From Psychostasis to the Discovery of Cardiac Nerves: The Origins of the Modern Cardiac Neuromodulation Concept

Simple Summary The review aims to explore the historical development of cardiac innervations and neuromodulation, tracing its origins back to the ancient Egyptian concept of "psychostasis"-the ritual weighing of the heart to determine one's fate in the afterlife. This ancient belief in the heart as the center of human wisdom, emotions, and memory laid the foundation for the later advancements in the scientific understanding of cardiac innervation. Importantly, this ancient cardiocentric worldview also established the ancestral ethical foundations for the study and application of cardiac neuromodulation. The Egyptians believed that the "lightness of the heart"-achieved through a balance of good and bad deeds-was crucial for one's wellbeing and fate in the afterlife. This ethical framework parallels the modern understanding of the importance of balanced cardiac autonomic control, mediated by the vagus nerve, for overall health and social engagement. The review chronicles key milestones, from Aristotle and Galen's early physiological studies, to the pioneering anatomical work of Leonardo da Vinci, Vesalius, and William Harvey's discovery of the circulatory system. It highlights the contributions of 17th century researchers like Richard Lower, who demonstrated the heart's neural control, and Albrecht von Haller, who discovered the heart's automaticity. The review emphasizes how the study of cardiac innervation and neuromodulation has regained prominence, particularly in understanding the cardiorespiratory symptoms and dysregulation observed in post-acute sequelae of SARS-CoV-2 infection (long COVID) and other acute respiratory infections. It draws parallels between the ancient concept of "weighing the heart" in psychostasis and the modern understanding of the "balance of different hormonal, chemical, electrical, and contrasting nervous stimuli" in cardiac neuromodulation. By tracing this historical evolution, the review aims to bridge the gap between ancient concepts like psychostasis and the modern applications of cardiac neuromodulation for cardiovascular health and disease management. Understanding the complex interplay between cardiac function, neural modulation, and overall wellbeing is crucial for addressing long-term cardiorespiratory issues, akin to the ancient notion of achieving "lightness of the heart". The review also highlights the relevance of the polyvagal theory, which emphasizes the role of the vagus nerve in regulating the heart's function and its connection to emotional and social engagement. This provides an ethical and physiological framework for understanding the importance of cardiac neuromodulation in promoting overall health and well-being.Abstract This review explores the historical development of cardiology knowledge, from ancient Egyptian psychostasis to the modern comprehension of cardiac neuromodulation. In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul". The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at G & ouml;ttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability", on which the heartbeat depended, and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of acute respiratory infections (ARIs) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 (coronavirus disease 2019) ARIs. This analysis explores the historical foundations of cardiac neuromodulation and its contemporary relevance. By focusing on this concept, we aim to bridge the gap between historical understanding and modern applications. This will illuminate the complex interplay between cardiac function, neural modulation, cardiovascular health, and disease management in the context of long-term cardiorespiratory symptoms and dysregulation of intrinsic cardiac innervations.