D. Wellens

The cerebral blood distribution in dogs and cats. An anatomical and functional study

On the basis of corrosion preparations and of microsphere studies, the following characteristics of the canine and feline cerebral circulation were observed. (1) In cats, a greater part of the vertebral arterial blood goes to the brain and it is more specifically restricted to the ponto-medullary and cerebellar structures. These structures received approximately 3 times more microspheres in cats than in dogs. (2) In dogs, an important amount of vertebral blood goes to the neck muscles, and the intracranial vertebral blood supply is spread over a greater area of the brain, including the thalamo-hypothalamic and posterior cortical zone. (3) In cats the thalamo-hypothalamic area receives a greater amount of blood via the common carotid artery than in dogs. (4) In both animal species, the vascular connections between the left and right side of the brain are more extensive in the vertebral than in the carotid bed. However, for either vascular bed, a more important left to right transmission was found in the dog.

Mechanisms of Vasodilatation and Antivasoconstriction

It is debatable whether vasodilator therapy is beneficial in patients with severe obstruction of arterial inflow to peripheral tissues. However, there is little doubt that in vascular disorders in which vasospasms are the main cause of the disease (e.g. Raynaud’s disease), or even in patients with mild occlusive lesions, &dquo;vasodilator agents&dquo; have beneficial effects, although it is not exactly understood why. Vasodilatation is an increase in blood vessel diameter due to relaxation of

Vascular and noradrenalic reactions in the musculocutaneous bed during hypothalamic stimulation.

When electrical stimulation is applied to the ventromedial hypothalamic zone one observes an increase in systemic blood pressure. There also occur blood pressure variations in the isolated femoral circuit: two distinct phenomena were observed. The early event, being either an increase or a decrease in peripheral resistance, is directly related to the amount of noradrenaline produced locally. The late event is due to catecholamines arriving from the general circulation. Inhibition of local catecholamine release through the baroreceptor reflex and inhibition of ganglionic transmission by a large and sudden increase in adrenaline blood levels do influence the response in the isolated femoral circuit. Moreover the peripheral vasomotor tonus seems to be influenced by yet another mechanism, independent of local catecholamine release. This delicate mechanism depends on the balance between the degree of excitation of hypothalamic pressor (medial) and depressor (lateral) zones.

Positive Hemokinetic Effects after Selective Calcium-Antagonism

producing a negative hemokinetic effect. Local factors, such as spasms or arteriosclerotic lesions, as well as general factors such as increased blood viscosity, elevated vasoconstrictor tone due to neural or humoral imbalance, myocardial insufficiency, or venous drainage problems may be involved in circulatory impairment. Vascular patients may complain of a wide variety of symptoms and it is often far from easy to evaluate the importance of the various causative factors contributing to the negative hemokinetic effect. The afferent nutritive blood supply, the capillary exchange function, and the venous return may all be affected to various degrees. In many processes of hemokinetic regulation the intracellular concentration of Ca++ is a key factor. Therefore, hemokinetics can profoundly be altered by calcium-antagonists, i.e., drugs preventing intracellular inflow of Ca++. Calcium-antagonists can exert positive as well as negative hemokinetic effects. The tissue-selectivity of calcium-influx inhibitors will determine to a great extent whether an adequate positive hemokinetic action can be elicited for the treatment of particular circulatory disturbances (Table 1). To evaluate therapeutic usefulness of calcium-antagonists in peripheral vascular disorders at least 4 major functions have to be considered: (1) maintenance or improvement of the myocardial pump function; (2) improvement of arteriolar perfusion; (3) improvement of capillary perfusion; (4) maintenance or improvement of venous return.

Characteristics of Hypotension Elicited by Electrical Stimulation of the Lateral Hypothalamus in Anaesthetized Dogs

Electrical stimulation of the lateral hypothalamus near the paraventricular nucleus hypothalami, resulted in : hypotension, light bradycardia, decrease of the left ventricular systolic pressure without increase of the left ventricular end-diastolic pressure or left ventricular output, femoral vasodilatation and occasionally renal vasodilatation. The hypotensive reactions were potentiated by baroreceptor deafferentation. They were not blocked by anticholinergic, antihistaminic or antidopaminergic agents.

Influence of electrical stimulation of the posterior hypothalamus on musculocutaneous and renal circulation in anesthetized dogs

SummaryHypertension and tachycardia were consistently induced by electrical stimulation of the median posterior hypothalamus in dogs under chloralose anesthesia, curarized and artificially ventilated. When renal and femoral vascular beds were perfused at a constant blood flow, the renal perfusion, pressure markedly increased, whereas only minor variations of the femoral perfusion pressure occurred. When the renal and femoral vessels were perfused by the heart at the prevailing blood pressure, peri-arterial electromagnetic flow measurements revealed that renal flow decreased and that femoral flow increased during hypothalamic hypertension, both before and after vagotomy. In the same animals, no significant changes of renal or femoral flow occurred during reflexogenic hypertension induced by carotid occlusion. These marked hemodynamic differences between the reflexogenic and the hypothalamic type of hypertension were consistently and repeatedly observed. The indications that baroreflex counter-regulation and ganglionic inhibition due to elevated catecholaminemia contribute to the relative lack of femoral vasoconstriction during hypothalamic hypertension, are discussed.

The Prevention of Ca2+ Overload in Vascular Smooth Muscle by Flunarizine as Detected by Laser Microprobe Mass Analysis (LAMMA):

In vitro exposure of depolarized caudal artery preparations of the rat to a high calcium concentration resulted in a strong contraction of the smooth mus cle cells. This muscle contraction was suppressed by flunarizine. It was shown cytochemically, using the combined oxalate-pyroantimonate method for the lo calization of calcium, that a considerable amount of electron-dense precipitate was seen over the depolarized muscle cells after incubation in a calcium contain ing medium. On the other hand this precipitate was not present on the smooth muscle cells when flunarizine was added to this incubation medium. The reac tion product was only present in the extracellular space. These results were controlled by Laser Microprobe Mass Analysis. By evap orating and ionizing small parts of the smooth muscle cells ( ± 1 μm), it was confirmed that the cytochemical method indeed demonstrated calcium, with negligible interference of other cations.

CATECHOLAMINES IN BLOOD DURING DIRECT STIMULATION OF THE HYPOTHALAMUS IN DOGS

AbstractElectrical stimulation by means of an electrode inserted through the infundibulum produces important changes in the plasma levels of adrenaline and noradrenaline. Increase of adrenaline in plasma is a constant feature. Noradrenaline is also enhanced at first but can subsequently disappear completely from the plasma especially when the plasma adrenaline levels are rising very high. The differing adrenaline and noradrenaline response could be explained by the ganglion blocking effect of high plasma adrenaline levels resulting in an interruption of the central orthosympathic excitation pathway and producing a fall in plasma noradrenaline.

Double-blind comparison of ketanserin with placebo in patients with essential hypertension

Two double-blind multicenter trials were performed to compare the antihy pertensive action of ketanserin, at an oral dosage of 20 mg three times daily, with that of placebo over a period of four to six weeks. A subset of patients was treated in a crossover fashion for either four weeks (36 patients) or six weeks (24 patients). The patients had essential hypertension, with a diastolic blood pressure ≥ 95 mmHg measured in sitting position at the end of a placebo run-in period of at least one week. In a first trial, 78 of 82 patients completed the four-week study period, where the mean drop of the systolic/diastolic blood pressure was -14/-12 mmHg in the ketanserin group (n = 32) versus — 8/ — 5 mmHg in the placebo group (n=46). This difference is statistically significant (p = 0.05/p < 0.01). In 13 patients who after the initial ketanserin treatment were further treated with placebo in crossover for four weeks, the blood pressure rose slightly (+1/+3 mmHg). In the alternative group (n =23), the blood pressure fell by -10/-7 mmHg after placebo and decreased further by -10/-8 mmHg after ketanserin. In a second trial, 24 patients completed a two by six week crossover treat ment. In 12 patients assigned to the sequence placebo-ketanserin, there was a drop of the systolic/diastolic blood pressure by — 7/ — 4 mmHg after placebo and an additional drop by — 26/ —10 mmHg after ketanserin. In the other 12 pa tients, who received the sequence ketanserin-placebo, the blood pressure de creased by -21/-15 mmHg during ketanserin and rose again by + 11/+8 mmHg during placebo. In both treatment groups, the antihypertensive action of ketanserin was significantly superior to that of placebo. The heart rate was not significantly influenced by ketanserin in any of these groups. Orthostatic hypotension was not observed in any of these patients. It is concluded that ketanserin is a well-tolerated antihypertensive agent, whose blood pressure-lowering effect is significantly superior to that of placebo.

[Catecholamine release into peripheral vessels during arterial hypertension, induced by electric stimulation of the hypothalamus].

SummaryEectric stimulation of the hypothalamus elicits an immediate systemic pressor reaction and a tenfold increase of adrenalme- and noradrenaline-concentration in venous blood of anaesthetized dogs. During the hypothalamic simulatlon, a slight increase of catecholamines occurs in the femoral venous blood returning from the pump-perfused hind leg. The induced hypertension is accompanied by a slight femoral vasoconstriction or even by a femoral vasodilatation in some cases. The haemo dynamic and biochemical findings clearly indicate that the femoral circulation has only a minor participation in the general orthosympathetic cardiovascular effect of hypothalamic stimulation.