Vasospastic Disorders Research Articles

Systemic blood pressure and capillary blood-cell velocity in glaucoma patients: a preliminary study.

Systemic hypotension and vasospasm have both been suggested as risk factors for glaucomatous damage. Furthermore, a relationship between the incidence of vasospastic disorders and systemic hypotension has been reported. This preliminary study investigated the relationship between these two risk factors. In 20 glaucoma patients suspected to have vascular risk factors, time of blood-flow standstill was measured under cold provocation in nailfold capillaries and 24-hour blood pressure was monitored. Nine were high-tension glaucoma patients but progressing despite medically well-controlled intraocular pressure, and 11 had normal-tension glaucoma. Thirteen patients were vasospastic, and seven were not. Patients without vasospasm had a significantly lower mean systolic blood pressure during the daytime (113.4 +/- 7.1 mmHg) than vasospastic patients (122.6 +/- 12.8 mmHg), p = 0.026. The time of blood-flow standstill in vasospastic patients, however, correlated with the lowest individual systolic blood pressure reading (r = -0.56; p = 0.049). These low readings occurred mostly during the night ("deepers").

Nonatherosclerotic Vascular Diseases and Vasospastic Conditions: Inflammatory Conditions(Part 1 of a 3-Part Series)

Atherosclerosis is the primary underlying disease in over 90% of those with peripheral vascular disease. A small but significant subset of patients with peripheral vascular disease, however, are affected by illnesses or conditions quite dissimilar from arteriosclerosis. Although the pathophysiology of vasospastic disorders generally is unknown, most display alterations in the normal function of the sympathetic nervous system. Many of these conditions are no less incapacitating than limb-threatening atherosclerotic arterial occlusions, yet they frequently are overlooked, neglected, and misunderstood. Such circumstances can cause a delay in diagnosis and optimal management. Many patients with Raynaud's syndrome do not have an underlying associated disease, whereas the presence of this syndrome may be one of the first symptoms of a more systemic disease. The posttraumatic pain syndromes remain poorly understood and, therefore, create a delay in diagnosis and proper treatment. For these reasons, we have prepared this 3-part review of nonatherosclerotic diseases and vasospastic conditions. Part 2 will focus on noninflammatory, nonatherosclerotic vascular disease, and the final section will cover vasospastic conditions.

Peripheral arterial disease

Peripheral arterial diseases are common problems because atherosclerosis, the most common cause of both occlusive peripheral arterial disease and aneurysmal disease, is a feature of an aging population. The less common types of occlusive peripheral arterial disease—the vasospastic disorders and the arteritides—although frequently not addressed to any extent in medical school curricula or in residency programs in family and internal medicine, offer the alert and informed clinician diagnostic and therapeutic opportunities that are too important to neglect. As a group, abnormalities of the peripheral arteries are easy to detect if careful observation and examination of the extremities is included in the physical examination and attention to functional disorders is included in the medical history. In this presentation, the clinical features, physical findings, complications, useful noninvasive diagnostic tests, imaging techniques, and therapeutic options for atherosclerotic occlusive peripheral arterial disease (both chronic and acute), uncommon types of occlusive arterial disease of both the lower and upper extremities, the vasospastic disorders, and the peripheral arterial presentations of the arteritides are reviewed. The application of natural history and comorbidity of a particular arterial disease, when available, is emphasized in the formulation of management for the individual patient.

Short communication: distal adrenergic innervation remains normal after perivascular sympathectomy.

Perivascular sympathectomy, which has been used for vasospastic disorders of the hands, was examined in experimental models. Perivascular sympathectomy was performed on the central ear vessels and forepaw metacarpal vessels of the rabbit and on the common digital vessels in the monkey. The effects on adrenergic nerves were studied using a glyoxylic acid-induced fluorescence method. Adrenergic nerves were removed only at the site of the perivascular sympathectomy and the distal adrenergic innervation appeared normal. Because the distal sympathetic nerves appeared normal after the operation, it should rather be called adventitectomy and we feel its clinical effects should be reevaluated.

Intraocular pressure and vasospastic disorders in normal tension glaucoma

Intraocular pressure and vasospastic disorders in normal tension glaucoma

Intraocular pressure and vasospastic disorders in normal tension glaucoma

The insulin-like growth factor-1 receptor (IGF1-R) is a cellular receptor overexpressed in many tumor cell lines and in some human tumors that seems to play a critical role in transformation, tumorigenicity, and metastasis. To date, a comprehensive evaluation of tissue distribution of IGF1-R in human carcinomas from different anatomical sites has been lacking. Using stage-oriented human cancer tissue microarrays, we studied IGF1-R expression and distribution in a group of 152 human carcinomas from a variety of anatomical sites and from 63 normal tissues through immunohistochemistry. The tumors included carcinomas from breast (8), ovary (9), endometrium (7), esophagus (5), stomach (7), pancreas (7), liver (4), colon (10), kidney (14), bladder (17), prostate (11), head and neck (31), salivary glands (8), lung (13), and skin (1). Formalin-fixed, paraffin embedded tissues of each case were immuno-stained using the avidin-biotin peroxidase method and an anti-IGF1-R rabbit polyclonal antibody. High-membranous IGF1-R staining was observed in 7 of 8 (87.5%) breast carcinomas, in 9 of 9 (100%) ovarian carcinomas, in 7 of 7 (100%) endometrial carcinomas, in 5 of 7 (71.1%) gastric carcinomas, in 4 of 7 (57.1%) pancreatic carcinomas, in 9 of 10 (90%) colon adenocarcinomas, in 11 of 13 (84.6%) lung carcinomas, in 6 of 11 (54.5%) prostatic adenocarcinomas, and in 17 of 17 (100%) transitional cell carcinomas of the bladder. Only a minority of squamous cell carcinomas of the head and neck and esophagus (34), salivary gland tumors (5), and renal cell carcinomas (14) were IGF1-R positive. This study demonstrates the overexpression of IGF1-R across a wide variety of human carcinomas of glandular or transitional cell origin.

Bertram M. Bernheim: A southern vascular surgeon

Bertram M. Bernheim: A southern vascular surgeon

Radical microarteriolysis in the treatment of vasospastic disorders of the hand, especially scleroderma

Arterial spasm due to exaggerated sympathetic response is an important mechanism for Raynaud's phenomenon in scleroderma associated often with periadventitial scarring. The results of cervical sympathectomy have been unsatisfactory in the upper limb because of additional sympathetic pathways. Flatt therefore devised a distal sympathectomy by stripping the vessels of their adventitia over a short length of artery. The results of this operation were found by Wilgis in a large series to be poor in patients with scleroderma. A radical distal microarteriolysis including adventitia and surrounding scar is described and the results in 13 patients, 11 with scleroderma, are reported. Minimum follow-up is one year. All patients had relief from pain at rest and healing of painful ulceration. Mild recurrence of small ulcers was seen in only four patients.

Acute vibration--its effect on digital blood flow by central and local mechanisms.

In order to establish underlying mechanisms responsible for the vasospastic disorder vibration white finger (VWF), the acute effect of vibration on digital blood flow was assessed. Thirteen patients with primary Raynaud's phenomenon (RP), 15 patients with WVF and 13 controls were exposed to acute vibration in the middle digit of one hand for 1 and 3 minutes. Blood flow was measured in that digit and in the middle finger of the contralateral hand using strain gauge plethysmography before and after vibration. The measurements were then repeated following digital nerve blockade using 2% Lignocaine in the vibrated digit. The results demonstrate that vibration affects digital blood flow through two independent mechanisms. Vibration appears to cause both an axonal vasoconstrictor reflex and an active local vasodilation phenomenon. In patients with established vasospastic disorders this vasoconstrictor reflex is exaggerated.

An objective test for the diagnosis and grading of vasospasm in patients with Raynaud's syndrome.

1. Reliable objective tests for the diagnosis and grading of vasospasm would be helpful in the assessment of patients with Raynaud's syndrome. 2. Measurements of finger blood flow at local finger temperatures from 32 degrees C down to 20 degrees C did not reliably distinguish between patients with Raynaud's syndrome and matched control subjects. 3. Using laser Doppler flowmetry to detect blood cell flux in fingertip skin, there was no significant difference (Wilcoxon's signed rank test) in the finger systolic blood pressure of 28 patients with Raynaud's syndrome and their matched controls when the fingers were warm at 32 degrees C. 4. Absence of flux was considered to indicate complete vasospasm and the degree of cooling required to abolish flux indicated the severity of the vasospastic condition in an individual patient. 5. Finger cooling for 5 min did not significantly alter finger systolic blood pressure in the control subjects, but abolished blood cell flux in the fingertip skin of 27 of the 28 patients with Raynaud's syndrome. 6. A grading scale was derived from the flux measurements. There was a significant correlation (r = 0.75, P less than 0.001) between the grading of disease severity as judged by the flux test and the clinical grade as assessed before the laboratory visit. 7. There was one false-negative result in the 28 patients with Raynaud's syndrome tested and no false-positive results in 28 matched control subjects. 8. This type of testing may prove helpful in the diagnosis and grading of vasospastic disorders.

Vascular reactivity of human internal mammary and gastroepiploic arteries

Patency rates of bypass graft conduits are thought to be influenced by the determinants of vascular tone. This study has comparatively examined the response of the human internal mammary and gastroepiploic arteries to potassium, noradrenaline, dopamine, 5-hydroxytryptamine, thromboxane, and histamine. The response to potassium was significantly greater in the gastroepiploic artery (E max = 79.5 ± 9.6 mN) than in the internal mammary artery (E max = 27.0 ± 6.4 mN). Dose-related constrictions were observed in both vessels to all agonists except histamine, which was ineffective in the gastroepiploic artery. Noradrenaline and dopamine produced comparable dose-related constrictions in each vessel, with similar EC 50 and E max (expressed as a percentage of potassium response) values, but 5-hydroxytryptamine (E max, gastroepiploic = 10.8% ± 1.9%; internal mammary = 71.8% ± 21.2%) and thromboxane (E max gastroepiploic = 116.7% ± 4.0%; internal mammary = 169.6% ± 19.4%) were more efficacious in their constriction of the mammary artery; the potencies were similar. We conclude that there is a heterogeneity of response to some vasoconstrictors between the human internal mammary and gastroepiploic arteries. The internal mammary artery may be more predisposed to events that initiate vasospastic disorders.

Effect of perivascular sympathectomy on the noradrenaline content of the distal vasculature of the rabbit ear

Perivascular sympathectomy has been used for the treatment of vasospastic disorders of the hand, with the idea that it causes distal adrenergic denervation. In this study perivascular sympathectomy was performed at the base of the central ear vessels on the left side in eight rabbits. The vessels on the right side were used as controls. The noradrenaline content of the vessels, examined by high performance liquid chromatography (HPLC) with electrochemical detection two days after the operation, was significantly lower in the distal vasculature on the operated side than on the control side (P < 0.0001) although still markedly higher than at the sympathectomy site itself (P < 0.0001). Thus the operation seems to cause partial but not total denervation of the distal adrenergic nerves.

Teil 2: Diagnose des vasospastischen Syndroms mit Hilfe der Nagelfalzkapillarvideomikroskopie*

Nailfold capillary videomicroscopy provides a very useful method to verify vasospastic disorders in ophthalmic patients. Capillary videomicroscopy at the nailfold in connection with a local cold exposure test are presented as a method with clinical applicability in vasospastic disease. This method allows not only differential diagnosis of Raynaud's phenomenon and evaluation of follow up but also to achieve pharmacological tests with different drugs which possess a specific action at the microvascular bed.

Clinical Pharmacokinetics of Ketanserin

Ketanserin is a serotonin S2-receptor antagonist introduced for the treatment of arterial hypertension and vasospastic disorders. Plasma concentrations of ketanserin (and some metabolites) can be measured with high performance liquid chromatography using ultraviolet or fluorescence detection, or by radioimmunoassay. The methods are sensitive, accurate and specific. Following oral administration ketanserin is almost completely (more than 98%) and rapidly absorbed and peak concentrations in plasma are reached within 0.5 to 2 hours. It is subject to considerable extraction and metabolism in the liver (first-pass effect) and the absolute bioavailability is around 50%. The compound is extensively distributed to tissues and the volume of distribution is in the order of 3 to 6 L/kg. In plasma ketanserin binds avidly to plasma proteins, mainly albumin, and the free fraction is around 5%. Ketanserin is extensively metabolised and less than 2% is excreted as the parent compound. The major metabolic pathway is by ketone reduction leading to formation of ketanserin-ol which is mainly excreted in the urine. Ketanserin-ol, which by itself does not contribute to the overall pharmacological effect, is partly reoxidised into ketanserin, and it is likely that the terminal half-life of the parent compound is related to the slow ketanserin regeneration from the metabolite. Following intravenous administration plasma ketanserin concentrations decay triexponentially with sequential half-lives of 0.13, 2 and 14.3 h. The terminal half-life is similar after oral administration. Following long term oral dosing (20 or 40 mg twice daily) the pharmacokinetics remain linear and steady-state concentrations, which can be predicted from single-dose kinetics, are reached within 4 days. During long term treatment with the common dosage of 40 mg twice daily, steady-state concentrations fluctuate between 40 micrograms/L (trough) and 100 to 140 micrograms/L (peak). The pharmacokinetic properties of ketanserin are predictable in a wide group of patients and there is no influence from the duration of treatment, age and sex of the patient or concomitant treatment with beta-blockers or diuretics. There is no direct relationship between plasma concentrations of ketanserin and the antihypertensive effect in a group of patients. Side effects, including prolongation of the Q-T interval, are dose-dependent and, at least in the individual patient, related to peak plasma concentrations. In separate studies the pharmacokinetics of ketanserin were investigated in special patient groups, namely the elderly and patients with hepatic and renal insufficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Long-Term Continuous Axillary Plexus Blockade Using 0.25% Bupivacaine

Three patients, presenting with various traumatic, vasospastic and chronic neuromuscular disorders of the upper body, received continuous axillary block ranging from 4 to 16 days. Intermittent injections of 0.25% bupivacaine were used to provide analgesia, sympathetic blockade and muscle relaxation. No systemic or neurological side-effects were recorded. Nerve function recovered promptly after stopping the injections. It is concluded that continuous brachial plexus blockade is a clinically safe and effective technique for the relief of acute traumatic pain and vasospastic disorders of the upper limb. The technique, its merits and possible complications are discussed.

Perivascular Sympathectomy of the Metacarpal Artery of the Rabbit Paw Fails to Remove Distal Adrenergic Innervation

Though vasospastic disorders of the hand are commonly treated by perivascular sympathectomy, which is believed to remove distal adrenergic innervation, our earlier experimental studies with rat saphenous vessels and rabbit ear vessels gave the opposite results. We therefore operated on 12 rabbits, carrying out perivascular sympathectomy of a metacarpal artery in the left forepaw, the right paw serving as a control. Six rabbits were killed after one week and the other six after three weeks, and the adrenergic nerves were examined by glyoxylic acid-induced fluorescence. Adrenergic innervation seemed to be normal in the distal vasculature after perivascular sympathectomy, and seemed to be missing only from the site of the operation.

Long‐term continuous axillary plexus blockade using 0.25% bupivacaine

Three patients, presenting with various traumatic, vasospastic and chronic neuromuscular disorders of the upper body, received continuous axillary block ranging from 4 to 16 days. Intermittent injections of 0.25% bupivacaine were used to provide analgesia, sympathetic blockade and muscle relaxation. No systemic or neurological side-effects were recorded. Nerve function recovered promptly after stopping the injections. It is concluded that continuous brachial plexus blockade is a clinically safe and effective technique for the relief of acute traumatic pain and vasospastic disorders of the upper limb. The technique, its merits and possible complications are discussed.

Systemic hemodynamic effects of endothelin in rats

Endothelin type 1 (ET-1) is an endothelial cell-derived 21-amino acid peptide with potent contractile effects on isolated vascular smooth muscle. The systemic hemodynamic effects of bolus intravenous injections of ET-1 and angiotensin II (ANG II, 300 pmol) were examined in anesthetized male Munich-Wistar rats by measurements of mean arterial (AP) and right atrial (RAP) blood pressures and cardiac index (CI, electromagnetic flowmetry) over a 60-min period. ET-1 induced a biphasic pressure response: transient hypotension occurred in the early phase with all doses, followed by a more prolonged dose-dependent elevation of blood pressure in the late phase. Because CI was unchanged during the early phase, the hypotension resulted from systemic vasodilation. On the other hand, the marked rise in AP produced by 300 pmol of ET-1 in the late phase was associated with a significant fall in CI, and thus total peripheral resistance index (TPRI) increased profoundly. A fall in right atrial pressure and significant hemoconcentration were associated with this pronounced vasoconstrictor effect, suggesting that a contraction of plasma volume contributed to the reduction of CI. Additionally, stroke and minute work indexes and peak flow velocity became significantly reduced in the late phase for the 300-pmol dose of ET-1. When compared with an equimolar dose of ET-1, 300 pmol of ANG II produced a prompt, more marked, but shorter-lived rise in AP with minimal changes in CI, TPRI, RAP, and hematocrit. These results raise the intriguing possibility that endothelin may play a role in both the control of normal vascular smooth muscle tone and in the pathogenesis of vasospastic disorders.

Spinal cord stimulation for chronic pain mainly in PVD, vasospastic disorders of the upper limbs and failed back surgery

Spinal cord stimulation for chronic pain mainly in PVD, vasospastic disorders of the upper limbs and failed back surgery

Spinal Cord Stimulation for Relief of Chronic Pain in Vasospastic Disorders of the Upper Limbs

Spinal Cord Stimulation for Relief of Chronic Pain in Vasospastic Disorders of the Upper Limbs