cvrc.brownmedicine.orgCardiovascular Research

Center —— Home Calendar Principal Investigators - Abid Laboratory - Choi Laboratory - Feng Laboratory - Koren Laboratory - Radice Laboratory - Sellke Laboratory - Usheva Laboratory Research - Cardiac Mechanotransduction - Coronary Artery Disease Program - Heart Rhythm Disorder Program - Pulmonary Hypertension and Heart Failure Opportunities Contact Us Home Calendar Principal Investigators Abid Laboratory Choi Laboratory Feng Laboratory Koren Laboratory Radice Laboratory Sellke Laboratory Usheva Laboratory Research Cardiac Mechanotransduction Coronary Artery Disease Program Heart Rhythm Disorder Program Pulmonary Hypertension and Heart Failure Opportunities Contact Us The Center (CVRC) performs interdisciplinary research in basic and translational, and clinical research to develop innovative therapies and cure cardiovascular diseases. The CVRC provides a home for a wide spectrum of investigation ranging from the molecular mechanisms of cardiac and vascular diseases to biomedical engineering. It links faculty interested in cardiovascular biology and disease across departments and campuses in Rhode Island Hospital, VA Medical Center, and Brown University in Providence, RI. The collaborative culture of CVRC fosters multidisciplinary research programs to bridge between basic and clinical science. CVRC in the News Rhode Island Hospital awarded $7.36 Million Grant for Rhode Island Hospital’s Center (CVRC) has been awarded a $7.36 million research project grant (R01) from the National Heart, Lung and Blood Institute of the National Institutes of Health to study sudden cardiac arrest. The research will be focused on mechanisms to develop new therapies and strategies to prevent sudden cardiac arrest and to measure the impact of genetic and environmental factors on risk for sudden cardiac death. The grant will be paid out over five years and is the largest grant of its kind to be paid to a Lifespan partner hospital. The grant is an R01 grant, the original and oldest grant mechanism used by the National Institutes of Health. Typically, R01 grants are for less than $250,000, and any organization requesting more than $500,000 per year must secure prior approval from the NIH to apply for the specialized grant. The grant issued to the CVRC at Rhode Island Hospital will be approximately $1.5 million per year, and is specific to the research project A Multi-Scale Approach to Cardiac Arrhythmia: from the Molecule to the Organ. R01 grants from the National Institutes of Health are incredibly difficult to come by and are highly competitive,” said Gideon Koren, M.D., director of the Center at Rhode Island Hospital. Major academic medical centers around the country bid for these grants each year in an effort to further their research to find cures, diagnostic tools and new therapies for the most pervasive and life-threatening diseases.” Koren continued, Receiving this award demonstrates that the NIH recognizes the quality and importance of the research being conducted at Rhode Island Hospital and specifically in the Center. It also demonstrates the commitment of its researchers to discover new ways to prevent sudden cardiac arrest.” In sudden cardiac arrest, which affects more than 300,000 people in the U.S. each year, the heart stops beating suddenly and unexpectedly, preventing blood from flowing to the brain and organs. The majority of those who suffer from sudden cardiac arrest die within minutes. According to the NIH, the risk of sudden cardiac arrest increases with age and men are two to three times more likely than women to suffer such an arrest. This award from the NIH is a remarkable achievement,” said Peter Snyder, Ph.D, senior vice president and chief research officer for Lifespan. It underscores the quality of the research at Rhode Island Hospital and provides our researchers with the means to continue to explore new treatments and preventative measures of an illness that takes thousands of lives each year in the U.S.” Koren was recruited to Rhode Island Hospital in 2005 to launch the Center. Among the largest cardiovascular research programs in the country, the CVRC now is home for 43 investigators including undergraduate students, graduate students, postdoctoral fellows, research associates and faculty, and receives over $3.8 million in direct costs from the federal government. The CVRC will work in collaboration with researchers at Brown University; Northeastern University; Pennsylvania State University; and the University of California, Los Angeles. The grant was funded by the NIH funding agency the National Heart, Lung and Blood Institute, (NHLBI), grant number HL110791. Rhode Island Hospital Studies Uncover Keys in Sudden Cardiac Death Researchers in Rhode Island Hospital’s Center have published two new studies focusing on the causes of arrhythmia and sudden cardiac death (SCD) when a genetic disorder is present. The studies use a first-ever genetic animal model the researchers developed in 2008 to further their understanding of a genetic disorder known as Long QT Syndrome (LQTS). The first study identified differential conditions and cellular mechanisms that can trigger SCD when LQTS is a factor, and the second study, for the first time, directly links sex hormones to the incidence of arrhythmia and SCD. Their findings are published in the Journal of Physiology and the HeartRhythm Journal . It is known that genetic mutations can predispose individuals to arrhythmia and/or SCD, a leading cause of death in the United States. Between one in 2,500 and one in 5,000 individuals are born with mutations that cause LQTS, a disorder of the heart’s electric system, and a determining factor in the development of arrhythmia and/or SCD. Ninety percent of the known mutations cause loss of function of ion channels responsible for LQTS types 1 and 2 (LQT1 and LQT2). LQTS leads to a prolonged "QT interval" on electrocardiograms. The QT interval refers to the time it takes the chambers of the heart to "repolarize" themselves so that the heart is ready for another contraction cycle. When this timeframe is lengthened, it is associated with triggering irregular arrhythmia that can cause sudden cardiac arrest. In 2008, Gideon Koren, M.D., a physician researcher and director of the Center at Rhode Island Hospital, and his colleagues developed a first-of-its-kind genetic rabbit model to study arrhythmia and SCD that mirrors what happens in individuals who have mutations of the LQT1 or LQT2 genes. In a new study published in the Journal of Physiology , the researchers used this animal model to identify differential conditions and cellular mechanisms that trigger arrhythmia in LQT1 or in LQT2 syndrome. In this study, Koren and the researchers studied early afterdepolarizations (EADs), an abnormal depolarization during the plateau phase of the heart electrical activity (action potential) that can initiate arrhythmia, and is a hallmark of LQTS. The focus was on mechanisms underlying different high-risk conditions that trigger EADs. Their findings indicate that the conditions required for EAD to occur in the animal models are genotype specific. For LQT2, the researchers found that conditions such as a slow heart rate or a slightly lower potassium ion concentration outside the heart cells (as seen in hypokalemia) can cause a dramatic prolongation of action potential and produce EADs. In LQT1, however, these conditions result in relatively limited prolongation and no EADs. In contrast, isoproterenol that mimics cardiac stimulation by the sympathetic nervous system causes arrhythmias in single cells only in LQT1 heart cells. Koren summarizes, "This study takes single cells out of the heart and reveals how arrhythmias are being initiated. What we are showing in this study is that single cells are responsible for generating an arrhythmia. Further, we found that different types of increased autonomic nervous system activity play a critical role in the cause of arrhythmias and...