Aman Mahajan

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (141)478.21 Total impact

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    ABSTRACT: Objective: Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. Methods: A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs (n=17) recorded electrophysiological function; Activation Recovery Interval (ARI) and Dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1-T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Results: Left or right DRTx decreased global basal ARI; Lt.DRTx 369 ± 12 to 319 ± 13 ms (p < 0.01) and Rt.DRTx 388 ± 19 to 356 ± 15 ms (p < 0.01). Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left (LSS) and right (RSS) stellate ganglion stimulation shortened ARIs (6±2% vs 17±3%), while increasing dispersion (+139% vs +88%,). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Conclusions: Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord mediated tonic inhibitory control of efferent sympathetic tone while maintaining intrathoracic cardio-centric neural networks.
    No preview · Article · Dec 2015 · AJP Regulatory Integrative and Comparative Physiology
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    ABSTRACT: Left ventricular (LV) dysfunction increases the risk for serious post-operative complications. Accurate assessment of LV wall motion is necessary to guide anesthetic management; however, traditional measures have a high degree of inter- and intra-observer variability. Myocardial deformation as measured by strain and strain rates is improving the diagnostic and prognostic utility of echocardiography to determine LV function in patients with cardiovascular disease. Strain can be measured using tissue Doppler and speckle tracking imaging from two-dimensional or three-dimensional echocardiography using various online and offline software packages. Tissue Doppler strain analysis provides excellent temporal resolution but is limited by the imaging angle of insonation. Speckle tracking strain imaging is angle independent and now the more commonly used modality. Strain has been demonstrated to guide therapy, monitor disease progression in various pathologic states, and is emerging as a strong predictor of clinical outcomes.
    No preview · Article · Oct 2015
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    ABSTRACT: Aims: Vagal nerve stimulation (VNS) has been shown to have anti-arrhythmic effects, but many of these benefits were demonstrated in the setting of vagal nerve decentralization. The purpose of this study was to evaluate the role of afferent fiber activation during VNS on efferent control of cardiac hemodynamic and electrophysiological parameters. Methods and results: In 37 pigs a 56-electrode sock was placed over the ventricles to record local activation recovery intervals (ARIs), a surrogate of action potential duration. In 12 of 37 animals atropine was given systemically. Right and left VNS were performed under six conditions: both vagal trunks intact (n=25), ipsilateral right (n=11), ipsilateral left (n=14), contralateral right (n=7), contralateral left (n=10), and bilateral (n=25) VNTx. Unilateral VNTx significantly affected heart rate, PR interval, Tau, and global ARIs. Right VNS after ipsilateral VNTx had augmented effects on hemodynamic parameters and increase in ARI, while subsequent bilateral VNTx did not significantly modify this effect (% change in ARI in intact condition: 2.2±0.9% vs. ipsilateral VNTx: 5.3±1.7% and bilateral VNTx: 5.3±0.8%, p<0.05). Left VNS after left VNTx tended to increase its effects on hemodynamics and ARI response (p=0.07), but only after bilateral VNTx did these changes reach significance (intact 1.1±0.5% vs. ipsilateral VNTx 3.6±0.7% and bilateral VNTx 6.6±1.6%, p<0.05 vs. intact). Contralateral VNTx did not modify VNS response. Effect of atropine on ventricular ARI was similar to bilateral VNTx. Conclusions: VNS activates afferent fibers in the ipsilateral vagal nerve, which reflexively inhibit cardiac parasympathetic efferent electrophysiological and hemodynamic effects.
    No preview · Article · Sep 2015 · AJP Heart and Circulatory Physiology

  • No preview · Article · Jun 2015 · Journal of cardiothoracic and vascular anesthesia
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    ABSTRACT: Modulation of human cardiac mechanical and electrophysiologic function by direct stellate ganglion stimulation has not been performed. Our aim was to assess the effect of low-level left stellate ganglion (LSG) stimulation (SGS) on arrhythmias, hemodynamic, and cardiac electrophysiological indices. Patients undergoing ablation procedures for arrhythmias were recruited for SGS. A stimulating electrode was placed next to the LSG under fluoroscopy and ultrasound imaging; and SGS (5-10 Hz, 10-20 mA) was performed. We measured hemodynamic, intracardiac and ECG parameters, and activation recovery intervals (ARIs) (surrogate for action potential duration) from a duodecapolar catheter in the right ventricular outflow tract. Five patients underwent SGS (3 males, 45 ± 20 years). Stimulating catheter placement was successful, and without complication in all patients. SGS did not change heart rate, but increased mean arterial blood pressure (78 ± 3 mmHg to 98 ± 5 mmHg, P < 0.001) and dP/dt max (1148 ± 244 mmHg/sec to 1645 ± 493 mmHg/sec, P = 0.03). SGS shortened mean ARI from 304 ± 23 msec to 283 ± 17 msec (P < 0.001), although one patient required parasympathetic blockade. Dispersion of repolarization (DOR) increased in four patients and decreased in one, consistent with animal models. QT interval, T-wave duration and amplitude at baseline and with SGS were 415 ± 15 msec versus 399 ± 15 msec (P < 0.001); 201 ± 12 msec versus 230 ± 28 msec; and 0.2 ± 0.09 mV versus 0.22 ± 0.08 mV, respectively. At the level of SGS performed, no increase in arrhythmias was seen. Percutaneous low-level SGS shortens ARI in the RVOT, and increases blood pressure and LV contractility. These observations demonstrate feasibility of percutaneous SGS in humans. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
    Preview · Article · Mar 2015

  • No preview · Article · Mar 2015 · Journal of the American College of Cardiology
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    ABSTRACT: The primary aim of this study was to use speckle-tracking strain imaging to evaluate the effect of general anesthesia (GA) and positive-pressure ventilation (PPV) on left atrial (LA) mechanics. The authors hypothesized that GA and PPV would be associated with a decrease in LA strain. The secondary aims were to investigate the effects of GA and PPV on traditional Doppler-derived measures of LA function and Doppler echocardiographic grade of diastolic function. A prospective observational study. A university hospital. Adult patients undergoing cardiac surgery. Transthoracic echocardiography was performed at baseline and under GA with PPV. Changes in LA function associated with GA and PPV were assessed using LA speckle-tracking strain imaging. A reduction was observed in LA peak longitudinal strain (24% v 18%, p<0.001) and preatrial contraction strain (13% v 8%, p<0.001). No difference was seen in LA contraction strain or atrial ejection fraction. Indexed LA volume and Doppler diastolic indices also were reduced significantly, and 39% of patients had a change in measured diastolic grade under GA with PPV. Speckle-tracking strain imaging of the left atrium demonstrated that GA and PPV had a significant impact on LA mechanics by decreasing strain measures of LA preload, with a lesser effect on LA contractility. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · Journal of Cardiothoracic and Vascular Anesthesia
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    ABSTRACT: -T-peak to T-end interval (Tp-e) is an independent marker of sudden cardiac death. Modulation of Tp-e by sympathetic nerve activation and circulating norepinephrine (NE) is not well understood. The purpose of this study was to characterize endocardial and epicardial dispersion of repolarization (DOR) and its effects on Tp-e with sympathetic activation. -In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia (SG) were exposed. A 56-electrode sock and 64-electrode basket catheter were placed around the epicardium and in the left ventricle (LV), respectively. Activation recovery interval (ARI), dispersion of repolarization (DOR), defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral SG stimulation and NE infusion. LV endocardial and epicardial ARIs significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial vs. endocardial differences in ARI during sympathetic stimulation and regional endocardial ARI patterns were similar to the epicardium. Tp-e prolonged during left (from 40.4±2.2 ms to 92.4±12.4 ms; P<0.01), right (from 47.7±2.6 ms to 80.7±11.5 ms; P<0.01), and bilateral (from 47.5±2.8 ms to 78.1±9.8 ms; P<0.01) stellate stimulation and strongly correlated with whole heart DOR during stimulation (P<0.001, R=0.86). Of note, NE infusion did not increase DOR or Tp-e. -Regional patterns of LV endocardial sympathetic innervation are similar to that of LV epicardium. Tp-e correlated with whole heart DOR during sympathetic nerve activation. Circulating NE did not affect DOR or Tp-e.
    Preview · Article · Dec 2014 · Circulation Arrhythmia and Electrophysiology
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    ABSTRACT: The purpose of this study was to examine the acute effects of pacing at different ventricular sites on hemodynamics and left ventricular (LV) rotational mechanics using speckle-tracking echocardiography (STE) in a porcine model. A prospective laboratory investigation. University research laboratory. Yorkshire pigs. In 9 pigs, after midline sternotomy, epicardial pacing was performed from the right ventricular outflow tract (RVOT), right ventricular apex (RVA), and LV free wall. Two-dimensional STE and conductance catheter-derived LV pressure-volume measurements were made to determine the impact of pacing from various sites on LV rotational parameters (twist/untwist) and hemodynamics. RVOT pacing caused the least decrease in end-systolic pressure from baseline (-9.5%), when compared with RVA (-19.1%) and LV (-23.4%). Systolic and diastolic parameters (Emax, Tau) also were different among RVOT (4.7±0.8 mmHg/mL, 32±4 ms), RVA (3.9±0.7 mmHg/mL, 37±6 ms), and LV sites (3.6±0.8 mmHg/mL, 42±7 ms). Similar to the effects of pacing on hemodynamics, RVOT pacing better preserved LV twist (11.1±1.8 v 8.6±1.7, 5.9±0.7 °) and untwisting rate (64.6±8.5 v 56.2±5.3, 48.2±8.5 °/s) when compared with RV apical pacing and LV pacing. Furthermore, prolongation of conduction from LV lateral to anteroseptal at LV base (26.5±3.8 v 13.8±3.3 ms, p<0.05) and LV midpapillary muscle level (35.6±5.6 v 14.1±2.4 ms, p<0.05) was observed with LV pacing compared with RVOT pacing. The present data showed that the LV twist/untwist and cardiac systolic and diastolic function were least affected by RVOT pacing. This finding may be explained by the proximity of this location to the native ventricular conduction system. Copyright © 2014 Elsevier Inc. All rights reserved.
    No preview · Article · Dec 2014 · Journal of cardiothoracic and vascular anesthesia

  • No preview · Article · Nov 2014 · Journal of Cardiothoracic and Vascular Anesthesia
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    ABSTRACT: Vagal nerve stimulation (VNS) has been proposed as a cardio-protective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial (n=12) and a 64-electrode catheter for endocardial (n=9) activation recovery interval (ARI) recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84±5 to 71±5 bpm, and 84±4 to 73±5 bpm), LV pressure (89±9 to 77±9 mmHg, and 91±9 to 83±9 mmHg), dP/dt max (1660±154 to 1490±160 mmHg/s, and 1595±155 to 1416±134 mmHg/s) and prolonged ARI (327±18 to 350±23 ms, and 327±16 to 347±21 ms), respectively, p < 0.05 vs. baseline for all parameters, p = NS for right vs. left VNS. No anterior-posterior-lateral regional differences in prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial, and apical ARI more than basal ARI during both right and left VNS. Changes in dP/dt max showed the strongest correlation with ventricular ARI effects (R(2) = 0.81, p < 0.0001) than either heart rate (R(2) = 0.58, p < 0.01), or LV pressure (R(2)=0.52, p < 0.05). Therefore, right and left VNS have similar effects on ventricular ARI in contrast to sympathetic stimulation that shows regional differences. Decrease in inotropy correlates best with ventricular electrophysiological effects.
    No preview · Article · Jul 2014 · AJP Heart and Circulatory Physiology

  • No preview · Article · Jul 2014 · Anesthesia & Analgesia
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    ABSTRACT: Oxidative stress has been implicated in cardiac arrhythmia, although a causal relationship remains undefined. We have recently demonstrated a marked upregulation of NADPH oxidase isoform 4 (NOX4) in patients with atrial fibrillation (AF), which is accompanied by overproduction of reactive oxygen species (ROS). In the present study we investigated impact on cardiac phenotype of NOX4 overexpression in zebrafish. One cell stage embryos were injected of NOX4 RNA prior to video recording of GFP-labeled (myl7:GFP zebrafish line) beating heart in real time at 24-31 hpf (hrs post fertilization). Intriguingly, NOX4 embryos developed cardiac arrhythmia that is characterized by irregular heartbeats. When quantitatively analyzed by an established LQ-1 program, the NOX4 embryos displayed much more variable beat-to-beat intervals (mean of SDs of beat-to-beat intervals was 0.027 sec/beat in control embryos, vs. 0.038 sec/beat in NOX4 embryos). Both the phenotype and the increased ROS in NOX4 embryos were attenuated by NOX4 morpholino (MO) co-injection, treatments of the embryos with PEG-SOD, or NOX4 inhibitors Fulvene-5, 6-dimethylamino-Fulvene and Proton Sponge Blue. Injection of NOX4-P437H mutant RNA had no effect on cardiac phenotype or ROS production. In addition, CaMKII phosphorylation was increased in NOX4 embryos but diminished by PEG-SOD, while its inhibitor KN93 or AIP abolished the arrhythmic phenotype. Taken together, our data for the first time uncover a novel pathway that underlies development of cardiac arrhythmia, namely NOX4 activation, subsequent NOX4-specific, NADPH-driven ROS production, and redox-sensitive CaMKII activation. These findings may ultimately lead to novel therapeutics targeting cardiac arrhythmia.
    Preview · Article · Jun 2014 · Journal of Biological Chemistry
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    ABSTRACT: The current commonly used cardiac ischemic preconditioning (IPC) protocol, involving three 5-min cycles of ischemia-reperfusion (I/R), may not be clinically beneficial because of its acutely deleterious effects on hemodynamics. This study attempted to assess the effects of a novel stepwise IPC scheme on cardiac function, infarct size, and arrhythmogenesis in a rabbit model of prolonged I/R. Anesthetized open-chest rabbits were subjected to 60-min occlusion of a proximal branch of the left coronary artery followed by 180-min reperfusion. Animals were divided into five groups (n = 6 each): (1) control group (no IPC); (2) 2-min IPC group (three cycles of 2-min IPC); (3) 5-min IPC group (three cycles of 5-min IPC); (4) 10-min IPC group (three cycles of 10-min IPC); and (5) stepwise IPC group (2-, 5-, and 10-min I/R). Compared with control group, 2-, 5-, and 10-min IPC decreased arrhythmia score by 16%, 67%, and 33%, respectively. Remarkably, stepwise IPC resulted in a 78% reduction of arrhythmias. Stepwise IPC also produced the least ventricular infarct size when compared with 2-, 5-, and 10-min IPC groups (16.4% versus 39.3%, 28.1%, and 38.5%, P < 0.05). These results suggest that stepwise IPC has better cardioprotective effects against prolonged I/R injury and may serve as an acceptable approach to clinical revascularization procedures on the heart, including catheter-based and surgical approaches.
    No preview · Article · Jan 2014 · Journal of Surgical Research

  • No preview · Article · Nov 2013 · Journal of cardiothoracic and vascular anesthesia
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    ABSTRACT: Left and bilateral CSD have been shown to reduce burden of ventricular arrhythmias acutely in a small number of patients with VT storm. The effects of this procedure beyond the acute setting are unknown. The purpose of this study was to evaluate the intermediate and long-term effects of left and bilateral cardiac sympathetic denervation (CSD) in patients with cardiomyopathy and refractory ventricular tachy-arrhythmias (VT) or VT storm. Retrospective analysis of medical records for patients who underwent either left or bilateral cardiac sympathetic denervation for VT storm or refractory VT between April 2009 and December 2012 was performed. Forty one patients underwent CSD (left CSD: n = 14; bilateral CSD: n = 27). There was a significant reduction in the burden of ICD shocks during follow up as compared to the 12 months prior to the procedure. The number of ICD shocks was reduced from a mean of 19.6±19 pre-procedure to 2.3±2.9 post-procedure, P<0.001, with 90% of patients experiencing a reduction in ICD shocks. At a mean follow up of 367±251 days post-procedure, survival free of ICD shock was 30% of in the left CSD group and 48% in the bilateral CSD group. Shock free survival was greater in the bilateral group than in the left CSD group, P=0.04. In patients with VT storm, bilateral CSD is more beneficial than left CSD. The beneficial effects of bilateral CSD extend beyond the acute post-sympathectomy period, with continued freedom from ICD shocks in 48% of patients and a significant reduction in ICD shocks in 90% of patients.
    No preview · Article · Nov 2013 · Heart rhythm: the official journal of the Heart Rhythm Society
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    ABSTRACT: The aim of this study was to determine the pertinent anesthetic considerations for patients undergoing surgical sympathectomy for electrical storm (incessant ventricular tachycardia (VT) refractory to traditional therapies). This is a retrospective review of a prospective database. This single-center study took place in a university hospital setting. Twenty-six patients were enrolled. Fifteen patients underwent left-sided sympathectomy, whereas 11 patients underwent bilateral sympathectomy. Anesthetic management of these patients was quite complex, requiring invasive monitoring, transesophageal echocardiography, one-lung ventilation, programming of cardiac rhythm management devices, and titration of vasoactive medications. Paired t test of hemodynamic data before, during, and after surgery showed no significant difference between preoperative and postoperative blood pressure values, regardless of whether the patient underwent unilateral or bilateral sympathectomy. Eight patients remained free of VT, three patients responded well to titration of oral medications, and one patient required 2 radiofrequency ablations after sympathectomy to control his VT. Three patients continued to have VT episodes, although reduced in frequency compared with before the procedure. Four patients were lost to followup. Overall, five patients within the cohort died within 30 days of the procedure. No patients developed any anesthetic complications or Horner's syndrome. The overall perioperative mortality (within the first 7 days of the procedure) was 2 of 26, or 7.7%. The anesthetic management of patients undergoing surgical sympathectomy for electrical storm can be quite complex, because these patients often present in a moribund and emergent state and cannot be optimized using current ACC/AHA guidelines. Expertise in invasive monitoring, transesophageal echocardiography, one-lung ventilation, cardiac rhythm device management, and pressor management is crucial for optimal anesthetic care.
    No preview · Article · Nov 2013 · Journal of cardiothoracic and vascular anesthesia

  • No preview · Article · Oct 2013 · Journal of cardiothoracic and vascular anesthesia

  • No preview · Article · Oct 2013

  • No preview · Article · Oct 2013 · Autonomic Neuroscience

Publication Stats

2k Citations
478.21 Total Impact Points

Institutions

  • 2001-2015
    • University of California, Los Angeles
      • • Department of Anesthesiology
      • • Division of Cardiology
      • • Department of Medicine
      Los Ángeles, California, United States
  • 2010
    • Stanford University
      • E. L. Ginzton Laboratory
      Stanford, CA, United States
  • 2009
    • Oregon Health and Science University
      • Department of Diagnostic Radiology
      Portland, Oregon, United States
  • 2006
    • California Institute of Technology
      • Department of Bioengineering
      Pasadena, CA, United States