O. Robert Levine

Electron Microscopic Alterations at the Alveolar Level in Pulmonary Edema

The electron microscopic alterations of the alveolar septum in advanced hemodynamin and alloxan-induced pulmonary edema were compared. Pulmonary edema was produced in anesthetized dogs by means of increased lefy atrial pressure and hemodilution and by allocan administration. Sections of pulmonary tissue from these dogs and similarly anesthetized controls were processed for and examined by light and electron microscopy. In the hemodynamic form of edema the interstitial fluid collects only in the collagen-containing portions of the septum. The endothelium, epithelium, their respective basement membranes and large portions of the air-blood barrier are unaffected. Alloxaninduced edema, in contrast, is characterized by degeneration of both endothelium and epithelium and by the appearance of fibrin within the alveoli. The hemodynamic type of pulmonary edema appears to result from an accentuation of the normal process of fluid exchange within the lung. Allocan-induced edema, on the other hand, is a pathologic process. The functional implications of these results are discussed.

The Application of Starling's Law of Capillary Exchange to the Lungs*

The forces governing the movement of water across the pulmonary capillaries were studied in 39 intact, spontaneously breathing dogs. A situation favoring the net movement of water out of the pulmonary capillaries was created by means of partial pulmonary venous obstruction (left atrial balloon catheter) followed by rapid saline hemodilution. A predetermined difference between pulmonary capillary and plasma colloid osmotic pressures was maintained for periods of 1 to 2 hours. Left atrial (P(LA)) and plasma colloid osmotic pressures (pi(pl)) were measured directly. The water content of the lungs was measured serially by an indicator-dilution technique, and at autopsy by drying the lungs. The rate of accumulation of lung water was measured in four groups of animals: in three of the groups, the capillary hydrostatic and colloid osmotic pressures were varied; in the fourth group, the right lymphatic duct was obstructed in addition. The average rate of water accumulation in the lungs varied in a nonlinear way with the level of the capillary hydrostatic-plasma colloid osmotic pressure difference and was unaffected by the level of the capillary hydrostatic pressure. At low levels of P(LA) - pi(pl), water accumulated in the lung at an average rate of 0.09 g per g dry lung per hour per mm Hg pressure difference. At higher levels of P(LA) - pi(pl) the average rate of accumulation was 0.22 g per g per hour per mm Hg DeltaP; in most of the experiments in this group water accumulated in the lungs slowly during the first 30 minutes of the test period and more rapidly as the period was extended. Obstruction of right lymphatic duct outflow did not alter the rate of water accumulation. Based on the control data of the present experiments, the pericapillary pressure in normal lungs is estimated to be of the order of - 9 mm Hg in the normal dog lung. The filtration coefficient for the pulmonary capillaries is estimated to be of the order of one-tenth to one-twentieth of that for canine muscle capillaries. The data of the present study indicate that edema formation in lung tissue cannot be defined solely in terms of intravascular forces, but may be governed to a significant degree by changes in pericapillary forces in the pulmonary interstitium.

Spontaneous complete closure of a congenital coronary artery fistula

The first documentation is reported of spontaneous closure of a coronary artery to right ventricle fistula that was demonstrated initially in a 14 month old boy. Over a 4 year period after diagnosis, the characteristic continuous murmur gradually disappeared. When the patient was 5 1/2 years of age, selective coronary arteriography showed normal coronary vessels and circulation. Six other cases of coronary fistula observed during the past 10 years are also reviewed. This study supports the rationale for clinical follow-up rather than obligatory surgical intervention in asymptomatic patients with a small shunt who have no evidence of myocardial dysfunction.

Quantitative Assessment of Pulmonary Edema

The present study has attempted to establish a reliable method for distinguishing quantitatively between pulmonary engorgement and engorgement plus edema. Pulmonary engorgement was produced in intact, anesthetized dogs by inflating a balloon in the left atrium followed by saline hemodilution. Hemodynamic events monitored included left atrial and pulmonary arterial pressures, and the colloid osmotic pressure. Clinical criteria, such as the rate and frequency of breathing, the chest roentgenogram, and the presence of audible rales, failed to distinguish reliably between engorgement and edema. The mechanics of breathing were more severely altered by engorgement and edema than by engorgement alone, but considerable overlap was present. Determination of the pulmonary blood volume and the extravascular water space of the lungs, by means of simultaneous T-1824 and tritiated water dilution curves, as described by Chinard and Enns, was a reliable method of detecting and quantifying pulmonary edema. The water space measured by this technique averaged 3.5 ml/kg body wt in normal, anesthetized dogs. It correlated well with the total lung water content determined at autopsy, measuring a constant fraction (approximately 50%) of the total lung water content, even in the presence of severe pulmonary edema. According to the results of the present study, pulmonary edema could be predicted reliably at autopsy when the extra-vascular water space was 6.0 ml/kg of body wt or greater.

Progressive pulmonary hypertension in children with portal hypertension

Three patients with portal hypertension developed progressive pulmonary hypertension during childhood which resulted in cor pulmonale and death. This complication was unrelated to hepatic parenchymal disease, splenectomy, or portal-to-systemic decompressive shunt. Studies of pulmonary and cardiovascular function revealed pulmonary vascular obstructive disease without evidence of primary lung disease and unresponsive to administration of oxygen or ganglionic blocking agents. The morphologic changes in the pulmonary vascular bed were suggestive of a chronic vasoconstrictive process; there was no evidence of thromboembolism. The factors responsible for chronic pulmonary vasoconstriction in these patients were not identified.

Aortic Origin of the Right Pulmonary Artery

The clinical course and pathologic findings in three cases of anomalous origin of the right pulmonary artery from the ascending aorta are described. The malformation is characterized by (1) absent right branch of the pulmonary artery, (2) a single large vessel arising from the ascending aorta, entering the hilus of the lung and constituting its sole arterial blood supply, and (3) normal size and structure of the right lung. A review of the literature indicates the rarity of this lesion as an isolated anomaly; patent ductus arteriosus is the most frequently described additional defect. Histologic examination of the right and left lungs reveals bilateral and symmetrical pulmonary vascular changes, despite the difference in their arterial supply. Some pathophysiologic observations based on the necropsy findings in these cases are discussed. Early diagnosis and surgical correction are imperative, since this malformation may lead to irreversible congestive heart failure and death in infancy. Surgical repair may be accomplished by transplanting the anomalous right pulmonary artery from the aorta to the main pulmonary trunk.

Interstitial Pressure of the Lung

The effects of alveolar and pleural pressures on pulmonary interstitial pressure were studied in 36 anesthetized dogs by application of Starlings law of transcapillary exchange. Fluid accumulation in the lung was produced by increasing left atrial pressure to levels always higher than alveolar pressure and by hemodilution with saline. Using a lung divider, a difference in alveolar pressure of from 5 to 14 mm Hg was achieved between the two sides in 24 dogs. Increased alveolar pressure did not reduce the rate of fluid accumulation, indicating its lack of effect on interstitial pressure. A relationship between the rate of fluid accumulation and the forces in the Starling equation was demonstrated when pleural pressure was included as an index of interstitial pressure. The rate of fluid accumulation increased markedly when interstitial pressure exceeded atmospheric. Fluid accumulation was considerably less in lobes statically inflated with plasma than in contralateral lobes ventilated with air (6 dogs); this difference could not be attributed to static inflation as opposed to ventilation (6 dogs). These findings suggest that surface tension opposes the transmission of alveolar pressure to the interstitial space. The interstitial pressure, as measured by application of Starlings law, acts on the small vessels within the alveolar-capillary membrane.

Pulmonary Capillary Flow Pulse and the Site of Pulmonary Vasoconstriction in the Dog

A nitrous oxide-plethysmographic method was used to measure simultaneously the instantaneous pulmonary capillary blood flow and the pressure gradient across the pulmonary vascular bed. The method entailed the use of lightly anesthetized, curarized dogs for the moment-to-moment measurement of nitrous oxide uptake and the corresponding pulmonary arterial and wedge pressures. After establishing the usual patterns of pulmonary capillary blood flow, the flow patterns were modified by atropine, norepinephrine, and acute hypoxia. Before the exhibition of these agents, pulmonary capillary flow was pulsatile, with peak rates of flow of approximately twice the mean. After atropine, the amplitude of the flow pulse decreased passively as stroke volume and the pulmonary arterial pulse pressure decreased. In contrast to atropine, acute hypoxia elicited precapillary vasoconstriction as manifested by an increase in pulmonary arterial pressure and an unchanged pulmonary arterial wedge pressure in conjunction with an unchanged, or diminished and blunted, pulmonary capillary flow pulse. The predominant effect of norepinephrine appeared to be exerted distal to the pulmonary capillary bed since pulmonary arterial and wedge pressures increased in parallel while the capillary flow pulse changed passively according to changes in stroke volume.

Digitalis intoxication in premature infants

During a previous study of the dosage of digoxin in healthy premature infants 13 infants developed electrocardiographic evidence of intoxication. The present report is an analysis of the toxic manifestations. There appeared to be a heightened susceptibility to digitalis toxicity during the first 72 hours of life. Toxicity was induced most often by a digitalizing dose of 75 mcg. per kilogram of digoxin, but was also encountered at lower dosages. Depression of sinoatrial rhythmicity, ectopic supraventricular beats and rhythms, and atrioventricular block were the most common manifestations. Reduction of the heart rate to less than 100 beats per minute or prolongation of the P-R interval appeared to portend the development of intoxication. These findings underscore the necessity for careful electrocardiographic monitoring of digitalization procedures in young infants.

Evaluation of an enlarged cardiothymic image in infancy

Abstract The relative contribution of the thymus and of cardiovascular structures to an enlarged or deformed mediastinal image on a roentgenogram of the chest may be difficult to evaluate in infants and children. Five cases are presented which posed problems in diagnosis: in the first, the thymus obscured the presence of dextroversion of the heart; in the second, the thymus widened the mediastinal image and gave the impression of cardiomegaly and hence of heart disease, where none existed; in the third, vascular structures including a persistent left superior vena cava were responsible for the deformed supracardiac image; in the fourth, an enlarged left lobe of the thymus resulted in distortion of the left heart border and the erroneous impression of corrected transposition of the great vessels; and in the fifth, an enlarged cardiothymic image in an infant with congenital heart disease decreased in size by spontaneous shrinkage of the thymus. The administration of adrenal glucocorticoid derivatives is suggested for the induction of temporary involution of the thymus gland in selected cases. This technic is of value when there is need to clarify the composition of an unusual cardiothymic image in order to estimate the size and configuration of the heart and great vessels.