Physiology in Clinical NeurosciencesBrain and Spinal Cord CrosstalksHemanshu Prabhakar Series Editor

Brain and Heart Crosstalk

Hemanshu PrabhakarIndu Kapoor Editors

Physiology in Clinical Neurosciences – Brain and Spinal Cord Crosstalks

Series Editor

Hemanshu PrabhakarDepartment of Neuroanesthesiology and Critical CareAll India Institute of Medical SciencesNew Delhi, India

Central nervous system that includes brain and spinal cord has high metabolic demand. The physiology of the brain is such that it is easily affected by any altered physiology of other systems which in turn may compromise cerebral blood flow and oxygenation. Together the brain and spinal cord control our body systems to function automatically. While other systems of body controls individual functions, central nervous system at the same time does many different functions, especially, controlling the function of other systems. However, only little is known that central nervous system itself affects almost all the other systems of the body for example, cardiovascular, respiratory, renal, genitourinary, gastrointestinal, hematological etc. This interaction of brain and spinal cord with other systems makes it important for us to understand how any kind of injury to the central nervous system may at times, produce complications in remote organs or systems of the body. It is these lesser known crosstalks between acutely or chronically affected brain and spinal cord and other systems of the body that is discussed in this book series. Each system would be considered in a separate book.

More information about this series at http://www.springer.com/series/16228

Hemanshu Prabhakar • Indu KapoorEditors

Brain and Heart Crosstalk

ISSN 2524-8294 ISSN 2524-8308 (electronic)Physiology in Clinical Neurosciences – Brain and Spinal Cord CrosstalksISBN 978-981-15-2496-7 ISBN 978-981-15-2497-4 (eBook)https://doi.org/10.1007/978-981-15-2497-4

© Springer Nature Singapore Pte Ltd. 2020This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed.The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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EditorsHemanshu PrabhakarNeuroanaesthesiology and Critical CareAll India Institute of Medical SciencesNew Delhi, India

Indu KapoorNeuroanaesthesiology and Critical CareAll India Institute of Medical SciencesNew Delhi, India

To our parents and our families, with whom lies our “heart,” and without whom our “brains” fail to function!

Hemanshu PrabhakarIndu Kapoor

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Preface

Central nervous system that includes the brain and spinal cord has high metabolic demand. The physiology of the brain is such that it is easily affected by any altered physiology of other systems which in turn may compromise cerebral blood flow and oxygenation. Together the brain and spinal cord control our body systems to func-tion automatically. While other systems of body controls individual functions, cen-tral nervous system at the same time does many different functions, especially, controlling the function of other systems. This interaction of the brain with other systems makes it important for us to understand how any kind of injury to the brain may at times produce complications in remote organs or systems of the body such as the heart. The nervous system is integrator of afferent information and modulates the efferent (neuro-humoral) mechanisms of homeostasis. The cardiovascular sys-tem performs a vegetative function and is central to homeostasis. It is teleological as well as natural for cardiovascular responses to be in consonance with ongoing func-tion of other organ systems of the body, for example, feeding, thermoregulation, reproduction, and muscle activity. It is therefore logical that neural control of car-diovascular system must interact with neural control of other organ systems like motor activity, reproduction, gastro-intestinal tract, thermoregulation, and so and so forth. It is these lesser known cross talks between acutely or chronically affected the brain and the heart that is discussed in this book.

We are ever grateful to the contributors who believed in the proposed format of the work. We are sure the readers would be benefited by the insights of the renowned experts. The purpose of this volume will be truly accomplished if we are able to improve the clinical conditions of our patients by providing better care.

New Delhi, India Hemanshu Prabhakar New Delhi, India Indu Kapoor

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Acknowledgement

We wish to acknowledge the support of the administration of the All India Institute of Medical Sciences (AIIMS), New Delhi, in allowing us to conduct this aca-demic task.

We thank our team for their unconditional support and tireless efforts in helping us fulfill our dreams—Charu Mahajan, Vasudha Singhal, and Nidhi Gupta. We thank the faculty and staff of the Department of Neuroanaesthesiology and Critical Care, AIIMS, New Delhi, for their support.

Special thanks are due to the team of Springer—Naren Aggarwal, Gaurav Singh, Jagjeet Kaur, and Suraj Kumar.

Hemanshu PrabhakarIndu Kapoor

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Contents

1 Neurophysiology of Heart . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1Ashok Kumar Jaryal, Akanksha Singh, and Kishore Kumar Deepak

2 Physiology of Cardiovascular System . . . . . . . . . . . . . . . . . . . . . . . . . . . 35Ashok Kumar Jaryal, Akanksha Singh, and Kishore Kumar Deepak

3 The Brain–Heart Crosstalk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103Anna Teresa Mazzeo, Valentina Tardivo, Simone Cappio Borlino, and Diego Garbossa

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About the Editors

Hemanshu Prabhakar, MBBS, MD, PhD is currently working as a Professor in the Department of Neuroanaesthesiology and Critical Care at All India Institute of Medical Sciences, New Delhi. He has research experience spanning over 20 years and is a member of numerous national and international societies. His extensive research in the field of neuroanesthesia and critical care has been published in vari-ous national and international journals. Dr. Prabhakar is an eminent author and writ-ten several books. He received the AIIMS Excellence Award 2012 for his contributions to academia. He was featured in the Limca Book of Records 2019.

Indu Kapoor holds an MBBS from the Lady Hardinge Medical College and an MD in Anesthesiology from University College of Medical Sciences, Delhi, and is currently an Associate Professor in the Department of Neuroanaesthesiology and Critical Care. She has published more than 75 research papers in national and inter-national journals and contributed numerous book chapters. She also received the prestigious Dr. TN. JHA Memorial award from the Indian Society of Anaesthesiologists and the Smt. Chandra and Sh. Narayan Wadhwani memorial award. She has edited three books related to neuroanesthesia, neurotrauma, and geriatric neuroanesthesia. She is also a reviewer for national as well as international journals.

1© Springer Nature Singapore Pte Ltd. 2020H. Prabhakar, I. Kapoor (eds.), Brain and Heart Crosstalk, Physiology in Clinical Neurosciences – Brain and Spinal Cord Crosstalks, https://doi.org/10.1007/978-981-15-2497-4_1

Chapter 1Neurophysiology of Heart

Ashok Kumar Jaryal, Akanksha Singh, and Kishore Kumar Deepak

Contents

1.1 Basic Architecture of Cardiac Control 31.2 Neural Substrate for Control of Heart 4

1.2.1 C1 Neurons of Ventrolateral Medulla (VLM) 51.2.2 Nucleus Ambiguus (NA) 81.2.3 Nucleus Tractus Solitarius (NTS) 9

1.3 Innervation of the Human Heart 111.3.1 Afferents from the Heart 131.3.2 Efferents to the Heart 151.3.3 Cardiac Plexus 161.3.4 Intrinsic Cardiac Nervous System 17

1.4 Effect of Sympathetic and Parasympathetic Drive on Heart 181.4.1 Laterality in the Autonomic Control of the Heart 191.4.2 Reciprocal Antagonism 191.4.3 Synergistic Co-activation 201.4.4 Sequential Activation 211.4.5 Context Specific Co-activation 21

1.5 Neural Organization for Cardiovascular Control 21 References 25

Heart begins to beat before we are born and occupies a central position both physi-ologically and philosophically in emotional travails of our lives. This chapter focuses on the neural substrate and the mechanisms that control functioning of the heart at rest and modulate it with changing physiological demands and behav-iour states.

Maintenance of continuous and adequate blood supply to each and every cell is prerequisite for survival of a multicellular organism. The success of multicellularity is dependent upon existence of such a mechanism for transport of the nutrients and other solutes from one part of the body to the other.

On an evolutionary timescale, the circulatory system evolved along with the digestive system and early neural structures in invertebrates and as such predates the evolution of respiratory and excretory system. The cardiovascular system and

A. K. Jaryal (*) · A. Singh · K. K. Deepak Department of Physiology, All India Institute of Medical Sciences, New Delhi, Indiae-mail: ashok.jaryal@aiims.edu

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neuro-humoral mechanisms integrate independent functioning organ systems into one whole organism. While the nervous and hormonal systems directly control the functioning of independent units, the cardiovascular system provides a means of transport of nutrients, hormones and other solutes to nervous system and in the pro-cess also gets controlled by the nervous and hormonal systems.

The mammalian cardiovascular system consists of a low-volume high-pressure systemic circulation in series with a low-pressure pulmonary circulation (Fig. 1.1a). The left ventricle of the heart provides the kinetic and potential energy for the move-ment of blood through the systemic vasculature. Blood is dispersed to all the parts of the body through the branches of aorta. The large arteries provide the elastic recoil to maintain a central head pressure during diastole. These large arteries branch into smaller muscular arteries that provide resistance to the flow resulting in fall of the intravascular pressure to lower values before the blood reaches capillary network of tissues where the exchange occurs. The arterial network converts the intermittent

Pulmonary Circulation

Right ChambersLeft Chambers

Systemic Circulation

Heart

Splanchnic circulation

Renal circulation

Cutaneous circulation

Musculo-skeletal circulation

neural circulation

LungseiretrAtiudnoCcitsalE

Resistance arteries Venules

Capacitance veins

a

b

Fig. 1.1 (a) Systemic and pulmonary circulation in series. (b) Architecture of cardiovascular system

A. K. Jaryal et al.

3

pulsatile aortic flow into a continuous flow at the level of capillaries. The blood returns to the heart through low-pressure high-compliance venous system to right atrium and is further pumped into the pulmonary system for exchange of gases (Fig. 1.1b).

From hydrodynamic perspective, the circulatory beds of all organ systems are arranged parallel to each other, and the driving force (central blood pressure in large conduit arteries) for circulation is provided by the heart. Such an organization has inherent vulnerability based on Ohm’s law that any change in the dimensions of vasculature (i.e. resistance and thereby flow) in any of organ system will affect the central blood pressure, thereby affecting the flow of blood to the other organ- systems. Similarly, a change in central blood pressure will affect the flow to all organ systems. The neural control of cardiovascular system provides mechanism to minimize the effect of changes in the circulatory bed of one organ system onto flow characteristic of the other while also maintaining the head pressure in central large arteries. Each organ system has independent local mechanisms (metabolic and myo-genic) to modulate regional blood flow according to its metabolic needs. The neural control provides a mechanism to modulate the vasculature of the organ-system in context of the whole organism. The neural control of cardiovascular system is also intimately intertwined to all other neural regulatory mechanisms because each neu-ral action leads to changes in metabolism in the target organ systems, thereby neces-sitating changes in blood supply to organ systems.

The cardiovascular control systems modulate the function of heart and vasculature in response to afferent information from peripheral receptors and feed-forward signals from higher centres. This chapter focuses on the neural substrates, their connectivity as well as afferent and efferent pathways that modulate the functioning of the heart. The regulation of vascular bed is beyond the scope of this chapter. Reference to it will be incidental and for the sake of completion of the present discussion.

1.1 Basic Architecture of Cardiac Control

Figure 1.2 shows the basic architecture of cardiac  control. The core regulatory nuclei are located in the medulla, viz. ventrolateral medulla (VLM) and nucleus ambiguus (NA) and nucleus tractus solitarius (NTS).

The efferent cardiac control is mediated by VLM and NA motor outputs. The VLM provides the efferent sympathetic drive not only to the heart, but also to vas-culature, renal system, adrenal glands and other sympathetically innervated struc-tures. VLM consists of an excitatory pressor region and an inhibitory depressor region. The VLM projects to the preganglionic sympathetic neurons in the interme-diolateral (IML) horn of thoracic spinal cord. The preganglionic sympathetic fibres arise from the neurons of the IML and synapse in ganglia of sympathetic chains. The post-ganglionic fibres from the ganglia then innervate heart and vasculature. The preganglionic and post-ganglionic sympathetic fibres to adrenal medulla pro-vide additional humoral mechanism to control the heart and vasculature. NA pro-vides the efferent parasympathetic drive to the heart. NA itself contains the

1 Neurophysiology of Heart

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preganglionic parasympathetic fibres which reach the heart via the vagal branches to synapse in ganglia located in the heart. The post-ganglionic parasympathetic fibres then innervate the heart.

The NTS receives sensory inputs from the heart, vasculature and respiratory sys-tem via the glossopharyngeal and vagus nerves. The sensory afferents from nasal tract (trigeminal), pain pathways, muscles and vestibular apparatus also reach the core cardiovascular nuclei in the medulla.

The sympathetic and parasympathetic fibres in the cardiac nerves of the sympa-thetic chain and vagus, respectively, form a plexus at the base of heart around aorta and pulmonary artery. Over last few decades, a distinct organized intrinsic cardiac nervous system (ICNS) in the heart has been identified in many species including humans. ICNS has been shown to play an important role in the integration of affer-ent information from the heart with sympathetic and parasympathetic efferent sig-nals from the core medullary network for beat-to-beat regulation of the heart [1].

The medullary cardiovascular  nuclei are under direct or indirect modulatory influence of multiple nuclei of the brainstem and the neural centres in cortical and sub-cortical regions of brain. These connections serve to integrate the cardiovascu-lar neural network with other neural networks. Each of the components of the neural substrate for control of the heart will be elaborated in detail in the following sections.

1.2 Neural Substrate for Control of Heart

The core neural substrate for cardiac control  consists of ventrolateral medulla (VLM), nucleus ambiguus (NA) and nucleus tractus solitarius (NTS) in the medulla. The VLM and NA provide efferent projections for sympathetic and parasympathetic control of cardiovascular system, respectively. The NTS receives afferent projec-tions from heart and vasculature and provides a mechanism of integration of these

MedullaryCore Nuclei

Heart, Vasculature, Lungs, Nasopharynx Heart

Supra-bulbar Nuclei

Vasculature

Ponto-medullary nuclei

NTSNA

VLM

vagu

s

Sym

path

etic

ner

ves

V, VII, IX, X

Vestibular apparatus

Muscle afferents

Fig. 1.2 Basic architecture of cardiac control

A. K. Jaryal et al.