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BACKGROUND: Repeated ischemia/reperfusion in a tissue/organ remote from the heart (remote ischemic conditioning, RIC) protects against injury from sustained myocardial ischemia/reperfusion (I/R). Platelets are considered as mediators/targets of RIC´s protection. We have recently reported that infusion of washed platelets, taken from healthy volunteers after RIC, reduced infarct size (IS) in isolated rat hearts (FASEB Journal 2021; 35; S1; DOI: 10.1096/fasebj.2021.35.S1.03444). Anti-platelet drugs are potential confounders of RIC. AIM: To study the impact of anti-platelet drugs, the cyclooxygenase inhibitor aspirin and the P2Y12 inhibitor ticagrelor, on the platelet-mediated transfer of cardioprotection. METHODS: We included 18 healthy volunteers. As a contemporary control, volunteers were subjected to RIC through 3 x 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/ 5 min deflation. After at least 2 weeks, these volunteers were again subjected to RIC 3 hours after pretreatment with oral aspirin (500-1000 mg) and again at least another 2 weeks later 2 hours after pretreatment with oral ticagrelor (180 mg). Venous blood samples were taken before RIC and 60 min after RIC, respectively. Washed platelets were prepared using apyrase, prostaglandin E1 and citrated Tyrode-buffer. The platelet count was adjusted to 2.5 x 105 platelets/µL. The functionality of washed platelets was tested in response to thrombin (1U/ml), aggregation measured with turbodimetric light transmission aggregometry and expressed as the increase in light transmission in percent of control. Platelet preparations with an aggregation

Purpose: The role of platelets during myocardial ischemia/reperfusion (I/R) is ambivalent. They contribute to injury but also to cardioprotection. Repeated blood flow restriction and reperfusion in a tissue/organ remote from the heart (remote ischemic conditioning, RIC) reduce myocardial I/R injury and attenuate platelet activation. Whether or not platelets mediate RIC’s cardioprotective signal is currently unclear. Methods and Results: Venous blood from healthy volunteers (without or with pretreatment of 500/1000 mg aspirin or 180 mg ticagrelor orally, 2–3 h before the study, n = 18 each) was collected before and after RIC (3 × 5 min blood pressure cuff inflation at 200 mmHg on the left upper arm/5 min deflation). Washed platelets were isolated. Platelet-poor plasma was used to prepare plasma-dialysates. Platelets (25 × 103/µL) or plasma-dialysates (1:10) prepared before and after RIC from untreated versus aspirin- or ticagrelor-pretreated volunteers, respectively, were infused into isolated buffer-perfused rat hearts. Hearts were subjected to global 30 min/120 min I/R. Infarct size was stained. Infarct size was less with infusion of platelets/plasma-dialysate after RIC (18 ± 7%/23 ± 9% of ventricular mass) than with platelets/plasma-dialysate before RIC (34 ± 7%/33 ± 8%). Aspirin pretreatment abrogated the transfer of RIC’s cardioprotection by platelets (after/before RIC, 34 ± 7%/33 ± 7%) but only attenuated that by plasma-dialysate (after/before RIC, 26 ± 8%/32 ± 5%). Ticagrelor pretreatment induced an in vivo formation of cardioprotective factor(s) per se (platelets/plasma-dialysate before RIC, 26 ± 7%/26 ± 7%) but did not impact on RIC’s cardioprotection by platelets/plasma-dialysate (20 ± 7%/21 ± 5%). Conclusion: Platelets serve as carriers for RIC’s cardioprotective signal through an aspirin-sensitive and thus cyclooxygenase-dependent mechanism. The P2Y12 inhibitor ticagrelor per se induces a humoral cardioprotective signal. Graphical abstract: [Figure not available: see fulltext.]. © 2022, The Author(s).

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.

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

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. © 2019 The Authors

© 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).

Ischemic postconditioning, a simple mechanical maneuver at the onset of reperfusion, reduces infarct size after ischemia/reperfusion. After its first description in 2003 by Zhao et al. numerous experimental studies have investigated this protective phenomenon. Whereas the underlying mechanisms and signal transduction are not yet understood in detail, infarct size reduction by ischemic postconditioning was confirmed in all species tested so far, including man. We have now reviewed the literature with focus on experimental models and protocols to better understand the determinants of protection by ischemic postconditioning or lack of it. Only studies with infarct size as unequivocal endpoint were considered. In all species and models, the duration of index ischemia and the protective protocol algorithm impact on the outcome of ischemic postconditioning, and gender, age, and myocardial temperature contribute. © Springer-Verlag 2009.

Ischemic postconditioning has emerged as a clinically feasible intervention for limiting infarction in the setting of percutaneous intervention. In ischemic postconditioning, a number of cycles of a brief period of reperfusion followed by a brief period of occlusion are applied immediately upon reperfusion of the ischemic heart. Although ischemic postconditioning is protective in both animals and man, the animal studies reveal that the algorithm used in selecting the duration of the occlusion and reperfusion periods is critical to the degree of protection realized and it varies with species. The question then arises what is the best algorithm for man? The available animal and clinical data are examined in an attempt to shed light on this perplexing problem.

Cardiovascular scientific production in Europe is growing both in quantity and quality. Promoting high-quality research is a major goal of the European Society of Cardiology (ESC).1–3 The ESC has two highly respected official general journals, namely the European Heart Journal and Cardiovascular Research , devoted to clinical and basic research respectively.1–3 The ESC also publishes several sub-speciality official journals covering the full spectrum of cardiovascular diseases and related techniques. Most European countries, however, also have their own cardiovascular journals. National Society Cardiovascular Journals (NSCJ) are time-honoured and classically disseminate high-quality scientific research mainly originating from each particular European country, although some, such as Heart, are now international in their content and distribution. The journals also play a major role in education and harmonization of clinical practice. Most NSCJ are published in local languages but many of them also incorporate English editions. Altogether, NSCJ provide a highly effective means to disseminate cardiovascular research produced in Europe. Scientific knowledge, however, has no barriers and many of these journals have gained an undisputed international profile. Some NSCJ, however, are just emerging and would benefit from networking support. It became clear that enhancing collaboration among NSCJ Editors would facilitate advancement in knowledge and further diffusion of scientific and educative contents. Developing a “Constitution Document” and “Mission Statement” was considered desirable to set the basis of future collaboration among NSCJ Editors. We assumed this responsibility in recognizing the crucial role of NSCJ in Europe. Our target was to produce and issue a core document with fundamental principles upon which all NSCJ Editors would agree. Common goals will be identified and agreed-on measures will be pursued. The constitution document presented herein was therefore developed to formalize the NSCJ Editors’ Club Task Force. All Editors-in-Chief of the official cardiovascular journals of …