Posts Tagged: reperfusion injury

Critical Issues for the Translation of Cardioprotection

Critical Issues for the Translation of Cardioprotection

Gerd Heusch

Lack of robust preclinical data, lack of phase II dosing and timing studies, and too loose inclusion criteria in clinical trials contribute to poor translation. Adapted from Rossello and Yellon6 with permission of the publisher. Copyright ©2016, American Heart Association, Inc. Authorization for this adaptation has been obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation. TIMI indicates thrombolysis in myocardial infarction. [Powerpoint File]

The Coronary Circulation as a Target of Cardioprotection

The Coronary Circulation as a Target of Cardioprotection

Gerd Heusch

Schematic diagram with the different manifestations of coronary vascular injury during acute myocardial ischemia/reperfusion and the protective interventions that attenuate these manifestations. IP indicates ischemic preconditioning; POCO, ischemic postconditioning; and RIC, remote ischemic conditioning. [Powerpoint File]

Extracellular Ribonucleic Acids (RNA) Enter the Stage in Cardiovascular Disease

Extracellular Ribonucleic Acids (RNA) Enter the Stage in Cardiovascular Disease

Alma Zernecke, Klaus T. Preissner

Contribution of extracellular RNAs (eRNAs) to vascular homeostasis and cardiovascular pathologies. After cell stress (such as hypoxia, injury, and pathogen exposure), eRNA is found to be expressed at various extracellular sites, both intravascularly and extravascularly. In addition, eRNA may be derived from damaged or apoptotic cells or becomes released on inflammatory cell activation and accumulates within atherosclerotic plaques in the course of disease development. The following functional activities of eRNA are promoted by direct interactions with specific extracellular proteins: (1) promotion of vascular hyperpermeability by eRNA as coreceptor/cofactor of vascular endothelial growth factor (VEGF) and by induction of vasculogenesis/angiogenesis. (2) Initiation of intrinsic blood coagulation (via the contact phase proteins) and thrombus formation. (3) Induction of recruitment of leukocytes to the inflamed vessel wall by eRNA-mediated elevation of expression of intercellular adhesion molecule-1 in endothelial cells or vascular cell adhesion molecule-1 and P-selectin in vascular smooth muscle cells. (4) Skewing of monocytes/macrophages toward the M1 proinflammatory phenotype, accompanied by an upregulated expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, inducible nitric oxide synthase (iNOS), and response factors, such as chemokines. Here, eRNA triggers TNF-α–converting enzyme (TACE) to liberate the functionally active TNF-α. (5) Promotion of cardiomyocyte death by inducing a hyperinflammatory cascade involving TNF-α in the context of ischemia–reperfusion injury. [Powerpoint File]

Acute Coronary Syndromes Compendium: Nonantithrombotic Medical Options in Acute Coronary Syndromes: Old Agents and New Lines on the Horizon


Acute Coronary Syndromes Compendium: Nonantithrombotic Medical Options in Acute Coronary Syndromes: Old Agents and New Lines on the Horizon

Victor Soukoulis, William E. Boden, Sidney C. Smith Jr, Patrick T. O’Gara

Mechanisms of reperfusion injury and no-reflow in the coronary vasculature. IL indicates interleukin; MPTP, mitochondrial permeability transition pore; and TNF, tumor necrosis factors. (Illustration credit: Ben Smith.) [Powerpoint File]

Cardioprotection and Myocardial Reperfusion: Pitfalls to Clinical Application

Cardioprotection and Myocardial Reperfusion: Pitfalls to Clinical Application

Richard S. Vander Heide, Charles Steenbergen

Schematic representation of mechanisms involved in ischemia–reperfusion injury and cardioprotection. Ado indicates adenosine; Ad R, adenosine receptors; ANP, atrial natriuretic peptides; Ca2+ Ch, calcium channel; CsA, cyclosporine; ERK, extracellular-related kinase; GPCR, G-protein–coupled receptors; GSK, glycogen synthase kinase; KATP, ATP-sensitive potassium channel; MEK, mitogen activated protein kinase (ERK kinase); MPT, mitochondrial permeability transition pore; NCX, Na+/Ca2+ exchange; NHE, Na+/H+ exchange; Nic, nicorandil; NOS, nitric oxide synthase; NP R, natriuretic peptide receptors; PI3K, phosphoinositol-3-kinase; PKC, protein kinase C; ROS, reactive oxygen species; and SNO, S-nitrosylation. [Powerpoint File]

Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

Current State of Clinical Translation of Cardioprotective Agents for Acute Myocardial Infarction

Robert A. Kloner

Schematic showing how reducing myocardial infarct size early could have benefit on long-term structure of the heart. The left hand drawings show a schematic derived from the wavefront concept of Reimer2 and Jennings. After proximal coronary occlusion, a portion of the left ventricle (LV) becomes ischemic, defined as the ischemic risk region. When a blue dye is injected into the vasculature the blue dye circulates to areas receiving blood flow and fails to penetrate the ischemic zone. If reperfusion occurs after ≈40 minutes of ischemia, irreversible myocardial damage–that is necrosis (pale white area) is confined to the subendocardial myocardium. Viable myocardium within the risk zone is stained red by triphenyl tretazolium chloride (TTC). If reperfusion is delayed (after 60 minutes) or after 3 to 6 hours, the extent of necrosis expands from subendcardium Figure (Continued). to midmyocardium to subepicardium within the ischemic risk zone. This march of necrosis becomes transmural or nearly transmural if reperfusion is not instituted within ≈3 to 6 hours or if reperfusion does not occur. Large transmural infarcts may then go on to result in severe LV remodeling with infarct expansion, LV cavity dilation, LV aneurysm formation, and eccentric hypertrophy of the noninfarcted tissue. If agents are administered to reduce infarct size or if very early reperfusion is instituted the size of the infarct can be limited (first transverse LV slice shown in right column). During the long term, this smaller infarct will shrink in size with a minimum of subendocardial scar tissue and substantial viable tissue remaining in the midmyocardial wall. LV remodeling will be minimized with less infarct wall thinning, less LV dilation, and less eccentric hypertrophy. In addition LV function will be better preserved. [Powerpoint File]