Physiology in Perspective: The Breath of Life.

Abstract

The breath of life is a primitive concept forming the basis of many religions and philosophies. In ancient Greek medicine, pneuma was a form of circulating air that was necessary for our body’s normal function or physiology. In the 3rd to 4th century BCE, the Greek physician Herophilus introduced the scientific method while studying at the Museum of Alexandria. Among his many contributions, Herophilus recognized that there are structural differences between arteries and veins, and he attributed the pulsations in arteries to the pumping action of the heart. He also recognized that the inhalation and exhalation motions of the chest wall and lungs reflected movement of air into and out of the lungs. His student Erasistratus, as with all good students, took the observations of Herophilus one step further. By recognizing that valves in the heart allowed blood flow in only one direction, he concluded that the right and left sides of the heart were separate but connected unidirectional pumps. On the right side, he noted that blood flowed to the lungs through the pulmonary artery. He postulated that, during inspiration, pneuma was drawn into the lungs through the mouth, nose, trachea, and bronchi. In the lungs, pneuma was then drawn into the blood by ventricular diastole, where it was mixed and then distributed from the left ventricle to the aorta and then the rest of the body. Unfortunately, this remarkably enlightened understanding of cardiopulmonary physiology nearly 1,800 years before William Harvey’s “discovery” of blood circulation was muddled in the following centuries by competing philosophies of the School of Athens. In the 2nd century CE, Claudius Galenus, known to us as Galen, enunciated formal medical doctrines, which were based on a long-held philosophy introduced by Aristotle and the School of Athens, although he was aware of the work of Herophilus and Erasistratus. Galen’s profound influence on medical thought prevailed for more than 1,500 years, impeding progress. According to the doctrine formalized by Galen, the movements of respiration served three purposes: 1) to inhale air to cool and regulate the innate heat of the heart; 2) to mix air into the blood, which was necessary to generate pneuma that was then distributed from the left side of the heart throughout the body via arteries; and 3) to eliminate “friligimous,” the foul vapor byproducts of the innate fire in the heart. Even during Herophilus’s time, it was recognized that blood in the arteries and veins differed in color, which Galen attributed to the difference in pneuma vs. friligimous foul vapors. However, the primary function of respiration in O2 and CO2 gas exchange was unknown in Greek medicine. Fast forward 1,500 years and the physical chemical understanding of gas introduced by Robert Boyle, John Mayow, Robert Hooke, Jacques Charles, Joseph Priestly, Carl Wilhem Scheele, Antoine Lavoisier, John Dalton, Joseph Louis Gay-Lussac, and Alexander von Humboldt among many helped move us away from the pneuma/friligimous (later modified to phlogiston) theory toward a modern understanding of respiration through physiological investigation. In this issue of Physiology, we continue our exploration of life functions, including the neural control of rhythmic breathing and the neurobiological basis of sleep, which in Galen’s time was thought to be a temporary separation of fire from the body’s earth, whereas death was a permanent separation. We also examine the cardiovascular system and its response to hypoxia and the impact of oxidative stress in intrauterine growth restriction. As recognized in antiquity, an understanding of how we breathe is at the core of human physiology. The remarkable ability of breathing to adapt to changes in metabolic, environmental, and behavioral demands stems from a complex integration of its rhythm-generating network into the wider central and peripheral nervous system. For more than a century, physiologists have searched for critical brain regions that give rise to the respiratory rhythm. Lesion experiments identified areas in the pons and medulla that are critical for various aspects of breathing. Yet, abolishing normal breathing through lesions does not mean that the lesioned region is responsible for respiratory rhythmogenesis. In addition, many brain areas provide important modulatory drive for breathing without being responsible for rhythm generation itself. In their review (5), Ramirez and Baertsch discuss criteria based on principles learned from small rhythmic networks of invertebrates that can be used to identify rhythmogenic elements of mammalian breathing. They examine how these elements interact to produce robust, dynamic breathing in mammals. The identification of these critical rhythmogenic elements has important implications for human physiology and pathophysiology. For example, neuronal loss in the preBötzinger complex, a cluster of interneurons in the ventrolateral medulla of the brain stem, has been implicated in Multiple Systems Atrophy. Understanding the critical rhythmogenic mechanisms should also lead to a better understanding of breathing disorders, including dysautonomia, central and obstructive sleep apnea, as well as sudden infant death syndrome (SIDS). Sleep is essential for our health and well-being. Evidence includes the persistence of sleep throughout the animal kingdom despite strong selection pressure to minimize its duration. When animals are deprived of sleep for long periods of time, they may die. Even with short lapses of sleep, cognitive function may be impaired. There is an increasing recognition that sleep loss or poor quality of sleep is a biomarker—and possibly even a causal factor—for various disease states. We sleep about one-third of our lives, yet we know little about why we do it, which molecular mechanisms are involved, and why changes in the brain’s electrical activity during sleep are associated with unconsciousness. In his review (2), Joiner discusses our evolving understanding of the mechanisms by which sleep is controlled and the complex relationship between sleep and disease states. A better understanding of the neural circuitry and molecular basis by which sleep and waking are controlled is likely to provide insight into how consciousness is controlled, how sleep affects memory EDITORIAL Gary C. Sieck, Editor-in-Chief Mayo Clinic, Rochester, Minnesota PHYSIOLOGY 33: 300–301, 2018.