Biosketch / Results /
Douglas HolmesAssistant Professor, Department of Medicine;Assistant Professor, Department of Pediatrics
NYU EKG Associates
560 First Avenue
New York, NY 10016
Research SummaryAtrial fibrillation (AF) is the most common clinical arrhythmia seen and results in significant morbidity and mortality. As a result, there is tremendous interest in understanding the mechanisms leading to and supporting AF. Clinically, AF starts with ectopic atrial activity originating from the pulmonary veins or the body of the left atrium. Should these atrial beats coincide with a vulnerable atrial substrate able to support multiple wavelet reentry, AF results. While there are currently no good animal models to study ectopic atrial activity, an atrial tachy-paced model is used to study the atrial changes resulting from high frequency electrical activity. While this model recapitulates many of the features of clinical AF, it also has numerous shortcomings. More recently, it has been observed that following congestive heart failure, atrial structures dilate and are thus susceptible to AF initiation. This model is more closely related to human pathophysiology. We are using a rabbit model of myocardial infarction to study the cellular changes induced by pressure overload atrial dilation.
At the cellular level, we are investigating the electrophysiologic alterations underlying abnormal automaticity and triggered activity. Failing cardiac tissues undergo remodeling of their ion handling proteins characterized by up or down regulation of protein expression. In general, these changes tend to amplify subthreshold electrical events into triggered activity. While the mechanisms behind ventricular ectopy have become well characterized, those of the atrium are less well understood. Among the differences between atrial and ventricular cells is the presence of IP3 receptors in atrial tissue. These calcium-releasing receptors are up regulated in failing atrium and may play a role in both triggered activity within the atrial free wall and abnormal automaticity from spontaneously firing cells within the pulmonary veins. Using confocal microscopy and patch clamp techniques, in a collaboration with the laboratory of Dr. William Coetzee and Michael Artman, we simultaneously measure subcellular calcium transients and sarcolemmal membrane currents. Interactions between excitation-contraction mechanisms and IP3 calcium release could form the basis of new atrial specific therapeutic targeting.
Research InterestsUnderstanding the cellular mechanisms underlying cardiac arrhythmias and sudden death. New therapies in the treatment of Atrial Fibrillation.
Atrial fibrillation ablation in patients with known sludge in the left atrial appendage
Hajjiri, Mohammed; Bernstein, Scott; Saric, Muhamed; Benenstein, Ricardo; Aizer, Anthony; Dym, Glenn; Fowler, Steven; Holmes, Douglas; Bernstein, Neil; Mascarenhas, Mark; Park, David; Chinitz, Larry
2014-04-25; 1383-875x,Journal of interventional cardiac electrophysiology - id: 909162, year: 2014 JOURNAL ARTICLE
Hemostasis of Left Atrial Appendage Bleed With Lariat Device
Hussain, Amena; Saric, Muhamed; Bernstein, Scott; Holmes, Douglas; Chinitz, Larry
2014-11-23; 0972-6292,Indian pacing & electrophysiology journal. IPEJ - id: 1355892, year: 2014 JOURNAL ARTICLE
The Role of Multimodality Imaging in Percutaneous Left Atrial Appendage Suture Ligation with the LARIAT Device
Laura, Diana M; Chinitz, Larry A; Aizer, Anthony; Holmes, Douglas S; Benenstein, Ricardo; Freedberg, Robin S; Kim, Eugene E; Saric, Muhamed
2014-06-01; 0894-7317,Journal of the American Society of Echocardiography - id: 1018862, year: 2014 REVIEW
The benign nature of mild induced therapeutic hypothermia-Induced long QTc
Weitz, Daniel; Greet, Brian; Bernstein, Scott A; Holmes, Douglas S; Bernstein, Neil; Aizer, Anthony; Chinitz, Larry; Roswell, Robert O
2013-06-26; 0167-5273,International journal of cardiology - id: 395462, year: 2013 JOURNAL ARTICLE
Narrow complex tachycardia with cycle length variability-what is the mechanism?
Aizer, A; Holmes, DS; Fowler, SJ; Chinitz, LA
2012-03-22; 1547-5271,Heart rhythm - id: 161151, year: 2012 JOURNAL ARTICLE