An Update on Cardioprotection

Gerczuk, Paul; Kloner, Robert A.

doi:10.1016/j.jacc.2011.07.054

Cited by 182 publications

(83 citation statements)

References 100 publications

(71 reference statements)

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“…18,19 After MI, cardiomyocyte death results in a noncontractile fibrotic scar and altered electric properties, including delayed impulse propagation across the scar region, which contributes to ventricular dysfunction. Because adult cardiomyocytes have a limited regenerative capability after an MI, 20 new treatment strategies are required to preserve ventricular function and prevent adverse remodeling.…”

Section: Discussionmentioning

confidence: 99%

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

et al. 2015

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C oronary heart disease is the leading cause of the rising incidence of heart failure worldwide.1 Following myocardial infarction (MI), the limited regenerative potential of the heart causes scar formation in and around the infarction, leading to abnormal electric signal propagation and desynchronized cardiac activation and contraction.2 The lack of electric connection between healthy myocardium and the scar with its islands of intact cardiomyocytes contributes to progressive functional decompensation. Injectable biomaterial has shown promise as an alternative biological treatment option after MI to reduce adverse remodeling and preserve cardiac function.3,4 Among their many advantages, injectable materials can be delivered alone or as a vehicle carrying combination therapies, including cells or growth factors, and may provide mechanical and functional support to the injured heart. Over the past decade, several injectable biomaterials such as collagen, 5,6 alginate, 7 and fibrin 8 have been extensively studied. Organic polymers that conduct electricity (conductive polymers) were first described in 1977, and this discovery was awarded the Nobel prize in 2000.9,10 Conductive polymers are particularly appealing because they exhibit electric properties similar to metals and semiconductors while retaining flexibility, ease of processing, and modifiable conductivity. The electric properties of these materials can be fine-tuned by altering their synthetic processes, including the addition of specific chemical agents.11 Biological applications of conductive polymersBackground-Efficient cardiac function requires synchronous ventricular contraction. After myocardial infarction, the nonconductive nature of scar tissue contributes to ventricular dysfunction by electrically uncoupling viable cardiomyocytes in the infarct region. Injection of a conductive biomaterial polymer that restores impulse propagation could synchronize contraction and restore ventricular function by electrically connecting isolated cardiomyocytes to intact tissue, allowing them to contribute to global heart function. Methods and Results-We created a conductive polymer by grafting pyrrole to the clinically tested biomaterial chitosan to create a polypyrrole (PPy)-chitosan hydrogel. Cyclic voltammetry showed that PPy-chitosan had semiconductive properties lacking in chitosan alone. PPy-chitosan did not reduce cell attachment, metabolism, or proliferation in vitro. Neonatal rat cardiomyocytes plated on PPy-chitosan showed enhanced Ca 2+ signal conduction in comparison with chitosan alone. PPy-chitosan plating also improved electric coupling between skeletal muscles placed 25 mm apart in comparison with chitosan alone, demonstrating that PPy-chitosan can electrically connect contracting cells at a distance. In rats, injection of PPy-chitosan 1 week after myocardial infarction decreased the QRS interval and increased the transverse activation velocity in comparison with saline or chitosan, suggesting improved electric conduction. Optical mapping showed incr...

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Section: Discussionmentioning

confidence: 99%

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

et al. 2015

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“…Despite advances in the treatment of acute myocardial infarction (AMI), many patients still develop progressive heart failure in several years as a result of declining cardiac function 1, 2, 3, 4. This situation suggests that there are missing pathophysiological mechanisms, which motivates researchers to explore viable strategies to preserve post‐AMI cardiac function.…”

Section: Introductionmentioning

confidence: 99%

Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4‐Dependent CCN1 Secretion

Cui

Xue

Yang

et al. 2018

JAHA

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BackgroundStress‐induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function.Methods and ResultsSenescence markers, including p16INK 4a, p21CIP 1/ WAF 1, and SA‐β‐gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence‐related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence‐related secretory phenotype factors, including CCN family member 1 (CCN1), interleukin‐1α, tumor necrosis factor α, and monocyte chemoattractant protein‐1. In vivo, a tail vein injection of AAV9‐Gata4‐shRNA significantly attenuated senescence‐related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence‐related secretory phenotype factors, CCN1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of AAV9‐Gata4‐shRNA in vivo.ConclusionsMyocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA‐binding factor 4‐CCN1 pathway.

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“…elective angioplasty, evolving myocardial infarction and cardiothoracic surgery, etc., and to the therapeutic interventions. All these thoughts and the various mechanical or pharmaceutical interventions are extensively presented, describing the chances, challenges and concerns related to the translation of the experimental findings into clinical practice [60,61]. Finally, some divergent results may be due to genetic differences of the study population (Asians vs. Europeans or Americans) and to the ability of some experienced groups of investigators to apply appropriate interventions, providing consistently positive results.…”

Section: Confoundersmentioning

confidence: 99%

Ischemic and Postischemic Conditioning of the Myocardium in Clinical Practice: Challenges, Expectations and Obstacles

et al. 2014

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Conditioning refers to endogenous mechanisms rendering the myocardium more tolerant against reperfusion injury. Application of brief ischemia-reperfusion cycles prior to the index ischemia has a beneficial effect and limits the infarct size. This is called preconditioning and is mainly mediated by activation of adenosine, bradykinin, opioid and other receptors, with subsequent activation of intracellular mediators leading to mitochondrial protection. A clinical equivalent of preconditioning is preinfarction angina. Benefits for the ischemic and reperfused myocardium are also provided by repetitive short-lived cycles of ischemia-reperfusion applied after the index ischemia. This is termed postconditioning, shares a common pathway with preconditioning, and is more useful and relevant in clinical practice. Finally, benefits are also derived from remote conditioning, i.e. ischemia applied in a remote vascular territory parallel with or immediately after the index myocardial ischemia. Several pharmacological interventions may interfere with these mechanisms leading to enhanced protection of the myocardium and limitation of the infarct size. Despite the huge interest and the great body of evidence that verify the effectiveness of conditioning, clinical application has remained limited due to controversies over the appropriate intervention protocol, but also interference of medication, comorbidities and other factors that may enhance or blur the protective effect.

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An Update on Cardioprotection

Cited by 182 publications

References 100 publications

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

A Conductive Polymer Hydrogel Supports Cell Electrical Signaling and Improves Cardiac Function After Implantation into Myocardial Infarct

Postinfarction Hearts Are Protected by Premature Senescent Cardiomyocytes Via GATA4‐Dependent CCN1 Secretion

Ischemic and Postischemic Conditioning of the Myocardium in Clinical Practice: Challenges, Expectations and Obstacles

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