THE EFFECTS OF RENAL HYPERTENSION ON THE VESSELS OF THE EARS OF RABBITS

1. The present experiments demonstrate by direct observation that peripheral arterioles in moat chambers in rabbits'' ears constrict during the development of renal hypertension, and that they remain persistently constricted, although not sufficiently to interrupt the blood supply to the tissues. The arteriolar constriction in the hypertensive animals was not dependent upon nerves, since it occurred in newly formed arterioles which had probably never been supplied with nerves, as well as in older arterioles with a functional nerve supply. 2. No capillary constriction was observed during or following the development of hypertension, although the walls of the capillaries could be very clearly seen. Persistent hypertension was associated in two examples with increased sticking of leukocytes to the walls of the capillaries and venules, some emigration of leukocytes, and a few small hemorrhages. 3. During development of hypertension, new arteriovenous anastomoses were observed to appear in the chambers. 4. No evidence of change was noted in the viscosity of the blood or in the appearance of the blood corpuscles in the hypertensive rabbits. 5. The constriction of the arterioles during and following the development of hypertension closely resembled that produced by intravenous injections of angiotonin.     

THE REACTION OF PERIPHERAL BLOOD VESSELS TO ANGIOTONIN,RENIN, AND OTHER PRESSOR AGENTS

1. Both renin and angiotonin in small doses cause constriction of the arterioles in the ears of normal rabbits, as seen directly with the microscope. Capillaries appear unaffected while venules exhibit slight or no constriction with small doses and moderate constriction with large doses. The flow of blood through the tissues is not reduced except when very large doses are administered. Tyramine and methylguanidine sulfate in isopressor amounts act somewhat similarly. 2. Isopressor amounts of epinephrine and pitressin, by contrast, elicit severe vasoconstriction of arterioles lasting longer than that due to angiotonin, and flow of blood is sharply reduced or abolished altogether. The degree of venular constriction was also greater, while the capillaries remained unaffected. 3. The vasoconstrictor action of angiotonin on peripheral vessels in moat chambers in normal rabbit''s ears is indistinguishable from that of renin, except that it is more rapid.     

STUDIES ON EXPERIMENTAL HYPERTENSION : VII. THE PRODUCTION OF THE MALIGNANT PHASE OF HYPERTENSION

The production of the acute malignant phase of experimental hypertension has been accomplished in seventeen dogs. The method used to produce this type of hypertension was the same as for the benign type (4), namely, constriction of the main renal arteries, or the equivalent, constriction of the aorta above the origin of both main renal arteries, but the constriction was especially severe. The malignant phase in the animals was characterized by hypertension, terminal renal insufficiency and the development of petechiae and larger hemorrhages in many internal organs, especially the alimentary tract. These were due to dissecting hemorrhage through, or rupture of, the wall of severely hyalinized or necrotic arterioles, or rupture of capillaries. Hyalinization and necrosis of arterioles were more severe and more widespread in animals that had a period of benign hypertension before the onset of renal insufficiency. In animals with a previous long period of benign hypertension, thickening of the media also occurred in arterioles, with or without hyalinized intima. Elevation of blood pressure (mechanical factor) and renal insufficiency (humoral factor) are at least two of the necessary conditions for the development of the necrotic arterioles and hemorrhages. Necrotic arterioles and hemorrhages have not yet been observed in animals that have had very high blood pressure for years without renal insufficiency, nor in animals with azotemia, due to removal of both kidneys, but without hypertension. Hyalinized retinal arterioles have been observed in dogs with persistent hypertension and with moderate or no disturbance of renal function. That ischemia is not the cause of the necrosis of the arterioles is shown by their absence from the ischemic kidneys of the dogs and their widespread presence in other organs that were not ischemic. These experiments show that the necrotic arterioles and hemorrhages are secondary to and not the primary cause of the malignant phase of hypertension.     

Peripheral vascular reactions in anaphylaxis of the mouse

Pronounced vascular changes occurring in the ears and claws of mice during anaphylactic shock are described. Practically at once after a foreign serum (pig, horse, or rabbit) enters the blood stream of sensitized animals both the arterial and venous vessels undergo marked, local or generalized constriction in the organs mentioned. Usually spasm of the vessel walls occurs simultaneously in the arteries and veins, but it may appear first in the arteries, or occasionally in the veins. When venous spasm precedes arterial spasm, the true capillaries become distended with cells; if the reverse order holds, the ears appear bloodless. There is no active constriction or dilatation of capillaries; the capillary behavior follows passively the changes in the large vessels. Peripheral vascular spasm occurs while the carotid blood pressure is high, but a few minutes later, while this still holds true, the ear vessels begin to relax and the circulation is resumed. Shortly afterwards the blood pressure falls to levels far below normal, but the vessels remain open. If the circulation of one ear is obstructed while anaphylactic shock is produced, no vascular spasm occurs in it. Release of the obstruction during the animal's recovery results in belated constriction of the blood vessels of this ear although by now the vessels in the other ear are dilated and the general systolic blood pressure is very low. The vascular reactions in the ears appear to be uninfluenced by the blood pressure in the large vessels, and they are not a response to nervous stimuli. They are local in origin. The vascular changes are often not clearly perceptible in the gross but are plainly to be seen under a low power of the microscope. They occur in some sensitized mice exhibiting no manifest signs of shock, differing only in degree from the changes taking place when shock is severe or fatal.     

THE EFFECT OF MULTIPLE EMBOLI OF THE CAPILLARIES AND ARTERIOLES OF ONE LUNG

1. Injection of a suspension of potato starch cells into the left branch of the pulmonary artery, in quantity sufficient ordinarily to give rise to markedly accelerated respirations, resulted in no change in respiratory rate. 2. A method for injecting substances into the pulmonary artery or its branches without interfering with the blood flow to the lungs has been described. 3. Injection of similar material into one lung when the other is excluded from the circulation either by ligation or by temporary clamping does give rise to rapid and shallow breathing (from a rate of 10 to 15 per minute to one of 60 or over) identical in character to that brought about by introducing emboli into both lungs. 4. A method for clamping and releasing the pulmonary artery or its branches in a dog breathing normally with closed thorax has been devised. This is described in detail in another paper. 5. After rapid breathing has been initiated by the effect of emboli lodged in the arterioles and capillaries of the right lung, reestablishing the circulation in the other lung by releasing the clamp on its artery may or may not restore the respiratory rate to its original, normal level. 6. This discrepancy in results has not been correlated with any difference in oxygen saturation of the arterial blood, or in carbon dioxide tension or pH of its plasma. 7. It is, however, believed to be related to the gross and microscopic anatomy of the lung of which the artery has been temporarily clamped. Photomicrographs are published, showing in one dog (No. 3), in which the respiratory rate returned to normal, a normal histological picture of the left lung, and in another dog (No. 4), in which the rate remained rapid after release of the clamp, a picture characterized by congestion and dilatation of arterioles and capillaries. 8. The fact that accelerated respirations result from emboli in the pulmonary capillaries and arterioles only after a certain quantity of material has been introduced, and the fact that emboli in one lung do not occasion accelerated respirations unless the circulation through the other lung is occluded or abnormal, leads us to the conclusion that the phenomenon is not an irritative stimulus due to foreign bodies, but is in some manner related to (a) diminution of the pulmonary vascular bed, (b) resistance to the blood flow through the lungs or (c) congestion or dilatation of the arterioles and capillaries of the lungs.     

比较脂质微泡与聚合物超声造影剂的微循环流变学

目的 探讨脂质微泡与高分子聚合物超声造影剂在大鼠肠系膜微循环中的流变学特征。方法 对10只大鼠经股静脉分别注射DiI标记的脂质微泡和高分子聚合物超声造影剂,通过倒置荧光显微镜观察两种不同造影剂在大鼠肠系膜微循环中的运动情况;比较注射前后小动脉、小静脉及毛细血管内径的变化,测定红细胞与两种造影剂在微循环内的流速。结果 注射后两种造影剂在大鼠肠系膜微循环内均可随血流移动,仅见少量脂质微泡短暂滞留。注射造影剂前后小动脉、小静脉及毛细血管内径无明显改变(P>0.05);两种造影剂在微循环内的流速与红细胞相似,差异无统计学意义(P>0.05)。结论 脂质微泡和高分子聚合物超声造影剂具有与红细胞相似的微循环流变学特征,均可作为红细胞示踪剂。     

STUDIES ON INFLAMMATION : II. A MEASURE OF THE PERMEABILITY OF CAPILLARIES IN AN INFLAMED AREA

1. By means of a colorimetric method the concentration of trypan blue in capillaries can be estimated by direct observation and its changes followed as the dye passes out of the circulating blood stream. 2. The change in concentration of trypan blue in the capillaries of both the normal and the inflamed mesentery of frogs can be described by two separate exponential equations of the type: y = be^-ax. 3. From these equations it is found that the rate of fall of concentration following intraventricular injection of the dye is almost twice as great in the capillaries of the inflamed as in those of the normal mesentery. This difference is a measure of increased permeability with inflammation.     

STUDIES ON EXPERIMENTAL HYPERTENSION : IX. THE EFFECT ON BLOOD PRESSURE OF CONSTRICTION OF THE ABDOMINAL AORTA ABOVE AND BELOW THE SITE OF ORIGIN OF BOTH MAIN RENAL ARTERIES

Constriction of the aorta just above the origin of both main renal arteries invariably resulted in elevation of the carotid systolic and carotid mean pressure. The hypertension was not immediate, but developed in about the same time as after constriction of the main renal arteries (3). Constriction of the aorta just below the origin of both main renal arteries had no significant effect on the carotid systolic or carotid mean pressure. Since these results were first reported (1), Rytand (88, 89) has shown by an indirect method, namely, the demonstration of the development of cardiac hypertrophy, that hypertension in the upper part of the body can be produced in the rat by constriction of the aorta just above the origin of both main renal arteries. The immediate effect of constriction of the aorta either below or above the main renal arteries is a fall of blood pressure (femoral mean pressure) below the site of the clamp, the extent of the fall being directly dependent upon the degree of constriction of the aorta. Of particular interest is the eventual elevation of the femoral mean pressure above the normal in some animals with the aorta constricted or even occluded above the origin of the main renal arteries. This was most pronounced and persistent in those animals in which, in addition, the aorta below the origin of the renal arteries, and, in some animals, the main renal arteries, also were constricted. The most important factors which determined this elevation of blood pressure in the lower part of the body were probably increased flow of blood into the vascular bed below the clamp and peripheral vasoconstriction of renal and humoral origin, as in the case of the hypertension produced by constriction of the main renal arteries alone (2–86). Although elevation of the carotid systolic or carotid mean pressure occurred invariably within 24 to 48 hours after the constriction of the aorta above the site of origin of both main renal arteries, yet there was a tendency, after a variable period, for the elevated blood pressure to become lower or even to drop to the original level. Increased constriction, and finally occlusion of the aorta, above the origin of the main renal arteries, and even constriction or occlusion of the aorta below the renal arteries, in addition, failed to induce hypertension that persisted for a long time at a high level. In order to produce this effect, it was necessary to constrict the main renal arteries as well. The possible explanation of the failure of the hypertension to persist for a long time after constriction of the aorta alone, is that the initial ischemia of the kidneys disappeared due to the improvement of the blood flow through the kidneys as a result of (a) the increase of the natural accessory circulation to the kidneys; (b) the increased blood pressure above the site of the clamp and consequent increased flow of blood into the part of the aorta below the clamp; (c) increased pressure below the site of the clamp due, in great part, to peripheral vasoconstriction, and in part to the increased inflow of blood into the lower part of the body through the aorta and collateral channels. For the dog, this method is not necessary for the production of persistent hypertension. Constriction of the main renal arteries is easily performed and is effective for the production of generalized hypertension (2–11). However, constriction of the aorta in addition to constriction of the renal arteries results in greatly elevated persistent hypertension. Constriction of the aorta alone above the origin of the main renal arteries would be useful in the dog only for the production of relatively short periods of hypertension in the upper part of the body. For small animals it may be a more effective and useful method. In the dog, the only technical difficulty encountered was the erosion of the wall of the aorta by the clamp. This may not occur in small animals. In previous studies (2–11) that have dealt with the constriction of the main renal arteries, this accident rarely occurred. When the constriction of the aorta above the origin of the main renal arteries was of moderate degree, or was gradually made very great, the resultant hypertension was not accompanied by impairment of renal excretory function, as determined by urea clearance or by the quantity of urea, creatinine or non-protein nitrogen in the blood, the benign phase of hypertension (3). When the constriction of the aorta was suddenly made very great, impairment of the renal excretory function usually followed, and the animal developed fatal convulsive uremia and characteristic vascular lesions, the malignant phase of hypertension (9). These facts, are all indicative of the renal origin of the hypertension which results from the constriction of the aorta just above the origin of both main renal arteries. Hypertension did not persist for a sufficiently long time to permit any conclusive comparison between the effect of the high and low pressures on the structure of the vascular system, above and below the site of the clamp, respectively. During the period of survival of these animals, no significant differences were observed between the appearance of the vascular system of the upper part of the body and that of the lower part of the body, and significant cardiac hypertrophy did not develop. In the aorta and large arteries, intimal arteriosclerosis was not observed. In the aorta of one old animal several small plaques of calcification were found in the media, but these were present in the portion of the aorta below, as well as above the clamp, and they were no larger or more abundant than were observed in some old dogs with normal blood pressure. Dogs 3–50 and 3–83, that are still alive, with very high blood pressure above the site of the aortic clamps, and relatively low pressure (though greater than normal) below the site of the aortic clamps, will be valuable for the determination of possible differences between the effects of the two levels of blood pressure in the large and small blood vessels. In these dogs also, it will be possible to determine the effect of the persistently high blood pressure on the myocardium. The possible application of the results of this study to the problem of the pathogenesis of human eclampsia is mentioned here for consideration. Since this condition occurs in pregnancy only at a time when the uterus is greatly enlarged, it is at least possible that the mass may press on the aorta or both main renal arteries sufficiently to produce renal ischemia. The suddenness with which the uremic convulsive phase of eclampsia develops is in keeping with this idea. In the dog, an aggravating effect of pregnancy on an already established hypertension has not been noted. As a matter of fact, most of the hypertensive dogs that have become pregnant, have shown a slight or moderate fall, rather than an increased rise of pressure. Since the dog stands with the body in a horizontal position, and does not lie on its back, pressure of the pregnant uterus on the aorta and blood vessels is less than in human beings who stand erect and frequently lie on their backs. The soundness of this suggestion could be tested by placing pregnant women, in the early stage of eclampsia, in a position which could relieve possible pressure on the aorta and main renal arteries. A possible explanation of the fall of pressure in the pregnant hypertensive dogs is the compensatory effect of the normal kidneys of the pups, as in the case of an animal with one main renal artery constricted and the other kidney normal. As has been shown (3, 31, 72), the presence of one normal kidney in an animal hypertensive due to constriction of the other main renal artery, results, after a variable period, in a return of the blood pressure to normal. How the normal kidney acts to produce this effect is not known.     

THE VESSELS INVOLVED IN HYDROSTATIC TRANSUDATION

The gradient of permeability which exists along the cutaneous capillaries and venules is accentuated and broadened in scope by increasing the venous pressure moderately. Under such circumstances transudation leading to edema takes place most abundantly from the venules. The permeability of the portion of the capillary web that is near the arterioles increases only when the venous pressure rises so high as to approximate that in the arteries. Under such circumstances the gradient of permeability along the small vessels disappears, the capillaries and venules everywhere leaking fluid. The character of the vital staining developing under such circumstances indicates, like the evidence of previous work, that the cause for the gradient is to be sought in a structural differentiation.     

CONDITION OF THE CAPILLARIES IN HISTAMINE SHOCK

1. Histamine exerts a local dilator effect upon capillaries and upon the smallest arterioles and venules which border the capillary system. There occurs also an opening up of large numbers of capillaries of which no trace can be seen before the application of histamine. 2. When injected intravenously in amounts sufficient to produce shock, histamine causes a quickly progressive dilatation of both the visible and the occult capillaries and of their immediately adjacent arterioles and venules, all of which become engorged with blood that moves through them in a strikingly sluggish manner. The circulatory failure which characterizes histamine shock results from the dilatation of the peripheral vascular bed.     

四肢血管损伤的急诊诊断与治疗(附73例报告)

目的：提高对四肢血管损伤的诊断水平。方法：对14年间收治的四肢主要动脉损伤73例进行分析。结果：切割、刺伤55例,闭合性损伤18例。急诊明确诊断59例。47例行对端吻合或自体静脉移植,43例成功。漏诊3例,截肢6例。结论：对四肢血管伤应高度警惕．及时诊断。应用多参数监护仪进行伤肢脉搏波血氧测定有助于早期诊断动脉损伤,能动态监护肢体血供,使用方便,诊断准确。主张及时作探查及血管修复手术治疗。     

THE R?LE OF THE THEBESIAN VESSELS IN THE CIRCULATION OF THE HEART

In summary, evidence has been presented to show a direct connection other than through the capillaries between the coronary arteries and the chambers of the heart. This connection was shown by perfusion, injections and serial sections to be through the Thebesian veins. Communications between the larger coronary veins and the Thebesian veins were also demonstrated by the same methods. Serial sections through Thebesian veins have shown capillaries draining directly into them. Under certain conditions it has been shown that as much as 90 per cent of the arterial flow may escape via the Thebesian vessels. Lastly, in the event of gradual closure of the orifices of the coronary arteries, the Thebesian vessels can supply the heart muscle with sufficient blood to enable it to maintain an efficient circulation.     

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.     

ETIOLOGY OF OROYA FEVER : VI. PATHOLOGICAL CHANGES OBSERVED IN ANIMALS EXPERIMENTALLY INFECTED WITH BARTONELLA BACILLIFORMIS. THE DISTRIBUTION OF THE PARASITES IN THE TISSUES.

The pathological changes observed in the organs in Macacus rhesus monkeys which have succumbed to severe infection with Bartonella bacilliformis are similar to those found in human organs in persons dying of Oroya fever. The characteristic changes in the liver are the zonal necrosis of the cells around the hepatic veins, involving active macrophagocytosis of invading polymorphonuclear leucocytes in the necrotic areas, and a marked endothelial hyperplasia in the sinusoids or around the portal veins. In some instances there is fatty infiltration of hepatic cells. In the spleen persistent hyperplasia of the endothelial cells of the capillaries leads to the formation of minute foci of infarction, owing to occlusion of the lumina. The follicles are dispersed or reduced, and there is an active macrophagocytosis of cellular débris, polymorphonuclear leucocytes, and erythrocytes. In some specimens an increase in normoblasts is noted. Pigment is sometimes present. The lymphatic system shows general progressive endothelial hyperplasia, with active invasion of macrophages which contain polymorphonuclear leucocytes, erythrocytes, and greenish or dark pigments. In the bone marrow there is increased activity of macrophagocytes. Numerous normoblasts are found in some instances. In one monkey, sacrificed during the course of infection, small, verruga-like nodules were found in the lungs and spleen. Bartonella bacilliformis has been detected microscopically, though in small numbers, in all tissues showing histological changes. Parallel cultural determinations of the presence of Bartonella bacilliformis in the blood, liver, spleen, lymphatic glands, bone marrow, and local lesions established the relationship between the pathological conditions and the presence of the parasite. The organism seems to persist longest in the lymphatic glands. Cultural methods offer a simple and conclusive means for the determination of the presence or absence of the infecting organism.     

STUDIES ON THE MECHANISM OF IMMUNITY IN TYPHUS FEVER : I. RICKETTSIA PROWAZEKI IN THE DIFFERENT STAGES OF THE TYPHUS LESION

This study of the lesions produced in the skin of guinea pigs inoculated intracutaneously with Mexican typhus virus, shows that there is an early polymorphonuclear response at the point of inoculation. As early as 24 hours after the virus is given, a mononuclear phagocytic infiltration, which is more pronounced around the larger vessels of the corium, vascularis, and muscularis, replaces the polymorphonuclear infiltration. The endothelial cells of capillaries and small vessels swell up, thus partially occluding the lumina. Rickettsia bodies are found in the swollen cells, in numbers which remind one of the intracellular Rickettsiae of the tunica in typhus infected guinea pigs. The mature Mooser''s cells are found in abundance on the 3rd to the 4th day after inoculation. They are found in various positions as follows: (a) in the endothelial cells of capillaries, particularly in places of little or no infiltration; (b) within the mononuclear nodules formed around the larger vessels and within the dense infiltration of the vascularis (the parasitized cells are usually traced to a capillary wall); and (c) less frequently the organisms are found within the swollen cells of arterioles and small veins. The organisms disappear gradually from the zones of increasing polymorphonuclear infiltrations, suggesting that the presence of such polymorphonuclears is due to the bursting of the infected cells. In the artificial lesions produced in the skin by the inoculation of considerable numbers of Rickettsiae, the tissue reactions are abnormally enhanced. One can see in the same slide different stages of the development of the lesions and their relationship to the infecting agent. The early perivascular infiltration by mononuclear phagocytes does not seem to be related to an actual infection of the endothelial lining by the inoculated virus, but seems rather, when properly controlled, to be primarily due to a nonspecific type of response. The capillaries or small vessels within these infiltrated zones may become parasitized and call forth a polymorphonuclear reaction which may thus transform the cytological picture of the nodule. The subsequent migration of macrophages terminates the histological sequence. In capillaries apart from areas of cellular infiltrations, the polymorphonuclear reaction is first to appear, when the Rickettsiae are liberated from the cells. One cannot safely generalize from the results observed in an artificial typhus lesion, but in the light of these observations, it is probable that the Rickettsia bodies are difficult to find in typhus patients or infected animals because they disappear rapidly from the nodules, or perhaps because some nodules are not necessarily related to an infected endothelium. At any rate, a late typhus lesion is not likely to reveal Rickettsiae which most probably have been removed by the early polymorphonuclear invasion.     

A STUDY ON THE MECHANISM OF INVASIVENESS OF STREPTOCOCCI

1. Menkin''s observations of the failure of inflammatory fixation in areas of acute inflammation due to Streptococcus haemolyticus have been confirmed. 2. The lack of inflammatory fixation in the presence of streptococci is not due to the passive nature of the streptococcus, but may be attributed to the production of (1) fibrinolytic, and (2) antifibrinogenic substances which dissolve the fibrin barrier, or prevent its formation, thus maintaining the patency of the lymphatics and capillaries and facilitating the dissemination of the organisms. 3. The production of fibrinolytic or antifibrinogenic substances, and the invasiveness of a given strain of streptococcus are correlative. 4. Both substances are relatively thermostable. Fibrinolysin is destroyed if held at 100°C. for 1 hour. The antifibrinogenic substance is weakened but is not destroyed under the same conditions. 5. There is evidence that both substances are antigenic, and exhibit some degree of type specificity. 6. The role of fibrinolysin and the antifibrinogenic factor in the invasion of the tissues by streptococci is discussed.     

STUDIES ON INFLAMMATION : IX. A FACTOR IN THE MECHANISM OF INVASIVENESS BY PYOGENIC BACTERIA

Trypan blue injected into an area of cutaneous inflammation induced by Staphylococcus aureus failed to drain readily to the tributary lymphatics when the dye was injected as early as 1 hour after the inoculation of the microorganisms. Trypan blue introduced into an area of cutaneous inflammation induced by Pneumococcus Type I was retained in situ when the dye was injected about 6 or more hours after the inoculation of the bacteria. When an area of cutaneous inflammation was induced by the inoculation of a culture of Streptococcus hemolyticus, trypan blue injected into it drained readily to the tributary lymphatics for the first 30 hours following the onset of the inflammatory reaction. When the inflammation had lasted for 45 hours or longer, the dye was fixed in situ and failed in most instances to reach readily the tributary lymphatics. The rapidity of fixation of the dye in the instances given would appear to depend on mechanical obstruction in the form of both a fibrinous network and thrombosed lymphatics or thrombosed lymphatics alone at the site of inflammation. Inasmuch as staphylococci, pneumococci, and streptococci spread from the site of cutaneous inoculation primarily through lymphatic channels, the difference in the rapidity with which mechanical obstruction is set up in the areas inflamed by them will help to explain the differing invasive abilities of these pyogenic organisms.     

STUDIES ON EXPERIMENTAL HYPERTENSION : XIX. THE PRODUCTION OF PERSISTENT HYPERTENSION IN SHEEP AND GOATS

Persistent hypertension has been produced in the goat and sheep by constriction of the main renal arteries. The presence or absence of accompanying uremia depends upon the degree of constriction of the renal arteries. In both sheep and goat, constriction of one main renal artery also caused elevation of the blood pressure which tended to persist longer than in the dog. Excision of the one kidney with main renal artery constricted resulted in a prompt (24 hours) return of the blood pressure to normal. In the animals with hypertension of long duration but without renal excretory insufficiency, (the "benign" phase) no significant arterio- or arteriolosclerosis developed as a result of the hypertension alone. In the animals that had both hypertension and renal excretory insufficiency, (the "malignant" phase) the typical terminal arteriolar lesions developed in many organs. These lesions consisted of necrosis and fibrinoid degeneration of arterioles and necrotizing arteriolitis which should not be confused with arteriolosclerosis. The same humoral mechanism which is responsible for experimental renal hypertension in the dog and other animals also obtains in the pathogenesis of experimental renal hypertension in the sheep and goat.     

Differential reactivity in the pulmonary circulation

A new method for relating regional intravascular resistance to pulmonary arterial, capillary, and venous pressure and volume was used to evaluate local differences of reactivity in the pulmonary blood vessels in the isolated lung lobe of the dog.Intravascular infusion of isoproterenol caused active dilatation of pulmonary arteries and veins. Capillary conductance (1/resistance) and volume increased, possibly as a result of the opening of previously closed capillaries. Serotonin infusion caused active constriction of both the pulmonary arteries and veins. A low dose of serotonin (1.5 mug/min per kg) caused predominant constriction of whichever vessels were upstream (arteries during forward perfusion, veins during reverse perfusion). A high dose of serotonin (4.5-5.0 mug/min per kg) caused constriction of both upstream and downstream vessels. Metabolic inactivation of serotonin by the lung is suggested as an explanation for these observations. Histamine infusion caused predominant venous constriction whether veins were upstream or downstream. Capillary volume and conductance decreased during forward and reverse perfusion, perhaps as a result of pericapillary edema formation. Large arterial vessels constricted slightly, whereas small arterial vessels appeared to be passively dilated.     

PATHOGENESIS OF EXPERIMENTAL SHOCK : III. A LETHAL FACTOR IN THE BLOOD OF RABBITS FOLLOWING OCCLUSION OF THE SUPERIOR MESENTERIC ARTERY

Donor rabbits were subjected to shock by occlusion of the superior mesenteric artery (SMAO shock). Portal blood was collected from these animals at certain intervals after release of the arterial ligature. Infusion of this blood into sub-lethally hemorrhaged rabbits caused the death of half of the tested animals; a mortality incidence which closely matched the per cent mortality in rabbits shocked by SMA occlusion alone. Blood from sham-operated donor animals did not prove lethal when infused into hemorrhage-prepared rabbits. Infusion of SMAO shock plasma did not result in the death of recipient animals, even though the whole blood source of the plasma had proven to be lethal upon infusion into hemorrhage-prepared rabbits. Moreover, following pretreatment of donor animals with a non-absorbable antibiotic per os, the number of actively reproducing bacteria in the intestinal fluids was reduced to less than 0.1 per cent of normal; nevertheless, the incidence of passive transfer of lethality from shocked donors receiving this pretreatment was not consistently reduced. Furthermore, when SMAO shock portal blood was tested for the presence of bacterial endotoxin by the sensitive dermal epinephrine reaction, although some blood samples demonstrated lesion-provoking activity, there was no correlation between this activity and the lethal properties of the blood samples. In seeking an explanation for the production of dermal epinephrine lesions by non-lethal shock blood, a positive correlation was demonstrated between the lesion-provoking activity of portal blood and the serotonin content of intestinal tissues of rabbits shocked by SMA ligation. In addition, small amounts of serotonin were shown to be capable of provoking dermal epinephrine reactions in rabbits, under the same conditions used to test the lesion-provoking activity of portal blood. It was therefore concluded that: (a) a toxic factor(s) is present in the portal blood of SMAO-shocked rabbits; (b) that this factor(s) is not likely to be a bacterial endotoxin; and (c) that the occasional provocation of a dermal epinephrine reaction by portal blood from SMAO-shocked rabbits, a property heretofore exclusively attributed to the presence of endotoxin in shock blood, can be entirely explained on the basis of elevated levels of serotonin in this blood.