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Mechanisms Underlying The Antiarrhythmic Effect Of Arumenamide-787 In Experimental Models Of The J Wave Syndromes And Hypothermia, José M. Di Diego, Hector Barajas-Martinez, Robert Cox, Victoria M Robinson, Joseph Jung, Mohamed Fouda, Mena Abdelsayed, Peter C Ruben, Charles Antzelevitch

Department of Medicine Faculty Papers

BACKGROUND: Brugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.

METHODS: We studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG …

Post-Discharge And Long-Term Follow-Up After An Acute Coronary Syndrome: International Collaborative Group Of Cncf Position Paper, Pierre Sabouret, Gilles Lemesle, Anne Bellemain-Appaix, Pierre Aubry, Pier-Paolo Bocchino, Erik Rafflenbeul, Loïc Belle, Jim Nolan, Marco Bernardi, Giuseppe Biondi-Zoccai, Michael P. Savage, Maciej Banach, Guillaume Cayla

Division of Cardiology Faculty Papers

Introduction: Long-term follow-up after an acute coronary syndrome (ACS) presents a crucial challenge due to the high residual cardiovascular risk and the potential for major bleeding events. Although several treatment strategies are available, this article focuses on patients who have undergone percutaneous coronary intervention (PCI) for ACS, which is a frequent clinical situation. This position paper aims to support physicians in daily practice to improve the management of ACS patients.

Material and methods: A group of recognized international and French experts in the field provides an overview of current evidence-based recommendations - supplemented by expert opinion where such evidence is …

Native Valve Endocarditis Complicated By Abscess Formation Caused By Rothia Mucilaginosa, S Haddad, Y Saade, B Ramlawi, B Kreidieh, B Gilbert, S Rao

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Rothia mucilaginosa is increasingly recognized as an emerging pathogen associated with endocarditis. It has mostly been reported a causative agent for prosthetic valve endocarditis. The previously reported cases of native valve endocarditis caused by this organism only required medical treatment with no surgical intervention. We report a case of R. mucilaginosa native valve endocarditis complicated by abscess formation requiring surgical intervention and review the literature of native valve endocarditis caused by this organism.

Health Care Policy And Congenital Heart Disease: 2020 Focus On Our 2030 Future, Devyani Chowdhury, Jonathan N Johnson, Carissa M Baker-Smith, Robert D B Jaquiss, Arjun K Mahendran, Valerie Curren, Aarti Bhat, Angira Patel, Audrey C Marshall, Stephanie Fuller, Bradley S Marino, Christina M Fink, Keila N Lopez, Lowell H Frank, Mishaal Ather, Natalie Torentinos, Olivia Kranz, Vivian Thorne, Ryan R Davies, Stuart Berger, Christopher Snyder, Arwa Saidi, Kenneth Shaffer

Division of Cardiology Faculty Papers

The congenital heart care community faces a myriad of public health issues that act as barriers toward optimum patient outcomes. In this article, we attempt to define advocacy and policy initiatives meant to spotlight and potentially address these challenges. Issues are organized into the following 3 key facets of our community: patient population, health care delivery, and workforce. We discuss the social determinants of health and health care disparities that affect patients in the community that require the attention of policy makers. Furthermore, we highlight the many needs of the growing adults with congenital heart disease and those with comorbidities, …

Regular Dipyridamole Therapy Produces Sustained Protection Against Cardiac Ischemia-Reperfusion Injury: Is It Time To Revisit Paris?, Vincent M. Figueredo, M.D., Chika Okusa, Kazuhiro Kaneda, Yoshitaka Inamura, Masami Miyamae

Division of Cardiology Faculty Papers

BACKGROUND: Increased activated Akt and eNOS expression coincide with this persistent cardioprotection. Emergent coronary reperfusion therapies are rarely carried out before considerable myocardial injury has occurred. Moreover, reperfusion after prolonged ischemia produces paradoxical ischemia-reperfusion injury, attenuating the efficacy of reperfusion therapies. This has provided impetus for identifying chronic therapies to protect against ischemia-reperfusion injury in those at risk. We previously found that regular dipyridamole therapy produces a chronic preconditioning-like effect mediated through adenosine A1 receptors.

METHODS: To determine how long this chronic preconditioning effect of dipyridamole remains present after discontinuing therapy, guinea pigs received 4 mg/kg/day in their water for …

Induction Of Autophagy Restores The Loss Of Sevoflurane Cardiac Preconditioning Seen With Prolonged Ischemic Insult., Mayumi Shiomi, Masami Miyamae, Genzou Takemura, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Shizuka Koshinuma, Yoshihiro Momota, Toshiaki Minami, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Sevoflurane preconditioning against myocardial ischemia-reperfusion injury is lost if the ischemic insult is too long. Emerging evidence suggests that induction of autophagy may also confer cardioprotection against ischemia-reperfusion injury. We examined whether induction of autophagy prolongs sevoflurane preconditioning protection during a longer ischemic insult. Isolated guinea pigs hearts were subjected to 30 or 45 min ischemia, followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2% sevoflurane for 10 min prior to ischemia (SEVO-30, SEVO-45). Chloramphenicol (autophagy upregulator, 300 µM) was administered starting 20 min before ischemia and throughout reperfusion in SEVO-45 (SEVO-45+CAP). To inhibit autophagy, 3-methyladenine (10 …

Novel Partial Anomalous Pulmonary Venous Connection Associated With Brain Abscess., Anish Koka, Md, Amit Sachdev, Md, Moussa F Yazbeck, Md, Rodney Bell, Md, Christopher Farrellc, Md

Department of Neurology Faculty Papers

BACKGROUND: Right-to-left vascular shunts are associated with brain abscess.

CASE REPORT: We present a 47-year-old female with a cryptogenic left thalamic abscess on which Streptococcus mitis grew upon aspiration. Computed tomography of the chest with contrast agent revealed an anomalous connection between the left superior pulmonary and brachiocephalic veins. A right-to-left shunt was confirmed in a transthoracic echocardiogram study in which bubbles were injected into the left arm; this shunt had not previously been noted upon right-arm injection.

CONCLUSIONS: We recommend aggressive evaluation for right-to-left shunts in patients who present with cryptogenic brain abscesses. In addition to imaging, this should …

Sevoflurane Induces Cardioprotection Through Reactive Oxygen Species-Mediated Upregulation Of Autophagy In Isolated Guinea Pig Hearts., Mayumi Shiomi, Masami Miyamae, Genzou Takemura, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Shizuka Koshinuma, Yoshihiro Momota, Toshiaki Minami, Vincent M. Figueredo

Division of Cardiology Faculty Papers

PURPOSE: Sevoflurane increases reactive oxygen species (ROS), which mediate cardioprotection against myocardial ischemia-reperfusion injury. Emerging evidence suggests that autophagy is involved in cardioprotection. We examined whether reactive oxygen species mediate sevoflurane preconditioning through autophagy.

METHODS: Isolated guinea pigs hearts were subjected to 30 min ischemia followed by 120 min reperfusion (control). Anesthetic preconditioning was elicited with 2 % sevoflurane for 10 min before ischemia (SEVO). The ROS-scavenger, N-(2-mercaptopropionyl) glycine (MPG, 1 mmol/l), was administered starting 30 min before ischemia to sevoflurane-treated (SEVO + MPG) or non-sevoflurane-treated (MPG) hearts. Infarct size was determined by triphenyltetrazolium chloride stain. Tissue samples were obtained …

Combination Of Necroptosis And Apoptosis Inhibition Enhances Cardioprotection Against Myocardial Ischemia-Reperfusion Injury., Shizuka Koshinuma, Masami Miyamae, Kazuhiro Kaneda, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

PURPOSE: Necroptosis has been proposed as a mode of cell death that is a caspase-independent programmed necrosis. We investigated whether necroptosis is involved in myocardial ischemia-reperfusion injury in isolated guinea pig hearts and, if so, whether simultaneous inhibition of necroptosis and apoptosis confers enhanced cardioprotection.

METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischemia and 4 h reperfusion (control = CTL, n = 8). Necrostatin-1 (necroptosis inhibitor, 10 μM), Z-VAD (apoptosis inhibitor, 0.1 μM) and both inhibitors were administered starting 5 min before ischemia and during the initial 30 min of reperfusion (Nec, Z-VAD, Nec + Z-VAD; …

Sevoflurane Confers Additive Cardioprotection To Ethanol Preconditioning Associated With Enhanced Phosphorylation Of Glycogen Synthase Kinase-3Β And Inhibition Of Mitochondrial Permeability Transition Pore Opening., Anna Onishi, Masami Miyamae, Hiroshi Inoue, Kazuhiro Kaneda, Chika Okusa, Yoshitaka Inamura, Mayumi Shiomi, Shizuka Koshinuma, Yoshihiro Momota, Vincent M. Figueredo

Division of Cardiology Faculty Papers

OBJECTIVE: The purposes of this study were to investigate whether sevoflurane (SEVO) enhances moderate-dose ethanol (EtOH) preconditioning and whether this additional cardioprotection is associated with glycogen synthase kinase-3β (GSK-3β), protein kinase B (Akt), mammalian target of rapamycin (mTOR), 70-kDa ribosomal s6 kinase-1 (p70s6K), and/or mitochondrial permeability transition pore (MPTP) opening.

DESIGN: In vitro study using an isolated heart Langendorff preparation.

SETTING: University research laboratory.

PARTICIPANTS: Male guinea pigs (n = 170).

INTERVENTIONS: Isolated perfused guinea pig hearts underwent 30-minute ischemia and 120-minute reperfusion (control). The EtOH group received 5% EtOH in the drinking water for 8 weeks. Anesthetic preconditioning was …

Periodontal Disease Is An Independent Predictor Of Intracardiac Calcification., Gregg S Pressman, Atif Qasim, Nitin Verma, Masami Miyamae, Kumiko Arishiro, Yasuhiro Notohara, Vitalie Crudu, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND: Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease.

HYPOTHESIS: We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis.

METHODS: Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification.

RESULTS: Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In …

Direct Evidence For Inhibition Of Mitochondrial Permeability Transition Pore Opening By Sevoflurane Preconditioning In Cardiomyocytes: Comparison With Cyclosporine A., Anna Onishi, Masami Miyamae, Kazuhiro Kaneda, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed …

Cardioprotection By Regular Ethanol Consumption: Potential Mechanisms And Clinical Application., Masami Miyamae, Kazuhiro Kaneda, Naochika Domae, Vincent M. Figueredo, M.D.

Division of Cardiology Faculty Papers

Epidemiological studies demonstrate that excessive drinking is associated with hypertension, cerebral bleeding and loss of cardiac contractility. Conversely, studies have shown that mortality rates for people who regularly drink ethanol in moderation are lower than in abstainers, primarily due to decreased fatal ischemic heart disease. Further, moderate ethanol consumers have lower rates of myocardial infarction compared with abstainers. These beneficial cardiac effects may be due to pleiotropic effects of ethanol on lipids, platelets, and fibrinolytic activity. During the past decade, studies conducted in several animal models have revealed that light to moderate regular ethanol consumption renders hearts more tolerant to …

Diverticular And Aneurysmal Structures Of The Left Ventricle In Adults: Report Of A Case Within The Context Of A Literature Review., Premraj Makkuni, Morris N Kotler, Vincent M. Figueredo

Department of Medical Genetics Faculty Papers

Left ventricular outpouchings are increasingly detected on cardiovascular imaging. Herein, we describe the case of a 45-year-old man who underwent noncardiac preoperative imaging and was found to have an asymptomatic left ventricular outpouching. The patient underwent successful surgical repair of the structure. When left ventricular outpouchings are detected, the main differential diagnoses are pseudoaneurysm, aneurysm, and diverticulum. The outcomes for these conditions differ substantially, and accurate diagnosis can be crucial in making clinical decisions. We review the relevant medical literature, outline the natural history of these left ventricular abnormalities, and discuss options in regard to their management.

Somnoforme: A Century After The Introduction Of The "Ideal" Anesthetic Gas, James W. Heitz, Md

Department of Anesthesiology Faculty Papers

Since the introduction of ether as a general anesthetic, there has been a continuous quest to develop the ideal anesthetic gas. The attributes of the ideal anesthetic gas have evolved over time. At the beginning of the 20th century, the search for the ideal anesthetic was focused upon finding an anesthetic gas with rapid inhalation induction and rapid emergence that could be delivered without cumbersome apparatus and would have limited potential for toxicity. Somnoforme was a mixture of ethyl chloride, methyl chloride, and ethyl bromide designed to provide powerful efficacy with low potential for side effects by blending of several …

Acute Memory Phase Of Sevoflurane Preconditioning Is Associated With Sustained Translocation Of Protein Kinase C-Alpha And Epsilon, But Not Delta, In Isolated Guinea Pig Hearts., Chika Okusa, Masami Miyamae, Shingo Sugioka, Kazuhiro Kaneda, Yoshitaka Inamura, Anna Onishi, Naochika Domae, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND AND OBJECTIVE: Anaesthetic preconditioning (APC) exerts cardioprotective effects by reducing infarct size and improving recovery of contractile function after ischaemia-reperfusion. The interval between brief exposure to volatile anaesthetic and sustained ischaemia, the acute memory phase, is dependent on intracellular signalling mediating this cardioprotection. Intramyocyte translocation of protein kinase C (PKC) is known to be a key mediator in APC. We examined the relationship between the time frame of the acute memory phase of sevoflurane preconditioning and intramyocyte translocation of PKC-alpha, delta and epsilon to the particulate fraction. METHODS: Isolated perfused guinea pig hearts were subjected to 30 min ischaemia …

Sevoflurane Enhances Ethanol-Induced Cardiac Preconditioning Through Modulation Of Protein Kinase C, Mitochondrial Katp Channels, And Nitric Oxide Synthase, In Guinea Pig Hearts., Kazuhiro Kaneda, Masami Miyamae, Shingo Sugioka, Chika Okusa, Yoshitaka Inamura, Naochika Domae, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

BACKGROUND: Volatile anesthetics and regular ethanol consumption induce cardioprotection mimicking ischemic preconditioning. We investigated whether sevoflurane enhances ethanol preconditioning and whether inhibition of protein kinase C (PKC) and mitochondrial K(ATP) channels attenuated this enhanced cardioprotection. The effects of regular ethanol consumption on expression of inducible (iNOS) and endothelial (eNOS) nitric oxide synthase were determined. METHODS: Isolated perfused guinea pig hearts underwent 30-min global ischemia and 120-min reperfusion (Control: CTL). The ethanol group (EtOH) received 2.5% ethanol in their drinking water for 6 wk. Anesthetic preconditioning was elicited by 10-min exposure to sevoflurane (1 minimum alveolar anesthetic concentration; 2%) in ethanol …

How To Prevent Perioperative Myocardial Injury: The Conundrum Continues, Jian-Zhong Sun, David Maguire

Department of Anesthesiology Faculty Papers

BACKGROUND: Perioperative myocardial injury (PMI) remains a major cause of perioperative morbidity and mortality but clinical strategies to prevent PMI are still uncertain.

METHODS AND RESULTS: We comprehensively searched PubMed for major research articles concerning clinical strategies to prevent PMI. The key findings are as follows: (1) the American College of Cardiology/American Heart Association guideline update for perioperative cardiovascular evaluation for noncardiac surgery is very useful to stratify cardiac risk preoperatively; (2) cardiac troponin has emerged as a biomarker to diagnose postoperative PMI and to predict clinical outcomes; (3) coronary revascularization before noncardiac surgery probably would provide cardiac protection in …