CARDIOPULMONARY PHYSIOLOGY

Respiration

Although volatile and gaseous anesthetics have changed over the past 150 years, there are two gases that will always be a part of anesthetic practice. How oxygen and carbon dioxide are consumed and produced and how they interact with the body has been the subject of intense research over the past 400 years. The ability to manipulate the pressure of these gases in the tissues has contributed much to the success of intensive care medicine. Because of the importance that carbon dioxide and oxygen have in the practice of anesthesiology, it is worth-while to consider how our understanding of respiration came about.

Galen (120–200 AD) and Aristotle (384–322 BC) both thought that the air moving in and out of the lungs served merely to cool the heart, which otherwise became overheated in working to sustain life.^[6] In 1678, Robert Hook (1635–1703) attached a bellows to the trachea of a dog with an open chest and demonstrated that the animal could be kept alive by rhythmic and sustained contraction of the bellows. Hook proved that movement of the chest wall was not the essential feature of respiration, but rather it was exposure of fresh air to the blood circulating through the lungs.^[7] Richard Lower (1631–1691), who also was the first to transfuse blood from one animal to another, demonstrated in 1669 that the blood absorbed a definite chemical substance necessary for life, that it changed the venous blood from dark blue to red, and that the process was the chief function of the pulmonary circulation.^[8]

The nature of the process that takes place in the lungs was misunderstood until the 1780s because of the generally accepted, but erroneous, phlogiston theory promoted by Georg Ernst Stahl (1660–1734).^[9] Stahl theorized that combustible substances were composed of phlogiston (Greek for "burnt") and calc ("ash") and that the phlogiston was released during burning and during respiration. Joseph Priestley (1733–1804) ( Fig. 1-1A ), a complex individual who was a dissenting minister in Leeds, England and later the "resident intellectual" to the Earl of Shelburne, observed that respiration and combustion had many similarities,^[10] because a candle flame would go out and an animal would die if left within a closed space. He thought this was because the air was putrefied with phlogiston. Priestley discovered photosynthesis by showing that placing plants that imbibed the "phlogistic matter" within the contained space could restore this "bad air." By heating mercuric oxide, he generated a gas that would make flames brighter and keep mice alive longer in a closed space. Priestley called it dephlogisicated air, and Carl Scheele^[11] (1742–1786) in Sweden, who found it earlier but failed to publish, called it feuer luft ("fire air"). Priestley thought this process absorbed phlogiston and informed the French chemist Antoine-Laurent Lavoisier (1743–1794) (see Fig. 1-1B ) of his discovery.

Lavoisier realized that heating mercuric oxides released a new element and called it oxygen. Lavoisier^[12] also showed that sulfur and phosphorus gained weight when

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Lavoisier thought respiration was accomplished in the lungs, but Humphry Davy (1778–1829) (see Fig. 1-1C ), a young English teenager who dropped out of school at the age of 16 years, read the works of Lavoisier and designed his own experiments to study the site of metabolism. Davy heated blood and collected the gases that were produced. By showing these gases were oxygen and carbon dioxide, he surmised that metabolism takes place in the tissues,^[13] a conclusion confirmed by Eduard Friedrich Wilhelm Pflüger^[14] (1829–1910) 60 years later. Davy also estimated the rates of oxygen consumption and carbon

Figure 1-1 A, Joseph Priestley was born in Fieldhead, England, and educated as a minister. His early career was spent as a schoolmaster in Leeds, England. In 1780, he accepted an appointment in Birmingham, as minister, where he joined Erasmus Darwin and James Watt in forming the Lunar Society, which met to discuss the new ideas in chemistry and physics emerging at that time. Because of his political views, his chapel and home were vandalized in 1789. Five years later, he joined his sons in Pennsylvania in the United States, where he died in 1804 at age 70. B, The portrait of Lavoisier and his wife, Marie Anne Pierrette Paulz, was painted in 1788 by the famous French artist Jacques Louis David. Marie Paulz, who married Lavoisier when she was only 14 years old, was taught to draw by David, and she drew many of the illustrations in Lavoisier's magnum opus, Traite Elementaire de Chimie.^[483] Several experimental devices and gasometers are shown on and below the table. C, Humphry Davy was born in Cornwall, England, and became apprenticed to a surgeon, J. B. Borlase of Penzance, at age 17. At 20 years of age, he was appointed Superintendent of the Beddoe's Pneumatic Institute, where he studied the effects of nitrous oxide inhalation. His later career in chemistry gained him fame and honors. He directed the Royal Institute and was made a baronet in 1818 at the age of 40. (Courtesy of the Wood Library-Museum of Anesthesiology, Park Ridge, IL.)

John S. Haldane (1860–1936) was a pioneer investigator in the study of respiration a century ago. His apparatus for measurement of blood gases was described in 1892.^[15] He was the first to promote oxygen therapy for respiratory disease,^[16] and in 1905, he discovered that the carbon dioxide tension of the blood was the normal stimulus for respiratory drive.^[17] Haldane experimented with self-administration of hypoxic mixtures and coined the ominous phrase that lurks within the inner recesses of the anesthesiologist's mind: "Anoxemia not only stops the machine but wrecks the machinery." He believed until his death, despite experimental evidence, that the lung actively secreted oxygen into the blood from the air. His landmark monograph Respiration, published in 1922, ^[18] summarized his studies on the respiratory system.

At the end of the 19th century, it was known that hemoglobin had a vital role in the transport of oxygen to the tissues. In 1896, Carl Gustav von Hufner (1840–1908) showed that the presence of hemoglobin in the blood greatly enhanced its oxygen carrying capacity, quantifying that 1 g of hemoglobin carried 1.34 mL of oxygen.^[19] It was soon observed that delivery of high concentrations of oxygen to patients with advanced pulmonary disease was often inadequate to fully maintain tissue respiration

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Further understanding of respiratory physiology arose because of the worldwide polio epidemic that occurred roughly between the years of 1930 and 1960. Thousands of afflicted patients were kept alive with mechanical respirators, but the adequacy of ventilation could not be assessed without some measure of carbon dioxide tension (PCO₂ ) in the blood. Several methods to measure PCO₂ indirectly were made by Donald D. Van Slyke^[21] (1883–1971) and Paul B. Astrup (1915–2000), but the modern solution rested on the development of the carbon dioxide electrode. This problem was solved in 1958, when John W. Severinghaus ^[22] (1922-) (see Fig. 1-2 ) improved the accuracy of a prototype carbon dioxide electrode produced by Richard Stow (1916-), which measured pH of a thin film of electrolyte separated from the blood by a Teflon membrane through which carbon dioxide could diffuse and equilibrate. Severinghaus and A. F. Bradley (1932-) constructed the first blood gas apparatus by mounting the carbon dioxide electrode and Clark's oxygen electrode in cuvettes in a 37°C bath. To measure blood PO₂ accurately, Severinghaus found it necessary to rapidly stir the blood in contact with Clark's electrode because of its high oxygen consumption rate. A pH electrode was added in 1959. Blood gas analysis made possible the rapid assessment of respiratory exchange

Figure 1-2 This photograph of Leland Clark and John Severinghaus, whose contributions led to modern techniques of blood gas analysis, was taken in Clark's laboratory at the Cincinnati Children's Hospital in 1982. (From Severinghaus JW, Astrup PB: History of Blood Gas Analysis. International Anesthesiology Clinics, Vol. 25, Boston, Little Brown, 1987.)

Until the mid-20th century, the saturation of hemoglobin could be determined only by directly measuring a sample of arterial blood, a technique that required an arterial puncture. Oximetry achieves the same measure noninvasively through a finger or ear probe by using optical measures of transmitted light. Glenn Millikan, working in the Johnson Foundation for Medical Physics at the University of Pennsylvania, devised the first ear oximeter in 1942, and it was used to detect hypoxia in pilots, who flew in open cockpits during World War II. Its introduction into anesthesia practice was delayed until the discovery of pulse oximetry by a Japanese engineer, Takuo Aoyagi.^[24] Pulse oximetry added the additional measure of heart rate, and it provided assurance that the signal was actually measuring a biologic parameter. A highly successful commercial product, the Nellcor pulse oximeter, was introduced in 1983 and had the unique feature of lowering the pitch of the pulse tone as the saturation dropped.