Active Constriction Research Articles

Filaments in the division furrow of mouse mammary cells.

Of the various theories that have been advanced to account for the mechanism of furrow formation and cytokinesis in animal cells (9, 21), the notion of active constriction in the equatorial cortex has recently received support from physical measurements such as those reported by Wolpert (22) and Rappaport (13) . A probable structural manifestation of the ring has been found through ultrastructural studies of cleaving invertebrate eggs, in which equatorially oriented filaments in the cleavage furrow suggest a region specialized for contraction (3, 7, 15, 17, 18) . These bundles of presumably contractile filaments have not been described in dividing cells of vertebrates or in dividing tissue cells of any organism . The present study reports the presence of a well organized filamentous component in the division furrows of mouse mammary epithelial cells .

In vivo measurement of dimensions of veins with implications regarding control of venous return.

Control of the capacity of the venous system has been postulated as necessary to provide increased venous return to initiate an increase in cardiac output. In chronic animal experiments, we have studied the dimensions of the liver, spleen, and the superior vena cava as venous reservoirs in relation to fright, exercise, and shock. Two methods used were miniature mutual inductance coils and ultrasonic transit time technique; the former is a relatively simple and reliable, but nonquantifiable method. The sonar method is quantifiable, but to date has been unsatisfactory for narrow ranges. The spleen in the dog is a superb volume reservoir, but the liver is not. The superior vena cava, in at least some circumstances, demonstrates active constriction. With the onset of exercise, flow increased in the cava before either an increase in heart rate or an increase in stroke volume. With hemorrhagic shock, pooling of blood in the mesenteric veins was sometimes found, but there was no evidence of failure of the neural mechanisms of venoconstriction, evidenced by a marked, agonal contraction. With endotoxin shock, no portal pooling was observed; earlier reports of pooling based on weight changes were probably due to extravasated plasma secondary to endothelial damage and marked portal venoconstriction. Venous pooling in the legs in man in shock can be prevented by elevation of the legs without the disadvantages of the head-down (Trendelenburg) position.

Pulmonary Vasoconstriction Due to Nonocclusive Distention of Large Pulmonary Arteries in the Dog

The pulmonary vascular changes caused by distention of the pulmonary artery with the lumen fixed were compared to those produced by occlusive arterial distention. In 13 urethane-anesthetized dogs, nonocclusive distention was produced by distention of a corrugated rubber cuff around a hollow metal cylinder affixed to the end of a cardiac catheter. In 10 other dogs, occlusive distention was produced by inflation of a standard balloon catheter. Pressures were measured in large and small pulmonary veins and in the left and right atria with transseptal techniques, and in the pulmonary and femoral arteries. Simultaneously, pulmonary blood volume and flow were measured with dyedilution techniques. Pulmonary arteriovenous shunting was studied with the hydrogen-electrode technique. Nonocclusive distention of a pulmonary artery greatly increased pulmonary arterial and venous pressure and decreased pulmonary blood volume without changing left atrial pressure or cardiac output. Pulmonary vascular resistances increased, and pulmonary arteriovenous shunting was detected. Occlusive distention of one pulmonary artery caused smaller increases in pressure in the pulmonary artery and vein of the unobstructed lung. Vascular resistances in the unobstructed lung decreased, while blood volume and flow in that lung doubled. Pulmonary arterial distention leads to active constriction of the pulmonary arteries and veins, but these responses may be obscured by the passive responses to increasing blood flow and volume.

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.

The relationship between active constriction and passive recoil of the veins at various distending pressures.

AbstractThe vasoconstrictor fibre influence on veins, exposed to varying distending pressures, was analysed with respect to the relative contribution of active venoconstruction and passive venous recoil, respectively, to total venous blood mobilization. The results indicate that active venoconstriction can produce only a minor reduction of venous capacity when venous transmural pressure is low but a considerable diminution of the capacity at higher venous pressures, provided the pressure is not so high as to “overstretch” the muscle elements. — The passive emptying of blood at vasoconstrictor fibre stimulation is very pronounced in the low pressure range, but becomes small at higher pressures, in accordance with the pressure‐volume characteristics of the veins, demonstrating an apparently very high distensibility at low pressures. This high “distensibility” is mainly due to changes of vessel geometry, associated with the collapse, and does not reflect true wall distensibility. … Consequently, when venous pressure is low, venous function is primarily governed by passive factors, while active shortening of venous smooth muscles will play a dominant role first when the vessels are kept well distended. — The implications of these findings for venous control is discussed, with special respect to man, where venous pressure varies greatly with body position. Some methods earlier used for assessing venous tone changes are critically analysed.

A smooth muscle contracting substance in extracts of human umbilical cord.

AT the birth of most mammals the umbilical cord is not ligatured and serious haemorrhage seldom occurs1. In man active constriction of the umbilical blood vessels follows delivery.

ROLE OF TRANSMURAL PRESSURE IN LOCAL REGULATION OF BLOOD FLOW THROUGH KIDNEY.

In the kidney of the anesthetized dog, the pressure in an occluded hilar lymphatic vessel was used as an index of tissue pressure. While elevation of renal vein pressure produced a large rise in lymphatic pressure, reduction of renal artery pressure had little effect. Similarly, while elevation of vein pressure at constant flow produced an almost equal rise in lymphatic pressure, large changes in blood flow and hence artery pressure had little effect, despite evidence of local regulation of resistance. Intra-arterial injection of vasoactive agents at constant flow, which produced large changes in renal artery pressure, had little effect on lymphatic pressure. Sudden transient increase in renal blood flow sometimes produced changes in perfusion pressure which could have resulted from active constriction subsequent to rise in transmural pressure. These findings provide little support for the tissue pressure theory of autoregulation but suggest that tissue pressure does participate in the vascular response to elevated vein pressure. The study also provides some evidence for a vascular myogenic response to change in renal vascular transmural pressure.

MECHANISM OF VOLUME REPLACEMENT AND VASCULAR CONSTRICTION FOLLOWING HEMORRHAGE.

Experiments in the anesthetized dog suggest that fluid moves into the vascular system following hemorrhage because of fall in capillary hydrostatic pressure subsequent to decrease in aortic and right atrial pressures and increase in precapillary resistance. Postcapillary resistance also rises but not sufficiently to prevent the fall in capillary pressure. The increase in precapillary resistance results from active constriction, passive constriction, and, very transiently, increase in blood viscosity. The active constriction of precapillary vessels is due to a baroreceptor-induced sympathico-adrenal discharge and to some nonadrenal, nonrenal circulating vasoconstrictor substance. The active vasoconstriction is not well maintained in forelimb, intestine, or kidney because of local regulation ("autoregulation") and baroreceptor-induced lessening of the sympathico-adrenal discharge subsequent to movement of tissue fluid into the vascular system. This waning constriction together with a rise in perfusion pressure permits partial recovery of flow. The increase in forelimb postcapillary resistance results mainly from passive constriction. Active constriction subsequent to the sympathico-adrenal discharge is seen only with large hemorrhage.

EXPERIMENTAL STUDIES ON THE INFLUENCE BY THE CHANGE OF RESPIRATORY PATTERN CONCERNING THE PULMONARY CIRCULATION AND ITS REGULATION

The magnitude of pulmonary vascular resistance will be one of the important criteria for pulmonary circulatory function, because it elevates pulmonary arterial pressure to bring about pressure load in the right ventricle of the heart. It being, however, known that, at the pulmonary circulatory system, its anatomical features give some limitation to the application of POISEUILLE-HAGEN Law, the change of pulmonary vascular resistance cannot necessarily result in the active constriction or the dilatation of pulmonary vessels. Meanwhile, since lungs are always influenced with the change of intrapleural pressure, the influence by the change of respiration in terms of its depth or its pattern, should always be taken in consideration. In light of this, the author had the following experiments using normal dogs and experimental pulmonary-hypertension dogs as the subjects : (1) the inflation of intratracheal pressure under the intermittent positive pressure breathing. (2) hyperventilation (by using a body respirator) (3) hypoventilation-lowtidal ventilation-(by using a body respirator) (4) stellectomie (5) intervenous infusion of C6 (6) vagotomy Through this experimentation, he observed the right ventricular function as well as how the change of each respiratory pattern mentioned in the above experiments affected pulmonary arterial pressure and pulmonary vascular resistance, and affected their regulatory mechanism. Materials and Mehtod As to both the normal dogs and the pulmonary-hypertension dogs (into the bronchi of which resin was infused), the circulatory dynamics, before and during the controlled respiration, and, before and during the blocking of the auto-nomic nervous system, were observed. In other words, the right ventricular function and the pressure-flow relationship in the pulmonary circulatory system were investigated using the cardiac catheterization method and the dye dilution method based on the modified BING-HOLZ method.

Murmurs Arising from Ductus Arteriosus in Normal Newborn Swine

The natural history of murmurs arising from the ductus arteriosus was investigated in normal newborn swine and compared with observations in other animals and infants at term. Ausenltation of 206 swine examined between birth and two weeks of age revealed a high incidence of continuous murmurs in the first six hours of life, crescendo systolic murmurs in 5% to 10% of animals during the first 24 hours and early systolic murmurs in a large proportion of the animals throughout the first week. Absence of a murmur was rare one to two hours after birth but, by 24 hours, less than 50% of the swine had murmurs of any type and after one week only one of 34 animals studied had a murmur. The continuous murmur was often preceded or followed by a crescendo systolic or early systolic murmur and it is proposed that all three murmurs arise from the ductus arteriosus under different conditions. Internal sound recordings with a phonocatheter in the thoracic aorta demonstrated a systolic murmur loudest at the orifice of the ductus arteriosus in all swine in the first six hours of life and in a decreasing proportion of animals thereafter. Evidence is presented to suggest that this murmur is closely linked to patency of the ductus arteriosus but is different in origin from the murmur normally heard on auscultation of the chest. In four animals under six hours of age the phonocatheter passed through the ductus into the pulmonary artery and a continuous murmur was recorded. In two older swine the phono-catheter traversed the ductus but in these cases the murmur in the main pulmonary artery was confined to systole. Since the occurrence of the different murmurs could not be satisfatorily explained on the basis of the systolic pressure gradient across the ductus nor on the basis of the anatomical size of the ductus at necropsy, it is postulated that the type of murmur generated is a reflection of the degree of narrowing of the lumen of the ductus produced by active constriction of its muscular wall during life.

Venous response of intestine to endotoxin.

Extensive congestion of the splanchnic bed has been observed in the dog after lethal injections of endotoxin. The purpose of this investigation was to determine the role of small mesenteric veins in the development of visceral pooling; isolated sections of small intestines were removed from dogs and continuously perfused with blood obtained from intact dogs administered lethal injections of E. coli endotoxin. Results show significant mesenteric venous responses to blood-borne agents. Increases in venous segment resistance and intestine weight were found during the postendotoxin period. Evidence indicates that the progressive development of splanchnic pooling is primarily due to active constriction of small veins in which responsiveness to epinephrine is enhanced by endotoxin.

Effect of epinephrine and norepinephrine on coronary vascular resistance in dogs.

The effects of intracoronary injection and infusion of epinephrine and norepinephrine have been studied in the beating and fibrillating dog heart. The heart performed no external work and coronary perfusion pressure was measured with the rate of blood flow through the coronary vascular bed held constant. Injection of both agents most often produced a fleeting rise in pressure followed by a prolonged fall in pressure. In the beating heart, the pressure rise preceded rise in heart rate. Slow infusion of norepinephrine often produced a small pressure rise whereas rapid infusion always produced a large pressure fall. Epinephrine sometimes produced similar changes but more often the pressure fell progressively as a function of the rate of infusion. The pressure rise frequently was unassociated with a change in heart rate or the proportion of a minute spent in systole. Both parameters, as well as oxygen consumption, increased with high rates of infusion. These findings suggest that the direct effect of these agents on coronary vessels is active constriction, whereas the indirect effect is active dilatation. In low concentrations the direct effect may predominate, resulting in a resistance increase, whereas in high concentrations the indirect effect always predominates, resulting in a decrease of resistance.

Some evidence for active constriction in the human pulmonary vascular bed.

Continuous infusion of norepinephrine in man caused a rise in pulmonary arteriolar resistance as measured by pulmonary artery-pulmonary wedge pressure differences. Since no change in flow occurred during the procedures, the data suggest active constriction of the pulmonary vascular bed under these circumstances.

A guide to the theory of arterial hypertension.

A GUIDE TO THE THEORY OF ARTERIAL HYPERTENSION IRVINE H. PAGE, M.D.; J. W. McCUBBIN, M.D.; AND A. C. CORCORAN, M.D.* Somewhat more than twenty-five years ago, study ofarterial hypertension slowly began to assume an importance quite unknown in the centuries before. This was due to both people and specific discoveries. Fortunately , it is unnecessary to choose which was the most important. Thus the past quarter-century has seen great growth in knowledge of the mechanisms of hypertension. As so often happens at the beginning, the problems seem relatively simple. But, as more and more is known, the complexity and beauty of nature's processes become evident, and, with this realization, humility replaces overconfidence. Most investigators now know that the end is not yet; hypertension will not yield its secrets easily. Yet there are many bright vistas along which we may look, andthese may well form the pattern ofdiscovery which will lead to understanding ofhow blood pressure is controlled. Our purpose in this article is to describe where we stand in 1958. I. Mechanisms ofHypertension A. ARTERIOLAR TONE AND REACTIVITY To provide a perspective ofhypertension, it seems appropriate to start by examining the mechanisms that determine arteriolar size, since increased arteriolar resistance to blood flow is largely accountable for most forms of hypertension. Some of these mechanisms are distant from the arteriole and are mediated by nerve impulses or circulating vasoactive agents. Several factors are local; others can be labeled as "intrinsic," and it is these that are perhaps the least understood, least studied, and most unappreciated . The main function of arterioles is to regulate blood flow * Research Division of the Cleveland Clinic Foundation and the Frank E. Bunts Educational Institute, Cleveland, Ohio. 307 through capillaries, and it is highly improbable that the regulatory function is not correlated with the proper need oftissues for blood. It is well known, for instance, that ischemia or exercise, which causes local accumulation of metabolites, causes extreme vasodilation. While these are dramatic examples of the ability of tissues to let their needs be known, there must be similar and continuous effects during more normal states, and it is not unreasonable to expect these influences to modify the intrinsic properties of smooth muscle as well as directly to affect arteriolar size. Arteriolar smooth muscle shows a degree ofinherent tension, or resistance to stretch, even when isolated from all known neurogenic or humoral stimuli. This intrinsic property ofsmooth muscle and the factors that influence it are little understood and should be chief targets for future research . We emphasize the important fact that a change in resting or basal tone causing only a small decrease in arteriolar diameter would result in a disproportionately large rise in resistance to blood flow. Closely associated with tone ofarteriolar muscle is automaticity, a property common to most smooth muscle. Some evidence indicates, for instance , that vascular smooth muscle responds to the stretching effect of blood pressure with active constriction, and other evidence indicates that it undergoes more or less continuous alternating constriction and dilation, even in the absence ofmechanical stimuli. Vasomotion of this sort is difficult to demonstrate clearly and has, therefore, received relatively little study; but it and the factors influencing it can be expected to modify importantly the total peripheral resistance to blood flow. It is logical to search for causes ofhypertension by examining the local mechanisms that influence the arterioles' normal function—-the regulation of blood supply to tissues. These intrinsic properties of arteriolar smooth muscle are very likely influenced significantly by intra- and extra-cellular sodium and potassium concentrations and by movement ofthese ions in and out ofmuscle cells. Sodium and potassium, as well as other ions, are importantly concerned in basic processes of smooth-muscle contraction; on the other hand, a local excess or shortage ofone ion or another, per se, does not seem to be the culprit. Rather, the factors that determine electrolyte metabolism of muscle in turn affect its intrinsic functions. These are numerous and run the gamut from neurogenic impulses through a wide range of humoral 308 /. H. Page,J. W. McCubbin, and A. C. Corcoran ¦ Arterial Hypertension Perspectives in Biology and Medicine · Spring 1958 agents. In this connection...

Active constriction of small pulmonary arteries in rabbit.

This communication deals with the demonstration of active pulmonary vasomotion by injecting plastic material (vinyl acetate) which forms casts of the small pulmonary arteries simultaneously on a control side and on the test side submitted to action of vasoconstrictor drugs. Comparisons were made by direct microscopic observations and by weighing the casts after the lung tissue had been digested. Other indices such as relative weight of the two lungs, relative denseness of vascularity and estimates of pulmonary resistance supplied supplementary evidence of pulmonary vasomotion.

Active constriction and dilatation in pulmonary circulation in response to acetylcholine.

Summary and conclusionsThe effects of acetylcholine on pulmonary vascular bed of intact dogs were studied in an experiment in which the drug could be excluded from the systemic circulation. While larger doses (usually greater than 0.1 mg) injected into the pulmonary artery were followed by increased pulmonary vascular resistance, smaller doses lowered pulmonary vascular resistance. Exclusion of extrapulmonary factors indicated active pulmonary vasoconstriction and vasodilatation. The larger doses also caused bronchomotor activity. However, the lack of intratracheal pressure changes with pulmonary vasodilating doses of acetylcholine or vasoconstricting doses of norepinephrine, and the absence of pulmonary hypertension with nebulization of acetylcholine indicated that pulmonary vascular resistance alterations were not dependent upon changes in bronchomotor tone.

Cardiovascular effects of acutely raised intracranial pressure.

Cardiovascular effects of acute elevations of intracranial pressure were studied, with special reference to three questions: a) whether vasoconstriction or cardiac stimulation is primarily responsible for the pressor response to this stimulus; b) whether the ultimate nature of the stimulus is neurogenic or humoral; and c) whether or not changes in venous tone occur in response to ICP elevation. It is concluded from the experimental findings that vasoconstriction was the dominant factor in the response, that the reflex is primarily neurogenic, and that the venomotor system shows an active constriction which accompanies the arterial pressure rise.

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.

Studies in the Pathology of Blood Vessels in Man. IV. Volume Changes in Human Finger-Tip Following Sudden Venous Obstruction.

SummarySecondary spontaneous diminution of volume of the finger-tip following sudden partial obstruction of the venous flow from the part is reported. The reaction seems to be due to active constriction of veins, venules and capillaries which may be initiated by increased tension within these vessels.

STUDIES IN INACCESSIBLE INTERNAL HEMORRHAGES

<h3>I. INTRODUCTION</h3> From a therapeutic point of view hemorrhages may be classified as<i>accessible</i>, i. e., those that can be directly influenced by drugs and<i>inaccessible</i>, i. e., those that can be influenced by drugs only through the circulation. In the former class come hemorrhages from the mouth, nose, throat, eye, wounds, etc., and such internal hemorrhages as can be reached by topical applications, viz., those from the uterus, urethra, bladder, stomach, rectum, etc. In the latter class may be listed intestinal, pulmonary, renal, uterine and cerebral hemorrhages. The value of adrenalin in accessible hemorrhages is well recognized, but so far its use in inaccessible hemorrhages has been condemned rather than commended by our best therapeutists. The chief reason for this is the fact that adrenalin, when introduced into the vascular system, not only causes an active constriction at the point of bleeding, but also raises the