Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon

M Roustit, M Hellmann, C Cracowski, S Blaise, J L Cracowski, M Roustit, M Hellmann, C Cracowski, S Blaise, J L Cracowski

Abstract

Digital skin vasoconstriction on local cooling is exaggerated in primary Raynaud's phenomenon (RP) as compared with controls. A significant part of such vasoconstriction relies on the inhibition of the nitric oxide (NO) pathway. We tested the effect of the phosphodiesterase 5 (PDE5) inhibitor sildenafil, which potentiates the effect of NO, on skin blood flow. We recruited 15 patients with primary RP, performing local cooling without sildenafil (day 1), after a single oral dose of 50 mg (day 2), and after a dose of 100 mg (day 3). Skin blood flow, skin temperature, and arterial pressure were recorded, and data were expressed as cutaneous vascular conductance (CVC). Sildenafil at 100 mg, but not 50 mg, significantly lessened the cooling-induced decrease in CVC. It also increased resting CVC and skin temperature. These data suggest that 100 mg sildenafil improves digital skin perfusion during local cooling in primary RP. The benefit of sildenafil "as required" should be confirmed in a randomized, controlled trial.

Conflict of interest statement

Conflicts of interest

JLC and MR have received research grants from Pfizer for other studies.

Figures

Figure 1
Figure 1
Effect of a single dose of 50 mg (red line) and 100 mg (green line) of sildenafil given orally on resting skin temperature in a temperature-controlled room (A); systolic (SAP), mean (MAP) and diastolic (DAP) arterial blood pressure (B); skin blood flux (C) and cutaneous vascular conductance (CVC) (D). APU: arbitrary perfusion units. * P

Figure 2

Effect of a single dose…

Figure 2

Effect of a single dose of 50 mg sildenafil given orally (red line)…

Figure 2
Effect of a single dose of 50 mg sildenafil given orally (red line) and 100 mg (green line) compared to control (blue line) on cutaneous vascular conductance (CVC). Local cooling was started one hour after oral administration. Local cooling (grey bar) was set at 15°C (A) and at 24°C (B) after a baseline at 33°C (black bar).

Figure 3

Effect of sildenafil on the…

Figure 3

Effect of sildenafil on the gradient of skin perfusion between the distal, middle…

Figure 3
Effect of sildenafil on the gradient of skin perfusion between the distal, middle and proximal phalanges and the dorsum of the hand. * Pvs control. Below are examples of skin perfusion assessed with laser Doppler imaging in the same patient without sildenafil (left), and after sildenafil at 50 mg (middle) and at 100 mg (right).

Figure 4

Study day schema. LDI: laser…

Figure 4

Study day schema. LDI: laser Doppler imaging.

Figure 4
Study day schema. LDI: laser Doppler imaging.
Figure 2
Figure 2
Effect of a single dose of 50 mg sildenafil given orally (red line) and 100 mg (green line) compared to control (blue line) on cutaneous vascular conductance (CVC). Local cooling was started one hour after oral administration. Local cooling (grey bar) was set at 15°C (A) and at 24°C (B) after a baseline at 33°C (black bar).
Figure 3
Figure 3
Effect of sildenafil on the gradient of skin perfusion between the distal, middle and proximal phalanges and the dorsum of the hand. * Pvs control. Below are examples of skin perfusion assessed with laser Doppler imaging in the same patient without sildenafil (left), and after sildenafil at 50 mg (middle) and at 100 mg (right).
Figure 4
Figure 4
Study day schema. LDI: laser Doppler imaging.

Source: PubMed

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