Digital Vasodilation Research Articles

Digital plethysmography and arginine metabolism in prehypertension: effect of nebivolol therapy.

Prehypertension is an important phenotype for cardiovascular risk and development of established hypertension. To better understand the early circulatory changes in this group, the authors studied 34 patients with prehypertension (blood pressure 120-139/80-89 mm Hg) using digital plethysmography for measurement of blood flow and reactive hyperemic index (RHI). Arterial augmentation index (AI) was also measured. Because prehypertension is associated with endothelial dysfunction and decreased availability of nitric oxide (NO), indices of arginine metabolism (l-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, and l-citrulline) were measured. Nebivolol (5 mg/d), a vasodilating β1 -antagonist with β3 -agonist activity, was studied in a double-blind fashion for 8 weeks. Nebivolol increases the bioavailability of NO. Prehypertension was associated with normal RHI and baseline digital blood flow. AI was abnormal and associated with diastolic blood pressure. ADMA concentration was increased at baseline. After 8 weeks of nebivolol therapy, RHI, ADMA, symmetric dimethylarginine, and AI showed no significant change, but digital blood flow and l-citrulline levels were significantly increased. Prehypertension is associated with increased ADMA and evidence of increased arterial stiffness and preserved RHI. Nebivolol therapy is associated with digital vasodilation and increased NO production, as depicted by increased levels of l-citruline and mean digital blood flow.

Persistent digital hyperthermia over a 48h period does not induce laminitis in horses

Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0 h, 24h or 48 h post-infusion. Mean ± SE hoof wall temperatures of the left forefoot (29.4 ± 0.25°C) were higher (P<0.05) than those on the right (27.5 ± 0.38°C). Serum insulin (15.0 ± 2.89 μIU/mL) and blood glucose (5.4 ± 0.22 mM) concentrations remained unchanged during the experiment. Histopathological evidence of laminitis was not detected in any horse. The results demonstrated that digital vasodilation up to 30°C for a period of 48 h does not trigger laminitis in the absence of hyperinsulinaemia. Thus, although digital hyperthermia may play a role in the pathogenesis of laminitis, it is not the sole mechanism involved.

Characterization of the responses of equine digital veins and arteries to calcitonin gene-related peptide

To compare responses of equine digital arteries (EDAs) and veins (EDVs) to human-αcalcitonin gene-related peptide (hαCGRP), evaluate effect of the endothelium, and characterize receptors and sources of endogenous CGRP. Palmar digital vessels (5 to 9/experiment) from healthy adult horses killed at an abattoir. Vessel rings were mounted under tension in organ baths containing Krebs-Henseleit solution at 30 °C, with relaxation responses examined in vessels preconstricted with a thromboxane-mimetic (3 × 10(-8)M). Responses of endothelium-intact (+e) and -denuded (-e) EDAs and EDVs to hαCGRP C10(-10) to 3 × 10(-7)M) were compared. Following incubation with an hαCGRP receptor antagonist (hαCGRP(8-37); 1 μM), responses of EDA(-e) and EDV(-e) to hαCGRP (10(-7)M) were obtained. Responses of endothelium-intact and -denuded arteries and veins to hαCGRP (3 × 10(-7)M) or capsaicin (10(-5)M) were evaluated as well as responses of endothelium-intact and -denuded EDA and EDV to hαCGRP (10(-10) to 10(-6)M) after incubation with endothelin-1 (ET-1; 10(-12)M). hαCGRP resulted in nonendothelium, concentration-dependent relaxation in EDAs and EDVs, with greater responses in EDAs. Treatment with hαCGRP(8-37) had minimal effect on responses to hαCGRP in either vessel type. Capsaicin induced relaxation in both vessel types. There were no differences between responses to hαCGRP for vessels pretreated with ET-1 or vehicle. Both hαCGRP and capsaicin induced digital vasodilation unaffected by a functional endothelium. This suggested that endogenous CGRP likely emanates from sensory-motor nerves and may contribute to digital vasodilation.

Rational use of calcium-channel antagonists in Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a peripheral circulatory disorder characterized by sudden episodes of digital artery spasm, often precipitated by cold temperature or emotional stress. Although the cause of RP is not fully known, it appears to involve inappropriate adrenergic response to cold stimuli. Treatment of RP is conservative in most patients, but in patients with severe disease includes the use of agents that promote digital vasodilation. The calcium-channel antagonists, particularly the dihydropyridine derivative nifedipine, are the most thoroughly studied drug class for the treatment of RP. Approximately two thirds of patients respond favorably, with significant reductions in the frequency and severity of vasospastic attacks. Nifedipine use is often limited by the appearance of adverse vasodilatory effects such as headache or peripheral edema. The newer second-generation dihydropyridines such as amlodipine, isradipine, nicardipine, and felodipine also appear to be effective in patients with RP and may be associated with fewer adverse effects.

Equine laminitis: its development coincides with increased sublamellar blood flow.

The effect of alimentary carbohydrate overload on hoof temperature was investigated to determine the state of the sublamellar vasculature preceding the onset of equine laminitis. Hoof, core and ambient temperatures and heart rate were logged continuously in 21 mature Standardbred horses kept in an environmental chamber set at 10 degrees C. Recording hoof temperature was a successful, noninvasive, method to measure indirectly, shifts in digital blood flow against a background of cold induced, physiological, vasoconstriction. High hoof temperatures were assumed to indicate digital vasodilation and low hoof temperatures digital vasoconstriction. Seven horses were either untreated or sham treated controls. A slurry of ground wheat flour (17.5 g/kg) was administered via nasogastric tube to 13 horses all of which were humanely killed 48 h later. Histological sections of the lamellar tissues were examined for evidence of laminitis. Analysis of mean hoof temperature graphs showed that horses judged laminitis positive had experienced a period of prolonged digital vasodilation 16-40 h after carbohydrate overload. Laminitis negative horses experienced no such period of vasodilation and never had hoof temperatures significantly (except once, at 28 h) above that of controls. The only parameter which significantly differentiated the laminitis positive from laminitis negative horses, between 12 and 32 h after carbohydrate overload, was foot temperature, which was significantly higher in laminitis positive horses (P < 0.05). Therefore, a period of sublamellar vasodilation, 12 to 40 h after alimentary carbohydrate overload precedes the onset of laminitis. If the digital circulation sustains vasoconstriction during this period then laminitis does not occur. We propose that the period of increased digital blood flow in laminitis positive horses, concomitant with the severe metabolic crisis brought on by the alimentary carbohydrate overload, may expose the lamellar tissues to a concentration of blood borne factors sufficient to trigger lamellar separation.

Nonneural Mediation of Digital Vasodilation during Menopausal Hot Flushes

Menopausal hot flushes are accompanied by profuse sweating, decreased skin resistance, modest tachycardia and cutaneous vasodilation. With the exception of the last effect, these events are consistent with an abrupt increase in sympathetic outflow. Blood flow in the human finger is controlled through sympathetic vasoconstricting nerves, and increased sympathetic activation results in digital vasoconstriction. We therefore sought to determine if digital vasodilation during hot flushes was mediated through efferent sympathetic nerves. Bilateral finger temperature and blood flow were recorded after the digital nerves on one hand had been blocked with a local injection of lidocaine. The effectiveness of the nerve blocks was verified by a reflex vasoconstriction test. Hot flushes were objectively defined using skin conductance responses recorded from the sternum. Fifteen hot flushes occurred in 8 women. Significant elevations in finger temperature and blood flow occurred during the flushes, in nerve-blocked and intact fingers. These findings suggest that digital vasodilation during hot flushes is due to a circulating vasodilating substance.

L-Arginine therapy in Raynaud's phenomenon?

Since L-Arginine is the substrate for nitric oxide synthesis by vascular endothelial cells the effects of L-arginine treatment on the digital vascular response to local stimuli were investigated in patients with primary or secondary Raynaud's phenomenon. After therapy, patients with Raynaud's phenomenon secondary to systemic sclerosis showed: (1) higher digital vasodilation after local warming, (2) cold-induced digital vasodilation, and (3) increase of plasma levels of tissue-type plasminogen activator.

Neurogenic cutaneous vasodilation in the cat forepaw

The present experiments were undertaken to determine, using Laser Doppler flowmetry, if elimination of efferent constrictor mechanisms would unmask cutaneous vasodilator responses following preganglionic sympathetic nerve stimulation in the forepaw of anesthetized cats. We also addressed the question of a potential causal relationship between neurally evoked vasodilator and sudomotor responses. Three separate anti-adrenergic regimens were utilized: (1) acute guanethidine administration (1–2 mg/kg); (2) chronic monoamine depletion with reserpine (5 mg/kg) and α-methyl-para-tyrosine (2 × 300 mg/kg); and (3) α-adrenoceptor blockade with prazosin (300 μg/kg) and yohimbine (0.5 mg/kg). Guanethidine treatment produced a significant depression of basal cutaneous blood flow whereas α-adrenoceptor blockade did not. In all three groups, stimulation of the preganglionic thoracic sympathetic nerve trunk produced intensity-dependent increases of digital skin blood flow along with near-maximal sympathetic cholinergic sudomotor (electrodermal) responses recorded simultaneously from the same paw. Vasodilator responses were not altered by intravenous propranolol (1 mg/kg) or atropine (1 mg/kg); however, evoked sudomotor responses were totally blocked by atropine. Low doses (1.5 mg/kg i.v.) of hexamethonium selectively abolished the cutaneous vasodilator responses but not concomitantly evoked sudomotor responses. These results demonstrate, using direct measurements of blood flow, that cutaneous digital vasodilation can be measured in cats following removal of vasoconstrictor mechanisms either pre- or postjunctionally. Neither muscarinic nor β-adrenoceptor mechanisms appear to be involved. These experiments also suggest that cutaneous vasodilation is not a consequence of concomitant sudomotor activation.

Acute Effects and Mechanism of Action of Ketanserin in Patients with Primary Raynaudʼs Phenomenon

This study evaluates the vasoactive effects and mode of action of ketanserin, a selective 5HT2 receptor antagonist, on digital circulation in 11 patients with primary Raynaud's phenomenon. Reflex digital vasoconstriction was induced by moderate body cooling. We found that ketanserin given intravenously in a dose of 10 mg, normalized digital skin temperature and digital blood flow as estimated by venous occlusion plethysmography and laser-Doppler flowmetry. However, effects of ketanserin on transcutaneously measured oxygen pressure were modest. This could imply a preferential effect of ketanserin on arteriovenous shunt flow. Pretreatment with high doses of the selective and nonselective alpha-adrenoreceptor antagonists prazosin and phentolamine did not abolish the effects of ketanserin on digital blood flow. However, under alpha-adrenoceptor blockade the small effects of ketanserin on normal blood pressure disappeared. Thus, in contrast to the effects in the systemic circulation, the principal mechanism underlying digital vasodilation after ketanserin is unlikely to involve alpha-adrenoceptor antagonism. We conclude that 5HT2 receptors are present in the digital vasculature. In patients with primary Raynaud's phenomenon, their activation plays an important role in cold-induced digital vasoconstriction.

Nonneural beta-adrenergic vasodilating mechanism in temperature biofeedback.

Although finger temperature feedback has been used to produce digital vasodilation in normal persons and those with Raynaud's disease, the mechanism and site of this effect have not been studied. In the present investigation, feedback-induced vasodilation was attenuated by brachial artery infusions of propranolol in infused, but not contralateral, hands and was not affected by digital nerve blockade. Quantitative measurements of finger blood flow demonstrated that this vasodilation occurred in arteriovenous shunts in normal persons and in the finger capillary bed in those with Raynaud's disease. Raynaud's disease patients who received finger temperature feedback reported 80 fewer percent symptoms 1 and 2 years after treatment and retained the ability to increase finger temperature and capillary blood flow at these times. These effects were not shown by patients given autogenic training, a relaxation procedure.

Evidence for Sympathetic Deactivation by Temporal Vasoconstriction‐ and Digital Vasodilation‐Biofeedback in Migraine Patients: A Reply to Elmore and Tursky and a New Hypothesis

SYNOPSISThe aim of this contribution is twofold: first, a reply is given to Elmore and Tursky.1 who hypothesized that temporal pulse amplitude biofeedback (TPA) works on the basis of sympathetic activation. Contrary to this point of view, some data are reported supporting the opposite tendency: i.e. sympathetic deactivation. Secondly, based on the first part of this article, a new hypothesis is formulated with the intention of explaining temporal vasoconstriction simultaneously found with digital vasodilation and handtemperature increase during handwarming biofeedback (HTB) resp. during volitional handwarming/relaxation.1,11 This new hypothesis postulates that temporal vasoconstriction occurs during handwarming/relaxation due to the fact that peripheral extracranial scalp and face arterioles dilate. As a result, blood and oxygen supply as well as carbon dioxide release is increased, which leads in turn to a reduction in arteriolar ischemia, hypoxia and acidosis. The improved blood delivery from the temporal arteries to the extracranial arterioles and tissue provokes a relative degree of vasoconstriction of the temporal arteries.

Conditioned Adaptation-Relaxation Reflex in Migraine Therapy

A new conditioned reflex, the adaptation-relaxation reflex, characterized by dilation of the peripheral blood vessels of the hand and arm, is associated with reduced blood flow in the area of the supraorbital and superficial temporal arteries. This reflex, learned through biofeedback training, is a central requirement for successful autonomic conditioning for migraine. In migraine patients whose conditions improve clinically, the finger-temperature feedback training is not associated with the conditioning of a single autonomic response, ie, digital vasodilation, but is associated with a general decrease of sympathetic tonic outflow.

Is volitional manipulation of hemodynamics a valid rationale for biofeedback therapy of migraine?

SYNOPSIS Responses of supraorbital (SA), superficial temporal (TA), and digital (F) arterial beds and the heart rate were studied in 5 normal subjects and 10 migraineurs, when their hand temperature was increased by volition and/or by heat. In normal subjects, volitional digital arterial dilation coincided with vasoconstriction in SA and TA. In migraineurs the response varied. Bradycardia resulted in most subjects except in unimproved migraineurs. Heat induced hand vasodilation led to dilation in SA and TA and to tachycardia. In those 8 migraineurs who improved clinically the finger temperature feedback training apparently did not result in conditioning of a single autonomic response (i.e. digital vasodilation), but in a general decrease of the sympathetic tonic outflow.

Is volitional manipulation of hemodynamics a valid rationale for biofeedback therapy of migraine?

SYNOPSISResponses of supraorbital (SA), superficial temporal (TA), and digital (F) arterial beds and the heart rate were studied in 5 normal subjects and 10 migraineurs, when their hand temperature was increased by volition and/or by heat. In normal subjects, volitional digital arterial dilation coincided with vasoconstriction in SA and TA. In migraineurs the response varied. Bradycardia resulted in most subjects except in unimproved migraineurs. Heat induced hand vasodilation led to dilation in SA and TA and to tachycardia. In those 8 migraineurs who improved clinically the finger temperature feedback training apparently did not result in conditioning of a single autonomic response (i.e. digital vasodilation), but in a general decrease of the sympathetic tonic outflow.