The peripheral vascular responses in non-freezing cold injury and matched controls

Abstract

New findings: What is the central question of this study? Does non-freezing cold injury (NFCI) alter normal peripheral vascular function? What is the main finding and its importance? Individuals with NFCI were more cold sensitive (rewarmed more slowly and felt more discomfort) than controls. Vascular tests indicated that extremity endothelial function was preserved with NFCI and that sympathetic vasoconstrictor response might be reduced. The pathophysiology underpinning the cold sensitivity associated with NFCI thus remains to be identified.

Abstract: The impact of non-freezing cold injury (NFCI) on peripheral vascular function was investigated. Individuals with NFCI (NFCI group) and closely matched controls with either similar (COLD group) or limited (CON group) previous cold exposure were compared (n = 16). Peripheral cutaneous vascular responses to deep inspiration (DI), occlusion (PORH), local cutaneous heating (LH) and iontophoresis of acetylcholine and sodium nitroprusside were investigated. The responses to a cold sensitivity test (CST) involving immersion of a foot in 15°C water for 2 min followed by spontaneous rewarming, and a foot cooling protocol (footplate cooled from 34°C to 15°C), were also examined. The vasoconstrictor response to DI was lower in NFCI compared to CON (toe: 73 (28)% vs. 91 (17)%; P = 0.003). The responses to PORH, LH and iontophoresis were not reduced compared to either COLD or CON. During the CST, toe skin temperature rewarmed more slowly in NFCI than COLD or CON (10 min: 27.4 (2.3)°C vs. 30.7 (3.7)°C and 31.7 (3.9)°C, P < 0.05, respectively); however, no differences were observed during the footplate cooling. NFCI were more cold-intolerant (P < 0.0001) and reported colder and more uncomfortable feet during the CST and footplate cooling than COLD and CON (P < 0.05). NFCI showed a decreased sensitivity to sympathetic vasoconstrictor activation than CON and greater cold sensitivity (CST) compared to COLD and CON. None of the other vascular function tests indicated endothelial dysfunction. However, NFCI perceived their extremities to be colder and more uncomfortable/painful than the controls.

Keywords: cold injury; pathophysiology; vascular.

FIGURE 1

Participant flow through trial. Participant flow through the trial for the three groups. COLD, cold‐exposed controls; CON, non‐cold‐exposed controls; NFCI, individuals with non‐freezing cold injury in their feet and/or hands.

FIGURE 2

Reported ability to cope with the cold. Reported ability to cope with the cold in the extremities and body in NFCI (individuals with NFCI; n = 16), COLD (cold‐exposed controls; n = 15), CON (non‐cold‐exposed controls; n = 13) from cold exposure questionnaire. Values given are the percentage of the group that thought they coped ‘better than average’ (□), ‘average’ (■) or ‘worse than average’ (■).

FIGURE 3

Cold intolerance. (a) Mean (SD) cold intolerance symptoms severity questionnaire (CISS) scores reported by NFCI (individuals with NFCI; n = 16), COLD (cold‐exposed controls; n = 16) and CON (non‐cold‐exposed controls; n = 13). (b) Percentage of the participants who were classified as having mild, moderate, severe or extremely severe cold intolerance for each group (no statistical tests were performed).

FIGURE 4

Deep inspiration vascular response. Maximum inspiratory gasp vascular response (IGVR) measured on the thumb (a, b) and great toe (c, d) at an ambient temperature of 24°C (a: NFCI n = 10; COLD n = 11; CON n = 10; c: NFCI n = 12; COLD n = 13; CON n = 13) and 30°C (b: NFCI n = 9; COLD n = 8; CON n = 10; d; NFCI n = 12; COLD n = 11; CON n = 12). Individual data points are shown for each group and the bars represent the median (IQR). The Kruskal–Wallis test indicated no between‐group differences for the thumb at 24° C (P = 0.636) or 30°C (P = 0.086) or toe at 24°C (P = 0.669). COLD, cold‐exposed controls; CON, non‐cold‐exposed controls; NFCI, individuals with non‐freezing cold injury.

FIGURE 5

Post‐occlusive reactive hyperaemia. Skin blood flow responses following occlusion of the thumb (a, c, e) and great toe (b, d, f). Individual values and median (IQR) are shown for the peak flux as a percentage of the baseline (a, b), PORH index (c, d) and the hyperaemic response (e, f). NFCI (individuals with NFCI ●, thumb n = 11; toe n = 13), COLD (cold‐exposed controls ○, thumb n = 11; toe n = 13) and CON (non‐cold‐exposed controls △, thumb n = 9; toe n = 12). No between‐group differences were seen in thumb for peak (P = 0.765), PORH index (P = 0.458) or area of hyperaemia (P = 0.520) or in toe for PORH index (P = 0.130) or area of hyperaemia (P = 0.739) using the Kruskal–Wallis test.

FIGURE 6

Response to ACh and SNP. Maximum cutaneous vascular conductance (CVC) to iontophoresis of acetylcholine (ACh, a, b) and sodium nitroprusside (SNP, c, d) on the forearm (a, c) and foot (b, d) for each group (NFCI: ● individuals with NFCI; COLD: ○ cold‐exposed controls; CON: △ non cold‐exposed controls). Individual values with mean (SD) following a cumulative current of 600 μA (n = 14 for each group) are shown for the forearm and median (IQR) following a cumulative current of 100 μA (NFCI n = 11, COLD n = 9, CON n = 12) for the foot. No between‐group differences were seen with ANOVAs in the forearm for ACh (P = 0.749) or SNP (P = 0.196) or with the Kruskal–Wallis test in the foot for ACh (P = 0.343) or SNP (P = 0.777).

FIGURE 7

Skin temperature during CST. Skin temperature of the great toe (a), coldest toe (b) and mean of all toes (c) during the cold sensitivity test for each group (NFCI: ● individuals with NFCI, n = 12; COLD: ○ cold‐exposed controls, n = 11; CON: △ non cold‐exposed controls, n = 12). Individual data and mean (SD) are shown for before immersion (Pre imm), 5 min of rewarming (5 min) and 10 min of rewarming (10 min). ANOVA showed no between‐group differences for great toe (P = 0.361) or mean toe (P = 0.059) skin temperature; pre‐immersion the coldest toe skin temperature did not differ between groups (P = 0.722).

FIGURE 8

Thermal sensation and comfort during CST. Thermal sensation (a) and thermal comfort (b) for the foot during the CST for each group (NFCI: ● individuals with NFCI, n = 12; COLD: ○ cold‐exposed controls, n = 11; CON: △ non‐cold‐exposed controls, n = 12). Individual data and mean (SD) are shown for before immersion (Pre imm), immersion, 5 min of rewarming (5 min) and 10 min of rewarming (10 min). Kruskal–Wallis test showed no between‐group differences pre‐immersion for thermal sensation (P = 0.776) or thermal comfort (P = 0.318).