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One or more keywords matched the following properties of Verrier, Richard
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overview My research concentrates on the major public health problem of sudden cardiac death, which claims approximately 325,000 lives per year in the United States alone and occurs without prodromes in at least 30% of cases. The main challenges have been to elucidate the complex pathophysiologic factors involved and to develop novel approaches for identifying individuals at risk for this mode of demise. In an extensive series of studies, my colleagues and I explored the mechanisms responsible for sudden arrhythmic death. Our investigations demonstrated the pivotal role played by sympathetic nerve activity in triggering life-threatening arrhythmias and defined contributions of beta-adrenergic receptors acting primarily on intracellular calcium handling. We also determined that vagus nerve activity opposes the deleterious influence of adrenergic activity by opposition to presynaptic release of norepinephrine and direct antagonism of second messenger effects. I developed an experimental model in canines that emulated the angerlike state and allowed us to demonstrate that intense behavioral arousal profoundly alters cardiac electrical instability and coronary reactivity, which in turn predispose to malignant arrhythmias. My group and I also systematically studied the impact of sleep states on coronary hemodynamic and cardiac electrophysiologic function. The knowledge base generated was published in Science, Circulation, New England Journal of Medicine, and other leading journals. My basic science studies on neural control of heart rhythm received NIH funding for more than 35 years. My most significant contributions to clinical innovation emerged during my appointment at Harvard Medical School in Beth Israel Deaconess Medical Center’s Division of Cardiovascular Medicine. In collaboration with my junior colleague, Dr. Bruce D. Nearing, a biomedical engineer, I discovered and published in Science in 1991 evidence that a fundamental electrophysiologic phenomenon, “T-wave alternans,” a beat-to-beat fluctuation in the magnitude of this waveform, is capable of stratifying risk for life-threatening arrhythmia. An extensive series of experiments revealed that T-wave alternans is tracks effects of neural factors, myocardial ischemia, and other proarrhythmic influences. Conversely, antiarrhythmic physiologic and pharmacologic interventions reduce the magnitude of alternans. These findings provided essential scientific underpinnings for utilizing alternans as a clinical marker of arrhythmic risk and target for therapeutic interventions. We developed, patented, and implemented methodologies for quantifying alternans that are compatible with routine ambulatory ECG monitoring and exercise stress testing and employed them to demonstrate that this phenomenon is capable of assessing risk for arrhythmic events in >1,600 post-myocardial infarction and heart failure patients based on ambulatory ECGs recordings. Prediction was also demonstrated in >3,500 consecutive patients with preserved left ventricular function who were referred for routine exercise testing. In 2011, I was lead author of a clinical consensus guideline on T-wave alternans by international experts that was published in Journal of the American College of Cardiology. In summary, my research program focuses on sudden cardiac death, with dual emphasis on elucidation of pathophysiologic mechanisms and translation from bench to bedside. Our patented, FDA-approved diagnostic risk assessment technology is now in use in clinics and hospitals worldwide.
One or more keywords matched the following items that are connected to Verrier, Richard
Item TypeName
Academic Article Primary vagally mediated decelerations in heart rate during tonic rapid eye movement sleep in cats.
Academic Article Role of the autonomic nervous system in sudden death.
Academic Article The enigmatic cardiac fat pads: critical but underappreciated neural regulatory sites.
Academic Article Effect of vagus nerve stimulation upon excitability of the canine ventricle. Role of sympathetic-parasympathetic interactions.
Academic Article The effect of vagus nerve stimulation upon vulnerability of the canine ventricle: role of sympathetic-parasympathetic interactions.
Academic Article Muscarinic effects of vagosympathetic trunk stimulation on the repetitive extrasystole (RE) threshold.
Academic Article Effects of clonidine on vulnerability to fibrillation in the normal and ischemic canine ventricle.
Academic Article Mechanisms of behaviorally induced arrhythmias.
Academic Article Neural activity and ventricular fibrillation.
Academic Article Vagal modulation of epicardial coronary artery size in dogs. A two-dimensional intravascular ultrasound study.
Academic Article Life-threatening cardiovascular consequences of anger in patients with coronary heart disease.
Academic Article Neural and psychologic mechanisms and the problem of sudden cardiac death.
Academic Article Effect of acute blood pressure elevation on the ventricular fibrillation threshold.
Academic Article The effects of psychological stress and vagal stimulation with morphine on vulnerability to ventricular fibrillation (VF) in the conscious dog.
Academic Article Influence of autonomic nervous system stimulation on the protective zone.
Academic Article Behavioral stress and cardiac arrhythmias.
Academic Article Experimental studies of psychophysiological factors in sudden cardiac death.
Academic Article Primary coronary vasodilation associated with pauses in heart rhythm during sleep.
Academic Article Influence of vagal tone on stellectomy-induced changes in ventricular electrical stability.
Academic Article Effect of posterior hypothalamic stimulation on ventricular fibrillation threshold.
Academic Article Neural influences and sudden cardiac death.
Academic Article Repetitive extrasystole as an index of vulnerability to ventricular fibrillation.
Concept Vagus Nerve
Concept Vagus Nerve Stimulation
Academic Article Vagus nerve stimulation reduces cardiac electrical instability assessed by quantitative T-wave alternans analysis in patients with drug-resistant focal epilepsy.
Academic Article Autonomic regulation therapy suppresses quantitative T-wave alternans and improves baroreflex sensitivity in patients with heart failure enrolled in the ANTHEM-HF study.
Academic Article Unmasking atrial repolarization to assess alternans, spatiotemporal heterogeneity, and susceptibility to atrial fibrillation.
Academic Article Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial.
Academic Article Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM-HF Trial.
Academic Article Novel method to assess intrinsic heart rate recovery in ambulatory ECG recordings tracks cardioprotective effects of chronic autonomic regulation therapy in patients enrolled in the ANTHEM-HF study.
Academic Article Quantitative evaluation of heartbeat interval time series using Poincaré analysis reveals distinct patterns of heart rate dynamics during cycles of vagus nerve stimulation in patients with heart failure.
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  • Vagus Nerve
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.