scholarly journals Innervation and Neuronal Control of the Mammalian Sinoatrial Node: A Comprehensive Atlas

2020 ◽  
Author(s):  
Peter Hanna ◽  
Michael J. Dacey ◽  
Jaclyn Brennan ◽  
Alison Moss ◽  
Shaina Robbins ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Neural Control ◽  
Sinoatrial Node ◽  
Phenotypic Diversity ◽  
Functional Characterization ◽  
Tissue Level ◽  
Geographic Region ◽  
Left Ventricular ◽  
Cholinergic Innervation ◽  
Right Atrial

AbstractCardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node as an initial discovery step. Here, we report an in-depth, multi-scale structural and functional characterization of the innervation of the sinoatrial node (SAN) by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies including tissue clearing, immunohistochemical and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiologic mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular (AV) conduction and left ventricular (LV) contractility. For the first time, we demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. This provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.

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

2021 ◽  
Vol 128 (9) ◽  
pp. 1279-1296
Author(s):  
Peter Hanna ◽  
Michael J. Dacey ◽  
Jaclyn Brennan ◽  
Alison Moss ◽  
Shaina Robbins ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Neural Control ◽  
Sinoatrial Node ◽  
Phenotypic Diversity ◽  
Functional Characterization ◽  
Geographic Region ◽  
Left Ventricular ◽  
Cholinergic Innervation ◽  
Right Atrial ◽  
Ventricular Contractility

Rationale: Cardiac function is under exquisite intrinsic cardiac neural control. Neuroablative techniques to modulate control of cardiac function are currently being studied in patients, albeit with variable and sometimes deleterious results. Objective: Recognizing the major gaps in our understanding of cardiac neural control, we sought to evaluate neural regulation of impulse initiation in the sinoatrial node (SAN) as an initial discovery step. Methods and Results: We report an in-depth, multiscale structural and functional characterization of the innervation of the SAN by the right atrial ganglionated plexus (RAGP) in porcine and human hearts. Combining intersectional strategies, including tissue clearing, immunohistochemical, and ultrastructural techniques, we have delineated a comprehensive neuroanatomic atlas of the RAGP-SAN complex. The RAGP shows significant phenotypic diversity of neurons while maintaining predominant cholinergic innervation. Cellular and tissue-level electrophysiological mapping and ablation studies demonstrate interconnected ganglia with synaptic convergence within the RAGP to modulate SAN automaticity, atrioventricular conduction, and left ventricular contractility. Using this approach, we comprehensively demonstrate that intrinsic cardiac neurons influence the pacemaking site in the heart. Conclusions: This report provides an experimental demonstration of a discrete neuronal population controlling a specific geographic region of the heart (SAN) that can serve as a framework for further exploration of other parts of the intrinsic cardiac nervous system (ICNS) in mammalian hearts and for developing targeted therapies.

scholarly journals Simultaneous variation of ventricular pacing site and timing with biventricular pacing in acute ventricular failure improves function by interventricular assist

2009 ◽  
Vol 297 (6) ◽  
pp. H2220-H2226 ◽  
Author(s):  
T. Alexander Quinn ◽  
Santos E. Cabreriza ◽  
Marc E. Richmond ◽  
Alan D. Weinberg ◽  
Jeffrey W. Holmes ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Maximum Rate ◽  
Systolic Function ◽  
Biventricular Pacing ◽  
Pressure Change ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Right Atrial ◽  
Hemodynamic Effects ◽  
Ventricular Failure

The goal of this work was to investigate the hemodynamic effects of simultaneous left ventricular (LV) pacing site (LVPS) and interventricular pacing delay (VVD) variation with biventricular pacing (BiVP) during acute LV failure. Simultaneously varying LVPS and VVD with BiVP has been shown to improve hemodynamics during acute right ventricular (RV) failure. However, effects during acute LV failure have not been reported. In six open-chest pigs, acute LV volume overload was induced by regurgitant flow via an aortic-LV conduit. Epicardial BiVP was implemented with right atrial and ventricular leads and a custom LV pacing array. Fifty-four LVPS-VVD combinations were tested in random order. Cardiac output was evaluated by aortic flow probe, ventricular systolic function by maximum rate of ventricular pressure change, and mechanical interventricular synchrony by normalized RV-LV pressure diagram area. Simultaneous LVPS-VVD variation improved all measures of cardiac function. The observed effect was different for each functional index, with evidence of LVPS-VVD interaction. Compared with effects of LVPS-VVD variation in a model of acute RV failure, hemodynamic changes were markedly different. However, in both models, maximum rate of ventricular pressure change of the failing ventricle was improved with synchronous interventricular contraction, suggesting that, in acute ventricular failure, BiVP can recruit the unstressed ventricle to support systolic function of the failing one. Thus simultaneously varying LVPS and VVD with BiVP during acute ventricular failure can improve cardiac function by “interventricular assist”, with hemodynamic effects dependent on the type of failure. This supports the potential utility of temporary BiVP for the treatment of acute ventricular failure commonly seen after cardiac surgery.

Cardiac function and pulmonary hypertension in Central Asian highlanders at 3250 m

2020 ◽  
Vol 56 (2) ◽  
pp. 1902474 ◽  
Author(s):  
Mona Lichtblau ◽  
Stéphanie Saxer ◽  
Michael Furian ◽  
Laura Mayer ◽  
Patrick R. Bader ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Cardiac Function ◽  
High Altitude ◽  
Chronic Exposure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Volume Index ◽  
Left Ventricular Ejection ◽  
Central Asian ◽  
Definition Of

The question addressed by the studyChronic exposure to hypoxia increases pulmonary artery pressure (PAP) in highlanders, but the criteria for diagnosis of high-altitude pulmonary hypertension (HAPH) are debated. We assessed cardiac function and PAP in highlanders at 3250 m and explored HAPH prevalence using different definitions.Patients and methodsCentral Asian highlanders free of overt cardiorespiratory disease, permanently living at 2500–3500 m compared to age-matched lowlanders living <800 m. Participants underwent echocardiography close to their altitude of residence (at 3250 m versus 760 m).Results173 participants (97 highlanders, 76 lowlanders), mean±sd age 49±9 years (49% females) completed the study. Results in lowlanders versus highlanders were systolic PAP (23±5 versus 30±10 mmHg), right ventricular fractional area change (42±6% versus 39±8%), tricuspid annular plane systolic excursion (2.1±0.3 versus 2.0±0.3 cm), right atrial volume index (20±6 versus 23±8 mL·m−2), left ventricular ejection fraction (62±4% versus 57±5%) and stroke volume (64±10 versus 57±11 mL); all between-group comparisons p<0.05. Depending on criteria, HAPH prevalence varied between 6% and 35%.The answer to the questionChronic exposure to hypoxia in highlanders is associated with higher PAP and slight alterations in right and left heart function compared to lowlanders. The prevalence of HAPH in this large highlander cohort varies between 6% according to expert consensus definition of chronic high-altitude disease to 35% according to the most recent definition of pulmonary hypertension proposed for lowlanders.

The Improvement of Torsion Assessed by Cardiovascular Magnetic Resonance Feature Tracking after Coronary Artery Bypass Grafting: A Sensitive Index of Cardiac Function

2017 ◽  
Vol 20 (1) ◽  
pp. 026 ◽  
Author(s):  
Nan Cheng ◽  
Liuquan Cheng ◽  
Rong Wang ◽  
Lin Zhang ◽  
Changqing Gao
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Feature Tracking ◽  
Artery Bypass ◽  
Left Ventricular ◽  
Rapid Acquisition ◽  
Left Ventricular Torsion ◽  
Ventricular Torsion

Objective: The aim of this study was to quantify left ventricular torsion by newly applied cardiovascular magnetic resonance feature tracking (CMR-FT), and to evaluate the clinical value of the ventricular torsion as a sensitive indicator of cardiac function by comparison of preoperative and postoperative torsion.Methods: A total of 54 volunteers and 36 patients with previous myocardial infarction (MI) and LV ejection fraction (EF) between 30%-50% were screened preoperatively or postoperatively by MRI. The patients’ short axis views of the whole heart were acquired, and all patients had a scar area >75% in at least one of the anterior or inferior segments. Their apical and basal rotation values were analyzed by feature tracking, and the correlation analysis was performed for the improvement of LV torsion and ejection fraction after CABG. The intra- and inter-observer reliabilities of torsion measured by CMR-FT were assessed.Results: In normal hearts, the apex rotated counterclockwise in the systolic period with the peak rotation as 10.2 ± 4.8°, and the base rotated clockwise as the peak value was 7.0 ± 3.3°. There was a timing hiatus between the apex and base untwisting, during which period the heart recoils and its suction sets the stage for the following rapid filling period. The postoperative torsion and rotation significantly improved compared with preoperative ones. However, the traditional indicator of cardiac function, ejection fraction, didn’t show significant improvement.Conclusion: Left ventricular torsion derived from CMR-FT, which does not require specialized CMR sequences, was sensitive to patients with low ejection fraction whose cardiac function significantly improved after CABG. The rapid acquisition of this measurement has potential for the assessment of cardiac function in clinical practice. 

An Unusual Association: Right Atrial Myxoma and Severe Left Ventricular Dysfunction. Case Report and Review of the Literature

2015 ◽  
Vol 17 (6) ◽  
pp. 285
Author(s):  
Lucian Florin Dorobantu ◽  
Ovidiu Chioncel ◽  
Alexandra Pasare ◽  
Dorin Lucian Usurelu ◽  
Ioan Serban Bubenek-Turconi ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Ventricular Dysfunction ◽  
Left Ventricular Systolic Dysfunction ◽  
Left Ventricular ◽  
Right Atrial ◽  
Left Ventricular Ejection ◽  
Cardiac Tumors ◽  
Severe Left Ventricular Dysfunction ◽  
Ventricular Ejection Fraction ◽  
Increased Risk

Myxomas comprise 50% of all benign cardiac tumors in adults, with the right atrium as their second most frequent site of origin. Surgical resection is the only effective therapeutic option for patients with these tumors. The association between right atrial myxomas and severe left ventricular systolic dysfunction is extremely rare and makes treatment even more challenging. This was the case for our patient, a 47-year-old male with a right atrial mass and a severely impaired left ventricular function, with a 20% ejection fraction. Global enlargement of the heart was also noted, with moderate right ventricular dysfunction. The tumor was successfully excised using the on-pump beating heart technique, with an immediate postoperative improvement of the left ventricular ejection fraction to 35%. The technique proved useful, with no increased risk to the patient.

Direct Myocardial Implantation of Human Fetal Stem Cells in Heart Failure Patients: Long-term Results

2010 ◽  
Vol 13 (1) ◽  
pp. 31 ◽  
Author(s):  
Federico Benetti ◽  
Ernesto Pe�herrera ◽  
Teodoro Maldonado ◽  
Yan Duarte Vera ◽  
Valvanur Subramanian ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Cardiac Function ◽  
Nyha Class ◽  
Left Ventricular ◽  
Long Term Results ◽  
Walk Test ◽  
The Mean ◽  
6 Minute Walk Test ◽  
Minute Walk

Background: End-stage heart failure (HF) is refractory to current standard medical therapy, and the number of donor hearts is insufficient to meet the demand for transplantation. Recent studies suggest autologous stem cell therapy may regenerate cardiomyocytes, stimulate neovascularization, and improve cardiac function and clinical status. Although human fetal-derived stem cells (HFDSCs) have been studied for the treatment of a variety of conditions, no clinical studies have been reported to date on their use in treating HF. We sought to determine the efficacy and safety of HFDSC treatment in HF patients.Methods and Results: Direct myocardial transplantation of HFDSCs by open-chest surgical procedure was performed in 10 patients with HF due to nonischemic, nonchagasic dilated cardiomyopathy. Before and after the procedure, and with no changes in their preoperative doses of medications (digoxin, furosemide, spironolactone, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, betablockers), patients were assessed for New York Heart Association (NYHA) class, performance in the exercise tolerance test (ETT), ejection fraction (EF), left ventricular end-diastolic dimension (LVEDD) via transthoracic echocardiography, performance in the 6-minute walk test, and performance in the Minnesota congestive HF test. All 10 patients survived the operation. One patient had a stroke 3 days after the procedure, and although she later recovered, she was unable to perform the follow-up tests. Another male patient experienced pericardial effusion 3 weeks after the procedure. Although it resolved spontaneously, the patient abandoned his control tests and died 5 months after the procedure. An autopsy of the myocardium suggested that new young cells were present in the cardiomyocyte mix. At 40 months, the mean (SD) NYHA class decreased from 3.4 0.5 to 1.33 0.5 (P = .001); the mean EF increased 31%, from 26.6% 4% to 34.8% 7.2% (P = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (P < .0001); the mean LVEDD decreased 15%, from 6.85 0.6 cm to 5.80 0.58 cm (P < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 113.1 seconds to 360 0 seconds (P = .01); the mean distance increased 64.4%, from 284.4 144.9 m to 468.2 89.8 m (P = .004); and the mean result in the Minnesota test decreased from 71 27.3 to 6 5.9 (P < .001).Conclusion: Although these initial findings suggest direct myocardial implantation of HFDSCs is feasible and improves cardiac function in HF patients at 40 months, more clinical research is required to confirm these observations.

scholarly journals Anesthetic Techniques for Fetal Surgery

2013 ◽  
Vol 118 (4) ◽  
pp. 796-808 ◽  
Author(s):  
Pornswan Ngamprasertwong ◽  
Erik C. Michelfelder ◽  
Shahriar Arbabi ◽  
Yun Suk Choi ◽  
Christopher Statile ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Function ◽  
Fetal Surgery ◽  
Left Ventricular ◽  
High Dose ◽  
Anesthetic Techniques ◽  
Uterine Blood Flow ◽  
Fetal Cardiac Function ◽  
Significant Difference ◽  
Fetal Acidosis

Abstract Background: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal–fetal hemodynamic instability and fetal myocardial depression. The authors’ preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal–fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. Methods: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. Results: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6–21.4; P &lt; 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P &lt; 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. Conclusion: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.

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