Comparative effects of dihydroergotamine and noradrenaline on resistance, exchange and capacitance functions in the peripheral circulation.
TL;DR: Since the constrictor effect of DHE seems confined mainly to the capacitance vessels, the drug may have beneficial effects in circulatory disorders characterized by impaired venomotor regulation.
Abstract: 1. A comparative quantitative study of the effects of dihydroergotamine (DHE) and noradrenaline (NA) on the precapillary and postcapillary resistance vessels, the precapillary ‘sphincters’, and the capacitance vessels was performed in a skeletal muscle and a skin region in healthy humans and in patients with orthostatic symptoms; further, the vascular effects of the drugs were analysed in muscle, skin, intestine and kidney in cats before and after sympathectomy. 2. The two drugs evoked a similar pattern of response in the cutaneous vascular bed, i.e. they both constricted resistance and capacitance vessels, increased the ratio of pre-/post-capillary resistance, but did not significantly influence precapillary sphincters. The reactions were similar in skeletal muscle for NA and also for DHE, with the important exception that the latter drug usually elicited a moderate dilator response in the muscle resistance vessels. 3. The average constrictor responses of the capacitance vessels were significantly larger for DHE than NA in skin and also in muscle despite the fact that DHE did not much affect the resistance vessels in muscle. 4. The effects of DHE on the intestinal and renal vascular circuits in the cat were comparatively small. 5. Since the constrictor effect of DHE seems confined mainly to the capacitance vessels, the drug may have beneficial effects in circulatory disorders characterized by impaired venomotor regulation.
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TL;DR: The low mortality compared with previous outcome studies strongly indicates that this therapy improves outcome for severe head injuries, however, a randomized, controlled study is needed to reach general acceptance of this new therapy.
Abstract: ObjectiveTo assess the new "Lund therapy" of posttraumatic brain edema, based on principles for brain-volume regulation and improved microcirculation.DesignA prospective, nonrandomized outcome study over a 5-yr period on severely head-injured patients with increased intracranial pressure, comparing
247 citations
TL;DR: The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine, and their wide use is based on long‐term experience.
Abstract: Ergotamine and dihydroergotamine share structural similarities with the adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they have wide-ranging effects on the physiologic processes that they mediate. Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D antimigraine receptors and, as a consequence, the plasma concentrations that are necessary to produce the appropriate therapeutic and physiologic effects are very low. The broad spectrum of activity at other monoamine receptors is responsible for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor actions. In acute migraine treatment, their mechanisms of action involve constricting the pain-producing intracranial extracerebral blood vessels at the 5-HT1B receptors and inhibiting the trigeminal neurotransmission at the peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is stronger for dihydroergotamine than for ergotamine. Their wide use is based on long-term experience.
182 citations
TL;DR: Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension, pharmacologically with 9‐alpha‐fluorohydrocortisone and dihydroergotamine mesylate and other agents may be tried but results have been less effective.
Abstract: Autonomic function may be adequately tested with noninvasive tests of sympathetic and parasympathetic pathways, including: the response of blood pressure to change in posture and isometric contraction, heart rate response to standing, variation in heart rate with respiration, Valsalva ratio, sweat tests, and plasma noradrenaline measurements. Abnormal results in two or more of these tests indicate autonomic dysfunction. Intraarterial catheterization and tests of vasomotor function are usually required only in doubtful cases or for research purposes. Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension. Orthostatic hypotension is best treated with physical measures, pharmacologically with 9-alpha-fluorohydrocortisone and dihydroergotamine mesylate. A number of other agents may be tried but results have been less effective.
169 citations
TL;DR: The Lund Concept is an approach to the treatment of severe brain trauma that is mainly based on hypotheses originating from basic physiological principles regarding brain volume and cerebral perfusion regulation.
Abstract: The Lund Concept is an approach to the treatment of severe brain trauma that is mainly based on hypotheses originating from basic physiological principles regarding brain volume and cerebral perfusion regulation. Its main attributes have found support in experimental and clinical studies. This review explains the principles of the Lund Concept and is intended to serve as the current guide for its clinical application. The therapy has two main goals: (1) to reduce or prevent an increase in ICP (ICP-targeted goal) and (2) to improve perfusion and oxygenation around contusions (perfusion-targeted goal). The Lund therapy considers the consequences of a disrupted blood–brain barrier for development of brain oedema and the specific consequences of a rigid dura/cranium for general cerebral haemodynamics. It calls attention to the importance of improving perfusion and oxygenation of the injured areas of the brain. This is achieved by normal blood oxygenation, by maintaining normovolaemia with normal haematocrit and plasma protein concentrations, and by antagonizing vasoconstriction through reduction of catecholamine concentration in plasma and sympathetic discharge (minimizing stress and by refraining from vasoconstrictors and active cooling). The therapeutic measures mean normalization of all essential haemodynamic parameters (blood pressure, plasma oncotic pressure, plasma and erythrocyte volumes, PaO2, PaCO2) the use of enteral nutrition, and avoidance of overnutrition. To date, clinical outcome studies using the Lund Concept have shown favourable results.
142 citations
Cites background from "Comparative effects of dihydroergot..."
...Dihydroergotamine may be more effective than other vasoconstrictors in breaking a high ICP by inducing vasoconstriction also on the venous side with its greater blood volume [60, 62]....
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TL;DR: It is concluded that in patients undergoing total-hip replacement, low-dose heparin prophylaxis is effective in reducing the frequency of life-threatening extensive thrombi in the femoral vein.
142 citations
References
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Journal Article•
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Journal Article•
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TL;DR: In this paper, it was shown that a marked and well sustained reduction in intestinal capillary filtration coefficient (CFC) is induced by vasoconstrictor fibre stimulation, which is considered to reflect a widespread closure of precapillary sphincters with an obstruction of corresponding capillaries.
Abstract: : Experiments are described which show that a marked and well sustained reduction in intestinal capillary filtration coefficient (CFC) is induced by vasoconstrictor fibre stimulation. This decrease in CFC is considered to reflect a widespread closure of precapillary sphincters with an obstruction of the corresponding capillaries. India ink injections indicate that this neurogenic obstruction of capillary flow particularly affects the intestinal mucosa. The fact that this marked neurogenic reduction of capillary blood supply to the mucosa takes place concomitantly with an only moderate increase of intestinal blood flow resistance suggests that a considerable redistribution of blood flow takes place within the intestine. The hemodynamic changes produced by the vasoconstrictor fibres in the intestine are compared with the drastically different situation in the skeletal muscles. Some functional implication of these findings are briefly discussed, as well as the possibility that intestinal blood flow is diverted to submucosal shunt vessels. (Author)
184 citations
TL;DR: The results suggest that the vasoconstrictor fibres, beside their powerful influence on the resistance and capacitance vessels, affect also the pre-capillary sphincters, which determine the number of capillaries open to flow.
Abstract: The influence of nervous and local chemical factors on the pre-capillary sphincter section of the muscle vascular bed has been studied in terms of changes in the filtration coefficient (CFC). The results suggest that the vasoconstrictor fibres, beside their powerful influence on the resistance and capacitance vessels, affect also the pre-capillary sphincters, which determine the number of capillaries open to flow. However, the influence exerted by the centrally controlled vasoconstrictor fibres on the pre-capillary sphincters in the skeletal muscles is rapidly overcome by ‘vasodilator metabolites’, accumulating when flow is reduced or metabolism is increased. Such local metabolic factors exert an especially powerful control of the sphincter section as compared with the neurogenic influence. Thus CFC in the skeletal muscles tends to rise at any decrease of blood flow/ tissue metabolism ratio e. g. from ‘resting’ values around 0.015 up to 0.04—0.05, during muscular exercise; an increase also occurs when flow is reduced. Flow reduction following mechanical arterial obstruction induces a relatively greater CFC increase than when flow is reduced by the constrictor fibres, which unmasks their weak but still significant influence on the pre-capillary sphincter section.
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