. A number of cardiac neural pathways mediate the beneficial effects of cardioprotective strategies such as ischaemic preconditioning and remote ischaemic conditioning, and nerve stimulation may therefore provide a novel therapeutic strategy for cardioprotection. In this article, we provide an overview of cardiac innervation and its impact on acute myocardial IRI, the role of extrinsic and intrinsic cardiac neural pathways in cardioprotection, and highlight peripheral and central nerve stimulation as a cardioprotective strategy with therapeutic potential for reducing MI size and preventing HF following AMI. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

Many treatments have been identified that confer robust cardioprotection in experimental animal models of acute ischemia and reperfusion injury. However, translation of these cardioprotective therapies into the clinical setting of acute myocardial infarction (AMI) for patient benefit has been disappointing. One important reason might be that AMI is multifactorial, causing cardiomyocyte death via multiple mechanisms, as well as affecting other cell types, including platelets, fibroblasts, endothelial and smooth muscle cells, and immune cells. Many cardioprotective strategies act through common end-effectors and may be suboptimal in patients with comorbidities. In this regard, emerging data suggest that optimal cardioprotection may require the combination of additive or synergistic multitarget therapies. This review will present an overview of the state of cardioprotection today and provide a roadmap for how we might progress towards successful clinical use of cardioprotective therapies following AMI, focusing on the rational combination of judiciously selected, multitarget therapies. This paper emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225. ; This paper is based upon work FROM COST ACTION EU-CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). Dr. Davidson was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Dr. Ferdinandy has been supported by the the National Research, Development and Innovation Office of Hungary (NVKP_16-1-2016-0017; OTKA KH 125570; and OTKA 115378) and by the Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic Development thematic programme of the Semmelweis University. Dr. Bøtker was supported by The Danish Council for Strategic Research (11-108354), Novo Nordisk Foundation (Conditioning Based Intervention Strategies–ConBis), and Trygfonden. Dr. Heusch was supported by the German Research Foundation (SFB 1116, B 08). Dr. Ovize has been supported by the OPeRa (ANR-10-IBHU-0004 OPeRa) and the RHU MARVELOUS (ANR-16-RHUS-0009) programs. Dr. Schulz was funded by the German Research Foundation SFB/CRC 1213/B05. Dr. Hausenloy was supported by the British Heart Foundation (FS/10/039/28270), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, Duke-National University Singapore Medical School, Singapore Ministry of Health's National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (NMRC/CSA-SI/0011/2017) and Collaborative Centre Grant scheme (NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (MOE2016-T2-2-021). Dr. Garcia-Dorado was supported by the Instituto de Salud Carlos III, CIBERCV-Instituto de Salud Carlos III, Spain (grant CB16/11/00479 to DGD, cofunded with European Regional Development Fund-FEDER contribution), and grants PIE/2013-00047 and PI 17/1397 ; Sí