D P Zipes

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States

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Publications (524)3880.31 Total impact

  • Douglas P. Zipes
    Heart Rhythm. 09/2014; 11(9):1501–1502.
  • Douglas P Zipes
    Heart rhythm: the official journal of the Heart Rhythm Society 09/2014; 11(9):1501-1502. · 4.56 Impact Factor
  • Source
    Lancet. 08/2014;
  • Mark J Shen, Douglas P Zipes
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    ABSTRACT: The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.
    Circulation Research 03/2014; 114(6):1004-21. · 11.86 Impact Factor
  • John C Lopshire, Douglas P Zipes
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    ABSTRACT: Spinal cord stimulation with implantable devices has been used worldwide for decades to treat regional pain conditions and cardiac angina refractory to conventional therapies. Preclinical studies with spinal cord stimulation in experimental animal models of heart disease have described interesting effects on cardiac and autonomic nervous system physiology. In canine and porcine animals with failing hearts, spinal cord stimulation reverses left ventricular dilation and improves cardiac function, while suppressing the prevalence of cardiac arrhythmias. In this paper, we present further canine studies that determined the optimal site and intensity of spinal cord stimulation that produced the most robust and beneficial clinical response in heart failure animals. We then explore and discuss the clinically relevant aspects and potential impediments that may be encountered in translating spinal cord stimulation to human patients with advanced cardiac disease.
    Journal of Cardiovascular Translational Research 02/2014; · 3.06 Impact Factor
  • Circulation 01/2014; 129(4):516-26. · 15.20 Impact Factor
  • Source
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    ABSTRACT: On the basis of the current state of knowledge of PEA, in conjunction with its increased prevalence compared with tachyarrhythmic cardiac arrests, its historically poor outcome, and emerging suggestions that opportunities for better outcomes may be feasible, the working group made a series of recommendations that constitute a road map for future research. The workshop participants produced a working definition of the PEA syndrome and, on the basis of the literature, support the differentiation of primary and secondary forms of PEA. It was recognized that many different experimental and clinical conditions may lead to the PEA syndrome. However, it is not clear whether there is a final common pathway at the cellular level for each of these conditions. Traditional experimental models of the PEA syndrome differ substantially from conditions in the majority of clinical cases. The Oregon SUDS, the Cardiac Arrest Registry to Enhance Survival, the Resuscitation Outcomes Consortium, and surveillance data on medication use before arrest suggest that there may be important patient “host factors” associated with PEA as the initial documented cardiac arrest rhythm. These observations are intriguing, but it is not clear whether these associations signal a causal relationship that may provide insight into the pathophysiological mechanisms underlying PEA. Several relatively simple and inexpensive modalities, potentially useful for further PEA classification, are readily available. Echocardiographic and end-tidal carbon dioxide observations provide real-time insight into the potential causes and prognosis of PEA, but little is known about the hemodynamics during clinical resuscitation. Therefore, methods to estimate the inotropic status and systemic vascular resistance during resuscitation would be potentially useful. The working group makes the following recommendations: 1. Develop a taxonomic classification of the known experimental and clinical conditions associated with PEA. 2. Conduct future experimental and clinical studies and report them using this taxonomic classification. 3. Identify new experimental models that better mimic the clinical conditions leading to the syndrome of PEA to elucidate the intracellular pathways that result in the syndrome of PEA. Development and refinement of such models should be a high priority, contributing to the design of pilot studies in humans. 4. Capture and analyze accurate additional data elements in existing and future cardiac arrest surveillance, notably prior illnesses and current medications, to further elucidate the relationship between patient host factors and the initial documented cardiac arrest rhythm. 5. Collect genetic, proteomic, and biomarker data on both experimental models and clinical subjects that may lead to a better understanding of the pathophysiology of PEA. 6. Obtain real-time hemodynamic information during resuscitation, particularly when PEA occurs, to guide pharmacological management. Perform noninvasive technologies such as bioimpedance and bioreactance in experimental cardiac arrest and PEA models to determine whether they can track hemodynamics accurately enough during low-flow states to be of potential use clinically. For those with promising results, consider conducting clinical studies of hemodynamically guided pharmacological intervention (eg, vasoconstrictor/vasodilator/inotropic therapy) during PEA. 7. Consider the merits of pilot testing of PEA-specific interventions in humans on the basis of promising experimental data such as synchronized mechanical chest compression and vasodilator therapy. 8. Conduct experimental and pilot clinical studies focusing on earlier application of therapeutic hypothermia, particularly when initiated during ongoing resuscitation.
    Circulation 12/2013; 128(23):2532-41. · 15.20 Impact Factor
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    ABSTRACT: BACKGROUND: Ischemia suppresses action potentials (AP) by elevating interstitial K(+) and activating KATP channels, and alters cytosolic Ca(2+) transients (CaT) via metabolic inhibition. OBJECTIVE: This study tested the hypothesis that AP and CaT respond to ischemia with different spatiotemporal courses and patterns. METHODS: Thirty-four transmural wedges were isolated from canine left ventricular free walls, perfused arterially, and stained with voltage and Ca(2+)-sensitive dyes. Twenty-eight wedges underwent 15 min of arterial occlusion during pacing at a cycle length (PCL) of 300 (n=19) or 600ms (n=9). Six other wedges had sequential reduction of perfusion flow from full to 50%, 25%, and 10% at 300ms PCL. AP and CaT were recorded on the cut-exposed transmural surfaces with an optical mapping system. RESULTS: Although ischemia suppressed APs, it enhanced CaT to 150±10% (more in the endocardium than epicardium) and induced CaT alternans during the first 2 min of arterial occlusion, and then suppressed CaT (PCL: 300ms). Enhancement of CaT (to 159±23%) also occurred during low flow (25%) perfusion (PCL: 300ms). Faster suppression of AP than of CaT occurred with subepicardial preference. After 15 min arterial occlusion, AP and CaT remained in only small regions during 300 ms PCL, but were preserved in most regions during 600ms PCL. CONCLUSIONS: Early ischemia induced a surge and alternans in CaT and caused its dissociation from AP both in time course of suppression and in spatial distribution. These results suggested there were different cellular regulatory mechanisms of AP and of CaT in responding to ischemia from arterial occlusion.
    Heart rhythm: the official journal of the Heart Rhythm Society 05/2013; · 4.56 Impact Factor
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    ABSTRACT: BACKGROUND: The risks of sports participation for implantable cardioverter-defibrillator (ICD) patients are unknown. METHODS AND RESULTS: Athletes with ICDs (age, 10-60 years) participating in organized (n=328) or high-risk (n=44) sports were recruited. Sports-related and clinical data were obtained by phone interview and medical records. Follow-up occurred every 6 months. ICD shock data and clinical outcomes were adjudicated by 2 electrophysiologists. Median age was 33 years (89 subjects <20 years of age); 33% were female. Sixty were competitive athletes (varsity/junior varsity/traveling team). A pre-ICD history of ventricular arrhythmia was present in 42%. Running, basketball, and soccer were the most common sports. Over a median 31-month (interquartile range, 21-46 months) follow-up, there were no occurrences of either primary end point-death or resuscitated arrest or arrhythmia- or shock-related injury-during sports. There were 49 shocks in 37 participants (10% of study population) during competition/practice, 39 shocks in 29 participants (8%) during other physical activity, and 33 shocks in 24 participants (6%) at rest. In 8 ventricular arrhythmia episodes (device defined), multiple shocks were received: 1 at rest, 4 during competition/practice, and 3 during other physical activity. Ultimately, the ICD terminated all episodes. Freedom from lead malfunction was 97% at 5 years (from implantation) and 90% at 10 years. CONCLUSIONS: Many athletes with ICDs can engage in vigorous and competitive sports without physical injury or failure to terminate the arrhythmia despite the occurrence of both inappropriate and appropriate shocks. These data provide a basis for more informed physician and patient decision making in terms of sports participation for athletes with ICDs.
    Circulation 05/2013; 127(20):2021-2030. · 15.20 Impact Factor
  • Journal of the American College of Cardiology 04/2013; · 14.09 Impact Factor
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    ABSTRACT: OBJECTIVES: To determine the availability of quinidine in the world. BACKGROUND: Quinidine is the only oral medication that is effective for preventing life-threatening ventricular arrhythmias due to Brugada syndrome and idiopathic ventricular fibrillation. However, because of its low price and restricted indication, this medication is not marketed in many countries. METHODS: We conducted a world survey of quinidine availability by contacting professional medical societies and arrhythmia specialists worldwide. Physicians were e-mailed questionnaires requesting information concerning the quinidine preparation available at their hospital. We also requested information concerning cases of adverse arrhythmic events resulting from quinidine unavailability. RESULTS: A total of 273 physicians from 131 countries provided information regarding quinidine availability: Quinidine is readily available in only 19 (14%) countries. In contrast, this medication is not accessible in 99 (76%) countries and is available but only through specific regulatory processes that require 4-30 days for completion in 13 (10%) countries. We were able to gather information concerning 22 patients who had serious arrhythmias probably related (10 cases) or possibility related (12 cases) to the absence of quinidine, including 2 fatalities possibly due to quinidine unavailability. CONCLUSIONS: The lack of quinidine accessibility is a serious medical hazard at the global level.
    Journal of the American College of Cardiology 04/2013; · 14.09 Impact Factor
  • Article: Ten Years.
    Douglas P Zipes
    Heart rhythm: the official journal of the Heart Rhythm Society 03/2013; · 4.56 Impact Factor
  • Matteo Vatta, Douglas P Zipes
    Journal of the American College of Cardiology 02/2013; · 14.09 Impact Factor
  • Source
    Douglas P Zipes
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2013; 10(1):1. · 4.56 Impact Factor
  • John C Lopshire, Douglas P Zipes
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    ABSTRACT: Heart failure is the final common pathway in many forms of heart disease, and is associated with excessive morbidity and mortality. Pathophysiologic alterations in the interaction between the heart and the autonomic nervous system in advanced heart failure have been noted for decades. Over the last decade, great advances have been made in the medical and surgical treatment of heart failure - and some of these modalities target the neuro-cardiac axis. Despite these advances, many patients progress to end-stage heart failure and death. Recently, device-based therapy targeting the neuro-cardiac axis with various forms of neuromodulatory stimuli has been shown to improve heart function in experimental heart failure models. These include spinal cord stimulation, vagal nerve stimulation, and baroreflex modulation. Human trials are now underway to evaluate the safety and efficacy of these device-based neuromodulatory modalities in the heart failure population.
    Current Cardiology Reports 07/2012; 14(5):593-600.
  • Douglas P Zipes
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    ABSTRACT: The safety of electronic control devices (ECDs) has been questioned. The goal of this study was to analyze in detail cases of loss of consciousness associated with ECD deployment. Eight cases of TASER X26 ECD-induced loss of consciousness were studied. In each instance, when available, police, medical, and emergency response records, ECD dataport interrogation, automated external defibrillator information, ECG strips, depositions, and autopsy results were analyzed. First recorded rhythms were ventricular tachycardia/fibrillation in 6 cases and asystole (after ≈ 30 minutes of nonresponsiveness) in 1 case. An external defibrillator reported a shockable rhythm in 1 case, but no recording was made. This report offers evidence detailing the mechanism by which an ECD can produce transthoracic stimulation resulting in cardiac electrical capture and ventricular arrhythmias leading to cardiac arrest. ECD stimulation can cause cardiac electrical capture and provoke cardiac arrest resulting from ventricular tachycardia/ventricular fibrillation. After prolonged ventricular tachycardia/ventricular fibrillation without resuscitation, asystole develops.
    Circulation 04/2012; 125(20):2417-22. · 15.20 Impact Factor
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    ABSTRACT: Objectives:  The aim of this study was to evaluate the safety and efficacy of spinal cord stimulation (SCS) for refractory angina. Materials and Methods:  This multicenter, randomized, single-blind, controlled trial evaluated SCS in two patient groups: high stimulation (HS) (treatment) and low stimulation (LS) (control). The HS group controlled SCS with a programmer for a minimum of two hours four times daily. The LS group received SCS therapy above the paresthesia threshold for one min once daily. The primary efficacy endpoint was number of angina attacks recorded by patients at six months. The primary safety endpoint was the major adverse cardiac event (MACE) rate at six months. Results:  Due to slow enrollment, a futility analysis was performed, resulting in early termination of the study. Sixty-eight patients were randomized after implantation. Mean change in angina attacks per day from baseline to six months was -1.19 ± 2.13 (HS) and -1.29 ± 1.66 (LS). The difference from baseline was significant within each group (both p < 0.001) but not between groups (p = 0.45). Total exercise time and time to angina onset increased significantly from baseline to six months within each group (both p = 0.02 and 0.002) but not between groups (p = 0.52 and 0.51). MACE was similar between groups. Conclusion:  Although this study was terminated early, the results obtained at six months suggest that SCS (HS) is not more effective than the control (LS) in patients with refractory angina.
    Neuromodulation 04/2012; · 1.19 Impact Factor
  • Jeffrey Olgin, Douglas P Zipes
    Ninth Edition 01/2012; Elsevier Inc..
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    ABSTRACT: Coronary sinus (CS) musculature connects the right atria (RA) and the left atria (LA). However, the functional significance of the electrical junctions between the atria and the CS musculature is still unclear. We investigated electrophysiological properties of the CS-atrial connections and their role in atrial fibrillation. By using an optical mapping system, we mapped action potentials at 256 sites on the epicardial surface of 16 isolated and arterial-perfused canine atrial tissues containing the entire musculature of the CS, lower RA, posterior LA, left inferior pulmonary vein, and vein of Marshal. We paced from each of the above regions to measure electrophysiological properties and inducibility of atrial tachyarrhythmias. The CS musculature connected to the RA at the ostium of the CS and to the LA at proximal and distal CS sites. Electrical conduction across each of these CS-atrial junctions was slow (P < .01), but not decremental. Rapid pacing often induced entrance block at the CS-atrial junctions and resulted in sequential changes of activation sequence in the CS. Macroreentrant circuit involving the CS musculature and the CS-atrial junctions occurred in association with conduction block at these junctions. The reentrant circuit was usually unstable and resulted in atrial fibrillation-like electrocardiographic activity. The anatomical and electrical connections between the CS musculature and the RA and the LA caused conduction slowing and block in the CS musculature and its atrial junctions, which frequently initiated unstable macroreentry and atrial fibrillation.
    Heart rhythm: the official journal of the Heart Rhythm Society 11/2011; 9(4):581-9. · 4.56 Impact Factor
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    ABSTRACT: Patients with heart failure (HF) are at increased risk for drug-induced torsades de pointes (TdP) due to unknown mechanisms. Our objective was to determine if sensitivity to drug-induced QT interval lengthening is enhanced in patients with HF. In this multicenter, prospective study, 15 patients with atrial fibrillation or flutter requiring conversion to sinus rhythm were enrolled: 6 patients with New York Heart Association class II to III HF (mean ejection fraction [EF], 30% ± 9%), and 9 controls (mean EF, 53% ± 6%). Patients received ibutilide 1 mg intravenously. Blood samples and 12-lead electrocardiograms were obtained prior to and during 48 hours postinfusion. Serum ibutilide concentrations at 50% maximum effect on Fridericia-corrected QT (QT(F)) intervals (EC(50)) were determined, and areas under the effect (QT(F) interval vs time) curves (AUECs) were calculated. Ibutilide concentration-QT(F) relationships were best described by a sigmoidal E(max) model with a hypothetical effect compartment. Median [interquartile range] AUEC from 0 to 4 hours was larger in the HF group than in controls (1.86 [1.86-1.93] vs 1.82 [1.81-1.84] s·h; P = .04). Median EC(50) was lower in the HF group (0.48 [0.46-0.49] vs 1.85 [1.10-3.23] μg/L; P = .008). Sensitivity to drug-induced QT interval lengthening is enhanced in patients with systolic HF, which may contribute to the increased risk of drug-induced TdP.
    The Journal of Clinical Pharmacology 11/2011; 52(9):1296-305. · 2.84 Impact Factor

Publication Stats

16k Citations
3,880.31 Total Impact Points

Institutions

  • 1973–2014
    • Indiana University-Purdue University Indianapolis
      • • Department of Medical and Molecular Genetics
      • • Department of Medicine
      • • Department of Electrical and Computer Engineering
      Indianapolis, Indiana, United States
  • 2013
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 1977–2012
    • Indiana University-Purdue University School of Medicine
      • Department of Medicine
      Indianapolis, Indiana, United States
  • 2011
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
    • Northwestern University
      Evanston, Illinois, United States
  • 2008
    • Duke University
      Durham, North Carolina, United States
    • Okayama University
      • Department of Cardiovascular Medicine
      Okayama, Okayama, Japan
    • American Heart Association
      Dallas, Texas, United States
  • 1998–2008
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
    • University Medical Center Utrecht
      • Department of Cardiology
      Utrecht, Provincie Utrecht, Netherlands
  • 1996–2007
    • Indiana University East
      Indiana, United States
  • 2006
    • University of California, San Francisco
      • Cardiovascular Research Institute
      San Francisco, CA, United States
    • Case Western Reserve University
      Cleveland, Ohio, United States
  • 2004
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, MD, United States
    • CUNY Graduate Center
      New York City, New York, United States
    • Semmelweis University
      • First Department of Internal Medicine
      Budapest, Budapest fovaros, Hungary
  • 1996–2004
    • Cornell University
      • • Biomedical Sciences
      • • Department of Clinical Sciences
      Ithaca, NY, United States
  • 2002
    • Methodist Hospitals
      Gary, Indiana, United States
    • Georgetown University
      • Department of Medicine
      Washington, D. C., DC, United States
    • Fondazione Salvatore Maugeri IRCCS
      Ticinum, Lombardy, Italy
  • 2001–2002
    • University of Pavia
      Ticinum, Lombardy, Italy
    • National Heart, Lung, and Blood Institute
      Maryland, United States
    • European Society of Cardiology
      Provence-Alpes-Côte d'Azur, France
  • 1995–2002
    • American College of Cardiology
      Washington, Washington, D.C., United States
  • 1984–2000
    • Richard L. Roudebush VA Medical Center
      Indianapolis, Indiana, United States
  • 1989
    • Indiana State Department of Toxicology
      Indianapolis, Indiana, United States
    • University of Texas Medical School
      Houston, Texas, United States
  • 1983
    • University of Illinois at Chicago
      • Section of Cardiology
      Chicago, IL, United States
  • 1982
    • Government of Ontario, Canada
      Guelph, Ontario, Canada
  • 1981
    • The University of Western Ontario
      London, Ontario, Canada
  • 1975
    • Marion General Hospital
      Marion, Indiana, United States
  • 1974
    • Masonic Medical Research Laboratory
      Utica, New York, United States