John W. Bean

FACTORS INFLUENCING CLINICAL OXYGEN TOXICITY

Since the early work of Priestley1 and Lavoisier? it has been recognized, though questioned by many,Y that breathing increased concentrations of 02 may have adverse as well as therapeutic effects on animal organisms. The exact mechanism of causation of these adverse reactions-which for want of a better name have been referred to as those of O2 poisoning-is not known. But there are numerous factors which influence its occurrence and severity. If the clinical use of O2 in increased concentrations, especially at high pressure, is to achieve the success which it certainly seems to promise, recognition of its potential dangers and limitations, as well as knowledge of the more important factors which contribute to O2 toxicity, is imperative.

Pulmonary Damage and Head Injury

Summary Experiments were carried out to investigate the effect of severe head injury on the lungs of 42 unanesthetized rats. Cerebral trauma was induced by means of a captive bolt mechanism producing sufficient force to cause immediate unconsciousness or death, apparently of respiratory origin, usually within a few minutes. Rats which showed any signs of regaining consciousness after trauma (36%) were immediately given a lethal dose of sodium pentobarbital. Gross pulmonary damage including edema and congestion and increased lung wt./body ratios were found in 92% of those rats dying from the impact and in 40% of the rats killed by the lethal dose of anesthetic given after impact. Pathology reports indicated the occurrence of moderate to severe brain and lung damage in traumatized rats. Control experiments in which animals succumbed during exposure to low oxygen have demonstrated that this pulmonary pathology cannot be attributed simply to low oxygen. Results indicate that hypoxia alone in rats does not induce the severe form of pulmonary damage resulting from cerebral trauma. It is tentatively concluded that these pulmonary changes are due in large part to nervous mechanisms of central origin. The data lend substantial support to the evidence previously reported that similar pathology which attends severe epileptiform convulsions induced by the toxic action of oxygen at high pressure and by chemical convulsants such as Metrazol and picrotoxin is in large part of CNS origin, and that this effect is mediated through the sympathetics and alterations in the cardiopulmonary hemodynamics and possibly also through changes in the pulmonary parenchyma itself.

Thyroid in Pulmonary Injury Induced by 02 in High Concentration at Atmospheric Pressure.

Summary 1. In a study of the influence of O2 in high concentrations (94% at atmospheric pressure) it was found that the administration of desiccated thyroid augments the adverse effects of O2 on normal and on hypophysectomized rats as shown 1) by a shortening of both the onset of the symptoms—hyperpnea, lethargy, dyspnea, coma—and the survival times, and 2) by increasing the severity of macroscopic pathological changes, including massive pleural effusion and hydrothorax, congestion, oedema and hepatization of the lungs and enlargement and congestion of the liver. 2. The pronounced protection which hypophy-sectomy provides against the adverse pulmonary effects of increased O2 is in large degree counteracted by the administration of thyroid to the hypophysectomized animal. This protection is, therefore, attributable not only to the loss of adrenocortical principles but also to the loss of thyrotropin. The possible involvement of an increased CO2 in the thyroid effects is discussed.

Alterations in C.N.S. Associated with Chronic Motor Disabilities Induced by O2 at High Pressure

The recovery of animals from the effects of exposure to O2 at high pressure (OHP) is frequently remarkably rapid but residual effects commonly persist for some time after the animals return to atmospheric pressure, varying from periods as short as a few minutes up to several days; and in some cases disabilities become permanent.1

Effect of High Oxygen Pressures on Blood Acidity, Oxygen Consumption, Volume Flow of Blood and Respiration.

With the purpose of throwing new light on the causes of hyperp-nea as seen in animals breathing pure oxygen at high pressures, apparatus was devised whereby respiration, blood pressure, blood acidity changes, and blood volume flow could be recorded on smoked paper, with the experimental animal exposed to increased oxygen pressure. A Hutchinson type spirometer was used; the bell counterbalanced by a solenoid around a glass tube; the writing point attached to a moveable iron core in the bore of the tube which was open to atmospheric pressure. Blood pressure was recorded in similar manner, the solenoid floating on the mercury; heart rate by an electrical contact device on the femoral artery; blood acidity changes by the continuous method (manganese dioxide electrode); volume flow of blood changes by the thermo-electrical method. The experimental animals were dogs of from 5 to 12 kg., anesthetized with morphine sulphate and urethane. The pressures used were from 3 to slightly less than 5 atmospheres pure oxygen. The results indicate an increase in the acidity of the arterial blood and decrease in the heart rate of the animals under high oxygen pressures. The oxygen consumption of animals under pressure showed some variation but the weight of the evidence pointed to a decrease in metabolism with a tendency to return after decompression to atmospheric pressure. In several experiments periodic respiration with an accompanying periodicity in the volume flow of blood in the common carotid artery was obtained. Hyperpnea was not invariably a response to high oxygen pressure exposure. On the contrary some individuals showed a decrease in respiratory rate to the extent of apnea.

Influence of Oxygen at Atmospheric and High Pressure on the Developing Tooth Germ in Rat Embryos

Repeated exposure of pregnant rats to oxygen at high pressure (65 psi) twice a day for seven days increased the height of the tooth germ and ameloblastic layer of the embryo, but the width and odontoblastic layer were not changed. Exposure of pregnant rats to oxygen at atmospheric pressure stimulated the body growth of the embryo in utero.

Effects of Exposure to Oxygen at High Barometric Pressure on Higher Functions of the C.N.S.

Conclusion The data were interpreted to mean (1) that successive intermittent exposures to O2 at high barometric pressure had no effect on the ability to learn a maze habit; (2) that the retention and memory of a maze previously mastered was adversely affected to a striking degree by intermittent exposures to increased O2 pressure; (3) that certain mental processes may suffer deleterious effects as a result of exposure to increased O2 pressure even when such exposure causes no evident motor dysfunction.

Differences in growth pattern of bone and incisor of rats exposed to O2 atmospheric and high pressure

Abstract Three groups of young rats (age 22 days) were exposed intermittently (49 times), over a period of 44 days, group 1 to O 2 at atmospheric pressure (OAP), group 2 to O 2 at high pressure (OHP) (60 psig) and the third to air at atmospheric pressure (AAP) as controls. The average food consumption for the AAP group was 18.85 g, for the OAP 17.55 g and for the OHP 17.07 g per rat per day. The change in the body weights of each of these groups was followed throughout the experiment which continued 13 days after the last exposures. Bone growth of the maxilla, mandible and femur diaphysis and incisor growth were not altered by the OAP exposures, but were decreased by the OHP exposures; incisor growth, however, was increased. Hardness of the bone (by Tukon Hardness Tester) was increased in the OAP and OHP exposures as compared with that of the AAP, but the hardness of the incisors was not altered.

Growth of the Tooth Germ in Newborn Rats Exposed to Oxygen at Atmospheric and High Pressure

Newborn rats were exposed intermittently to oxygen at high pressure (93 psig) 15 times for a period of eight days. Growth of the tooth germs was the same as that of the control rats in air at atmospheric pressure, with the exception of the enamel and dentin layers, which grew less. The width of the tooth germ of rats exposed to oxygen at atmospheric pressure increased.

Somatic Reflexes and Blood Oxygenation Under Positive Intrapulmonic Pressure

Abrupt or gradual application of positive intrapulmonic pressure (20 cm H2O) in young adult men caused an augmentation of the patellar reflex, an increased respiratory minute-volume and a shift from abdominal to thoracic breathing; all of which persisted throughout the period of increased pressure. In controlled ventilation and frequently also in free breathing, positive intrapulmonic pressure caused a predominant decrease, following an inconstant and transient initial increase in O2 saturation of the blood in the tissues as determined by continuous oximeter readings from the ear. This decreased O2 saturation is explained not only by the diminished blood flow but also by the finding that in dogs under constant ventilation in air, positive intrapulmonic pressure decreased oxygenation of the blood in the lungs. It is concluded that the augmentation of the knee-jerk induced by positive intrapulmonic pressure is due in large part to the resultant diminished blood flow and decreased oxygenation of the blood in the lungs, and that the attendant hypo-oxia and increased acid metabolites may potentiate the reflex through an anticholinesterase action on the neuromyal junction and possibly also central nervous structures. The increased respiration induced by positive intrapulmonic pressure is a counterpart of, and has etiological factors in common with, the augmentation of the patellar reflex. Submitted on April 18, 1956