87,467 research outputs found

    Mechanisms of Volatile Anesthetic-Induced Myocardial Protection

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    Volatile anesthetics protect myocardium against reversible and irreversible ischemic injury. Experimental evidence from several in vitro and in vivo animal models demonstrates that volatile agents enhance the recovery of stunned myocardium and reduce the size of myocardial infarction after brief or prolonged coronary artery occlusion and reperfusion, respectively. This protective effect persists after the anesthetic has been discontinued, a phenomenon known as anesthetic-induced preconditioning (APC). Recent clinical data also demonstrates evidence of APC in patients during cardiac surgery. Thus, administration of volatile anesthetics may represent a novel therapeutic approach that reduces morbidity and mortality associated with perioperative myocardial ischemia and infarction. The mechanisms responsible for APC appear to be similar to those implicated in ischemic preconditioning, but nonetheless have subtle differences. Accumulating evidence indicates that APC is characterized by complex signal transduction pathways that may include adenosine receptors, G proteins, protein kinase C, reactive oxygen species, and sarcolemmal or mitochondrial KATP channels. Opioid analgesics may further enhance APC as well. This article will review recent advances in the understanding of mechanisms responsible for volatile anesthetic-induced myocardial protection

    A review of the molecular mechanisms underlying the development and progression of cardiac remodeling

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    Pathological molecular mechanisms involved in myocardial remodeling contribute to alter the existing structure of the heart, leading to cardiac dysfunction. Among the complex signaling network that characterizes myocardial remodeling, the distinct processes are myocyte loss, cardiac hypertrophy, alteration of extracellular matrix homeostasis, fibrosis, defective autophagy, metabolic abnormalities, and mitochondrial dysfunction. Several pathophysiological stimuli, such as pressure and volume overload, trigger the remodeling cascade, a process that initially confers protection to the heart as a compensatory mechanism. Yet chronic inflammation after myocardial infarction also leads to cardiac remodeling that, when prolonged, leads to heart failure progression. Here we review the molecular pathways involved in cardiac remodeling, with particular emphasis on those associated with myocardial infarction. A better understanding of cell signaling involved in cardiac remodeling may support the development of new therapeutic strategies towards the treatment of heart failure and reduction of cardiac complications. We will also discuss data derived from gene therapy approaches for modulating key mediators of cardiac remodeling

    Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

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    Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection

    Combination GLP-1 and Insulin Treatment Fails to Alter Myocardial Fuel Selection Versus Insulin Alone in Type 2 Diabetes

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    Context Glucagon-like peptide-1 (GLP-1) and the clinically available GLP-1 agonists have been shown to exert effects on the heart. It is unclear whether these effects occur at clinically used doses in vivo in humans, possibly contributing to CVD risk reduction. Objective To determine whether liraglutide at clinical dosing augments myocardial glucose uptake alone or in combination with insulin compared to insulin alone in metformin-treated Type 2 diabetes mellitus. Design Comparison of myocardial fuel utilization after 3 months of treatment with insulin detemir, liraglutide, or combination detemir+liraglutide. Setting Academic hospital Participants Type 2 diabetes treated with metformin plus oral agents or basal insulin. Interventions Insulin detemir, liraglutide, or combination added to background metformin Main Outcome Measures Myocardial blood flow, fuel selection and rates of fuel utilization evaluated using positron emission tomography, powered to demonstrate large effects. Results We observed greater myocardial blood flow in the insulin-treated groups (median[25th, 75th percentile]: detemir 0.64[0.50, 0.69], liraglutide 0.52[0.46, 0.58] and detemir+liraglutide 0.75[0.55, 0.77] mL/g/min, p=0.035 comparing 3 groups and p=0.01 comparing detemir groups to liraglutide alone). There were no evident differences between groups in myocardial glucose uptake (detemir 0.040[0.013, 0.049], liraglutide 0.055[0.019, 0.105], detemir+liraglutide 0.037[0.009, 0.046] µmol/g/min, p=0.68 comparing 3 groups). Similarly there were no treatment group differences in measures of myocardial fatty acid uptake or handling, and no differences in total oxidation rate. Conclusions These observations argue against large effects of GLP-1 agonists on myocardial fuel metabolism as mediators of beneficial treatment effects on myocardial function and ischemia protection

    Role of Caveolae in Cardiac Protection

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    Myocardial ischemia/reperfusion injury is a major cause of morbidity and mortality. The molecular signaling pathways involved in cardiac protection from myocardial ischemia/reperfusion injury are complex. An emerging idea in signal transduction suggests the existence of spatially organized complexes of signaling molecules in lipid-rich microdomains of the plasma membrane known as caveolae. Caveolins—proteins abundant in caveolae—provide a scaffold to organize, traffic, and regulate signaling molecules. Numerous signaling molecules involved in cardiac protection are known to exist within caveolae or interact directly with caveolins. Over the last 4 years, our laboratories have explored the hypothesis that caveolae are vitally important to cardiac protection from myocardial ischemia/reperfusion injury. We have provided evidence that (1) caveolae and the caveolin isoforms 1 and 3 are essential for cardiac protection from myocardial ischemia/reperfusion injury, (2) stimuli that produce preconditioning of cardiac myocytes, including brief periods of ischemia/reperfusion and exposure to volatile anesthetics, alter the number of membrane caveolae, and (3) cardiac myocyte-specific overexpression of caveolin-3 can produce innate cardiac protection from myocardial ischemia/reperfusion injury. The work demonstrates that caveolae and caveolins are critical elements of signaling pathways involved in cardiac protection and suggests that caveolins are unique targets for therapy in patients at risk of myocardial ischemia

    BNP, TnI and Lactic Acid variations in Warm Blood Cardioplegia vs Cold Crystalloid Cardioplegia in Coronary Artery Bypass Grafting (CABG)

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    Introduction: Myocardial protection is one of the key points during cardiac surgery. Inadequate myocardial protection in cross-clamping period is an issue of concern in cardiac surgery.  Cardioplegic solutions improve the tolerance of ischemia and reperfusion by preserving myocardial energy reserves, preventing osmotic, electrolyte imbalances and acidosis. Warm blood cardioplegia (WBC) has had a profound impact, especially in coronary artery bypass surgery and there have been many studies that compared it with Cold crystalloid cardioplegia (CCC). A good myocardial protection will be reflected especially on patients outcome, on postoperative ICU strategy, morbidity and mortality as well. Brain Natriuretic Peptide (BNP), Troponin I (TnI) and Lactic Acid LA) are very significant biomarkers that reflects an adequate myocardial and organ perfusion/protection. The purpose of this study is to determine if warm blood cardioplegia offers any advantages in comparison with CCC in Coronary Artery Bypass Grafting (CABG) based primary on variations of BNP, TnI and Lactic Acid. Patients and method: 60 patients with coronary artery disease (CAD) that will have Coronary Artery Bypass Surgery (CABG), were retrospectively randomized in two groups of 30 patients with different techniques of myocardial protection: group A had CCC, and group B had warm blood cardioplegia (WBC), according to Calafiore [1] protocols). Intraoperative and postoperative variables were used to assess primary outcomes. Results: This study found benefits of warm blood cardioplegia in clinical outcome after CABG Keywords:Myocardial protection, Cardiac surgery, Cardiopulmonary Bypass, Calafiore, Cardioplegia, Coronary Artery Bypass Grafting (CABG), Brain Natriuretic Peptide (BNP), Troponin I (TnI) and Lactic Acid LA) DOI: 10.7176/ALST/95-02 Publication date: November 30th 202

    Lidoflazine and myocardial protection

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    The role of Volatile Anesthetics in Cardioprotection: a systematic review.

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    This review evaluates the mechanism of volatile anesthetics as cardioprotective agents in both clinical and laboratory research and furthermore assesses possible cardiac side effects upon usage. Cardiac as well as non-cardiac surgery may evoke perioperative adverse events including: ischemia, diverse arrhythmias and reperfusion injury. As volatile anesthetics have cardiovascular effects that can lead to hypotension, clinicians may choose to administer alternative anesthetics to patients with coronary artery disease, particularly if the patient has severe preoperative ischemia or cardiovascular instability. Increasing preclinical evidence demonstrated that administration of inhaled anesthetics - before and during surgery - reduces the degree of ischemia and reperfusion injury to the heart. Recently, this preclinical data has been implemented clinically, and beneficial effects have been found in some studies of patients undergoing coronary artery bypass graft surgery. Administration of volatile anesthetic gases was protective for patients undergoing cardiac surgery through manipulation of the potassium ATP (KATP) channel, mitochondrial permeability transition pore (mPTP), reactive oxygen species (ROS) production, as well as through cytoprotective Akt and extracellular-signal kinases (ERK) pathways. However, as not all studies have demonstrated improved outcomes, the risks for undesirable hemodynamic effects must be weighed against the possible benefits of using volatile anesthetics as a means to provide cardiac protection in patients with coronary artery disease who are undergoing surgery

    The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

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    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
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