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Hyperlipidaemia is a well-established risk factor for cardiovascular diseases and therefore, many animal model have been developed to mimic the human abnormal elevation of blood lipid levels. In parallel, extensive research for the alleviation of ischaemia/reperfusion injury has revealed that hyperlipidaemia is a major co-morbidity that attenuates the cardioprotective effect of conditioning strategies (preconditioning, postconditioning and remote conditioning) and that of pharmacological interventions by interfering with cardioprotective signalling pathways. In the present review article, we summarize the existing data on animal models of hypercholesterolaemia (total, low density and HDL abnormalities) and hypertriglyceridaemia used in ischaemia/reperfusion injury and protection from it. We also provide recommendations on preclinical animal models to be used for translations of the cardioprotective strategies into clinical practice. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc. © 2019 The British Pharmacological Society

Hyperlipidaemia is a well-established risk factor for cardiovascular diseases and therefore, many animal model have been developed to mimic the human abnormal elevation of blood lipid levels. In parallel, extensive research for the alleviation of ischaemia/reperfusion injury has revealed that hyperlipidaemia is a major co-morbidity that attenuates the cardioprotective effect of conditioning strategies (preconditioning, postconditioning and remote conditioning) and that of pharmacological interventions by interfering with cardioprotective signalling pathways. In the present review article, we summarize the existing data on animal models of hypercholesterolaemia (total, low density and HDL abnormalities) and hypertriglyceridaemia used in ischaemia/reperfusion injury and protection from it. We also provide recommendations on preclinical animal models to be used for translations of the cardioprotective strategies into clinical practice.

Dike B Ojji,1,2 Sandrine Lecour,2 Olusoji M Adeyemi,3 Karen Sliwa2,4 1Cardiology Unit, Department of Medicine, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria; 2Department of Medicine, Faculty of Health Sciences, Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, Cape Town, South Africa; 3Department of Medical Laboratory Sciences, University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria; 4Mary McKillop Institute for Health Research, ACU, Melbourne, VIC, Australia Purpose: ST2 receptor, which is a member of the Toll-like/interleukin-1 (IL-1) receptor family, has been found to be increased in the serum of patients 1day after myocardial infarction. Several other studies have shown that soluble ST2 levels correlate with severity of heart failure (HF), left ventricular ejection fraction, creatinine clearance, B-type natriuretic peptide and C-reactive protein, and are predictors of mortality in HF. Most of these studies were not only limited to ischemic heart disease but also concentrated on left-sided HF. We therefore decided to study the relationship between soluble ST2 and some markers of right ventricular (RV) function in a cohort of hypertensive HF subjects.Patients and methods: This is a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, over a 12-month period. ST2 was measured in plasma sample by the enzyme-linked immunosorbent assay (ELISA) method. Right ventricular diameters in diastole (RVDD) and right atrial area (RAA) were obtained on echocardiography, while right ventricular systolic pressure (RVSP) was estimated from echocardiography by the addition of the pressure gradient between the right ventricle and right atrium (RA) to the pressure in the RA.Results: There was a significant correlation between RVSP and soluble ST2 (t=0.75, p

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.

© 2016, The Author(s).In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients’ cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia–reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients’ outcome.

© 2016, The Author(s).To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research.

To commemorate the auspicious occasion of the 30th anniversary of IPC, leading pioneers in the field of cardioprotection gathered in Barcelona in May 2016 to review and discuss the history of IPC, its evolution to IPost and RIC, myocardial reperfusion injury as a therapeutic target, and future targets and strategies for cardioprotection. This article provides an overview of the major topics discussed at this special meeting and underscores the huge importance and impact, the discovery of IPC has made in the field of cardiovascular research. © 2016, The Author(s).

Cardioprotection; Drug development; Infarction Cardioprotección; Desarrollo de fármacos; Infarto Cardioprotecció; Desenvolupament de fàrmacs; Infart Acute myocardial infarction (AMI) and the heart failure (HF) which may follow are among the leading causes of death and disability worldwide. As such, new therapeutic interventions are still needed to protect the heart against acute ischemia/reperfusion injury to reduce myocardial infarct size and prevent the onset of HF in patients presenting with AMI. However, the clinical translation of cardioprotective interventions that have proven to be beneficial in preclinical animal studies, has been challenging. One likely major reason for this failure to translate cardioprotection into patient benefit is the lack of rigorous and systematic in vivo preclinical assessment of the efficacy of promising cardioprotective interventions prior to their clinical evaluation. To address this, we propose an in vivo set of step-by-step criteria for IMproving Preclinical Assessment of Cardioprotective Therapies (‘IMPACT’), for investigators to consider adopting before embarking on clinical studies, the aim of which is to improve the likelihood of translating novel cardioprotective interventions into the clinical setting for patient benefit. This article is based on the work from COST Action EU-CARDIOPROTECTION CA16225 supported by COST (European Cooperation in Science and Technology). DJH is supported by the 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). SL is supported by grants from the South African Department of Science and Technology and the South African National Research Foundation. SMD is supported by grants from the British Heart Foundation (PG/19/51/34493 and PG/16/85/32471). GH is supported by the German Research Foundation (SFB 1116 B8). MRM is supported by the Spanish Institute of Health Carlos III (FIS PI19/01196 and CIBER-CV). RS is supported by Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [Project number 268555672—SFB 1213, Project B05]. PF is supported by the National Research, Development and Innovation Office of Hungary (Research Excellence Program—TKP, National Heart Program NVKP 16-1-2016-0017) and by the Higher Education Institutional Excellence Program of the Ministry of Human Capacities in Hungary, within the framework of the Therapeutic Development thematic program of the Semmelweis University.

Includes bibliographical references (leaves 150-177)., Ischemic preconditioning is a protective mechanism whereby repetitive transient ischaemia confer protection against the subsequent prolonged lethal ischaemia that is observed during myocardial infarction. This protective phenomenon that lessens myocardial infarction can be mimicked by the cytokine tumor necrosis factor alpha (TNFα) but the signalling pathways involved still remain unclear.