Publications by authors named "Peter Hanna"

61 Publications

Comprehensive Anatomy of the Pericardial Space and the Cardiac Hilum: Anatomical Dissections With Intact Pericardium.

JACC Cardiovasc Imaging 2021 Jun 9. Epub 2021 Jun 9.

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, California, USA; Molecular, Cellular & Integrative Physiology Program, UCLA, Los Angeles, California, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jcmg.2021.04.016DOI Listing
June 2021

Neuroscientific therapies for atrial fibrillation.

Cardiovasc Res 2021 Jun;117(7):1732-1745

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, UCLA, 100 Medical Plaza, Suite 660, Los Angeles, CA 90095, USA.

The cardiac autonomic nervous system (ANS) plays an integral role in normal cardiac physiology as well as in disease states that cause cardiac arrhythmias. The cardiac ANS, comprised of a complex neural hierarchy in a nested series of interacting feedback loops, regulates atrial electrophysiology and is itself susceptible to remodelling by atrial rhythm. In light of the challenges of treating atrial fibrillation (AF) with conventional pharmacologic and myoablative techniques, increasingly interest has begun to focus on targeting the cardiac neuraxis for AF. Strong evidence from animal models and clinical patients demonstrates that parasympathetic and sympathetic activity within this neuraxis may trigger AF, and the ANS may either induce atrial remodelling or undergo remodelling itself to serve as a substrate for AF. Multiple nexus points within the cardiac neuraxis are therapeutic targets, and neuroablative and neuromodulatory therapies for AF include ganglionated plexus ablation, epicardial botulinum toxin injection, vagal nerve (tragus) stimulation, renal denervation, stellate ganglion block/resection, baroreceptor activation therapy, and spinal cord stimulation. Pre-clinical and clinical studies on these modalities have had promising results and are reviewed here.
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http://dx.doi.org/10.1093/cvr/cvab172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208752PMC
June 2021

Alvimopan as part of the Enhanced Recovery After Surgery protocol following radical cystectomy is associated with decreased hospital stay.

Int J Urol 2021 06 26;28(6):696-701. Epub 2021 Mar 26.

Departments of, Department of, Urology, University of Minnesota, Minneapolis, MN, USA.

Objective: To study the effect of alvimopan and the Enhanced Recovery After Surgery protocol on length of hospital stay in patients undergoing radical cystectomy.

Methods: Our retrospective study involved 296 consecutive patients undergoing radical cystectomy for bladder cancer at our institution from 2010 through 2018. Patients were grouped according to three stages of the Enhanced Recovery After Surgery protocol implementation: (i) pre-Enhanced Recovery After Surgery (group A; n = 146); (ii) pre-alvimopan Enhanced Recovery After Surgery (group B; n = 102); and (iii) Enhanced Recovery After Surgery plus alvimopan (group C; n = 48). The primary outcome was the length of hospital stay. Secondary outcomes were time to first bowel movement, time to tolerate a regular diet, the incidence of postoperative ileus, postoperative complications and 30-day readmission rate.

Results: Group C showed a significantly shorter median length of hospital stay (7 days, P = 0.003), shorter gastrointestinal recovery time (4 days, P = 0.018) and a lower rate of postoperative ileus (14.6%, P = 0.005). The reduction in length of hospital stay, gastrointestinal recovery time and a lower rate of postoperative ileus was significant after controlling for other confounders on multivariable regression analysis. With the open approach, group C showed a significantly shorter length of hospital stay and gastrointestinal recovery time (P = 0.005, P = 0.001, respectively); however, in robotic cohorts, no significant differences were observed. There was no difference among groups in the 30-day readmission rate or postoperative complications.

Conclusions: Patients undergoing radical cystectomy and managed by an Enhanced Recovery After Surgery protocol experience a significantly shorter length of hospital stay when receiving alvimopan as part of the protocol. Patients seem to derive the optimum benefits of alvimopan when it is used with an open approach; however, these benefits become less obvious with the robotic approach.
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http://dx.doi.org/10.1111/iju.14546DOI Listing
June 2021

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

Circ Res 2021 Apr 25;128(9):1279-1296. Epub 2021 Feb 25.

Department of Medicine, Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, University of California, Los Angeles (UCLA; P.H., M.J.D., M.A.S., P.S.R., S.M., J.E.H., R.L.L., J.D.T., J.L.A., K.S.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCRESAHA.120.318458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284939PMC
April 2021

Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection.

Am J Physiol Heart Circ Physiol 2020 11 9;319(5):H1059-H1068. Epub 2020 Oct 9.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by preexisting cardiovascular disease. Disruption of homeostatic mechanisms secondary to pulmonary pathology ranks high on the list, and there is growing evidence that direct infection of cardiac cells can occur. Angiotensin-converting enzyme 2 (ACE2) plays a central role in COVID-19 and is a necessary receptor for viral entry into human cells. ACE2 normally not only eliminates angiotensin II (Ang II) by converting it to Ang-(1-7) but also elicits a beneficial response profile counteracting that of Ang II. Molecular analyses of single nuclei from human hearts have shown that ACE2 is most highly expressed by pericytes. Given the important roles that pericytes have in the microvasculature, infection of these cells could compromise myocardial supply to meet metabolic demand. Furthermore, ACE2 activity is crucial for opposing adverse effects of locally generated Ang II, so virus-mediated internalization of ACE2 could exacerbate pathology by this mechanism. While the role of cardiac pericytes in acute heart injury by SARS-CoV-2 requires investigation, expression of ACE2 by these cells has broader implications for cardiac pathophysiology.
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http://dx.doi.org/10.1152/ajpheart.00681.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789968PMC
November 2020

Cardiac Neuroanatomy for the Cardiac Electrophysiologist.

J Atr Fibrillation 2020 Jun-Jul;13(1):2407. Epub 2020 Jun 30.

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, Department of Medicine, UCLA, Los Angeles, CA.

The cardiac neuraxis is integral to cardiac physiology, and its dysregulation is implicated in cardiovascular disease. Neuromodulatory therapies are being developed that target the cardiac autonomic nervous system (ANS) to treat cardiac pathophysiology. An appreciation of the cardiac neuroanatomy is a prerequisite for development of such targeted therapies. Here, we provide a review of the current understanding of the cardiac ANS. The parasympathetic and sympathetic nervous system are composed of higher order cortical centers, brainstem, spinal cord, intrathoracic extracardiac ganglia and intrinsic cardiac ganglia. A series of interacting feedback loops mediates reflex pathways to exert control over the cardiac conduction system and contractile tissue. Further exploration of this complex regulatory system promises to yield neuroscience-based therapeutics for cardiac disease.
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http://dx.doi.org/10.4022/jafib.2407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533134PMC
June 2020

Enhanced recovery after surgery (ERAS) following radical cystectomy: is it worth implementing for all patients?

World J Urol 2021 Jun 11;39(6):1927-1933. Epub 2020 Sep 11.

Department of Urology, University of Minnesota, 420 Delaware St. S.E.MMC 394, Minneapolis, MN, 55455, USA.

Purpose: To report the overall effect of ERAS protocol implementation in patients undergoing radical cystectomy and its impact on the length of hospital stay (LOS) and surgical outcomes considering their comorbid conditions.

Methods: Retrospective cohort study including 296 patients (146 non-ERAS patients vs. 150 ERAS patients) undergoing radical cystectomy and urinary diversion from 2010 to 2018. Age-adjusted Charlson Comorbidity Index (ACCI) score eight was set as cut off value between low-risk and high-risk patients. The primary outcome was LOS. Secondary outcomes were time to bowel movements, tolerance of regular diet, the incidence of postoperative ileus, postoperative complications, and 30- and 90-day readmission rates.

Results: A higher comorbidity burden was identified in the ERAS group compared to non-ERAS patients (p = 0.04). Median (IQR) LOS for non-ERAS was group 8(4) and 8(5) for ERAS group (p = 0.07). ERAS group demonstrated shorter time to resume bowel movements as well as time to tolerance of regular diet (p = 0.007, p = 0.023, respectively). Low-risk patients managed by the ERAS protocol demonstrated a significantly shortened gastrointestinal (GIT) recovery time (p = 0.001) as well as a reduction of LOS (p = 0.04). No significant reduction of LOS was identified for patients with higher comorbidity when placed on the ERAS protocol (p = 0.65). There were no significant differences in postoperative complications or readmission rates between groups.

Conclusion: ERAS protocol implementation following radical cystectomy showed significant improvements in GIT recovery, nevertheless, it did not result in a decrease in LOS or readmission rates. Low-risk patients appeared to derive more benefit from ERAS protocol implementation than high-risk patients.
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http://dx.doi.org/10.1007/s00345-020-03435-1DOI Listing
June 2021

Reply by Authors.

J Urol 2020 11 10;204(5):988. Epub 2020 Sep 10.

Urology Department, University of Minnesota, Minneapolis, Minnesota.

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http://dx.doi.org/10.1097/JU.0000000000001153.03DOI Listing
November 2020

Mechanism of Ventricular Premature Beats Elicited by Left Stellate Ganglion Stimulation During Acute Ischemia of the Anterior Left Ventricle.

Cardiovasc Res 2020 Aug 27. Epub 2020 Aug 27.

Amsterdam UMC, University of Amsterdam, Heart Center, Dept of Medical Biology, Dept of Experimental Cardiology, Meibergdreef 9 Amsterdam, The Netherlands.

Aims: Enhanced sympathetic activity during acute ischemia is arrhythmogenic, but the underlying mechanism is unknown. During ischemia, a diastolic current flows from the ischemic to the non-ischemic myocardium. This "injury" current can cause ventricular premature beats originating in the non-ischemic myocardium, especially during a deeply negative T wave in the ischemic zone. We reasoned that shortening of repolarization in myocardium adjacent to ischemic myocardium increases the "injury" current and causes earlier deeply negative T waves in the ischemic zone, and re-excitation of the normal myocardium. We tested this hypothesis by activation and repolarization mapping during stimulation of the left stellate ganglion (LSGS) during left anterior descending coronary artery (LAD) occlusion.

Methods And Results: In 9 pigs, five subsequent episodes of acute ischemia, separated by 20 min of reperfusion, were produced by occlusion of the LAD and 121 epicardial local unipolar electrograms were recorded. During the third occlusion, LSGS was initiated after 3 min for a 30-sec period, causing a shortening of repolarization in the normal myocardium by about 100 msec. This resulted in more negative T waves in the ischemic zone and more ventricular premature beats (VPBs) than during the second, control, occlusion. Following decentralization of the LSG (including removal of the right stellate ganglion and bilateral cervical vagotomy), fewer VPBs occurred during ischemia without LSGS. During LSGS, the number of VPBs was similar to that recorded before decentralization.

Conclusion: LSGS, by virtue of shortening of repolarization in the non-ischemic myocardium by about 100 msec, causes deeply negative T waves in the ischemic tissue and VPBs originating from the normal tissue adjacent to the ischemic border. In this setting, decentralization of the LSG is antiarrhythmic.

Translational Perspective: Cardiac sympathetic denervation is a promising therapy for reducing arrhythmias during acute ischemia. Currently it is not clear which patients with ischemic heart disease would benefit from cardiac sympathetic denervation and for which patients it is unlikely to have an effect. This is important because cardiac sympathetic denervation by removing the stellate ganglia often results in severe side effects and morbidity. Our results indicate that left stellate ganglion activity is pro-arrhythmic and that left stellectomy is beneficial for the prevention of arrhythmias during anterior wall ischemia. When the ischemic zone is in the lateral and posterior wall, the effects of LSGS will be different because it will directly affect the ischemic myocardium, and might even be antiarrhythmic. Thus, the effect of left stellate stimulation can be pro or antiarrhythmic, depending on the location of myocardial ischemia.
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http://dx.doi.org/10.1093/cvr/cvaa253DOI Listing
August 2020

Acute Kidney Injury following Enhanced Recovery after Surgery in Patients Undergoing Radical Cystectomy.

J Urol 2020 Nov 29;204(5):982-988. Epub 2020 May 29.

Urology Department, University of Minnesota, Minneapolis, Minnesota.

Purpose: We assessed the effect of enhanced recovery after surgery protocol related fluid restriction on kidney function and the incidence of postoperative acute kidney injury and 3-month kidney function.

Materials And Methods: In a retrospectively collected, single institution cohort we studied 296 consecutive patients (146 pre-enhanced recovery after surgery vs 150 enhanced recovery after surgery) who underwent radical cystectomy from 2010 to 2018. The primary outcome was the incidence of postoperative acute kidney injury. Secondary outcomes were length of hospital stay, time to bowel movements, time to tolerate regular diet, postoperative complications and 30-day readmission rate. Study limitations include its retrospective design and relatively modest sample size.

Results: We observed an increased rate of postoperative acute kidney injury in patients on the enhanced recovery after surgery protocol (42.7% vs 30.1%, OR 1.725, p=0.025). On multivariate analysis enhanced recovery after surgery protocol remained a significant predictor of acute kidney injury even when controlling for other covariates including baseline kidney function (OR 1.8, 95% CI 1.04-3.30, p=0.036). Patients with postoperative acute kidney injury demonstrated significantly higher odds of stage 3 chronic kidney disease at 3 months even after controlling for baseline renal function (OR 2.5, 95% CI 1.3-4.9, p=0.016).

Conclusions: Use of an enhanced recovery after surgery protocol following radical cystectomy was associated with a higher risk of postoperative acute kidney injury in patients who had baseline chronic kidney disease which could be related to the restricted perioperative fluid management mandated by enhanced recovery after surgery. Use of the enhanced recovery after surgery protocol did not impact the length of hospital stay or readmission rates.
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http://dx.doi.org/10.1097/JU.0000000000001153DOI Listing
November 2020

Cryoballoon pulmonary vein isolation: Effects on neural control of the heart.

Int J Cardiol 2020 09 19;314:77-78. Epub 2020 Apr 19.

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2020.04.037DOI Listing
September 2020

Stellate ganglion stimulation causes spatiotemporal changes in ventricular repolarization in pig.

Heart Rhythm 2020 05 7;17(5 Pt A):795-803. Epub 2020 Jan 7.

Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands; L'Institut de RYthmologie et de modélisation Cardiaque (LIRYC), Université Bordeaux, Bordeaux, France. Electronic address:

Background: Dispersion in ventricular repolarization is relevant for arrhythmogenesis.

Objective: The purpose of this study was to determine the spatiotemporal effects of sympathetic stimulation on ventricular repolarization.

Methods: In 5 anesthetized female open-chest pigs, ventricular repolarization was measured from the anterior, lateral, and posterior walls of the left ventricle (LV) and right ventricle using up to 40 transmural plunge needles (4 electrodes each) before and after left stellate ganglion stimulation (LSGS) and right stellate ganglion stimulation. In addition, LSGS was performed in 3 pigs (2 male, 1 female) before and after verapamil (5-10 mg/h) administration.

Results: LSGS yielded a biphasic response in repolarization in the lateral and posterior walls of the LV, with prolongation at ∼5 seconds (10 ± 1.5 ms) and shortening at 20-30 seconds of stimulation (-28.9 ± 4.4 ms) during a monotonic pressure increase. While the initial prolongation was abolished by verapamil, late shortening was augmented. Sequential transections of the vagal nerve and stellate ganglia augmented repolarization dispersion responses to LSGS in 2 of 5 hearts. An equal pressure increase by aortic occlusion resulted in a homogeneous shortening of repolarization in the LV, and the effects were smaller than those during LSGS. Right stellate stimulation shortened repolarization mainly in the anterior LV wall, but the effects were smaller than those of LSGS.

Conclusion: LSGS first prolongs (through the L-type calcium current) and then shortens repolarization. The effect of LSGS was prominent in the posterior and lateral, not the anterior, LV walls.
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http://dx.doi.org/10.1016/j.hrthm.2019.12.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196037PMC
May 2020

Skeletal Muscle and Fat Mass Indexes Predict Discharge Disposition after Radical Cystectomy.

J Urol 2019 12 17;202(6):1143-1149. Epub 2019 Jul 17.

Department of Urology, University of Minnesota, Minneapolis, Minnesota.

Purpose: Skeletal muscle and fat mass indexes have emerged as easily obtained, objective and useful tools to assess susceptibility to unfavorable postoperative outcomes. We examined the association between skeletal muscle and fat mass indexes, and the discharge disposition after radical cystectomy.

Materials And Methods: In a retrospectively collected, single institution cohort we studied patients who underwent radical cystectomy with pelvic lymphadenectomy of primary, nonmetastatic muscle invasive bladder cancer between 2009 and 2015. Included patients had undergone adequate axial computerized tomography at the L3 level within 90 days prior to surgery. Skeletal muscle and fat mass indexes were measured on preoperative computerized tomography and relationships to the outcomes of interest were analyzed. Multivariable logistic regression analysis was performed to assess the effect of the skeletal muscle and fat mass indexes on the discharge disposition while controlling for age, comorbidities, complications and previous neoadjuvant chemotherapy.

Results: A total of 136 patients met study inclusion criteria. The median skeletal muscle index among women and men in our study cohort was 36.4 and 47.6 cm/m, respectively. On multivariable logistic regression analysis a decreased skeletal muscle index (OR 0.94, 95% CI 0.90-0.98) and an increased fat mass index (OR 1.24, 95% CI 1.04-1.48) were associated with greater odds of discharge to a facility. Higher fat mass-to-skeletal muscle [corrected] index ratios were also associated with greater odds of discharge to a facility (OR 1.69, 95% CI 1.22-2.44). Study limitations include the retrospective design and unknown confounders.

Conclusions: Low skeletal muscle and high fat compositions are independent predictors of discharge to a facility after radical cystectomy of nonmetastatic muscle invasive bladder cancer.
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http://dx.doi.org/10.1097/JU.0000000000000450DOI Listing
December 2019

Neuromodulation for Ventricular Tachycardia and Atrial Fibrillation: A Clinical Scenario-Based Review.

JACC Clin Electrophysiol 2019 08 19;5(8):881-896. Epub 2019 Aug 19.

University of California, Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, California. Electronic address:

Autonomic dysregulation in cardiovascular disease plays a major role in the pathogenesis of arrhythmias. Cardiac neural control relies on complex feedback loops consisting of efferent and afferent limbs, which carry sympathetic and parasympathetic signals from the brain to the heart and sensory signals from the heart to the brain. Cardiac disease leads to neural remodeling and sympathovagal imbalances with arrhythmogenic effects. Preclinical studies of modulation at central and peripheral levels of the cardiac autonomic nervous system have yielded promising results, leading to early stage clinical studies of these techniques in atrial fibrillation and refractory ventricular arrhythmias, particularly in patients with inherited primary arrhythmia syndromes and structural heart disease. However, significant knowledge gaps in basic cardiac neurophysiology limit the success of these neuromodulatory therapies. This review discusses the recent advances in neuromodulation for cardiac arrhythmia management, with a clinical scenario-based approach aimed at bringing neurocardiology closer to the realm of the clinical electrophysiologist.
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http://dx.doi.org/10.1016/j.jacep.2019.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773263PMC
August 2019

Anesthetizing the Fibrillating Heart.

J Am Heart Assoc 2019 05;8(10):e012713

1 University of California, Los Angeles (UCLA), Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence David Geffen School of Medicine UCLA Los Angeles CA.

See Article Lee et al.
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http://dx.doi.org/10.1161/JAHA.119.012713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585315PMC
May 2019

Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies.

Nat Commun 2019 04 26;10(1):1944. Epub 2019 Apr 26.

Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, University of California - Los Angeles (UCLA), Los Angeles, CA, 90095, USA.

Heart rate is under the precise control of the autonomic nervous system. However, the wiring of peripheral neural circuits that regulate heart rate is poorly understood. Here, we develop a clearing-imaging-analysis pipeline to visualize innervation of intact hearts in 3D and employed a multi-technique approach to map parasympathetic and sympathetic neural circuits that control heart rate in mice. We identify cholinergic neurons and noradrenergic neurons in an intrinsic cardiac ganglion and the stellate ganglia, respectively, that project to the sinoatrial node. We also report that the heart rate response to optogenetic versus electrical stimulation of the vagus nerve displays different temporal characteristics and that vagal afferents enhance parasympathetic and reduce sympathetic tone to the heart via central mechanisms. Our findings provide new insights into neural regulation of heart rate, and our methodology to study cardiac circuits can be readily used to interrogate neural control of other visceral organs.
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http://dx.doi.org/10.1038/s41467-019-09770-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486614PMC
April 2019

Neuroinflammation as a mechanism for cardiovascular diseases.

Int J Cardiol 2019 08 4;288:128-129. Epub 2019 Apr 4.

Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155386PMC
August 2019

Targeting the Cardiac Ganglionated Plexi for Atrial Fibrillation: Modulate or Destroy?

JACC Clin Electrophysiol 2018 10;4(10):1359-1361

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, California; Molecular, Cellular, and Integrative Physiology Program, David Geffen School of Medicine, UCLA, Los Angeles, California. Electronic address:

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http://dx.doi.org/10.1016/j.jacep.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098458PMC
October 2018

Calming the Nervous Heart: Autonomic Therapies in Heart Failure.

Card Fail Rev 2018 Aug;4(2):92-98

David Geffen School of Medicine, University of California Los Angeles (UCLA) Los Angeles, CA, USA.

Heart failure (HF) is associated with significant morbidity and mortality. The disease is characterised by autonomic imbalance with increased sympathetic activity and withdrawal of parasympathetic activity. Despite the use of medical therapies that target, in part, the neurohormonal axis, rates of HF progression, morbidity and mortality remain high. Emerging therapies centred on neuromodulation of autonomic control of the heart provide an alternative device-based approach to restoring sympathovagal balance. Preclinical studies have proven favourable, while clinical trials have had mixed results. This article highlights the importance of understanding structural/functional organisation of the cardiac nervous system as mechanistic-based neuromodulation therapies evolve.
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http://dx.doi.org/10.15420/cfr.2018.20.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125704PMC
August 2018

Anticoagulation Reversal and Risk of Thromboembolic Events Among Heart Transplant Recipients Bridged with Durable Mechanical Circulatory Support Devices.

ASAIO J 2019 Sep/Oct;65(7):649-655

From the Division of Heart Failure and Transplantation.

Anticoagulation reversal agents (ARAs) can minimize bleeding complications associated with mechanical circulatory support devices (MCSDs) explantation at the time of heart transplantation (HT); data on thromboembolic (TE) risk associated with ARAs are limited in this patient population. In this single-center study, we retrospectively analyzed 118 consecutive adults who were supported with durable MCSDs and underwent HT between May 2013 and October 2016. Patients were categorized based on intraoperative use of ARAs (recombinant factor VIIa [n=23], 4-factor prothrombin complex concentrate [n=48], or factor IX complex [n=2]) at the time of HT; these agents were used at discretion of implanting surgeons for bleeding control. The primary outcome of interest was presence of venous or systemic TE events within 3 months of HT. Multivariable logistic regression analyses were used to assess association between TE events and use of ARAs. A total of 71 (60%) patients received ARAs, and a total of 32 patients (27.1%) had TE events (25 venous [median time to diagnosis: 11.5 days; interquartile range {IQR}: 9-31 days], and 10 systemic [median time to diagnosis: 5.5 days; IQR: 4-8 days]); 26 (81.2%) of those with TE events had ARAs used at the time of HT. Multivariable analysis identified use of ARAs as an independent predictor of TE events (multivariable odds ratio: 3.06; 95% CI: 1.09-8.58; p = 0.034). Unplanned intraoperative use of ARAs to control bleeding was associated with a significantly higher risk of TE events among HT recipients bridged with durable MCSD. Future studies are required to further assess safety of these agents and their impact on patient outcomes.
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http://dx.doi.org/10.1097/MAT.0000000000000866DOI Listing
May 2020

Percutaneous Hemodynamic Assist Devices: Unloading the Left Atrium to Prevent Atrial Remodeling.

J Am Coll Cardiol 2018 08;72(7):751-753

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, California; and the Molecular, Cellular & Integrative Physiology Program, David Geffen School of Medicine, UCLA, Los Angeles, California.

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http://dx.doi.org/10.1016/j.jacc.2018.06.015DOI Listing
August 2018

Neural ablation to treat ventricular arrhythmias.

Europace 2018 12;20(12):1880-1881

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Program of Excellence, David Geffen School of Medicine, UCLA, 100 UCLA Medical Plaza, Suite 660, Los Angeles, CA, USA.

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http://dx.doi.org/10.1093/europace/euy134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275468PMC
December 2018

Cardiac neuroanatomy - Imaging nerves to define functional control.

Auton Neurosci 2017 Nov 29;207:48-58. Epub 2017 Jul 29.

University of California Los Angeles (UCLA) Cardiac Arrhythmia Center and Neurocardiology Research Center of Excellence, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA; Molecular, Cellular & Integrative Physiology Program, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Electronic address:

The autonomic nervous system regulates normal cardiovascular function and plays a critical role in the pathophysiology of cardiovascular disease. Further understanding of the interplay between the autonomic nervous system and cardiovascular system holds promise for the development of neuroscience-based cardiovascular therapeutics. To this end, techniques to image myocardial innervation will help provide a basis for understanding the fundamental underpinnings of cardiac neural control. In this review, we detail the evolution of gross and microscopic anatomical studies for functional mapping of cardiac neuroanatomy.
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http://dx.doi.org/10.1016/j.autneu.2017.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680093PMC
November 2017

Validation of venous duplex ultrasound imaging in determining iliac vein stenosis after standard treatment of active chronic venous ulcers.

J Vasc Surg Venous Lymphat Disord 2016 07 26;4(3):307-12. Epub 2016 Mar 26.

Department of Surgery, Robert C. Byrd Health Sciences Center/West Virginia University, Charleston Area Medical Center, Vascular Center of Excellence, Charleston, WVa.

Objective: Chronic venous ulcer (CVU) is a potentially debilitating condition that remains the most common etiology for leg ulcers. The condition has significant associated costs and effect on patient quality of life. That truncal reflux can be worsened by iliac vein occlusive disease is well known. However, there has not been systematic investigation of venous duplex ultrasound (VDUS) criteria to correlate common femoral vein (CFV) reflux with iliac vein stenosis. We sought to correlate VDUS criteria for predicting iliac vein stenosis and to investigate venous outflow factors associated with CVU recurrence.

Methods: We conducted a systematic retrospective review of a consecutive series of 36 patients who received standard therapies, including compression therapy along with ablation of incompetent great saphenous veins for treating CVU, but in whom the treatment failed. Elevated CVF reflux was considered as reflux duration (RD) measured by VDUS to last >1 second. A receiver operator characteristic curve analysis was performed to determine the optimal CFV threshold value to predict 50% iliac vein stenosis measured by intravascular ultrasound.

Results: The 36 patients presented with 54 CVUs on 38 limbs. The median (25th-75th quartiles) age was 61.2 (57.6-68.8) years, body mass index was 36.8 (25.2-52.3) kg/m(2), CFV RD was 2.7 (1.6-3.5) seconds, ulcer diameter was 4.2 (3.0-4.0) cm, and ulcer depth was 2.5 (2.0-3.0) mm. The optimal cutoff RD value was >2.5 seconds by receiver operator characteristic curve analysis, with an area under the curve of 0.77 (P = .001). CVUs associated with an RD >2.5 seconds had significantly more iliac vein stenosis >50% by intravascular ultrasound (24 of 30; 80%) than those with an RD <2.5 seconds (6 of 24; 25%; P < .001). Likewise, >50% stenosis for those above and below an RD >1 second was 61.4% vs 30%, respectively (P = .089). Significantly less recurrence of CVU was found for patients taking pentoxifylline (43.6% vs 80.0%; P = .031) and those with stents placed (40.0% vs 70.8%; P = .031). A nonsignificant trend was found for iliac vein interrogation (44.4% vs 72.2%; P = .082).

Conclusions: This study highlights the utility of VDUS in diagnosing iliac vein stenosis with 2.5 seconds to predict ≥50% iliac vein stenosis. Stent placement and pentoxifylline were associated with ulcer healing and reduced risk of venous ulcer recurrence.
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http://dx.doi.org/10.1016/j.jvsv.2016.02.002DOI Listing
July 2016

Longer Ambulatory ECG Monitoring Increases Identification of Clinically Significant Ectopy.

Pacing Clin Electrophysiol 2016 Jun 22;39(6):592-7. Epub 2016 Apr 22.

Department of Medicine, University of California San Francisco, California, San Francisco.

Background: Frequent premature ventricular contractions (PVCs) can cause a reversible reduction in systolic function. Most studies use 24-hour ambulatory electrocardiograms (AECGs) to assess PVC burden; however, PVC counts vary across 24-hour periods. We hypothesized that extended AECG monitoring would better identify clinically significant ectopy.

Methods: All 14-day AECGs performed at the San Francisco Veterans Affairs Medical Center between 2012 and 2015 (N = 694) were reviewed, and individuals with PVC counts ≥1.0% of total heartbeats were included (N = 101). Daily PVC counts and the range of these values across 24-hour periods were assessed. Median time for these ranges to cross clinically significant thresholds (PVCs ≥ 10%, 15%, or 20% of total heartbeats) was determined.

Results: Median PVC burden was 2.6% of total heartbeats (interquartile range [IQR]: 1.6-5.4%) and the median range across 24-hour periods was 3.6% (IQR: 2.0-9.1%). Individual ranges of daily PVC burden crossed thresholds of 10%, 15%, and 20% of total heartbeats in 26.7%, 16.8%, and 6.9% of patients, respectively. Median time to detecting an individual's maximum PVC burden was 6 days (IQR: 2-11 days). While 75% of those who reached the 20% threshold did so on day one of monitoring, only 53% of those reaching the 10% threshold did similarly, with a continually increasing yield throughout the 14-day monitoring period.

Conclusions: PVC burden varies widely from day-to-day. While most patients with PVC burdens ≥20% were detected with 24 hours of monitoring, extended monitoring nearly doubled the identification of those reaching the 10% threshold.
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http://dx.doi.org/10.1111/pace.12852DOI Listing
June 2016

Spermatophore affects the egg-spawning and egg-carrying behavior in the female giant freshwater prawn, Macrobrachium rosenbergii.

Anim Reprod Sci 2015 Oct 31;161:129-37. Epub 2015 Aug 31.

Department of Anatomy, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. Electronic address:

In crustaceans, mating occurs during the ecdysis after female molting. During this period, a male transfers its spermatophore into a female which, in some species, stores the spermatophore for a long period prior to spawning and fertilization. However, in some species including the giant freshwater prawn, Macrobrachium rosenbergii, the male deposits its spermataphore onto the external surface of the thoracic segment of the female which affects the spawning time and maternal behavior. This study investigated the spawning behavior of the M. rosenbergii females, which was divided into pre-spawning, spawning, and post-spawning phases. It was revealed that mated female prawns with attached spermatophore exhibited an earlier spawning than unmated individuals, leading to assessment of the factors that may elicit this phenomenon. Four groups of female prawns were allocated to groups including mating females with spermatophore still attached, mating females with the spermatophore removed, artificially inseminated females with spermatophores, and an unmated control. There was a significant reduction in the time of egg-spawning in the presence of spermatophores, and the mating activity was also a contributing factor. Furthermore, over 90% of the mated and artificially inseminated females in which spermatophores were deposited carried the eggs in the abdominal brood chamber until completion of embryonic development while others discarded the eggs within 2 days post-spawning. This study implies that the spermatophore may contain ovulation-inducing factors which stimulate an earlier spawning and fostering of brooding behavior.
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http://dx.doi.org/10.1016/j.anireprosci.2015.08.015DOI Listing
October 2015

In silico Neuropeptidome of Female Macrobrachium rosenbergii Based on Transcriptome and Peptide Mining of Eyestalk, Central Nervous System and Ovary.

PLoS One 2015 29;10(5):e0123848. Epub 2015 May 29.

Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand.

Macrobrachium rosenbergii is the most economically important of the cultured freshwater crustacean species, yet there is currently a deficiency in genomic and transcriptomic information for research requirements. In this study, we present an in silico analysis of neuropeptide genes within the female M. rosenbergii eyestalk, central nervous system, and ovary. We could confidently predict 37 preproneuropeptide transcripts, including those that encode bursicons, crustacean cardioactive peptide, crustacean hyperglycemic hormones, eclosion hormone, pigment-dispersing hormones, diuretic hormones, neuropeptide F, neuroparsins, SIFamide, and sulfakinin. These transcripts are most prominent within the eyestalk and central nervous system. Transcript tissue distribution as determined by reverse transcription-polymerase chain reaction revealed the presence of selected neuropeptide genes of interest mainly in the nervous tissues while others were additionally present in the non-nervous tissues. Liquid chromatography-mass spectrometry analysis of eyestalk peptides confirmed the presence of the crustacean hyperglycemic hormone precursor. This data set provides a strong foundation for further studies into the functional roles of neuropeptides in M. rosenbergii, and will be especially helpful for developing methods to improve crustacean aquaculture.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123848PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449106PMC
April 2016

Variation of prostaglandin E2 concentrations in ovaries and its effects on ovarian maturation and oocyte proliferation in the giant fresh water prawn, Macrobrachium rosenbergii.

Gen Comp Endocrinol 2015 Nov 8;223:129-38. Epub 2015 May 8.

Department of Anatomy, Faculty of Science, Mahidol University, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. Electronic address:

Prostaglandins (PGs) are important bioactive mediators for many physiological functions. In some decapod crustaceans, prostaglandin E2 (PGE2) has been detected in reproductive organs, and may play a role in the control of ovarian maturation. However, in the freshwater prawn, Macrobrachium rosenbergii, the presences of PGE2 and key enzymes for PGE2 biosynthesis, as well as its effects on ovarian maturation have not yet been investigated. In this study we reported the presence of PGE2, cyclooxygenase1 (COX1) and prostaglandin E synthase (PGES) in the ovarian tissues of M. rosenbergii, using immunohistochemistry. Intense immunoreactivities of PGE2 (PGE2-ir), COX1 (Cox1-ir) and PGES (PGES-ir) were detected in previtellogenic oocytes (Oc1 and Oc2), while the immunoreactivities were absent in the late vitellogenic oocytes (Oc4). This finding supports the hypothesis that the PGE2 biosynthesis occurs in the ovary of this prawn. To ascertain this finding we used LC-MS/MS to quantitate PGE2 concentrations during ovarian developmental cycle. The levels of PGE2 were significantly higher in the early ovarian stages (St I and II) than in the late stages (St III and IV). Moreover, we found that administration of PGE2 stimulated the ovarian maturation in this species by shortening the length of the ovarian cycle, increasing ovarian-somatic index, oocyte proliferation, and vitellogenin (Vg) level in the hemolymph.
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http://dx.doi.org/10.1016/j.ygcen.2015.04.019DOI Listing
November 2015

Changes of phosphatidylcholine and fatty acids in germ cells during testicular maturation in three developmental male morphotypes of Macrobrachium rosenbergii revealed by imaging mass spectrometry.

PLoS One 2015 17;10(3):e0120412. Epub 2015 Mar 17.

Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Shizuoka, Japan.

Testis maturation, germ cell development and function of sperm, are related to lipid composition. Phosphatidylcholines (PCs) play a key role in the structure and function of testes. As well, increases of polyunsaturated fatty acids (PUFA) and highly unsaturated fatty acids (HUFA), especially arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are essential for male fertility. This study is the first report to show the composition and distribution of PCs and total fatty acids (FAs) in three groups of seminiferous tubules (STs) classified by cellular associations [i.e., A (STs with mostly early germ cells), B (STs with mostly spermatids), and C (STs with spermatozoa)], in three morphotypes of Macrobrachium rosenbergii, [i.e., small male (SM), orange claw male (OC), and blue claw male (BC)]. Thin layer chromatography exhibited levels of PCs reaching maxima in STs of group B. Imaging mass spectrometry showed remarkably high signals corresponding to PC (16:0/18:1), PC (18:0/18:2), PC (18:2/20:5), and PC (16:0/22:6) in STs of groups A and B. Moreover, most signals were detected in the early developing cells and the intertubular area, but not at the area containing spermatozoa. Finally, gas chromatography-mass spectrometry indicated that the major FAs present in the testes were composed of 14:0, 16:0, 17:0, 18:0, 16:1, 18:1, 18:2, 20:1, 20:2, 20:4, 20:5, and 22:6. The testes of OC contained the greatest amounts of these FAs while the testes of BC contained the least amounts of these FAs, and there was more EPA (20:5) in the testes of SM and OC than those in the BC. The increasing amounts of FAs in the SM and OC indicate that they are important for spermatogenesis and spermiogenesis. This knowledge will be useful in formulating diets containing PUFA and HUFA for prawn broodstocks in order to improve testis development, and lead to increased male fecundity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120412PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4363669PMC
December 2015