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Peripheral thermal responses in normal and cold-sensitive individuals to sublingual Glyceryl Trinitrate (GTN)


Non-freezing cold injury (NFCI) is caused by prolonged exposure of the extremities to cold. The long-term sequelae of NFCI, include cold-sensitivity and pain[1]. The cold sensitivity is characterised by a reduction in basal skin blood flow and augmented vasoconstriction during cold exposure. We tested the hypothesis that sublingual GTN would increase blood flow in the peripheral microcirculation during and after a mild cold challenge in individuals who had not been diagnosed with NFCI, but were cold-sensitive.


In air at 30 °C, seven control and six cold-sensitive participants undertook 12 min of gentle exercise prior to immersing their right foot (protected by a thin plastic bag) into 15 °C water for 2 min, followed by 10 min of spontaneous rewarming. Two minutes prior to immersion, participants were given either 400 µg GTN or placebo sublingually in a single-blinded, counter-balanced order. Toe pad skin temperature (Tsk) and blood flow (SkBF) were measured using infrared thermography and laser Doppler flowmetry respectively.


In the placebo condition, Tsk was significantly lower in Cold-sensitive participants compared to controls throughout the test (P < 0.001) as was SkBF (P < 0.05).

GTN increased the rate of rewarming (°C.min-1) and absolute Tsk of the coldest toe after the cold challenge in Cold-sensitive (placebo: 0.62(0.14) °C.min-1, 28.03(0.92) °C; GTN: 1.08(0.29) °C.min-1, 32.20(2.43) °C; p < 0.001) but not control individuals (Figure 1). GTN also increased the blood flow in the great toe during rewarming in some cold-sensitive individuals.

Figure 1
figure 1

Mean (SD) T sk of coldest toe before and after foot immersion in 15 °C water in Cold-sensitive group following placebo (l) or GTN (¡) * P < 0.05, ** P < 0.001


We accept our hypothesis that impairment in the vasodilatory response seen in individuals with cold-sensitivity can be overcome by the use of GTN, an endothelial-independent nitric oxide donor, and thereby improve the rewarming of cooled peripheral tissues.


Individuals with cold-sensitivity show increased vasoconstrictory tone, both at rest and during warming after a cold stimulus, compared to controls. The use of GTN to overcome this implies an abnormal endothelium and nitric oxide pathway in this condition.


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Correspondence to Katrina Hope.

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Hope, K., Eglin, C.M., Golden, F. et al. Peripheral thermal responses in normal and cold-sensitive individuals to sublingual Glyceryl Trinitrate (GTN). Extrem Physiol Med 4 (Suppl 1), A34 (2015).

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  • Nitric Oxide
  • Laser Doppler Flowmetry
  • Skin Blood Flow
  • Infrared Thermography
  • Nitric Oxide Donor