The relationship between mortality caused by cardiovascular diseases and two climatic factors in densely populated areas in Norway and Ireland.

BACKGROUND: Seasonal variations in mortality due to cardiovascular disease have been demonstrated in many countries, with the highest levels occurring during the coldest months of the year. It has been suggested that this can be explained by cold climate. In this study, we examined the relationship between mortality and two different climatic factors in two densely populated areas (Dublin, Ireland and Oslo/Akershus, Norway). METHODS: Meteorological data (mean daily air temperatures and wind speed) and registered daily mortality data for three groups of cardiovascular disease for the period 1985-1994 were obtained for the two respective areas. The daily mortality ratio for both men and women of 60 years and older was calculated from the mortality data. The wind chill temperature equivalent was calculated from the Siple and Passels formula. RESULTS: The seasonal variations in mortality were greater in Dublin than in Oslo/Akershus, with mortality being highest in winter. This pattern was similar to that previously shown for the two respective countries as a whole. There was a negative correlation between mortality and both air temperature and wind chill temperature equivalent for all three groups of diseases. The slopes of the linear regression lines describing the relationship between mortality and air temperature were a lot steeper for the Irish data than for the Norwegian data. However, the difference between the steepness of the linear regression lines for the relationship between mortality and wind chill temperature equivalent was considerably less between the two areas. This can be explained by the fact that Dublin is a much windier area than Oslo/Akershus. CONCLUSION: The results of this study demonstrate that the inclusion of two climatic factors rather than just one changes the impression of the relationship between climate and cardiovascular disease mortality.

Mortality from cardiovascular diseases and its relationship to air temperature during the winter months in Dublin and Oslo/Akershus.

In many countries increased winter mortality from cardiovascular diseases (CVD) has been documented. A causal relationship between change in air temperature and change in number of deaths has been suggested. There is also evidence for a delay between a fall in air temperature and death (lag effect). We have investigated these relationships using mortality data for CVD (ICD-9: 390-459) and daily air temperatures in selected winter months (December to March) from two densely populated areas in Norway and Ireland, Oslo/Akershus and Dublin. A specially designed computer programme was used to select data from specific days in the ten years period. The days selected depended on the temperature change chosen between two consecutive days. We examined 2 types of temperature change, a large change and little or no change. An analytical technique involving the use of Spearman's correlations coefficients was used to investigate delays in mortality following a particular change in temperature. For groups of selected days, an inverse relation between mortality and air temperature was found. For neither the Oslo/Akershus nor the Dublin data was it possible to see a sudden increase in mortality following a large, sudden decrease in temperature and no evidence for a delay between a change in temperature and a change in mortality rate was found.

Physiological and haematological responses to cold exposure in the elderly.

Throughout Europe, including Norway, increased winter mortality from cardiovascular diseases (CVD) is well described. However, while there are associations between high CVD mortality and cold climate, the reason for the excess deaths is not entirely known. Recent epidemiological evidence suggests that brief outdoor exposure to cold conditions may be linked to increased winter mortality in the elderly. However, the question as to whether alterations in the haemostatic system following exposure to cold could be responsible for the increased winter risk has been little investigated in elderly subjects. In this study, we have compared the effect of exposing lightly clothed healthy elderly men and women (60-70 years) for 90 minutes to either a mild cold stress (16 degrees C) or thermoneutral conditions (28 degrees C). Measurements of a variety of autonomic and haematological parameters were made in order to compare to what extent exposure to cold stress affects production of thrombogenic risk factors. The overall autonomic responses clearly showed that the subjects were mildly cold exposed. The main changes in the blood system were a cold exposure increase in hemoconcentration and an increase in the fibrinolytic parameter, t-PA. This coupled with other changes support previous findings and it is concluded that short term mild cold exposure in the elderly initiates a mild inflammatory reaction and a tendency for an increased state of hypercoagulability.

The effect of short-term cold exposure on risk factors for cardiovascular disease.

The aim of this study was to see if a short-term period of exposure to cold in young healthy subjects causes changes in hematological factors known to be associated with the promotion of thrombogenesis. Over a period of 48 hours, changes in the distribution of erythrocytes, granulocytes, and blood platelets, as well as several coagulation, inflammatory, and fibrinolytic parameters, were monitored in 11 young healthy male subjects following a short period (1 hour) of cold exposure (CE) (ambient temperature, 11 degrees C) or exposure to thermoneutral conditions (ambient temperature, 26 degrees C) in winter (November). The major findings were: (1) a CE-induced hemoconcentration as indicated by an increase in erythrocyte count (3.2% increase); (2) after appropriate adjustments for changes in hemoconcentration, a cold-induced mobilization of granulocytes (14.5% increase) and a cold-induced decrease in lymphocytes (7% decrease); (3) thromboxane B2 release following endotoxin stimulation of whole blood was increased by 27.4% in the CE experiments; (4) diurnal rhythms were observed in granulocytes, blood platelets, middle plate volume, tissue plasminogen activator, and plasma activator inhibitor; and (5) CE caused no significant changes in lipopolysaccharide-induced tissue factor, nor in the blood coagulation factor VII or cytokines, interleukin-6, and tumor necrosis factor. It is concluded that short-term cold exposure in young healthy subjects initiates a mild inflammatory reaction and a tendency for an increased state of hypercoagulability.

Seasonal variations in mortality caused by cardiovascular diseases in Norway and Ireland.

BACKGROUND: Seasonal variations in mortality resulting from cardiovascular diseases (CVD) have been demonstrated in many countries, with the highest levels observed during the coldest months of the year. We studied the seasonal changes in CVD mortality in Norway and the Republic of Ireland, two countries which are demographically quite similar, but climatically different; we also examined the relation between CVD mortality and air temperature. METHODS: Registered monthly data for mortality from CVD for the period 1985-1995 were obtained from the Norwegian Central Bureau of Statistics and the Irish Central Statistics Office. Meteorological data were provided by the Norwegian Institute of Meteorology and Met Eireann, in Ireland. Monthly mortality ratio for both men and women aged 60 and older was calculated from the mortality date. Mean monthly air temperatures for the two countries were calculated from the meteorological data. RESULTS: For the 10-year period investigated, the lowest and highest monthly mortality ratios were on average found in August and January, respectively, and mean excess winter mortality, expressed as the difference between the August and January values for the entire 10-year period, was 22% (Norway) and 35% (Ireland). However, when the percentage difference in the months with the respective highest and lowest mortality ratios were calculated for each year, the average of these differences for each of the 10 individual years was 29% and 45%. Mortality ratio was found to increase much more steeply with decreasing air temperature in Ireland than in Norway. CONCLUSION: Although the seasonal variation between CVD mortality in both countries is similar, the different relation with climatic conditions may result from differences in housing standards, allowing outdoor temperatures to have a greater influence on indoor temperature in Ireland than in Norway.

Thermogenic responses to body cooling during fever induced by Staphylococcus aureus cell walls in rabbits.

Hypothalamic temperature (Thypo) and metabolic heat production (M) were measured in seven conscious rabbits injected intravenously with either saline or with Staphylococcus aureus, (8.10(7) cell walls.kg-1) while being subjected to a 3-h period of ramp-like total body cooling using a chronically implanted intravascular heat exchanger. In pyrogen-injected animals cooling started (1) at the time of injection or (2) 70 min after injection. In (1) the fall in Thypo induced by heat extraction was similar (1.0 degree C) in afebrile and febrile animals. In (2) there was a transient increase in Thypo of about 0.5 degree C at a time corresponding to the start of fever resulting in a significantly smaller fall in Thypo at the end of the 3-h cooling period (0.5 degree C vs 0.9 degree C, P < 0.05, n = 5). At this time in both (1) and (2) M was lower than theoretically expected from the increase in shivering threshold during fever. However, most of this effect can be explained when available data showing a decrease in thermosensitivity during S. aureus-induced fever are taken into account. After cessation of cooling in both groups of febrile animals Thypo rose to about 1 degree C higher than the precooling level, which is comparable to the fever level in a separate series of experiments with S. aureus injection without cooling (1.2 degrees C).

Thermosensitivity is reduced during fever induced by Staphylococcus aureus cells walls in rabbits.

Thermosensitivity (TS) and threshold core temperature for metabolic cold defence were determined in six conscious rabbits before, and at seven different times after i.v. injection of killed Staphylococcus aureus (8 x 10(7) or 2 x 10(7) cell walls x kg(-1)) by exposure to short periods (5-10 min) of body cooling. Heat was extracted with a chronically implanted intravascular heat exchanger. TS was calculated by regression of metabolic heat production (M) and core temperature, as indicated by hypothalamic temperature. Threshold for cold defence (shivering threshold) was calculated as the core temperature at which the thermosensitivity line crossed preinjection resting M. The shivering thresholds followed the shape of the fever response. TS was significantly reduced (up to 49%) during the time course of fever induced by the highest dose of pyrogen only. At both high and low doses of pyrogen TS correlated negatively with shivering threshold (r = 0.66 and 0.79 respectively) with similar slopes. The reduction in TS during fever was thus associated with the increase in shivering threshold resulting from the pyrogen injection and not by the dose of pyrogen. Model considerations indicate, however, that changes in sensitivity of the thermosensory input to the hypothalamic controller may affect threshold changes but cause negligible TS changes. It is more likely that the reduction in TS is effected in the specific hypothalamic effector pathways.

Effect of total body core cooling during poly I:C-induced fever in rabbits.

At ambient temperature (Ta) 20 and 10 degrees C, metabolic heat production and hypothalamic temperature (Thypo) were measured to determine the fever response in six rabbits injected with polyriboinosinic-polyribocytidylic acid (poly I:C; 5 mg/kg iv). Similar measurements were made in afebrile and febrile animals subjected to 3 h of body cooling, in which heat was extracted with a chronically implanted intravascular heat exchanger in a ramplike manner. The fever time course showed a biphasic pattern. During cooling in the febrile experiments, Thypo remained constant or even slightly increased during the time corresponding to the first phase of fever but rapidly fell during the second phase because of a depressed shivering response. The net effect at the end of the cooling period was that Thypo decreased by 0.4 and 0.6 degree C more than in the afebrile cooling experiments at Ta 20 and 10 degrees C, respectively. The results indicate normal shivering responses during phase I of poly I:C-induced fever and depressed shivering in phase I, possibly because of a reduced thermosensitivity.

Poly I:C-induced fever elevates threshold for shivering but reduces thermosensitivity in rabbits.

Shivering threshold and thermosensitivity were determined in six conscious rabbits at ambient temperature (Ta) 20 and 10 degrees C before and at six different times after saline injection (0.15 ml iv) and polyriboinosinic-polyribocytidylic acid (poly I:C)-induced fever (5 micrograms/kg iv). Thermosensitivity was calculated by regression of metabolic heat production (M) and hypothalamic temperature (Thypo) during short periods (5-10 min) of square-wave cooling. Heat was extracted with a chronically implanted intravascular heat exchanger. Shivering threshold was calculated as the Thypo at which the thermosensitivity line crossed resting M as measured in afebrile animals at Ta 20 degrees C. There were negligible changes in shivering threshold and thermosensitivity in saline-injected rabbits. In the febrile animals, shivering threshold generally followed the shape of the biphasic fever response. At Ta 20 degrees C, shivering threshold was higher than regulated Thypo during the initial rising phase of fever and was lower during recovery. At Ta 10 degrees C the shivering thresholds were always higher than regulated Thypo except during recovery. Thermosensitivity was reduced by 30-41% during fever.

Enhancing tolerance to cold exposure--how successful have we been?

The risk of accidental hypothermia is always present in persons living at high latitudes, with cold water immersion representing the most extreme challenge. While most of the effort concerned with protection against cold exposure has involved finding ways of decreasing heat loss by improving insulation some attempts have been made in finding ways of improving cold tolerance by modifying the thermoregulatory response to cold. The main strategies that have been used are: - thermal acclimation, physical exercise, dietary enhancement of thermogenesis, pharmacological enhancement of thermogenesis and manipulation of thermoregulatory set-point. This paper briefly reviews the success of these strategies. While none of the strategies examined have resulted in concrete methods which are routinely used to improve cold tolerance, it is concluded that the pharmacological enhancement of cold thermogenesis using ephedrine in combination with methylxanthine represents the most promising method for delaying the onset of hypothermia in humans.

The shivering response during cross-circulation in the common eider duck (Somateria mollissima).

The possible role of humoral factors in the control of shivering in the common eider duck (Somateria mollissima) was investigated using a cross-circulation technique. Pairs of animals were coupled so that the arterial system of one animal was connected to the venous system of the other. The rate of blood transferral was 12.8 ml min-1. By adequate heparinization of the extracorporeal blood supply, cross-circulation could be maintained for periods of up to 12 h. The temperature of blood entering each animal Tinlet) was controlled by heat exchangers. During control experiments Tinlet was maintained at a temperature close to normal body temperature. During cooling experiments Tinlet was maintained at c. 20 degrees C. Changes in metabolic heat production and oesophageal temperature in response to blood cooling were measured in cross-circulated pairs of animals cooled simultaneously or individually. Based on analysis of the metabolic responses under the different experimental situations, no evidence was found to indicate that blood-borne substances are involved in the shivering response in these animals.

Selective brain cooling in resting and exercising Norwegian reindeer (Rangifer tarandus tarandus).

The threshold body core temperature for selective brain cooling (SBC) as well as the slope of brain cooling were determined in three Norwegian reindeer (Rangifer tarandus tarandus) during rest and during exercise. Brain temperature was measured in the hypothalamus (Thypo) and blood temperature (Tblood) was measured either in the right carotid artery or in a few cases in the right atrium of the heart. During rest the animals were subjected to ramp-like increases of Tblood by means of a thermostatically controlled water circulated heat exchanger (HE) introduced into the rumen via a chronically implanted rumen cannula. During exercise the animals ran on a treadmill at a speed of between 5.5-8.0 km hr-1 and a slope of 13.5 degrees for periods of 30-60 min. The elevation of Tblood during both rest and exercise resulted in significant amounts of SBC. The mean threshold for SBC (Thypo = Tblood) during rest was 38.7 degrees C. The threshold for SBC was elevated significantly to 39.5 degrees C during exercise. The mean slope of SBC (increase of SBC per degree increase of Tblood) was 0.82 both during rest and exercise.

The effect of rate of cooling, time of day and light regime on the shivering response in rabbits.

In man hypothermia exists when core temperature (Tc) falls below 35 degrees C. The onset of hypothermia is often insidious in that it can occur without any particular symptoms of serious discomfort. There is evidence that this decrease in thermosensitivity is most likely to occur when the rate of body cooling is slow. In addition there is some evidence that the susceptibility to become hypothermic varies with the circadian rhythm of Tc, particularly in animals maintained under constant light conditions. A systematic investigation has been carried out to determine whether the thermoregulatory response to body core cooling is affected by the rate of change of body temperature, the time of day at which the cooling takes place and/or by the light regime under which the animals are maintained. The investigation was made in rabbits maintained either under a 12-h light/dark (LD) cycle or under conditions of continuous light (LL). Thermosensitivity (relationship between falling Tc and the induced increase in metabolic heat production) was determined at two different rates of body cooling (1 degrees C decrease in core temperature in either 30 or 160 min.) and at different times of the day. A chronically implanted intravascular heat exchanger was used to extract heat from the animals. The results indicate that neither the rate of body cooling nor the time of day at which the cooling took place had any clear effect on the shivering response. Likewise there was no clear difference in the shivering response of the animals maintained under (LD) conditions as compared to those maintained under (LL) conditions.

The shivering response in animals and man.

The physiological response to body cooling may be regarded as a homeostatic response embracing the concept of negative feedback. The metabolic response to falling body temperature is normally both appropriate and adequate. However, there are reports of inadequate or absent responses to body cooling and of non-febrile animals shivering at elevated body temperature. The reasons for these paradoxical findings are not fully understood, particularly since the controller of body temperature receives the largest proportion of its thermal afferent information from temperature sensors located within the body core. During anaesthesia and certain phases of sleep the shivering response to hypothermia may be impaired. It also appears that other factors such as the rate of cooling and disturbances of the circadian machinery (altered light conditions, phase shifting of activity patterns) may be of importance. These factors are relevant for people working in the arctic, especially since many of them are shift workers.

Total calorimetry and temperature regulation in the nine-banded armadillo.

Cold exposure in the nine-banded armadillo causes vigorous shivering and a rise in core temperature (Tc). The increase in metabolic rate and Tc depends upon exposure temperature, but may be as much as six times and 3 degrees C respectively (Johansen 1961). These findings might indicate an insensitivity to Tc, which is puzzling since internal temperature is thought to be the primary and regulated variable. It is suggested that positive feedback may play a role in temperature regulation in these animals. To investigate this problem two series of experiments were performed in the same species. Series 1. Measurements of changes in heat loss (direct calorimetry) and heat production (indirect calorimetry) following transferral from a thermoneutral to a cold environment. The difference between these measurements determines whether heat storage is positive due to the increased core temperature or negative due to reduction in the size of the core with the increased temperature. Series 2. Investigation of core thermosensitivity (body core cooling using colonic thermode) under different environmental conditions. The results of the first series showed that the rise in Tc was accompanied by positive heat storage in the body. The second series demonstrated core thermosensitivities similar to those previously reported for a variety of other homeothermic mammals.

Selective cooling of the brain in reindeer.

Cineangiographic examination of reindeer exposed to local (hypothalamic) or general heating and cooling revealed that the angular oculi veins are constricted during cold stress but dilated during heat stress. Moreover, during heat stress a segment of the facial vein appeared to be occluded, causing the cold venous return from the nasal mucosa to be routed directly to the cavernous sinus for selective cooling of the brain. Histological examination of the vasoactive segment of the facial vein showed unusually thick longitudinal and circular layers of smooth muscle cells. Obstruction of angular oculi blood flow by clamping of the veins in the heat-stressed animal resulted in an immediate rise in brain temperature. When reindeer under heat stress shift from closed- to open-mouth panting, only the expiratory phase of the respiratory cycle takes place through the mouth, whereas inspiration through the nose is continued. In this way, cooling of the nasal mucosa and, hence, cooling of the brain, is maintained.

Appropriate and inappropriate hypothalamic cold thermosensitivity in Willow ptarmigan.

Hypothalamic thermosensitivity has been investigated in conscious Willow Ptarmigan (Lagopus lagopus lagopus) provided with chronically implanted hypothalamic perfusion thermodes. The birds were exposed to either cold (Ta - 10 degrees C) or warm (Ta + 25 degrees C) ambient conditions while hypothalamic temperature (Thy) was clamped for periods of 20 min at different set levels between 28 degrees C and 43 degrees C. The responses of the animals to hypothalamic thermal stimulation were classified by comparing them with those normally found in mammals. At Ta - 10 degrees C hypothalamic heating inhibited ongoing shivering, causing a fall in body-core temperature (Tc) (appropriate mammalian-like response). Strong levels of hypothalamic cooling (Thy less than 34.0 degrees C) also caused a fall in Tc due to inhibition of shivering (inappropriate mammalian-like response). However, weaker levels of hypothalamic cooling (Thy 34-36 degrees C), facilitated ongoing shivering, resulting in small increases in Tc (appropriate mammalian-like response). At Ta + 25 degrees C hypothalamic heating facilitated ongoing panting while weak (Thy 38 degrees C) levels of hypothalamic cooling inhibited ongoing panting (both mammalian-like responses). The observation of a weak mammalian-like cold hypothalamic thermosensitivity in Willow Ptarmigan indicates that these birds possess some specific cold thermosensors in the hypothalamic region. This finding suggests that hypothalamic temperature dependence in birds and mammals is fundamentally similar.

Partition of heat loss in resting and exercising winter- and summer-insulated reindeer.

Partition of heat loss was performed in resting (standing) and exercising (running; 9.2 km . h-1 for 40 min) winter- (W) and summer- (S) insulated conscious reindeer (Rangifer tarandus tarandus) in a climatic chamber set to an ambient temperature (Ta) of -30, 0, or 25 degrees C. Heat loss and production were determined using indirect calorimetry. The relative importance of radiant heat loss was greatest during rest at low Ta's, both during winter and summer (44-58% at Ta's -30 and 0 degrees C). At high Ta's, especially during exercise, a large proportion of total heat loss occurred through evaporation [45% at Ta 25 degrees C during rest and 47% at Ta 0 degrees C during exercise (W); 38% at Ta 25 degrees C during exercise (S)]. The proportion of heat lost through convection during rest and exercise was 38-52 and 46-72%, respectively, depending on Ta and season. The legs were found to represent an important avenue for radiant heat loss, particularly in heat stress situations. Their importance for convective heat loss was even greater, especially during exercise.