Vasomotor Apparatus Research Articles

Age-dependent neurovascular dysfunction and damage in a mouse model of cerebral amyloid angiopathy.

Accumulation of amyloid-β in cerebral blood vessels occurs in familial and sporadic forms of cerebral amyloid angiopathy and is a prominent feature of Alzheimer disease. However, the functional correlates of the vascular pathology induced by cerebral amyloid angiopathy and the mechanisms involved have not been fully established. We used male transgenic mice expressing the Swedish, Iowa, and Dutch mutations of the amyloid precursor protein (Tg-SwDI) to examine the effect of cerebral amyloid angiopathy on cerebrovascular structure and function. Somatosensory cortex cerebral blood flow was monitored by laser-Doppler flowmetry in anesthetized Tg-SwDI mice and wild-type littermates equipped with a cranial window. Tg-SwDI mice exhibited reductions in cerebral blood flow responses to whisker stimulation, endothelium-dependent vasodilators, or hypercapnia at 3 months when compared with wild-type mice, whereas the response to adenosine was not attenuated. However, at 18 and 24 months, all cerebrovascular responses were markedly reduced. At this time, there was evidence of cerebrovascular amyloid deposition, smooth muscle fragmentation, and pericyte loss. Neocortical superfusion with the free radical scavenger manganic(I-II)meso-tetrakis(4-benzoic acid) porphyrin rescued endothelium-dependent responses and functional hyperemia completely at 3 months but only partially at 18 months. Tg-SwDI mice exhibit a profound age-dependent cerebrovascular dysfunction, involving multiple regulatory mechanisms. Early in the disease process, oxidative stress is responsible for most of the vascular dysfunction, but with advancing disease structural alterations of the vasomotor apparatus also play a role. Early therapeutic interventions are likely to have the best chance to counteract the deleterious vascular effects of cerebral amyloid angiopathy.

Peculiarities of vasomotor reaction of cerebral vessels in arterial hypertension

We studied vasomotor activity of rat cerebral vessels. Peculiarities of endothelium-dependent reactions of cerebral arteries in induced arterial hypertension were revealed. Quantitative and qualitative relationships between the parameters of the vasomotor apparatus of cerebral arteries and parameters of circulatory homeostasis were determined.

Brain cooling in humans--anatomical considerations.

Vascular arrangements allowing a bulky transfer of venous blood from the skin of the head and from nasal and paranasal mucous membranes to the dura matter provide an excellent anatomical basis for the convection process of cooling, caused by evaporation of sweat or mucus. The dura mater, with its extraordinarily high vascularization controlled by a potent vasomotor apparatus, may transmit temperature changes to the cerebrospinal fluid (CSF) compartment. Temperature gradients of the CSF may in turn influence the temperature of brain parenchyma (1) directly, along the extensive contact area between the cerebrocortical surface and the CSF-compartment, or (2) indirectly, via brain arteries that extend over long distances and arborize within the subarachnoid space before entering the pial vascular network and brain parenchyma. Numerous subarachnoid and pial arterial branches exposed to the CSF have diameters in the range of the vessels of the retia mirabilia of animals in which selective brain cooling has been clearly established experimentally. It is also shown that the arrangements of venous plexuses within the vertebral canal provide anatomical preconditions for a cooling of the spinal cord via the CSF. The possibility of spinal cord and spinal ganglia cooling by temperature convection via venous blood--cooled in the venous networks of the skin of the back--flowing through numerous anastomoses to the external and internal vertebral plexuses and, finally, into the vascular bed of the spinal dura is discussed on the basis of anatomical facts.

Clinical significance of intravascular coagulation.

In conclusion, intravascular coagulation in the microcirculation is an important intermediary mechanism of disease. It is always secondary to a primary etiologic factor, but often accounts for some of the major pathological and clinical manifestations of many diseases. It may be acute or chronic, local or disseminated, and is a major factor in the development of hypercoagulable blood with secondary thrombosis of large veins or arteries. Comprehension of its biological significance requires knowledge of the pathological anatomy as well as the physiological and biochemical changes in the blood and vasomotor apparatus in each individual disease or patient.

STUDIES ON HYPERTENSION

HIGH spinal anesthesia was employed in previous studies 1 to lower the blood pressure of patients with essential hypertension. From these studies certain information and conclusions have been drawn regarding the probability that the drop in blood pressure is due to interruption of vasomotor function. The work of Smith and his associates 2 and Rovenstine and his associates 3 suggested that the fall in blood pressure due to spinal anesthesia is due to decreased cardiac output resulting from decreased venous pressure and diminished venous return to the heart. In view of the fact that both of these studies were done on subjects with normal blood pressure, it appears necessary that these observations be applied to patients with essential hypertension. It is conceivable that the role played by the vasomotor apparatus in maintaining normal blood pressure may be different from the role of this mechanism in maintaining elevations of arterial

STUDIES ON HYPERTENSION

HIGH spinal anesthesia was employed in previous studies 1 to lower the blood pressure of patients with essential hypertension. From these studies certain information and conclusions have been drawn regarding the probability that the drop in blood pressure is due to interruption of vasomotor function. The work of Smith and his associates 2 and Rovenstine and his associates 3 suggested that the fall in blood pressure due to spinal anesthesia is due to decreased cardiac output resulting from decreased venous pressure and diminished venous return to the heart. In view of the fact that both of these studies were done on subjects with normal blood pressure, it appears necessary that these observations be applied to patients with essential hypertension. It is conceivable that the role played by the vasomotor apparatus in maintaining normal blood pressure may be different from the role of this mechanism in maintaining elevations of arterial

THE ELECTROCARDIOGRAM IN DIPHTHERIA

Circulatory failure has long been recognized as a frequent cause of death in cases of diphtheria. Investigators differ as to the exact mechanism of this process. Some believe that the fall of blood pressure and the circulatory collapse is a result of a myocardial weakness, while others insist that it is due to primary failure of the vasomotor apparatus, either central or peripheral. Electrocardiographic studies1made during the acute stage of the infection show evidences of myocardial damage in a majority of cases. Changes during the acute period are chiefly those of disturbances in auriculoventricular and intraventricular conduction. It is well known that in the late and convalescent periods, an acute collapse or sudden death may occur, usually after slight exertion. There are no reliable clinical criteria by which such a cardiac involvement may be detected during this stage. With a view of determining whether the string galvanometer may give

Observations on the Mechanism of Circulatory Failure in Diphtheria.

This report consists of study by means of the string galvanometer of the effects of diphtheria toxin upon the heart. It has long been known that a circulatory collapse may occur in diphtheria, which frequently results in death. There is still considerable uncertainty, however, as to whether it is the heart or the vasomotor apparatus which is primarily effected.In the present study electrocardiographic observations were carried out (1) on a series of diphtheria patients (2) on animals injected with diphtheria toxin.Previous observers1, 2, 3, 4 have noted electrocardiographic changes indicating myocardial injury during the acute stage of diphtheria. The present investigation was made during the convalescent or late stage of the disease, since circulatory failure may occur during this period also.Readings were taken of 15 diphtheria patients during the period of convalescence, beginning usually in the 3rd or 4th week of their illness. In all cases, the local throat condition had entirely cleared up, and the ...

A STUDY OF THE CIRCULATION, BLOOD PRESSURE, AND RESPIRATION OF SHARKS

The average branchial blood pressure in sand sharks was 32 mm. of mercury. The highest recorded in a resting animal was 43 mm. The average dorsal or systemic pressure was 23.3 mm.; highest 30 mm. The ratio of branchial to systemic pressure is about 3 to 2. The pressure in both systems keeps up well under trauma; but under experimental conditions, with or without manipulation of viscera, slowly falls after several hours. It rises with muscular effort, and a long rise usually follows stoppage of struggling. It rises when sodium carbonate is injected. The adrenalin curve resembles that in a mammal. Spontaneous rises and falls not attributable to the heart occur. Light in some animals increases blood pressure. It is suspected that these fishes have a vasomotor apparatus. The heart rate except after trauma is practically always the same as the respiration rate, and there is some reason for believing that the heart rate is determined by the respiration rate. When not in step with respiration, the heart is slower and often in a simple ratio with respiration. The heart is inhibited by all sorts of stimuli applied practically anywhere (except to the liver?). This effect is abolished by atropin. Respiration is faster in small animals and averages 24 per minute. Respiration slowly decreases in strength with little change in rate. Usually respiration ceases long before the heart stops.

THE USE OF STRYCHNIN AND CAFFEIN AS CARDIOVASCULAR STIMULANTS IN THE ACUTE INFECTIOUS DISEASES

For decades many physicians have relied, with unquestioning faith, on strychnin in the treatment of certain grave symptoms occurring in pneumonia, typhoid fever and other acute infectious diseases. Within the last twenty-five years some physicians have preferred to use caffein (and other drugs) when confronted with these symptoms. The symptoms referred to are those which are thought to signify an approaching or an already existing failure of the circulation, and strychnin and caffein are often believed to be powerful and rapid stimulants for the cardiovascular apparatus in such a state. It is the object of this communication to discuss briefly the question whether failure of either the heart or the vasomotor apparatus is the chief cause of death in the infectious diseases ; and to examine, with the aid of new data, the pharmacological and clinical evidence for and against the use of strychnin and caffein as cardiovascular stimulants

Variations in the response of different arteries to blood serum and plasma

Recent work by Brodie, Sollmann, and O'Connor has shown that the blood contains substances acting on the vasomotor apparatus other than suprarenin. Even before the work of these investigators it had been noticed by Stevens and Lee that the use of defibrinated blood for the perfusion of isolated organs was often unsatisfactory because of the gradual diminution in outflow. This was not investigated thoroughly until 1900 by Brodie. He observed that the injection of blood serum into the jugular vein of a cat caused an immediate fall in blood pressure. The cat's own serum was as efficient in this respect as the serum of any other animal. The cat, however, is the only animal which responds in this manner, for Brodie's experiments were negative on the dog and rabbit. The mechanism in this case appears to be a reflex inhibition of the vasomotor center from excitation of the pulmonary branches of the vagus. The importance of Brodie's work lies in the fact that he was the first to show that plasma and serum are not identical in their physiological activities, for, whereas the effect just described is produced by serum, plasma is entirely inactive. The process of clotting liberates some substance to which this action is to be attributed. It was probably these experiments of Brodie which guided O'Connor in the analysis of the constrictor effect produced by blood serum on the hind limbs of the frog. He was able to show that the constriction produced by serum is not entirely due to its suprarenin content. Another substance comes into play which causes constriction and which is present only in the serum. We have investigated the vasomotor effect of plasma and serum in different vessels of the body, especially in regard to their mode of action.

SMOKELESS POWDERS.THE NATURE AND EFFECTS OF THE DELETERIOUS GASES GIVEN OFF IN THEIR EXPLOSION.

Ever since the introduction of the so-called smokeless powders, injurious effects have been observed from their use. In small quantities, the gases resulting from the explosion of powders of this class, cause varying degrees of disturbance in the cardiac and vasomotor apparatus. "Dynamite headache" has become a common phrase among those who work in the manufacture of the powders; among miners, who use them for blasting purposes, and among sportsmen, soldiers and rifle shots, who use them in firearms. In larger quantities, these gases have produced profound intoxications, and have caused numerous fatalities. Haldane¹says: "In the gold mines in India and in the Transvaal, accidents involving the loss of as many as twenty men at a time have sometimes occurred in this way from dynamite catching fire underground, and serious injury to health may easily be caused by the fumes of imperfectly detonated high explosives where the ventilation is bad." Key²says: