A double blind placebo controlled trial of recombinant tissue plasminogen activator in the treatment of digital ischemia in systemic sclerosis.

The treatment of digital ischemia in systemic sclerosis remains inadequate. We report a double blind, placebo controlled trial of recombinant tissue plasminogen activator (rtPA), a potent thrombolytic agent. Ten patients received rtPA. A potent, acute fibrinolytic effect was observed. During the infusion of rtPA, improvements in skin blood flow were seen. These improvements were shortlived.

Discrimination of capillary and arterio-venular blood flow in skin by laser Doppler flowmetry.

The scattering and absorption of light by tissue and blood is wavelength dependent; the tissue penetration of green light (lambda = 543.5 nm) is about 60 per cent of that of red light (lambda = 632.8 nm) but the absorption of green light by blood is about 20 times greater than for red light. The effect of this difference has been studied by observing the responses of skin blood flow to heat and weal, measured by laser Doppler flowmetry at the two wavelengths. By using time autocorrelation function analysis (ACF) of the scattered light measured, low and high frequency components have been associated with capillary and larger vessel flow, respectively. The comparison of ACF from scattered green and red light has shown that measurements cannot be interpreted by only considering light penetration depth through a homogeneous tissue. Light absorption and multiple scattering by blood at the individual microvessel level, blood rheology and vessel morphology are parameters which are considered for greater attention.

Measurement of blood flow in the chick egg yolk sac membrane.

Blood vessels of the yolk sac membrane are the transport route by which a chick embryo obtains nutrients from the egg yolk. After 4 days of incubation at 37 degrees C a sparse network of blood vessels are visible within the membrane and they become denser over the following days. The preparation has been used to assess angiogenesis. Using visual inspection to assess the growth of new vessels towards pellets of test substances placed on the membrane surface, responses are judged negative or positive. Laser Doppler flowmetry has been used to investigate the potential of this technique to quantify blood flow through the yolk sac membrane. Measurements have been taken from capillary beds and single larger vessels over a range of temperatures and from avascular yolk and egg white using a Perimed PF3 with PF310 bent-tipped probe. Capillary beds exhibited vasomotion (about one cycle per minute) and oscillations of longer duration (about five cycles per hour). Cardiac pulses, strongly present in larger vessels (mean 90 pu, pulse 75 pu), were not easily identified in the capillary bed. Avascular yolk measurements gave flux values (due to Brownian motion of yolk proteins) which were greater than for capillary beds but without oscillations. Angiogenesis was stimulated by pellets containing 2 micrograms of basic fibroblast growth factor. There were significant increases in single vessel blood flow after 24 h compared with blank control pellets placed on the same egg.

Skin blood flow and limited joint mobility in insulin-dependent diabetes mellitus.

Hand skin blood flow in 32 insulin-dependent (IDDM) diabetics was compared with 13 healthy controls at room temperature and after immersion of the hands in warm and cold water. Subjects were examined for limited joint mobility (LJM) to analyse the association between this and blood flow. Digital arteries remained patent in IDDM compared to controls after cold challenge (p = 0.0001), and the difference persisted to a lesser degree 15 min (p = 0.009) and 30 min (p = 0.03) after recovery. Capillary blood flow was reduced in IDDM at room temperature at the finger nailbeds (p less than 0.02) and the palms (p = 0.004) and remained so after warm water immersion in the palms (p = 0.002), where further vasoconstriction was observed immediately after cold water immersion (p less than 0.001) and 15 and 30 min into recovery (p = 0.07 and p = 0.009 respectively). Thermographic analysis confirmed a pattern of predominantly distal rewarming after cold challenge in IDDM with a greater mean index finger temperature than the controls. Together, these features suggested enhanced arteriovenous anastomotic blood flow. All IDDM and IDDM males with LJM had reduced palm capillary flow immediately after cold challenge (p less than 0.05). After warm water (p less than 0.03) and 30 min after cold challenge (p less than 0.05) IDDM males with LJM had reduced palm capillary flow compared to those IDDM without. A microvascular aetiology for LJM is proposed by virtue of reduced nutritional blood flow and evidence of enhanced arteriovenous shunting in the hands of insulin-dependent diabetics.

Altered hand skin blood flow in type 1 (insulin-dependent) diabetes mellitus.

Disturbed upper limb skin blood flow has been described in insulin-dependent (Type 1) diabetes mellitus, but the pathophysiological mechanism remains unclear. Hand skin blood flow was therefore measured at room temperature and following immersion of hands in cold and warm water in 13 healthy control subjects, in 10 patients with Type 1 diabetes mellitus and cardiovascular autonomic neuropathy, and a further 10 Type 1 diabetic patients with normal cardiovascular autonomic tone. Following cold challenge there was failure of digital artery clampdown in all diabetic patients in comparison with healthy control subjects (p less than 0.005), and the index finger temperature fell less (p less than 0.05). Laser Doppler flow was reduced at the palms at room temperature or following the warm challenge (p less than 0.008), as well as on the dorsum at room temperature (p less than 0.05), in all diabetic patients. In addition laser Doppler flow in the diabetic patients was reduced at the palms and dorsum immediately following cold water challenge (p less than 0.004) and this reduction persisted 15 min (p less than 0.05) and 30 min (p less than 0.01) into the recovery phase. In comparison to those diabetic patients with normal cardiovascular tone, those with cardiovascular autonomic neuropathy had reduced laser Doppler flow at the pulp 15 min after cold water immersion (p less than 0.05), at the nailbed immediately after cold water immersion (p less than 0.01), and at the palms immediately after warm water challenge (p less than 0.01).

Acute effects of sublingual nifedipine in patients with Raynaud's phenomenon.

Measurements of peripheral blood flow using bolometry, thermography, ultrasonic Doppler index, and laser light scattering were made in nine patients with primary Raynaud's phenomenon before and after administration of 20 mg sublingual nifedipine and matching placebo. Following nifedipine treatment, there was some evidence of protection against reduction in blood flow, suggesting that this way of taking nifedipine is helpful. Self-administration of sublingual nifedipine before cold exposure may be an effective way of preventing the development of attacks of Raynaud's phenomenon in contrast with the conventional form of regular oral administration.

Aspects of laser light scattering from skin tissue with application to laser Doppler blood flow measurement.

Studies of both intensity and Doppler shifted linewidths of light scattered from skin tissue have been made using photon correlation spectroscopy and optical fibre techniques. Measurements as a function of the separation of input and detecting fibre positions show characteristic features. These features are interpreted in terms of the positions of the scattering red blood cells and the tissue structure. Evidence is given for an interpretation of the differences in the scattered light for scattering from superficial vessels including capillary loops and from deeper lying larger vessels and shunts. Measurements using various laser wavelengths are discussed. The results of this study are important in the development of laser light scattering instruments for the measurement of peripheral blood flow and microcirculation.