OBSERVATIONS ON RESISTANCE TO THE FLOW OF BLOOD TO AND FROM THE LUNGS

1. Embolism of pulmonary arterioles and capillaries produced by the intravenous injection of starch grains results in a dilatation of the pulmonary artery and the right chambers of the heart. This has been demonstrated both by x-ray studies and direct inspection. 2. The dilatation of the pulmonary artery and heart occurs synchronously with the acceleration of respirations. 3. Dilatation of these structures produced by other means, such as obstruction to the flow of blood to and from the lungs, by gradually clamping either the pulmonary artery (cat and dog) or pulmonary veins (cat) does not, however, give rise to rapid and shallow breathing. 4. The effect of these maneuvers on respiration does not become apparent until respirations suddenly cease. 5. Neither does sudden restriction of the pulmonary vascular bed by clamping the left branch of the pulmonary artery give rise to rapid and shallow breathing, though this procedure may cause an increase in CO₂ tension and in hydrogen ion concentration of the blood. 6. Since rapid and shallow breathing is not the result of (1) anoxemia, (2) increased pCO₂ and hydrogen ion concentration of the serum, (3) restriction of pulmonary vascular bed by nearly half, (4) increase in resistance to the flow of blood to and from the lungs) (5) the presence of starch grains in the lungs acting as a local irritant, it must be the result of the secondary pathological changes which occur in the pulmonary parenchyma following embolism. 7. The nature of these changes, congestion and edema, has been discussed elsewhere. Whether they operate directly on nerve endings or through their influence on lung volume and tissue elasticity is not certain. 8. Various important clinical analogies have been emphasized.     

A STUDY OF THE HERING-BREUER REFLEX

1. Cutting one vagus nerve, while recording the pulmonary ventilation of each lung separately, has no unique effect on the ventilation of the denervated lung. Both lungs respond to unilateral vagotomy by an equivalent slowing and deepening of respiratory movement. 2. When the bronchus to one lung is blocked the first effect is a slowing and deepening of the respiratory movements recorded by the opposite lung. As oxygen want develops these movements become rapid and shallow. 3. With a combination of these two conditions, i.e., when the bronchus to one lung is blocked and its vagus nerve is severed, the pulmonary ventilation recorded by the opposite lung exhibits the same changes as may result from unilateral vagotomy alone, unaccompanied by occlusion of the bronchus. 4. From these facts it may be concluded that the slowing and deepening of breathing which follows unilateral vagotomy does not depend for its occurrence upon the passage of air in and out of the bronchus of the lung whose vagus nerve has been sectioned. 5. The slowing of respirations after occlusion of the bronchus to one lung and section of the corresponding vagus nerve still occurs even though the phrenic nerve on the same side has been divided. This indicates that the slowing of respirations following unilateral vagotomy does not depend on the movements of the diaphragm on the side of vagal section. 6. When the pulmonary artery to one lung has been ligated and the vagus nerve on the same side cut, the response of the other lung is the same as has been described, namely, its respiratory movements become slower and deeper. This is taken as evidence that the results of unilateral vagotomy are not dependent upon an intact pulmonary circulation. 7. The general conclusions from these experiments are that the slowing and deepening of respirations following unilateral vagotomy do not depend upon: (a) Passage of air in and out of the trachea. (b) Expansion and collapse of the lung. (c) Existence of a normal pulmonary circulation in the vagotomized lung. (d) Normal fluctuations in alveolar carbon dioxide tension, (e) Contraction and relaxation of the diaphragm on the side of vagotomy. 8. The slowing and deepening of respirations, alluded to, may be presumed to indicate that a normal reflex (the Hering-Breuer reflex) has been interrupted. Since this interruption occurs in spite of all the conditions enumerated under Paragraph 7, we must conclude that none of these conditions is essential to the existence of this reflex.     

CHANGES IN CARBON DIOXIDE TENSION AND HYDROGEN ION CONCENTRATION OF THE BLOOD FOLLOWING MULTIPLE PULMONARY EMBOLISM

1. The production of multiple emboli of the pulmonary capillaries and arterioles results in rapid and shallow breathing which may be associated with anoxemia, but is not dependent for its occurrence upon anoxemia. 2. Similarly there may occur an increase in the partial pressure of CO₂ in the blood as well as an increase in hydrogen ion concentration. 3. These changes must be regarded as the result of the impaired pulmonary function. 4. They are not, however, the cause of the rapid and shallow respirations, since the abnormal type of breathing may occur without the attendant blood changes. 5. The characteristic type of response to increase in CO₂ tension is an increased rather than a decreased depth of respiration.     

A STUDY OF THE RELATION OF PULMONARY AND BRONCHIAL CIRCULATION

The most striking point brought out in this study is that as long as a definite pressure is maintained in either the pulmonary or bronchial circulations, the admixture of bloods is extremely limited. It is easily conceivable that more mixture occurs normally than under the conditions of the experiment, but there is no reason for considering this to be a large difference. If, however, in either system the pressure sinks to zero the possibility of supply by the other system becomes evident. It takes much longer for the mass injected through the bronchial arteries to penetrate to all parts of the lung than when the mass is injected through the pulmonary artery; but when accomplished, the injection reaches to all capillaries including those of the pleura, the only vessels remaining uninjected being the larger trunks of the pulmonary artery. On the other hand, the injection of the bronchial vessels by way of the pulmonary arteries is not complete with normal pressure, but occurs rapidly when a high pulmonary pressure is employed. It is therefore probable that either circulation can suffice for the simple nutritive demands of the lung if the other system is interfered with. It has been shown that embolism of the pulmonary artery, without other circulatory disturbance, does not lead to necrosis of the affected area of the lung, but it is probable that the preservation of circulation is not due to collateral bronchial circulation so much as to the free anastomosis and early division into capillaries of the pulmonary artery. In support of this statement is the fact that the appearance is not altered when the bronchials are ligated at their origin. The same ligation shows no subsequent interference with the nutrition of the bronchi up to a period of five weeks, demonstrating that the pulmonary circulation is sufficient to provide for the nutrition of the bronchi. If, however, as Virchow has shown, the pulmonary artery supplying an entire lobe be occluded, the bronchial circulation can and does suffice for the nutrition of the lobe. In the case of the occlusion of a branch of the pulmonary artery the pressure in the area interfered with does not sink to zero because of the collateral circulation in this area; whereas, if the main trunk is occluded no collateral supply is available, the pressure sinks to zero, and the bronchial artery becomes available as a source of blood supply. It must be remembered that the lung tissue, as a whole, has ready access to oxygen and this gas is the nutritive element acquired by the blood in the lungs. From these studies it would appear that the part of the lung tissue not in intimate contact with oxygen in the air is supplied by oxygenated blood of the bronchial arteries, and that the tissues through which the pulmonary blood circulates take up whatever organized nutriment they need from the pulmonary blood and possibly provide for their oxygen and carbon dioxide interchange (which must be very slight) either directly with the alveolar air, or by finding sufficient oxygen in the venous blood of the pulmonary artery. The studies of the injected specimens confirm Küttner''s findings of a very rapid breaking up of the pulmonary artery into capillaries. In all the specimens studied it was found that although the pleural vessels can be injected by way of the bronchial arteries when there is zero pressure in the pulmonary arteries, yet when the two sets of vessels are injected simultaneously in the dog, the pleural vessels invariably derive their supply of injection mass from the pulmonary artery.     

THE RAPID SHALLOW BREATHING RESULTING FROM PULMONARY CONGESTION AND EDEMA

These experiments record the effects of the experimental production of pulmonary congestion and edema in a lung completely isolated from the general circulation, but with an intact nerve supply. The resulting changes are: a slowing of the heart rate, a fall in systemic blood pressure and a temporary inhibition of respiration succeeded by rapid shallow breathing. The pulse rate and blood pressure show a rapid and spontaneous return to initial conditions. The respirations show a partial but not a complete return to their former rate and depth. The effects on respiration are similar to those described by Dunn and Binger and Moore which follow multiple embolism of the pulmonary circuit with starch granules. The alterations in the pulse rate and blood pressure are characteristic of the effects of vagal stimulation. A chemical effect on the respiratory center is excluded by the nature of the preparation. These results, therefore, add further evidence to support the hypothesis that the rapid shallow breathing attending congestion and edema of the lungs is due to the stimulation of nerve endings in the lungs.     

Pulmonary capillary pressures during hypoxia and hypoxemia: experimental and clinical studies

Unlike the systemic circulation, the pulmonary vasculature constricts in response to hypoxia to divert blood flow to better-ventilated segments. The site of this response, the hypoxic pulmonary vasoconstriction, has been reported as precapillary in numerous experimental models of isolated animal lungs. In the present study, the response of intact chest dog and human lungs to hypoxia and hypoxemia, respectively, was also precapillary vasoconstriction. In dogs, hypoxia in the ipsilateral lung attenuated the normal vertical blood flow gradient. Contralateral hypoxia did not alter pulmonary regional blood flow, precapillary (Ra), postcapillary, or total pulmonary vascular resistance. In patients, an elevated alveolar-arterial oxygen pressure gradient of 50 to 150 torr resulted in significantly increased Ra. Further hypoxemia did not increase this response. In addition, the effective pulmonary capillary pressure did not bear a constant relationship to the pulmonary artery occlusion or wedge pressure (WP). Therefore, in patients in respiratory failure, WP does not reliably estimate hydrostatic pressure at the pulmonary capillaries.     

AN EXPERIMENTAL STUDY OF DIATHERMY : V. THE ELEVATION OF TEMPERATURE IN THE PNEUMONIC LUNG.

1. An experimental pneumonia with more or less lobar distribution has been produced in dogs by the method of intrabronchial insufflation of B. friedlænderi, Type B, and Pneumococcus, Type I. 2. Such dogs as showed evidences of a pulmonary lesion when photographed by x-ray were selected for lung temperature measurements. 3. Measurements of lung temperature were made by means of thermocouples before and during diathermy. 4. The thermocouples which recorded the temperature in the consolidated lobes showed in most instances a more rapid rate of heating during diathermy than those in the normal lobes. The final increase in temperature in the pathological lobes over the normal lobes amounted to slightly more than 1°C. 5. When local heating occurred during diathermy it was of the order of magnitude found in a lung in which the branch of the pulmonary artery supplying it had been clamped. 6. Histological examination of the lungs showed the pathological reaction to consist of intraalveolar exudate composed of polymorphonuclear leucocytes and desquamated alveolar epithelium. In some sections the exudate was sufficient to cause compression and emptying of the alveolar capillaries. 7. The local heating, we believe, depends upon this ischemic state of the smaller vessels. 8. Further evidence for an imparied circulation in the pneumonic lung is furnished by injection preparations in which the uninjected area corresponded exactly to the gross pathological lesion.     

THE STATE OF THE VESSELS OF THE MESENTERY IN SHOCK PRODUCED BY CONSTRICTING THE LIMBS AND THE BEHAVIOR OF THE VESSELS FOLLOWING HEMORRHAGE

1. Direct observations of the arteries, arterioles, capillaries, veins, and lymphatics in the mesentery of anesthetized cats put into shock by incomplete occlusion of the circulation of the limbs showed that: (a) Marked constriction of the arteries and arterioles, produced by muscular contraction, occurred usually within an hour after incomplete occlusion of the limbs, lasted several hours, and finally gave way in most instances to relaxation an hour or more before death. The constriction reduced the blood supply to the mesentery and intestine and the venous return from them. It did not, however, interrupt the blood flow. No pooling or stagnation of blood was seen even as a terminal phenomenon. (b) The veins of the mesentery also became constricted but showed less tendency to dilate as death approached. The lymphatics likewise became somewhat narrowed. Even during the terminal stage the leukocytes moved along without change in shape or sticking to the walls of the capillaries or venules. (c) Hematocrit determinations showed progressive hemoconcentration of moderate degree. (d) Autopsy usually showed the presence of small hemorrhages in many parts of the body, especially the heart, liver, spleen, and lungs. (e) Bilateral nephrectomy, suprarenalectomy, and pancreatectomy did not significantly alter the morphological picture elicited by shock induced by restriction of the circulation to the limbs. 2. Removal of large amounts of blood was always followed within a short time by constriction of arteries, arterioles, veins, and lymphatics of the mesentery. 3. Fall in arterial pressure produced by pithing was not accompanied by change in diameter of the arteries, arterioles, veins, or lymphatics, or by blanching of the mesentery or gut.     

AN EXPERIMENTAL STUDY OF DIATHERMY : II. THE CONDITIONS NECESSARY FOR THE PRODUCTION OF LOCAL HEAT IN THE LUNGS.

1. Prevention of the access of air to one lung, while its circulation is intact, results in little, if any, change in the rate of heating of the lung by the diathermy current. 2. Occlusion of a main branch of the pulmonary artery during the flow of the current results in a sudden rise in temperature in the lung whose artery has been occluded, with subsequent heating, however, at the original rate. Under these circumstances death of the animal is accompanied by a precipitous rise in the temperature of both lungs. 3. When the pulmonary veins as well as the artery to one lung are ligated the circulation through the bronchial vessels is also stopped. Diathermy then results in a local rise in temperature in the lung equivalent to that seen in the other lung after death.     

STUDIES ON ENDOTHELIAL REACTIONS : VII. CHANGES IN THE DISTRIBUTION OF COLLOIDAL CARBON NOTED IN THE LUNGS OF RABBITS FOLLOWING SPLENECTOMY.

The changes in the distribution of intravenously administered colloidal ink in splenectomized rabbits may be interpreted somewhat as follows: The removal of the spleen throws an increased amount of ink into the other hematopoietic organs and the lung and liver. While we should expect the liver or the bone marrow to compensate for the loss of the spleen and to take up this ink and remove it from the circulation, that is not the case. The lungs appear to play the chief part in the process, slowly passing on the removed material, contained in macrophages, to the liver, or retaining these ink-laden cells in their tissues and capillaries. By an increase in the capillary endothelium and by a process of engorgement of the capillaries with cells presumably derived therefrom, the lungs remove by far the greater part of the foreign material that has been introduced into the circulation. At the same time there is an increase in the number of ink-bearing macrophages in the lymphatics and capillaries of the lung, indicating that these cells are entering the circulation and the lymph stream (Fig. 8). The only organ where they lodge in any quantities, outside of the peribronchial lymph nodes, is the liver, the sinusoids of which contain an increasing number of macrophages as time goes on. It is possible that these cells are destroyed in the sinusoids and the carbon transferred to the liver epithelium; there is evidence to support this assumption. After the lungs, the liver comes next in degree of intensity of pigmentation; the bone marrow contains far less than either of these organs.     

STUDIES ON THE RESPIRATORY MECHANISM IN LOBAR PNEUMONIA : A STUDY OF LUNG VOLUME IN RELATION TO THE CLINICAL COURSE OF THE DISEASE.

1. The functional residual air (defined as the lung volume at the end of normal expiration) has been determined in a series of normal individuals and in ten patients with lobar pneumonia at different stages of the disease. 2. The rate, depth, and minute volume of respirations were measured in the same individuals by a graphic method. 3. When appreciable cyanosis was present the oxygen content and capacity of the arterial blood were determined. 4. A constant relationship has been found to exist between the persistence and disappearance of symptoms (fever, accelerated heart rate, rapid and shallow breathing, cyanosis) and fluctuations of the functional residual air. When these symptoms persisted the functional residual air decreased; during their disappearance the volume of the functional residual air rose towards normal. The rise was detected soon after the crisis. 5. A close parallelism has been observed also between alterations in radiographic shadow, physical signs, and the volume of the functional residual air. The lung volume, measured at normal expiration, is diminished during the persistence of pathological signs in the lungs, and returns to normal as the pathological signs disappear. The average time required, in cases which recovered, for the functional residual air to become constant was 11 to 12 days, counting from the onset of the disease.     

Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion

In order to evaluate separately changes in vascular tone occurring in arteries and veins, we measured pulmonary capillary red blood cell (RBC) concentration under zone II (waterfall) conditions in isolated dog lungs rapidly frozen with Freon 12. The lungs were frozen while being perfused from artery to vein and from vein to artery breathing normal and hypoxic gas mixtures and during infusions of serotonin and histamine. Changes in capillary RBC concentration which occurred during the experimental conditions indicated an alteration in vascular resistance upstream from the capillaries. Alveolar hypoxia caused a significant decrease in capillary RBC concentration during forward perfusion, but no change from the control values during reverse perfusion. Serotonin infusion caused a decrease in RBC concentration during forward perfusion comparable with that of hypoxia and a small but significant decrease during reverse perfusion. Histamine infusion caused no change in RBC concentration from control values during forward perfusion, but a large decrease during reverse perfusion. We conclude that vasoconstriction occurs (a) exclusively in arteries during alveolar hypoxia, (b) predominantly in arteries but to a lesser extent in veins during serotonin infusion, and (c) exclusively in veins during histamine infusion.     

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 (π_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.     

Acute respiratory failure following pharmacologically induced hyperventilation: an experimental animal study

The pulmonary effects of hyperventilation following infusion of sodium salicylate into the cisterna magna was studied in 16 spontaneously breathing adult sheep. We found a fall in PaO₂, a decrease in the static compliance of the respiratory system, abnormal chest roentgenographic films, and grossly abnormal lungs following 3.5 to 13 h of hyperventilation. A control group of 15 sheep (10 sheep similarly injected with sodium salicylate, but then sedated and paralyzed and ventilated at normal tidal volume and respiratory rate on a mechanical ventilator, and 5 sheep infused with saline alone and breathing spontaneously) showed no pulmonary or arterial blood gas abnormalities. We conclude that prolonged hyperventilation under the conditions of this experiment precipitated events that resulted in acute lung injury.     

Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats

1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Subpleural microvascular flow velocities and shear rates in normal and septic mechanically ventilated rats

Changes in pulmonary microhemodynamics are important variables in a large variety of pathological processes. We used in vivo fluorescent videomicroscopy of the subpleural microvasculature in mechanically ventilated rats to directly monitor microvascular flow velocity (FV) and shear rate in pulmonary arterioles, capillaries, and venules in healthy rats and in septic rats 20 h after cecal ligation and puncture (CLP). Observations were made through a small thoracotomy after injection of fluorescent microspheres (D = 1 microm) into the systemic circulation. The FVs were calculated off-line by frame-by-frame measurements of the distance covered by individual microspheres per unit of time. In healthy rats, inspiratory FV were 1322 +/- 142 microm/s in subpleural arterioles and 599 +/- 25 microm/s in capillaries. The highest FV was found in venules (1552 +/- 132 microm/s). The calculated shear rates were 547 +/- 62/s in arterioles and 619 +/- 19/s in capillaries. The highest shear rates were detected in venules (677 +/- 59/s). No significant changes in FV and shear rates were observed throughout the 1-h observation period in any of the microvascular compartments. Pulmonary microvascular FV and shear rates found in sham-operated rats in the CLP experiments were not significantly different from values of healthy rats. The CLP caused a significant increase in leukocyte sequestration in the lungs and a mean of 27% to 34% decrease in FV in all sections of the pulmonary microvasculature (P < 0.001 in capillaries and P < 0.05 in venules). Also, CLP caused a 23% decrease in capillary shear rate that reached only borderline statistical significance (P < 0.06) and a significant 35% decrease in mean shear rate in venules (P < 0.05). Fluorescent videomicroscopy is offered as a stable and reproducible method for in vivo determinations of pulmonary microhemodynamics in clinically relevant models of sepsis.     

Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40^–/–). In vivo, hypoxemia was more severe in Cx40^–/– mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40^–/–, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α_1G subtype Ca²⁺ channels, cytosolic phospholipase A₂, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner.     

THE RELATION OF APICAL TUBERCULOSIS OF ADULTS TO THE FOCAL TUBERCULOSIS OF CHILDREN

The age incidence of focal tuberculous lesions of the lungs demonstrates that they have their origin in most instances in childhood. Focal lesions which heal have been found at all ages after the 2nd year of life, but in more than half of all individuals these lesions are acquired between the ages of 10 and 18 years. In the period between 18 and 30 years at least 85 per cent of all individuals have ''acquired focal tuberculous lesions. The occurrence of tuberculous infection in the lungs, in regional lymphatic nodes, or in some other organs of the body such as the gastrointestinal tract and its lymphatic system, is nearly universal but doubtless a few individuals escape. That focal tuberculous lesions of the lung are occasionally acquired during adult life is shown by the slight increase in the proportion of those with these lesions as age increases from 18 years to old age. Apical lesions of the lung make their appearance in later childhood and occur with increasing frequency from adolescence to old age (50 per cent). After the 2nd year of life focal tuberculous lesions occurring in situations other than the apices of the lungs tend to heal and after the 10th year focal lesions are almost invariably encapsulated and latent or healed. Fatal tuberculosis after the 10th year is with few exceptions apical in origin. The apices are not only more susceptible to infection in later life but once infected afford less resistance to the extension of the lesion. The present series of cases has furnished opportunity to observe the character of the apical lesion in lungs of individuals previously infected with tuberculosis. With one exception the apical lesion (in eight instances) has pursued a chronic course and, encapsulated by fibrous tissue, has remained limited to the extreme apex of the lung. In one instance in a woman with advanced malignant disease chronic pulmonary tuberculosis has been progressive. Tuberculosis of the apices in those who have previously acquired a focal tuberculous lesion has pursued a chronic course and in most instances has remained latent or has completely healed. A very small group of instances of fatal pulmonary tuberculosis suggests that apical lesions in those who have not undergone previous infection may assume an unusually severe character. One instance of apical tuberculosis unaccompanied by focal lesions and followed by tuberculosis of the thoracic duct and disseminated miliary tuberculosis has been especially significant. Apical tuberculosis unaccompanied by evidence of preexisting tuberculosis may be accompanied by tuberculosis of the regional lymphatic nodes, whereas apical tuberculosis in an individual with a preexistent focal tuberculous lesion is not followed by tuberculosis of adjacent lymphatic nodes. It is well known that tuberculosis in previously uninfected animals is followed by tuberculosis of adjacent lymphatic nodes, whereas a second infection fails to implicate the regional lymphatic nodes. This relation has been well illustrated by the lungs of a monkey which acquired in confinement acute tuberculous pneumonia limited to the left lung; the lymphatic nodes on this side were greatly enlarged and caseous. The following observations indicate that apical tuberculosis of adults is not the result of infantile tuberculosis but is caused by subsequent infection: (a) Apical tuberculosis does not have its highest incidence, in accordance with common belief, in early adult life when focal infections acquired in childhood are relatively fresh and active but is more common in later life when the focal lesions of childhood have in most instances completely healed. It is noteworthy that most of these apical lesions of later life pursue a chronic course and are discovered at autopsy in individuals who have died from other causes. (b) The well characterized lesions of tuberculosis acquired in childhood and found in adults with apical lesions are almost invariably calcified and healed. The apical lesion is in most instances relatively fresh and caseous whereas the focal pulmonary lesion and associated lesions of regional lymphatic nodes exhibit no evidence of activity. (c) In a large proportion of instances of associated focal and apical tuberculosis the focal lesion is in one lung, whereas the apical lesion is limited to the opposite apex. This relation affords no support to the view that tuberculous lesions may be transmitted to the apex by way of the lymphatics.     

Trophoblastic pulmonary embolism

Trophoblastic embolism is subclinical in normal pregnancy, pronounced in eclampsia, and massive in hydatidiform mole. Self-limited acute respiratory distress arises in 3% to 10% of molar pregnancies at the time of uterine evacuation. Infrequently death occurs; the principal findings are trophoblastic emboli in the pulmonary arterioles, edema of the lungs, and dilatation of the right side of the heart. Hyperthyroidism may develop, and fibrin may line the alveolar walls. Pathogenetic mechanisms include heart failure, hyperthyroidism, dilutional anemia, and pulmonary arteriolar blockage. Infusions of fluid and whole blood tend to cause pulmonary overload, which may precipitate right-sided heart failure. Preferred therapy consists of diuresis and ventilatory support, especially with oxygen under positive end-expiratory pressure.     

Effects of prostaglandins B2 and B1 on the pulmonary circulation in the intact dog.

The effects of prostaglandins (PG) B2 and B1 on the pulmonary circulation were studied in the intact spontaneously breathing dog under conditions of controlled blood flow using right heart and transseptal catheterization techniques to isolate and perfuse the left lower lung lobe. Infusion of PGB2 and PGB1 into the left lower lung lobe increased lobar arterial and lobar venous pressure but had no significant effect on left atrial pressure. PGB2 and PGB1 increased pressure gradients between the lobar artery and lobar small vein and between the lobar small vein and the left atrium. PGB2 and PGB1 increased isometric tension in isolated helical segments of lobar vein (3-5 mm diameter) but had little or no effect on lobar arterial segments of the same size. These results indicate that in the intact dog prostaglandins of the B series increase pulmonary vascular resistance by constricting lobar veins and to a lesser extent vessels upstream to lobar small veins, presumably small lobar arteries. PGB2 and PGB1 both produced large increases in pulmonary vascular resistance in the dog with PGB2 being about 10 times as potent as PGB1. It is concluded that PGB2 is one of the most potent pressor substances in the canine pulmonary vascular bed.