Response of digital arteries to endothelium dependent and independent vasodilators in patients with Raynaud's phenomenon.

The cause of the digital artery spasm seen in Raynaud's phenomenon (RP) is unclear. A dysfunction of endothelium-dependent vasodilation might contribute to the development of this spasm. We studied the digital artery responses to endothelium-dependent and independent vasodilators in eight Raynaud's phenomenon patients and eight sex-matched controls. A sequential series of infusions alternating with physiological saline were administered at a rate of 1 mL min-1 via the radial artery. The infusions contained acetylcholine chloride (ACh) 110 nm mL-1 and 550 nm mL-1, L-arginine 50 mumol mL-1, prostacyclin (PGI2) 2.5 ng mL-1 and glyceryl trinitrate (GTN) 4.5 nm mL-1. Digital artery diameter (DAD) and cutaneous temperature were measured. DAD was measured using a high frequency A-mode ultrasound scanner. There was no significant difference in mean brachial artery pressure, digital cutaneous temperature and DAD between the two groups at the start of the study. Comparing responses in the groups, there was a significantly greater increase in DAD and cutaneous temperature to Ach (endothelium-dependent vasodilator) at both concentrations in controls. A significantly greater increase in DAD was obtained in response to GTN (endothelium-independent vasodilator) in the RP subjects. There was no significant difference in response to L-arginine and PGI2 between the groups. These results suggest that a dysfunction of endothelium-dependent vasodilation is present in RP patients.

Digital artery calibre measurement--a new technique of assessing Raynaud's phenomenon.

This study evaluated the use of a high frequency A-mode ultrasound scanner (CUTECH DM70) for monitoring the digital artery vasospasm of Raynaud's Phenomenon (RP). The technique was evaluated on 12 RP patients and 12 age and sex matched controls. The diameter of a single digital artery was measured in these subjects over a range of finger temperatures between 14-35 degrees C. The reproducibility of the measurements was assessed by repeating the procedure in two subjects (a control and an RP patient) on 5 separate days. The results confirmed that the technique is reproducible and monitored vasospasm occurring in all 12 RP patients. In the temperature range tested, none of the controls developed digital artery vasospasm. At finger temperatures greater than 25 degrees C the response to thermal stimuli of the digital arteries in RP patients and controls was similar. However, at temperatures less than 25 degrees C a marked vasoconstriction leading to complete digital artery closure was seen in the RP patients and not in the controls. This technique may prove useful in monitoring RP patients.

Ultrasound imaging of digital arteries.

This study assessed the use of high frequency ultrasound (CUTECH DM70) in the measurement of digital artery diameters. The accuracy of the technique was assessed using a model. Four silicone tubes of different diameters were embedded in opaque agar. Three independent observers measured the diameter of the tubes using the CUTECH DM70 and the measurements obtained were compared with those obtained using a travelling light microscope. The technique was then evaluated on digital arteries. Ten recordings of digital artery diameter were made at a fixed point on the index finger in two subjects at 20 degrees C and at 30 degrees C. There was no statistical difference between the mean diameters obtained by the three observers using the CUTECH DM70 on the model. No statistical difference was noted when the mean diameters measured using the travelling microscope were compared with those obtained by the three observers. The diameter differences between the tubes were all highly significant (P less than 0.001 Mann Witney). The variability in the recordings of digital artery diameter in the two subjects was very low (maximum coefficient of variance less than 4%). A significant difference in the mean measured vessel diameter at the two different temperatures was obtained (P less than 0.001 Mann Witney). We conclude that digital artery diameter can be measured using the CUTECH DM70.

An epidemiological survey of Raynaud's phenomenon.

A questionnaire was sent to 1000 patients with Raynaud's phenomenon (RP) and an equal number of controls in order to accumulate one of the largest patient data banks currently available. Five-hundred and seventy-one correctly completed paired returns were processed so as to investigate the association between Raynaud's phenomenon and other factors suspected of influencing the condition. The involvement of female sex hormones in RP was indicated by the predominance of women (93%), a 6% (P less than 0.02) higher incidence of infertility and the influence of menstruation (15%), the menopause (73%) and pregnancy (53%) on symptoms. Patients with scleroderma had a 5% higher incidence of stillbirths. A familial predisposition for RP was noted dependent on age at onset of symptoms (age less than 30, 14% greater than 30, 4.9%). The Raynaud's group overall had a significantly higher percentage who had been treated for migraine (7% higher P less than 0.01), angina (3% higher P less than 0.05) and duodenal ulcer (3% higher P less than 0.001). Of the respondents who had undergone sympathectomy (n = 140, 24.5% of the total), 18.6% claimed lasting benefit and 66.4% claimed no benefit after one year. The mean age at sympathectomy was 38.6 years (S.D. +/- 13 range 14-78) with a mean age of start of symptoms of 29.2 years (S.D. +/- 14.7, range 0-70). There was no significant difference between the effects of sympathectomy on those patients with and those without associated conditions.

Thermal entrainment methods for studying Raynaud's phenomenon.

Entrainment occurs when an externally applied periodic temperature stimulus forces the peripheral bloodflow component of thermoregulation to oscillate at the same frequency. This phenomenon can be demonstrated using frequency transforms to analyse the spectral content of the bloodflow, and can be used as a diagnostic test for Raynaud's phenomenon. Correlations were performed between the clinical diagnosis and the objective tests. The average inter-clinical correlation coefficient was r = 0.66. When the average clinical diagnosis was compared with a combination of thermal entrainment and digital patency testing the correlation coefficient rose to r = 0.68. These results highlight the difficulties encountered when assessing patients with Raynaud's phenomenon and the necessity of applying both physiological and clinical techniques.

Reflex vascular responses in the finger to contralateral thermal stimuli during the normal menstrual cycle: a hormonal basis to Raynaud's phenomenon?

1. Raynaud's phenomenon is a condition which primarily affects women and it must be assumed that hormonal influences are responsible. 2. To further investigate this assumption the effect of cyclic sex hormone fluctuations on the digital vascular reactivity of ten normal young women was studied by the diagnostic techniques of thermal entrainment of finger blood flow and Doppler ultrasound mapping of the digital arteries. 3. In the immediate pre-ovulatory period the results obtained were comparable with those found in patients with established Raynaud's phenomenon, suggesting that oestrogen has an important modulating effect in vivo on reflex peripheral vasomotor responses to thermal stimuli. 4. 'Primary' Raynaud's phenomenon may represent an exaggerated response to oestrogen.

Natural progesterone and antihypertensive action.

In a placebo controlled, double blind crossover study natural progesterone was given by mouth, in increasing doses, to six men and four postmenopausal women with mild to moderate hypertension who were not receiving any other antihypertensive drugs. When compared with values recorded before treatment and during administration of placebo progesterone caused a significant reduction in blood pressure, suggesting that progesterone has an antihypertensive action rather than a hypertensive one as has been previously thought. This possible protective effect of progesterone should be investigated further.

Peripheral vasomotor control and menopausal flushing--a preliminary report.

Menopausal flushing can be considered as an intermittent loss of peripheral vasomotor control. Thermal entrainment testing has been used to assess the degree of peripheral vasomotor control in a preliminary study of seven women receiving oestrogen replacement therapy in the form of percutaneous cream. Significant improvement was demonstrated in the degree of control over a 3-month period in those patients who were symptomatically improved. We suggest that oestrogen exerts an influence on peripheral vasomotor control and flushes and sweats occur when this influence is removed.

Thermal entrainment and human ovulation.

The changes in the peripheral vascular response to temperature have been studied for ten menstrual cycles by calculating thermal entertainment levels. The entrainment levels exhibited peaks at around the time of ovulation, a result which we believe is due to the fluctuating levels of the hormones oestrogen and progesterone in the blood. An attempt has been made to explain the influence of these hormones on the vasomotor control system and where interactions may occur.

Raynaud's phenomenon and thermal entrainment: an objective test.

A new objective test for diagnosing Raynaud's phenomenon was assessed in practice. The test is based on entrainment of the thermal vasomotor control system and entails non-invasive measurement of blood-flow responses in one hand while alternating thermal stimuli are applied to the contralateral hand. A significant (p less than 0.001) abnormality of vasomotor control was found in patients with Raynaud's phenomenon compared with normal subjects. When applied clinically this test is diagnostic and indicates the severity of the disease and the effect of treatment.