European Journal of Applied Physiology

, Volume 89, Issue 5, pp 411–426

Finger cold-induced vasodilation: a review

Authors

Original Article

DOI: 10.1007/s00421-003-0818-2

Cite this article as:
Daanen, H.A.M. Eur J Appl Physiol (2003) 89: 411. doi:10.1007/s00421-003-0818-2

Abstract

Cold-induced vasodilation (CIVD) in the finger tips generally occurs 5–10 min after the start of local cold exposure of the extremities. This phenomenon is believed to reduce the risk of local cold injuries. However, CIVD is almost absent during hypothermia, when survival of the organism takes precedence over the survival of peripheral tissue. Subjects that are often exposed to local cold (e.g. fish filleters) develop an enhanced CIVD response. Also, differences between ethnic groups are obvious, with black people having the weakest CIVD response. Many other factors affect CIVD, such as diet, alcohol consumption, altitude, age and stress. CIVD is probably caused by a sudden decrease in the release of neurotransmitters from the sympathetic nerves to the muscular coat of the arterio-venous anastomoses (AVAs) due to local cold. AVAs are specific thermoregulatory organs that regulate blood flow in the cold and heat. Their relatively large diameter enables large amounts of blood to pass and convey heat to the surrounding tissue. Unfortunately, information on the quantity of AVAs is lacking, which makes it difficult to estimate the full impact on peripheral blood flow. This review illustrates the thermospecificity of the AVAs and the close link to CIVD. CIVD is influenced by many parameters, but controlled experiments yield information on how CIVD protects the extremities against cold injuries.

Keywords

Arterio-venous anastomosesCold induced vasodilationFinger blood flow

Introduction

Millions of people are daily exposed to cold and face the challenge to maintain their body core temperature at about 37°C. Peripheral vasoconstriction is a powerful mechanism to reduce the heat loss, but results in strong cooling of the extremities. However, the extremities possess the ability to prevent the occurrence of local cold extremes. About 5–10 min after the initiation of cold exposure of the hand, blood vessels in the finger tips suddenly vasodilate, which increases the peripheral blood flow and subsequently the temperature of the finger tips. This cold-induced vasodilation (CIVD) is followed by a new phase of vasoconstriction. This process repeats itself and is called 'the hunting reaction' (Lewis 1930). Arterio-venous anastomoses (AVAs) are thought to play a major role in the mechanism of CIVD, but the exact mechanism is still subject to debate. The CIVD reaction and the related blood vessels are important issues for thermal physiologists, since CIVD is thought to reduce the risk of local cold injuries (Iida 1949). Wilson and Goldman (1970) found in their experiments that freezing did not take place when CIVD occurred. It is likely that CIVD also improves the manual dexterity and tactile sensitivity during work in the cold. Since the blood flow increases substantially in the fingers during CIVD, this increases the blood circulation in the large vessels of the forearm, with the consequence of increasing the temperature of the forearm muscles (Ducharme et al. 1991), and likely contributes to improved manual performance by improving muscle function. The increased skin temperature due to CIVD will increase the firing rate of the pressure transducers in the skin and thus increase tactile sensitivity.

CIVD can occur at several locations in the human body. The focus in this review is placed on finger CIVD, since the finger is a common site for local cold injuries and most data are available for this body part.

It is the purpose of this article to review the current knowledge on finger CIVD, to describe the effects of several parameters such as core temperature, diet and acclimatization on finger CIVD and to discuss the possible mechanisms involved.

Definitions and terminology

CIVD and hunting reaction

Cold-induced vasodilation can be defined as vasodilation of cold-exposed blood vessels, in particular the small arteries. The term hunting reaction or hunting response (Lewis 1930) is used to describe the alternating periods of vasodilation and vasoconstriction during cold exposure. Some authors use the term Lewis reaction instead of hunting reaction (Kramer and Schulze 1948; Werner 1977).

Purkayastha et al. (1992) argue that the hunting reaction is only one out of four possible reactions of blood vessels to extreme local cold. The other responses observed in the fingers after immersion in cold water are: (1) a continuous state of vasoconstriction, (2) slow steady and continuous rewarming and (3) a proportional control form in which the blood vessel diameter remains constant after an initial phase of vasoconstriction.

The majority of the vascular responses to immersion of the finger in cold water can be classified as the hunting reaction. Daanen (2001) observed that the hunting reaction was present in 210 out of 226 investigated male subjects (93%) who immersed their finger in ice water. The reactions of the remaining subjects were difficult to classify.

Arterio-venous anastomoses (AVAs)

AVAs are thought to play a major role in CIVD. These blood vessels have a thick muscular wall and a lumen, measuring on average 10–30 μm (Gray 2000), 35 μm (Roddie 1983) or even 50 μm (Sherman 1963). Under the influence of the sympathetic nervous system, with its rich supply of non-myelinated fibres on the wall of the vessel, they are capable of complete closure. When the AVAs are open, large amounts of blood can pass. Anastomoses are not fixed structures, but may come and go on demand: they can develop when necessary and disappear when they are no longer needed. Hale and Burch (1960) observed that AVAs develop if blood requirement increases at the finger tip. Clark and Clark (1934) estimated that the formation of new AVAs requires 2–3 days.

In their studies, Hale and Burch (1960) and Clara (1939) mentioned the following sites of AVAs: the skin of the inside of the hand and foot, the nail bed, the elbow, lips, cheeks, ears and the nose. There is some discussion about the presence of AVAs in the skin of the head.

Grant and Bland (1931) found 501 AVAs per cm2 surface area in the nail bed, 236 in the finger tip, 150 on the palmar side of the distal phalanx, 20 on the palmar side of the medial phalanx and 93 on the palmar side of the proximal phalanx. They found no AVAs on the dorsal side of the hand. However, the numbers were derived from only one index finger from only one subject, although they claim that similar results were found in three other subjects. Masson (1937) only counted three to four AVA's per cm2 at the top of the finger and about ten in the nail bed. Clara (1939) argued that Grant and Bland (1931) counted the same AVA several times. AVAs are tortuous and they did not account for that in their counting technique.

The limited information on the number of AVAs in the fingers and the disagreement in the existing studies necessitates new research to address this topic. Moreover, there is a strong need for more accurate data on the amount of AVAs in the human body, in particular to improve current computer models on blood flow and heat transfer.

Methodology

Several methods are available to quantify the amount of vasodilation in the finger skin. Direct measurement of the diameter of blood vessels is extremely difficult, if not impossible, and therefore indirect measures are used. When the blood vessel diameter increases, the blood flow increases (if the viscosity of the blood remains the same) and this can be measured by laser Doppler flowmetry and strain gauge plethysmography. Some authors determine the blood flow by the wash out of a marker added to the blood (e.g. Coffman 1972). The increased blood flow raises the tissue temperature and thus the temperature at the finger tip. The finger skin temperature is the most frequently used method to determine CIVD. The increased finger skin temperature leads to a higher heat transfer to the environment, which can be assessed by heat flux sensors and calorimetry. The most common methods to quantify CIVD are briefly discussed below.

Strain gauge plethysmography

The principle of this technique is that a cuff is placed and inflated proximal to the measuring site in such a way that blood can enter, but not leave the measured extremity. During the obstruction a linear increase is seen in circumference due to the accumulating blood. The increase in circumference is an estimator of blood flow (Elkington 1968). Since fingers are almost free of skeletal muscle tissue, their volume changes mainly represent alterations in the blood volume in the cutaneous blood vessels (Okuda 1942).

Laser Doppler flowmetry

Laser Doppler flowmetry is a method that yields information on local skin blood flow. The emitted laser light from a small probe on the skin is backscattered from moving red blood cells or static skin structures. Light scattered from moving objects is shifted in frequency (Doppler shift) in proportion to the velocity of the moving target. A photodetector, located close to the laser beam end, measures the backscattered light.

The penetration depth of the laser in the skin is determined by the wavelength of the laser Doppler system, the fibre separation (Hirata et al. 1988) and local properties of the skin (Tenland 1982). Nagasaka et al. (1988) argues that only a minimal part of the AVAs can be "seen" by laser Doppler flowmetry using He-Ne lasers. Wollersheim (1988), however, shows that at least part of the shunt flow is included in the laser Doppler results. This issue is not resolved, but it can be expected that new laser Doppler systems will have the ability to set the penetration depth.

Skin nutritional blood flow through the capillaries is generally related to total blood flow of an extremity. For instance, Johnson et al. (1984) found a good relationship between laser Doppler flow and forearm blood flow (r=0.94–0.98). However, there are also situations, such as reflex vasodilation, in which skin perfusion is regulated independently from total blood flow (Hirata et al. 1988).

Finger skin temperature

Finger skin temperature is the most commonly used measure for CIVD. A small thermocouple is generally attached to the palmar side of the distal phalanx with tape. The measured temperature is a mix of the finger skin temperature and the temperature of the surrounding cooling medium. Careful attachment of a small thermocouple to the skin minimizes the influence of the cooling medium temperature.

The nail bed is also often used as a measuring site, since it is known that AVAs are abundant there. However, Yoshimura (1966) showed that the temperature reaction measured on the pad of the finger is more sensitive and reproducible than that on the nail bed.

The measured finger skin temperature is a slow indicator of what occurs in the tissue underneath. Daanen (1997) observed that CIVD onset measured using the finger skin temperature occurred 90 (48) s later than measured using laser Doppler flowmetry.

The changes in finger skin temperature profile during cold exposure are quantified using the terminology shown in Fig. 1.
  • The minimum temperature (Tmin) is the lowest finger skin temperature just before CIVD starts.

  • The maximum temperature (Tmax) is the highest finger skin temperature during CIVD.

  • The onset timetonset) is the time from immersion to Tmin.

  • The amplitude is the difference between Tmin and Tmax.

  • The peak timetpeak) is the time interval between Tmin and Tmax.

  • The mean finger skin temperature (Tmean) denotes the finger skin temperature averaged over the immersion period. As a rule, the onset time is not included, since during this period the heat in the hand is removed. In practice, the first 5 min data are removed.

  • The frequency of the hunting reaction is expressed as the number of waves (vasodilation/vasoconstriction period) within a certain time frame.

Fig. 1.

Parameters derived from a temperature profile of a finger tip immersed in cold water. The onset time (Δtonset) is the time from immersion to the minimum temperature (Tmin). The amplitude is the difference between Tmin and Tmax. The peak time (Δtpeak) is the time interval between Tmin and Tmax. The mean finger skin temperature (Tmean) denotes the finger skin temperature averaged over the immersion period, excluding onset time

Yoshimura and Iida (1952) quantified the magnitude of the CIVD reaction using the Resistance Index for Frostbite (RIF) in which Δtonset, Tmin and Tmean were included. Short onset times and high minimal or mean finger skin temperatures were rated by 3 points and long onset times and low temperatures by 1 point, leading to summated RIFs from 3 to 9. This RIF index is used by many other authors, in particular from Japan.

General reactions observed during CIVD

Reflex vasoconstriction and reflex vasodilation

When one body part is cooled, vasoconstriction also occurs in other parts of the body. This phenomenon is known as reflex vasoconstriction. Similarly, if heat is applied to another part of the body, such as a leg, the vessels open up and the hand gets warm (Gibbon and Landis 1932). This phenomenon is called reflex vasodilation. Sensors in the skin react to the external stimulus and transfer information to the vasomotor centre. This centre integrates the information and sends an adequate response to the effector organs. Pickering (1932) showed that blood temperature also plays an important role in this mechanism. He found no reflex vasodilation when the venous return of a heated hand was blocked.

Reflex vasodilation and vasoconstriction are also noted during the hunting reaction. Immersion of the feet in cold water during the hunting reaction in fingers reduced the magnitude of the hunting reaction (Keatinge 1957). Lewis (1930) observed that cooling the forearm suppressed CIVD in the fingers. Page and Brown (1953) and Livingstone et al. (1978) observed that Eskimos had less reflex vasoconstriction in the fingers upon cold water immersion of a foot than control subjects. Thus, Eskimos are able to maintain good dexterity when the feet are cold. Werner (1983) showed that reflex vasodilation or vasoconstriction not only depends on the skin and core temperatures but also on the rate of change of these temperatures.

Pain

Immersion in cold water is often a painful experience. LeBlanc (1975) and Heus and Daanen (1993) noted that the most painful period occurred during vasoconstriction, and that the vasodilation phase was often felt as a relief. The pain during strong vasoconstriction may be seen as a warning signal for exceptional cooling. Kreh et al. (1984) found a close relationship between pain intensity and degree of vasoconstriction. If the cooling continues, the tissue temperature may decrease below the threshold for nerve conduction (7–8°C, Vanggaard 1975). If that threshold is reached no information from the periphery can reach the central nervous system and the extremity feels numb. Sawada et al. (2000) observed that pain diminished after repeated cold water immersions.

Experimental factors affecting CIVD

Ambient temperature and body temperature

The regulation of blood flow to the extremities is, at low ambient temperatures, primarily determined by the thermal state of the body as a whole. Even at air temperatures below −30°C, the skin temperature of bare hands can be sustained above 21°C (Rapaport et al. 1949). Therefore, it is rather likely that the body core temperature influences the hunting reaction. In Table 1 results of relevant articles in the literature are summarized.
Table 1.

Influence of body temperatures on the hunting reaction. [Tre Rectal temperature (°C), Tsk mean body skin temperature (°C), Tmean mean finger skin temperature (°C), Tmin minimum temperature of finger skin during immersion (°C), Δtonset time from immersion to Tmin in minutes]

Author(s)

Body temperatures

Hunting reaction

Induction

Measurement

Induction

Measurement

Variables

Results

Variables

Results

Adams and Smith (1962)

Room temp. 7 and 22°C for 1 h

Index finger for 20 min in 0°C

Finger skin temp

Δtonset increased in cool subjects

Bader and Mead (1949)

Room temp. 13 and 32°C

Terminal phalanx in ice water or 0°C air

Finger skin temp. and plethysmography

Blood flow not dependent on local temp. (cold water or air) but on ambient temp.

Blaisdell (1951)

Room temp. 28, 25, 15 and 12°C for 2–3 h

Tre, Tsk

Tre not different between room temp. Tsk at 28°C: 33.1°C. Tsk at other room temp.: 25°C

Hand in 0, 5, 10 and 15°C air

Finger nail bed temp. and plethysmography

Tmin lower when chilled (3.8°C versus 7.8°C at 28°C room temp.), no differences in frequency and amplitude

Daanen et al. (1997)

Drinking 0°C and 43°C beverages

Tre, Tsk and Tear

Tear 36.5 and 37.1°C

Hand for 30 min in water of 8°C

Finger skin temp

Cold body: low hunting frequency and small hunting magnitude

Daanen and Ducharme (2000)

Whole body cold water immersion; hot water perfused suit

Tes, Tre and Tsk

Tes 36.1 and 38.0°C

Hand for 40 min in water of 5°C

Finger skin temp, skin perfusion (laser Doppler)

Cold body: long onset times, small CIVD magnitude

Edwards and Burton (1960)

Room temp. "neutral" and 9–17°C

Finger in ice water

Plethysmography, calorimetry

Reduced blood flow and heat transfer in cold room

Elsner et al. (1960)

Room temp. 18°C unclothed and 22°C clothed

Hand for 30 min in water of 5°C

Calorimetry

More heat loss in warm room

Folkow et al. (1963)

Indirect warming and cooling

Hands in ice water

Venous occlusion plethysmography

More blood flow when indirectly warmed

Greenfield et al. (1951)

Room temp. 14.5°C, 20.5°C and 22.5°C

Toes in water 0–6°C

Calorimetry

More heat loss when room temp. increases

Keatinge (1957)

6°C water bath; Room temp. 5–6°C (1 h) and 17–18°C with clothing and exercise

Index finger in ice water

Calorimetry

Finger heat loss. Hot: 65% of max. Cold: 5% of max. Cold bath: 13% of max.

Kramer and Schulze (1948)

Room temp, hot drinks, daily and seasonal variations

Hands in cold air of −18 to 10°C

Finger skin temp

Mean finger skin temp. increased when warm

Lee et al. (1996)

30 min in 27°C air (N), 60 min in 20°C water (H)

Tes, Tre

N: Tes: 36.85°C; Tre: 37.02°C; H: Tes: 36.18°C; Tre: 36.29°C

Right middle finger in 4°C water

Finger skin temp

Mean finger skin temp. lower in H amplitude also lower

Spealman (1945)

Room temp. 16, 24 and 32°C for 3 h

Hands for 3 h in water of 2 to 35°C

Blood flow by venous occlusion plethysmography

Blood flow higher at high ambient temp. and when water temp. is higher or lower (CIVD) than 15°C

Tanaka (1971b)

Room temp. 25, 30 and 35°C

Middle finger for 30 min in 0°C

Finger skin temp

With increasing room temp: higher Tmin and Tmean and shorter Δtonset

Werner (1977)

Room temp. 15 (for 0.5 h), 30 and 45°C

Tre

Hands in air at 0.5 m°s-1 at −5, 0 and 5°C

Finger skin temp

Tmean higher when ambient and hand temp. increase No. of fluctuations at 45°C ambient temp.

Yoshimura and Iida (1950)

Room temp. 4–36°C

Middle finger for 30 min in 0°C

Finger skin temp

Tmin increases with room temp. Tmean increases with room temp. Δtonset decreases with room temp.

In most investigations the effects of body temperature were investigated by putting subjects in a relatively cold or warm room. Unfortunately, the resulting core and mean body skin temperatures were often not recorded. The general image emerging from Table 1 is that a high ambient or core temperature leads to higher mean finger skin temperatures during the hunting reaction. Also, the onset time of CIVD was observed to be shorter. Daanen et al. (1997) and Daanen and Ducharme (1999) found that onset time was mainly related to the mean skin temperature of the body and that mean finger skin temperatures were mainly related to body core temperatures.

Ambient temperature may change body core temperature, but the core temperature is also modified by exposure to ambient light and changes in melatonin variations during the day (Burgess et al. 2001), and during the year (seasonal) (Yoneyama et al. 1999). The effects of these changes in core temperature on CIVD, as reported in the literature, are:
  • The hunting reaction is more pronounced in the afternoon, than in the morning or the night (Kramer and Schulze 1948).

  • Schulze (Kramer and Schulze 1948) measured his CIVD each month at room temperature with his hand in a cold air box and found an average maximal finger skin temperature of 28°C in the summer and 16°C in the winter during immersion, indicating a vasoconstrictive state during winter.

  • Tanaka (1971b) measured CIVD during middle finger immersion in 0°C water during summer and winter under identical ambient conditions and also observed that the CIVD reaction was more pronounced in summer.

In summary, it appears that in the afternoon and in the summer, when the core temperature is relatively elevated, the hunting reaction is more pronounced.

Cooling medium

To evoke CIVD, two media are commonly used: water and air. Immersion in cold water is used most often. The thermal conductivity of water is about 25 times higher than that of air, so cooling is rather quick.

Kramer and Schulze (1948) cooled fingers in a cold air box, and compared the results with those of other studies in which the fingers where cooled in water. The frequency of the hunting response in 0°C water showed most similarity with that in −18°C air. Kramer and Schulze (1948) observed that the frequency of the hunting reaction decreased when the air temperature in the cooling box around the hand increased: four to six hunting periods were observed in 2 h at an air temperature of −18°C and only one at 10°C air temperature.

There is no agreement in the literature concerning the water temperatures at which CIVD occurs. The lowest temperature in the studies equals 0°C, the temperature of stirred water with ice. Lewis (1930) and Yoshimura (1960) performed their experiments at this temperature, since they wanted a maximal response. Lewis (1930) did not see a hunting reaction in water temperatures above 18°C. Hirai et al. (1970) saw no response at 15°C and advised an optimal temperature for investigation of 5°C, since the differences between two investigated populations were optimal then.

Havenith et al. (1992) and Chen et al. (1994) observed CIVD when subjects were touching cold materials, but decided not to use and process the data for their cooling models. Chen et al. (1994) observed CIVD in 14% of the recordings. This low percentage is probably due to two factors. First, a part of the thermocouple was in direct contact with the aluminium bar, thus underestimating the finger tip temperature. Second, the cold stress was not severe enough: the aluminium surface was –7, 0 or 7°C in a climatic chamber of 10 or 30°C.

Surface area cooled

Sendowski et al. (1997) investigated the differences in finger CIVD response between immersing a finger, hand or forearm in 5°C water. The finger CIVD was more pronounced (faster onset and higher amplitude) after finger immersion than after hand or forearm immersion. Two main explanations were given. The first explanation was that the arterial blood was cooler in the finger after hand/forearm immersion due to pre-cooling in the hand or forearm. This explanation was recently confirmed by Ducharme et al. (2001), who observed reduced CIVD when the forearm tissue was cooled. The second explanation was that sympathetic activity was higher during hand/forearm immersion, which was illustrated by higher scores for pain sensation. Moreover, cardiovascular changes were found during hand/forearm immersion and not during finger immersion. To investigate the sympathetic influence in more detail, Sendowski et al. (2000) co-immersed the left hand with the right middle finger. Increased plasma norepinephrine during co-immersion showed that sympathetic activity was elevated. The CIVD amplitude reduced during co-immersion, and this is likely to be attributed to increased sympathetic activity. On the other hand, blood cooling due to the left hand immersion cannot be completely ruled out.

Altitude

A significant reduction in the hunting reaction is found during exposure to high altitude, where cold co-exists with systemic hypoxia (Mathew et al. 1977). Takeoka et al. (1993) showed that Tmean during the hunting reaction was lower in seven Japanese men at an altitude of 4860 m (ambient temperature 9°C) as compared to 2260 m (ambient temperature 12°C). Recently, Daanen and Van Ruiten (2000) observed that CIVD was reduced in magnitude at an altitude of 5000 m, even when the body core was warmer than at sea level. Therefore, it seems that systemic hypoxia reduces the magnitude of the hunting reaction. During prolonged stay at altitude, the CIVD reaction gradually improves (Daanen and Van Ruiten 2000).

Individual factors affecting CIVD

Age

In the elderly, the CIVD reaction occurs later and is less pronounced (Sawada 1996; Spurr et al. 1955). Also, Tan and Tregenza (2002) observed that the CIVD responses of a group of 18-year old students was more pronounced than that of their parents (40–50 years old). The reduced CIVD reaction is attributed to the diminished sympathetic vasoconstrictor responses with the advancing age (Khan et al. 2002) which is in line with the observations that the onset time and peak time are considerably delayed by age and the finger skin temperatures are only slightly changed. Also, an age-related decrease in core temperature due to a decreased basal metabolic rate and reduced physical activity (Van Someren et al. 2002) will likely affect the CIVD response.

For younger people, the results are less consistent. Yoshimura and Iida (1952) observed that children had lower RIF values than adults, but higher values than in puberty. In contrast, Miller and Irving (1962) found that the finger temperature of Eskimo children dropped more than that of adults during cold exposure. However, this may be attributed to their drop in body temperature, which was not controlled for.

Gender

Hand and finger blood flow in thermoneutral conditions is higher for men than for women as measured by laser Doppler flowmetry and plethysmography, due to increased vasomotor tone in women (Cooke et al. 1990). By contrast, after total body warming of both genders, the blood flow was greater in females than in males.

When warm hands (about 32°C) are exposed to cold, women show an enhanced vascular reactivity as compared to men, which causes a more pronounced decrease in peripheral blood flow and skin temperatures in females (Bartelink et al. 1993; Pollock et al. 1993). The reactivity is most pronounced in women using oral contraceptives, followed by premenopausal women and postmenopausal women (Bartelink et al. 1993). These three different hormonal conditions thus have a strong impact on vascular reactivity, but age may also play a role here. Cooke et al. (1990) found no relation between female hand blood flow and levels of serum oestrogen or progesterone.

Miller and Irving (1962) observed no differences in finger temperature response to cold air between three Eskimo women and eight Eskimo men and between eight Eskimo boys and four Eskimo girls. Also, Yoshimura and Iida (1952), Tanaka (1971b) and Yoshimura et al. (1958) found no sex differences in the hunting reaction. Reading et al. (1997) observed higher finger skin temperatures for males than for females during a 2-h exposure to 0°C air, during which hunting occurred.

In summary, females tend to have lower hand blood flows when exposed to cold due to increased vascular reactivity, but the limited amount of available studies showed no indication that the temperature profiles of the hunting reaction differed between males and females. It was expected that the reduced vascular reactivity to cold of males as compared to females would be reflected in a delayed CIVD reaction, similar to the observations of CIVD with age. This, however, was not the case and further research is needed to elucidate this point.

Physical fitness and fatigue

Moriya and Nakagawa (1990) observed in 14 females that the RIF was not related to the maximum oxygen uptake divided by body weight. The latter variable is considered to be a good estimator of physical fitness. They found a significant correlation between absolute maximum oxygen uptake in l/min and RIF, but this was only in one subject and insufficient to draw conclusions. More research is needed to establish the effect of physical fitness on CIVD.

O'Brien et al. (1999) observed that the onset time was reduced in subjects after 5 days of repeated strenuous physical exertion with insufficient recovery. This effect was attributed to increased circulating norepinephrine levels that reduce the sensitivity to sympathetic stimulation.

Mental stress

Meehan (1957) showed that the hunting reaction was abolished in a stressed subject who had just completed an exam, in contrast to three previous experiments in which the hunting reaction had been clearly present. This finding was confirmed by Adams and Smith (1962). They showed that a strong emotional stress given during the vasodilation phase led to an immediate strong vasoconstriction. This demonstrates the functional integrity of efferent vasomotor nerves and receptors during CIVD. Mental stress increases the activity of the vasomotor centre which increases the intensity of vasoconstriction in the skin (Marriott et al. 1990). When the sympathetic vascular tone is high, however, mental tasks may lead to paradoxical vasodilation (Cooke et al. 1990; Halperin et al. 1983). Also, humans are able to voluntary vasodilate the blood vessels in the finger pad, and thus increase their finger temperature (Carter 1978).

Acclimatization to cold

Acclimatization refers to physiological or behavioural changes occurring within an organism that reduce the strain or enhance the endurance of strain caused by stressful changes, in particular climatic factors (IUPS Thermal Commission 2001). People working with their hands in a cold environment (e.g. fish-filleters) have increased blood flow through their hands in the cold as compared to unacclimatized subjects (Krog et al. 1960; LeBlanc et al. 1960). CIVD occurs at an earlier stage of cold exposure in the acclimatized subjects (Nelms and Soper 1962). Tanaka (1971a) found that ice chamber workers had a higher mean finger skin temperature, a higher minimal finger temperature and shorter onset time of CIVD than cool room workers. Purkayastha et al. (1992, 1993) showed that tropical residents developed a more pronounced hunting reaction 7 weeks after an airlift to an arctic region and that the response was indistinguishable from the response of arctic residents. Table 2 summarizes the findings on the effects of local cold acclimatization on CIVD.
Table 2

. Summary of investigations concerning acclimatization and/or adaptation of finger CIVD. (CA Cold adapted/acclimatized, N-CA not cold adapted/acclimatized)

Authors

Population

Onset time (min) of CIVD

Minimal finger temperature (°C)

Mean finger skin temperature (°C)

Experimental setup

CA

N-CA

CA

N-CA

CA

N-CA

CA

N-CA

Bridgman (1991)

Divers

Non-divers

9.4

9.1

Index finger at 0°C

Elkington (1968)

After Antarctic trip

Before Antarctic trip

7.4

7.3

Index finger at 0°C

Elsner et al. (1960)

Arctic Indians

Scientists

4.7

7.5

2.3*

0.6*

Index finger at 0°C

Arctic Indians

Scientists

2.3

3.3

Index finger at 4–5°C

Hirai et al. (1970)

Japanese

Caucasians

6.5

9.1

9.7

6.9

10.5

8.3

Middle finger at 5°C – both groups actually not CA

Iampietro et al. (1959)

Caucasians

Negroes

9.2

15.9

2.9

1.0

7.2

2.7

All fingers at 0°C

Itoh et al. (1970)

Hokkaido natives

Main island natives

6.2

7.8

2.3

1.2

5.9

4.2

Middle finger at 0°C

Jackson et al. (1989)

Caucasians

Negroes

4.2

6.6

6.5

5.7

7.6

6.8

Middle finger at 5°C

Krog et al. (1960)

Laps

Norwegian students

5.4

9.1

1.6

1.2

Middle finger at 0°C

Fishermen

Norwegian students

6.9

9.1

1.7

1.2

Middle finger at 0°C

Leblanc et al. (1960)

Fishermen

Labourers

>4.0

3.5

Index and middle finger at 0°C; only 10 min immersion

Livingstone (1976b)

Military personnel after 2-week arctic stay

Military personnel before arctic stay

9.3

12.4

5.4

3.9

9.8

7.5

Middle finger at 0°C

After 7 days of cold exposure

Before cold exposure

10.4

13.3

4.6

3.5

7.5

5.5

Middle finger at 0°C

Meehan (1955)

Alaskan Natives

Caucasians

4.2

2.2

59

4.4

Median of index finger at 0°C

Caucasians

Negroes

2.2

0.0

4.4

1.4

Median of index finger at 0°C

Miller and Irving (1962)

Cold-accustomed Caucasians

Not cold-accustomed Caucasians

6.3

5.6

Mean of 5 fingers at about −7°C air

Eskimo

Not-cold-accustomed Caucasians

15.2

5.6

Mean of 5 fingers at about −7°C air

Nelms and Soper (1962)

Fish filleters

Technical staff officers

4.5

9.9

2.0

0.4

Middle finger at 0°C

Purkayastha et al. (1992)

Arctic natives

Tropical residents

8.2

11.1

8.0

5.6

10.3

6.6

Index finger at 4°C

Takeoka et al. (1993)

Tibetans

Japanese

9.2

12.0

Middle finger at 0°C at 4860 m altitude

Tibetans

Japanese

8.3

9.0

middle finger at 0°C at 2260 m altitude

Tanaka (1971a)

Ice chamber workers

Cool room workers

6.7

8.9

7.6

1.7

11.5

6.9

Middle finger at 0°C

*These results are indirectly derived from Nelms and Soper (1962)

Adaptation to cold

The term genotypic adaptation refers to "a genetically fixed condition of a species or subspecies, or its evolution, which favours survival in a particular total environment" (IUPS Thermal Commission 2001). This type of adaptation for cold is generally deduced from a comparison between populations who inhabit different locations. Studies on cold adaptation are included in Table 2.

The results of the studies depend on the method that is used to measure the changes in finger circulation.

The results were unambiguous when finger skin temperatures were measured. It was generally found that the cold adapted/acclimatized (CA) subjects had a shorter onset time and a higher minimal and mean temperature (Table 2). Only a few publications were not consistent with this statement. Takeoka et al. (1993) found that the cold-adapted Tibetans had a lower Tmean than the Japanese controls. In this case however, hypoxia coexists with cold, which may alter the response. Bridgman (1991) found no differences between divers and non-divers, probably due to an insufficient stimulus for acclimatization. The other publications in which finger temperatures were measured were in general agreement. Meehan (1955) found that the mean skin temperature of the fingers during ice water immersion was highest for Alaskan natives, followed by Caucasians and Negroes respectively. Elsner et al. (1960) showed an earlier onset of vasodilation in arctic Indians as compared to a control group. Itoh et al. (1970) showed that natives of the colder Hokkaido island had a more pronounced hunting reaction (earlier onset, higher mean finger skin temperature and higher minima) than subjects born on the main island. Iampietro et al. (1959) showed that Negroes and Caucasians reacted similarly to whole-body cold exposure, but that Negroes had a reduced hunting reaction to local cold exposure.

Yoshimura and Iida (1952) observed that the RIF was higher for populations living in cold areas, such as Chinese, Mongol and Orogon people (6.2–8), than for the Japanese (5.8). Analogous to the findings in the fingers, Elsner (1963) showed that foot temperatures were higher in Australian aboriginals and Indians as compared to Caucasians during cold exposure.

When blood flow or heat transfer methods were used, the observations were ambiguous (Table 2). Brown and Page (1952) showed that Eskimos had a higher blood flow of the hand than Canadian students. Hellström and Andersen (1960) found no differences in heat output between Arctic fishermen and controls. Also, Krog et al. (1960) found no differences between Laps and Norwegian controls in blood flow, but noticed that CIVD occurred more vigorously in Laps.

In most investigations, differences between groups could not be attributed to either genetic differences or acclimatization, since one of the ethnic groups is usually also exposed to more intense cold. However, there are a few investigations in which the distinction between the two could be made, but the results of these investigations are conflicting.

The Negroes and Caucasians in the survey of Meehan (1955) had similar cold exposure, but different genetic backgrounds. The persisting differences in the hunting reaction between both groups favours an (genetic) adaptation hypothesis over acclimatization. However, Purkayastha et al. (1993) found that acclimatized tropical residents showed the same hunting reaction as arctic residents and this favours an acclimatization hypothesis over adaptation.

Hirai et al. (1970) investigated differences in the hunting reaction between two populations, neither of which were exposed to cold on a regular basis: Japanese and Caucasians. In a water bath of 5°C they found that Japanese showed a more pronounced hunting reaction (earlier onset, higher mean finger skin temperature and higher minimum). If, however, Japanese and Caucasians living in the same area are compared, no differences were found. This leads to the conclusion that ambient factors, such as diet and acclimatization, may be of greater importance than ethnic differences.

In some experiments, the subjects were not only exposed to local cold, but also to general body cooling. In these investigations the results may have been dependent on the most severe stress. When general cold exposure was the dominant stress, whole-body acclimatization effects may prevail, while local cold acclimatization dominates in local cold stress. Livingstone et al. (1989) measured the acclimatization in four subjects who crossed the North Pole on skis. Both an enhanced hunting reaction and insulative-hypothermic acclimatization were shown. Savourey et al. (1996) immersed both legs of eight subjects in 0–5°C water twice a day for a month. Again, both local cold acclimatization (higher leg skin temperatures) and general insulative-hypothermic cold acclimatization occurred. Elkington (1968), Hampton (1969), Wyndham et al. (1964) and Livingstone (1976b) found no difference or even increased vasoconstriction in the hands after prolonged cold exposure. Here, whole-body cold exposure might have been predominant. It can be hypothesized that hypothermic acclimatization leads to reduced CIVD responses due to the reduced body core temperature and that insulative acclimatization has less impact on CIVD. This hypothesis has not been tested yet.

Cold resistance training

Several authors tried to increase the resistance against cold by daily cold water immersions.

Yoshimura and Iida (1952) describe an experiment in which boys and soldiers immersed their legs in ice water for 15 or 30 min daily for 1 month. Adams and Smith (1962) immersed the terminal two phalanges of the index finger in ice water four times daily for 1 month. In both experiments, an increased mean toe or finger temperature was found during immersion at the end of the training phase. These effects were not found when the peripheral cold exposure was limited to 1 min at 4°C daily for 9 days (Glaser and Whittow 1957). In all experiments the pain at the end of the training was less than at the start.

In summary, an intense cold stimulus that is repeated on a regular basis may lead to increased local skin temperatures and reduced pain. However, Yoshimura and Iida (1952) warn of side-effects: pain and nausea occurred during the training. A milder training regime might have the same beneficial results without these side-effects.

Diet

Yoshimura et al. (1952) showed that a daily intake of excessive protein (150–200 g/day) or excessive salt (>45 g/day) increased the reactivity of the hunting reaction after about 1 week. These observations can be explained by diet-induced thermogenesis, which causes an increase in core temperature. The increased core temperature leads to an increased finger blood flow (Hirai et al. 1991; Takano and Kotani 1989).

Also, vitamin C intake (2 g/day for 1 month) enhances the hunting reaction (Livingstone 1976a). In particular, the onset time is shortened. The beneficial effect of vitamin C may be attributed to its antioxidant properties, metabolic and thermogenic properties, collagen synthesis, anti-stress activity and restoration of intercellular substances as well as to better maintenance of the rheological status of the blood (Purkayastha et al. 1999).

Thus, dietary changes may improve the hunting response and, indirectly, the resistance against frostbite.

Alcohol ingestion

Granberg (1991) reviewed the effects of alcohol on human responses in the cold and concluded that experimental studies on humans during relatively short exposure to moderate cold have given inconsistent results regarding the effect of alcohol on heat balance. These inconsistencies may be attributed to differences in the amount of ingested alcohol and to the cooling method employed.

Longer exposure (several hours) to colder environments has revealed alcohol-induced enhancement of heat loss, at least in males (Graham and Lougheed 1985). Alcohol delays the onset of shivering. Vasoconstriction after exposure of the hands to cold occurs rather slowly due to alcohol (Kramer and Schulze 1948; Mills et al. 1986). However, Mills et al. (1986) found no differences in hunting frequency between sober and intoxicated subjects, but reported higher finger skin temperatures when intoxicated. Kramer and Schulze (1948) observed that the onset of CIVD occurred sooner when alcohol had been taken.

The ingestion of alcohol thus seems to result in vasodilation. Granberg (1991) observed that intoxicated subjects are less likely to suffer from severe freezing cold injuries.

Tobacco smoking

It is well known that tobacco smoking leads temporarily to peripheral vasoconstriction. The rewarming rate of cooled fingers was slow shortly after smoking a cigarette (Cleophas et al. 1982). When the experiment was repeated after a 24-h abstinence from smoking, rewarming was much faster for all eight tested subjects. In the latter case it was assumed that the vasoconstriction due to smoking was no longer present.

Daanen (2001) observed that the RIF value of 114 non-smoking mariners was less [6.7 (1.7)] than that of 95 smoking mariners [7.4 (1.5)] (p<0.01). The smokers showed a faster onset of CIVD and higher finger skin temperatures as compared to non-smokers. Smoking was not allowed for at least 3 days prior to the measurement, so there was no direct effect of smoking on the blood vessels. It is hypothesized that the repeated changes between peripheral vasodilation and vasoconstriction in abstinent smokers may lead to desensitization of blood vessels to local vasoactive stimuli, resulting in an enhanced hunting response. More research is necessary to clearly establish the effect of smoking on the hunting response and evaluate the hypothesis.

Vascular pathology

Jobe et al. (1985) investigated the hunting reaction of the right middle finger in eight subjects with Raynaud's disease type I, an idiopathic vasospastic disorder of the peripheral vasculature, and in nine normal subjects. At 10°C and 15°C water bath temperature, the Raynaud's disease subjects showed a less pronounced hunting reaction as compared to the normal subjects (e.g. longer time to the first rise of finger skin temperature). At 5°C water temperature, the differences were marginal.

Jobe et al. (1982) showed that the digital temperatures during cold exposure of subjects suffering from Raynaud's disease could be increased by 2.2°C with adequate training as compared to a group of patients without training. The training consisted of a 10-min hand immersion in hot water (43°C) while the dressed body was exposed to cold (0°C). The training was repeated 3 times a day, 3 days a week for 3 weeks. The success was ascribed to a Pavlovian reaction (classical conditioning). The conditioned stimulus (whole body exposure to 0°C air) was paired to the unconditioned stimulus (hands in warm water) which resulted in a conditioned response (vessels in the fingers vasodilate when the body is exposed to cold air).

Gasser et al. (1992) compared the reaction to cold in 39 subjects with general complaints of cold hands, but absence of vasospastic disease, with a control group of similar size. One hand was immersed in water of 4°C for 30 s and the other was measured. The Doppler blood flow was continuously higher in the control group. The reactivity of the vessels was not different from controls, but an increased vasomotor tone seemed to be present.

Meehan (1955) observed that 21 subjects with cold injuries of at least second degree severity showed no or little CIVD upon ice water immersion. The underlying mechanism is unclear.

The mechanism of CIVD

The involvement of AVAs

Grant and Bland (1931) were able to show AVAs dilation in rabbit ears as a reaction to central body heating, and thus showed the involvement of AVAs in thermoregulation. Coffman (1972) measured total fingertip blood flow by strain gauge plethysmography and nutritional flow by a Na131I washout technique in ten subjects. The measurements were made in a warm room (28.3°C), relatively cool room (20.0°C) and with and without norepinephrine infusion in a neutral room (25.5°C). Cold exposure and norepinephrine infusion reduced the total blood flow with only a minor decrease in nutritional blood flow. The AVAs are the only structures which can explain this difference, and it is concluded that they are actively involved in thermoregulation in humans. Indirect evidence that AVAs are involved in CIVD is mainly derived from the finding that CIVD occurs mainly at the AVA locations (Fox and Wyatt 1962). Another argument for the involvement of AVAs may be that the blood flow through the capillaries is insufficient to explain the magnitude of heat transfer found during CIVD. Spealman (1945) found a blood flow of 5.9 ml per 100 ml hand volume per minute when the hands were immersed in water of 35°C. At a temperature of 15°C the blood flow was only 0.9 ml per 100 ml hand volume per minute. At 5°C the blood flow had increased again to 4.3 ml per 100 ml hand volume per minute. Recently, Bergersen et al. (1999) used different Doppler techniques to provide more evidence that AVAs are actively involved in CIVD.

Hypothesis on the mechanism of CIVD

Many hypotheses of the mechanism of CIVD have been proposed since its first description in 1930 by Sir Thomas Lewis. An updated list of most important hypotheses for CIVD includes the following hypotheses.

Hypothesis 1: axon reflex

Lewis (1930) concluded from denervation experiments that an axon reflex had to be the primary cause of CIVD. An axon reflex or antidromic vasodilation is a reaction in which:
  1. 1.

    noxious stimuli excite receptive nerve endings of unmyelinated neurons,

     
  2. 2.

    the evoked impulses are conveyed centrally and antidromically via the axon branches,

     
  3. 3.

    the excited sensory nerve endings release vasoactive substances, which cause cutaneous vasodilation (Hornyak et al. 1990).

     

This mechanism explains the presence of CIVD after sympathectomy and the absence of CIVD after nerve degeneration. Recently, a renewed interest in the axon reflex has been shown, probably because laser Doppler flowmetry enables measurement of the resulting vasodilation. The axon reflex can be invoked by cold (Lewis 1930) but also by electrical stimulation on the skin (Hornyak et al. 1990; Magerl et al. 1987; Westerman et al. 1987), and other methods such as injection of histamine (Izumi and Karita 1991).

Daanen and Ducharme (2000) used electrical stimulation to evoke axon reflexes in a cold hand during the hunting reaction. Despite strong and painful stimulation of the skin, which resulted in clear axon reflexes in a warm hand, no perfusion increase was found in the hand immersed in cold water as observed by Doppler flowmetry data. This makes the axon reflex hypothesis an unlikely explanation of the CIVD response.

Hypothesis 2: dilating substance entering the blood

This hypothesis has been put forward by Aschoff (1944). He postulated that a dilating substance (yet unknown) was formed when local temperature decreased under a certain threshold. The increased blood flow washed the substance away. The concentration of the substance should be dependent on the temperature. Several experiments pointed out that CIVD only occurs when the peripheral nerves were intact. This means that the vasodilating substance should be related to the nervous system. Cooling increases the release of nitric oxide (NO), a powerful vasodilator in the endothelium of blood vessels, in cutaneous vessels of rabbit ears, but not in deep arteries, during cholinergic stimulation (Fernández et al. 1994). Also, cooling reduces the contraction in response to adrenergic activation in cutaneous vessels of rabbit ears (García-Villalón et al. 1992). The role of NO in CIVD has not been investigated so far, but it may be one of the substances that Aschoff (1944) was aiming at.

Hypothesis 3: decreased release of norepinephrine from adrenergic nerve endings

Gardner and Webb (1986) observed that CIVD did not occur in a rat tail when norepinephrine was continuously perfused, causing a state of maximal vasoconstriction. This led them to the conclusion that CIVD can only be achieved by a cessation of transmitter release from adrenergic nerve endings. After iontophoresis of norepinephrine through the skin of human fingers, however, CIVD was still found with an amplitude of about one-third of the normal response (Keatinge 1961), but the concentration may not have been high enough to cause maximal contraction of the blood vessels. The sensitivity of the α2-receptors for norepinephrine increases in the cold (Freedman et al. 1992), inducing a decrease in tissue temperature which may become so low that a nervous blockade occurs. Therefore, interruption of the adrenergic neurotransmission in the cold is a likely explanation of CIVD.

Hypothesis 4: effect of cold on vascular smooth muscle activity

Folkow et al. (1963) hypothesized that "it is not unreasonable to assume that the inherent smooth muscle activity will be considerably depressed or even abolished when the tissue temperature is reduced to low levels, producing a vasodilation". Keatinge (1970) showed that low tissue temperatures enhances the contractile status of the blood vessel wall. Below a certain threshold, however, the contractile system relaxes and CIVD occurs (Keatinge and Harman 1980). The formation of cross-bridges in the contractile system is inhibited. This hypothesis is frequently mentioned in physiology textbooks (e.g. Guyton and Hall 1996). The strong reduction in CIVD response after norepinephrine iontophoresis favours hypothesis 3 over hypothesis 4: the muscular vascular coat reaches very low temperatures, but does not respond with a relaxation.

Conclusions and recommendations

It can be concluded that the CIVD reaction is more pronounced when the body core and skin is warm, medium temperature is very low, at low altitudes and without mental stress. Although it is different to distinguish between adaptation and acclimatization effects, it seems that the CIVD reaction is more pronounced for people born in cold areas and for people that have exposed their hands to cold for a prolonged period of time. The differences in CIVD reaction between males and females and the effect of age on CIVD are still not clear. Protein, salt, vitamin C and alcohol intake may improve the hunting response.

CIVD is believed to protect against the occurrence of local cold injuries (Iida 1949) and may be beneficial for improving dexterity and tactile sensitivity. Only Keatinge (1970) argues that CIVD may have negative effects: "the main practical consequence of cold vasodilation is the adverse one of increasing heat loss". However, CIVD is almost completely abolished when core temperature is decreased so that increased body heat loss is negligible.

It would be a useful application of CIVD if the risk for cold injuries could be assessed on an individual basis. Thus, people at risk could be warned before cold exposure and appropriate protective measures could be taken. However, many factors influence CIVD and good reproducibility of the CIVD reaction is required to achieve this goal. The few studies that are available on reproducibility of CIVD showed that it was fair. Meehan (1955) reported Tmean values within a range of 0.5°C and Tmin values within 1.0°C for repeated immersions. Daanen (1997) found less reproducible results with a standard deviation of 1.0°C within subjects for Tmean and of 0.7°C for Tmin. Yoshimura and Iida (1952) reported RIF values within ±1 point.

Carlson (1966) proposed a standard procedure for CIVD determination to achieve a good reproducibility. Carlson suggested a room temperature of 27 (0.5)°C, relative humidity <50%, minimal air movement, seated posture of the subject with hand at heart level and immersion of the first two phalanges of the middle finger in stirred ice water. Based on the available literature we can now refine the standardization procedure. A small thermocouple should be located on the fingertip and not at the nail bed for more reproducible results (Yoshimura 1966). Since considerable differences exist in the hunting reaction between fingers, the use of only one finger supplies limited information and it is better to immerse and measure all fingers. Immersion of the entire hand causes no more pain than immersion of a finger, since pain is not spatially summated (Burton and Edholm 1955). It has to be realized however that the CIVD response of immersed fingers only differs from that of an immersed hand.

Even though a water temperature of 0°C is easy to achieve using stirred ice water, one may consider using 5°C water. It is shown that a water temperature of 5°C is less painful and gives similar or even better results (Elsner et al. 1960; Hirai et al. 1970; Kregel et al. 1992). Carlson proposed an immersion time of at least 15 min. This is too short to determine the hunting frequency. The immersion time should be at least 30 min and preferably 40 min. The subjects should be preconditioned with regards to body thermal status, diet, smoking and the experiment should ideally be conducted at the same time of day.

The mechanism of CIVD is still subject to debate, but it is likely that cold decreases the release of norepinephrine and thus starts the CIVD. This means that the onset of CIVD has a peripheral origin. The role of local vasodilating agents such as NO is not clarified yet. However, it has been observed that the onset time shortens when the core temperature and in particular mean skin temperature increase (Daanen et al. 1997). The sympathetic drive will be reduced and the norepinephrine release will be at a lower level, leading to an earlier opening of the AVAs. Once, the AVAs are opened up, the relatively warm blood will cause a higher magnitude of the CIVD response.

Acknowledgements

The author is indebted to Dr. M.B. Ducharme, Professor Dr. G.W.J.M. Tangelder, Professor Dr. R.S. Reneman, M. Simons, MD and Dr. W.A. Lotens for the review of the manuscript.

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© Springer-Verlag 2003