Q J Med 1999; 92: 747-751
© 1999 Association of Physicians
Commentary |
Cold adaptation and the seasonal distribution of acute myocardial infarction
From the Thrombosis Research Institute, London, UK
Dr F. De Lorenzo, Department of Clinical Trials, Thrombosis Research Institute, Manresa Road, London SW3 6LR. e-mail: dlorenzo{at}tri-london.ac.uk
 |
Introduction |
|---|
 Top Introduction Seasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
Numerous studies have reported an increased mortality from coronary heart disease (CHD) during the winter.1–5 Observational epidemiological data in England and Wales have shown that mortality from cardiovascular disease (CVD) increases linearly with decrease in diurnal minimum from 17 °C, accounting for about half of all excess cold-related mortality,1,2 which is approximately 50 000 per year in Britain alone.3 This effect is particularly pronounced in the elderly, in whom there is a 30% increase in deaths from this cause. Mortality increases more with a given fall of temperature in regions with `warm' winters.6 These deaths may therefore represent a graded effect of mild to severe environmental cold, rather than a specific effect of severe cold stress. The short temporal relation between temperature drop and mortality observed in Taiwan, where ambient temperature fluctuates greatly, supports the hypothesis that temperature effect may be a major factor which contributes to the increased mortality in winter.7 Increased CVD mortality has been related to thrombosis due to haemoconcentration in the cold.8,9 Mortality from CVD increased significantly with short-term falls in temperature. Short term falls in temperature also significantly increase blood pressure, haemoglobin (Hb), erythrocyte count, packed cell volume and serum albumin—changes that persist for 1–2 days.10
The secondary effects of winter respiratory infections may contribute to CVD deaths as observed during influenza epidemics,11 probably because of increases in blood fibrinogen during infections.12 However, most of the coronary deaths occur some hours after the exposure to cold, and before respiratory deaths increase.13 There is also epidemiological evidence for an increased incidence of strokes during winter, however, the data regarding the increase in case-fatality rate are somewhat equivocal.14
The decline in seasonality of coronary mortality in the US since 1970 may be linked to increasing access to microclimatic control (air-conditioning) in countering the environmental effects of cold.15
|
Seasonal variations in coagulation factors and plasma lipids |
|---|
|
TopIntroductionSeasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
Seasonal variations in CVD risk factors such as blood pressure, serum lipids and coagulation factors are well-recognized.16,17 A longitudinal cohort study in the elderly showed significant winter–summer differences in plasma fibrinogen and factor VII clotting activity (FVIIc),12 both independent risk factors for fatal and non-fatal coronary heart disease.18 Several mechanisms have been suggested whereby raised plasma fibrinogen could produce vascular disease, including involvement in early atherosclerotic plaque formation, the response to endothelial damage, platelet aggregability, and increased plasma viscosity.19 Raised FVIIc may indicate the presence of a hypercoagulable state, with increased thrombin and a greater chance of occlusive thrombus formation in response to fissuring of an atheromatous plaque.20 Others have demonstrated seasonal changes in low-density-lipoprotein cholesterol (LDL cholesterol) concentration, with peak levels in winter months17,21 with a 3% to a 5% increase of total cholesterol in winter.22 Elevations of fibrinogen, neutrophilia and C-reactive protein may be secondary to an increase in winter infections.23,24 Keatinge et al. have also shown increases in platelets, red cells, blood viscosity, and plasma cholesterol in healthy individuals exposed to 6 h mild surface cooling in moving air at 24 °C with little fall in core temperature (0.4 °C).8
Haemoconcentration in the cold can in part explain the increase concentration in clotting factors and serum lipids.9 Haemoconcentration is induced by peripheral vasoconstriction, increase peripheral resistance, changes in Starling's forces and fluid shift from intravascular to interstitial spaces.9
These results show a series of changes able to account for increased thrombosis in the cold during normal thermoregulatory adjustment.
|
Haemodynamic and hormonal response to cold |
|---|
|
TopIntroductionSeasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
Graded and consecutive cardiovascular adjustments accompany exposure to cold. Cutaneous thermo- and nociceptors induce ortho-sympathetic reflexes, causing tachycardia and vasoconstriction.25–27 Increased cardiac workload follows increased afterload (vasoconstriction, increased blood pressure) and the need to continue feeding the oxygen demands of thermal shivering by increasing cardiac output.28–31 Tachycardia and cold-induced coronary vasoconstriction can further increase myocardial stress32 in patients with ischaemic heart disease.
Thermoceptor-reflex-induced increases in plasma levels of noradrenaline and adrenaline after cold air exposure are well-recognized.27,33–36 Cold exposure induces an increase in circulating atrial natriuretic peptide (ANP)37 due to peripheral vasoconstriction, increase in central blood volume38 and increased plasma norepinephrine levels.39 The elevated ANP concentrations in the cold may additionally contribute to the diuresis and haemoconcentration.
During exposure to cold, rises in blood pressure, oxygen uptake, heart rate, and cardiac workload increase the risk of CHD.
|
Mechanisms and effects of adaptation to cold |
|---|
|
TopIntroductionSeasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
Repeated exposure of humans to cold induces physiological changes of an adaptive nature documented in studies of humans both in their natural environment and the laboratory.40–44 A spectrum of physiologically distinct adaptation categories are described: (i) metabolic adaptation, characterized by increased metabolic heat production, higher skin temperatures and normal rectal temperature (observed in Indians of Tierra del Fuego, Arctic Indians, and Inuits);40–44 (ii) insulative adaptation, characterized by a lower mean skin temperature and normal rectal temperature (observed in the coastal tribes of northern Australia and in cold adaptation by water immersion);45–47 (iii) hypothermic adaptation, characterized by a lower rectal temperature with less metabolic compensation, leading to a greater body cooling (observed in the bushmen of the Kalahari desert and Peruvian Indians);48–51 and (iv) insulative-hypothermic adaptation (observed in central Australian tribes, nomadic Lapps, and Korean and Japanese diving women).45,52–54. Adaptation by short intermittent exposure to severe cold has been observed in humans subjected to repeated exposure to cold water55 or cold air.51 These physiological variations may result from variations in exposure (continuous or discontinuous, moderate or severe cold stress), the time allowed for adaptation, the nature of cold stress (natural or artificial), diet, physical characteristics (physical fitness, body fat content, etc.) or associated stresses (e.g. cold and altitude in Peruvian Indians).47–55 Cold acclimatization in a repetitive cold-water immersion program resulted in (i) delay in the onset of shivering; (ii) lower body temperatures at the onset of shivering and (iii) a lower heat debt.56 Cold adaptation results in changes to mechanisms controlling thermal homeostasis with an attenuated cold sensation.57 Non-adapted individuals on cold exposure show a typical metabolic response (increase in rectal temperature) associated with significant diuresis and increased norepinephrine excretion, as opposed to the hypothermic response seen in cold-adapted individuals.58
This shift from a metabolic to hypothermic response has been shown in animals and humans.59–63 The adaptation process is graded and follows a different time–exposure relationship for different components (tachycardia, non-shivering thermogenesis, tachypnoea, etc.) of the adaptive response.64,65 The frontal cortex has been implicated in acceleration of the plastic changes occurring in the subcortical level, and in rats the reticular system appears to be involved in cold adaptation.66–68
We have recently reported a significant reduction of the rate-pressure product (heart ratexsystolic blood pressure) in a group of a cold-adapted humans,69 indicative of a decline in sympathetic stimulation. These haemodynamic responses are similar to observations by Muza et al.70 in a group of men who showed increased blood pressure during their first cold water exposure, but not during their last immersion. Both observations are consistent with the short intermittent adaptation process described by Radomski et al.58
We suggest that the decreased sympathetic activity during this type of short intermittent adaptation is related to habituation, repeated exposures to severe cold producing a decline in the sympathetic response to cold and an enhancement of the vagal response.59,71
We have also observed in cold-adapted subjects a mild increase in PAI-1, decreases in von Willebrand factor and plasma viscosity, but no significant changes in fibrinogen, factor VII:c, t-PA, platelet count, and D-dimer following cold stress.72
An increase in circulating PAI-1 can attenuate physiological fibrinolytic activity and the rate of clot lysis.73 However, the evidence for PAI-1 as a predictor of coronary heart disease is equivocal, possibly because its concentration varies with age, sex, risk factors and the degree of atherosclerosis in an individual.74
Increased plasma concentrations of von Willebrand factor have been reported in various vascular disorders.75 Thus increases in the concentration of this factor in patients at high risk for coronary thrombotic occlusion may reflect endothelial perturbation. The results of our study showed that cold adaptation leads to attenuation of some cold-induced adverse changes of haemostatic variables previously reported.8,9
We have also reported earlier a significant reduction of total and LDL cholesterol in a group of patients with hypercholesterolemia after 90 days of cold adaptation.76 On the other hand, there is little doubt of the link between cold stress and increased level of serum lipid levels, fibrinogen, factor VII, platelet count, and plasma viscosity12 and myocardial infarction1–4 in humans who are not cold-adapted.
|
Conclusions |
|---|
|
TopIntroductionSeasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
The excess incidence of acute events and case fatality from coronary heart disease associated with a cold environment are a significant public health problem. Understanding how cold exposure is pathogenically linked to the natural history of arteriosclerosis is of singular importance in addressing this. Presently this mortality can be reduced only by measures which postpone the complications of the disease.
The association of cold weather with the manifestations of coronary heart disease may be explained in many ways. Cold weather can precipitate atherothrombotic events acutely, or may accelerate its progress over long periods of time.
The acute effects of cold on the heart and circulation may explain some of the cardiac complications associated with a cold environment. Stimulation of the cold receptors of the skin, in particular, induces stimulation of the sympathetic nervous system, as indicated by increased levels of catecholamines in the blood. Thermoceptor-nocioceptive reflexes result in vasoconstriction in the skin, increased heart rate, systolic blood pressure, and increased central blood volume. This results in increases in cardiac filling pressure, left ventricular end-diastolic pressure and volume, and stroke volume. These factors increase cardiac workload and oxygen requirement. This chain of events may precipitate a variety of cold-induced functional abnormalities that may be clinically relevant in patients with ischaemic heart disease.
In cold-adapted humans, the reduced activity of the sympathetic nervous system, in response to cold stress (due to a gradual induced decline in autonomic stimulation) may decrease the physiological perturbation during cold exposure. Furthermore, cold adaptation may mitigate cold-stress-induced changes in serum lipids and haemostatic risk factors.
Research into changes in the physiological variables associated with the seasonal variation of acute myocardial infarction may provide further insights into the mechanisms by which abrupt rupture of atherosclerotic plaques and vascular thrombosis occur. Further work is therefore required to test the hypothesis that adaptation to cold might reduce the risk of ischaemic heart disease due to sudden cold exposure, by modulating homoeostatic responses (neurohormonal activation and adrenergic control of coronary vasomotor tone in patients with CHD) and altering risk factors.
|
References |
|---|
|
TopIntroductionSeasonal variations in...Haemodynamic and hormonal...Mechanisms and effects of...ConclusionsReferences |
|---|
1. Bull GM, Morton J. Environment, temperature and death rate. Age Ageing 1978; 7:210–24.
2. Alderson MR. Season and mortality. Health Trends 1985; 17:87–96.
3. Keatinge WR, Donaldson GC. Cardiovascular mortality in winter. Arct Med Res 1995; S2:16–18.
4.
Spencer FA, Goldberg RJ, Becker RC, Gore JM, for the Participants in the National Registry of Myocardial Infarction. Seasonal Distribution of Acute Myocardial Infarction in the Second National Registry of Myocardial Infarction. J Am Coll Cardiol 1998; 31:1226–33.
5. Curwen M. Excess winter mortality: a British phenomenon? Health Trends (UK) 1991; 22:169–75.
6. The Eurowinter Group. Cold exposure and winter mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes in warm and cold regions of Europe. Lancet 1997; 349:1341–6.[ISI][Medline]
7. Yeh CJ, Chan P, Pan WH. Values of blood coagulating factors vary with ambient temperature: the cardiovascular disease risk factor two-township study in Taiwan. Chin J Physiol 1996; 39:111–16.[Medline]
8. Keatinge WR, Coleshaw SRK, Cotter F, Mattock M, Murphy M, Chelliah R. Increases in platelet and red cell counts, blood viscosity, and arterial pressure during mild surface cooling: factors in mortality from coronary and cerebral thrombosis in winter. Br Med J 1984; 289:1405–8.
9. Neild PJ, Syndercombe-Court D, Keatinge WR, Donaldson GC, Mattock M, Caunce M. Cold induced increases in erythrocyte count, plasma cholesterol and plasma fibrinogen of elderly people without a comparable rise in protein C or factor X. Clin Sci 1994; 86:43–8.[Medline]
10. Donaldson GC, Robinson D, Allaway SL. An analysis of arterial disease mortality and BUPA health screening in men, in relation to outdoor temperature. Clin Sci 1997; 92:261–8.[Medline]
11. Meier CR, Jick SS, Derby LE, Vasilakis C, Jick H. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet 1998; 351:1467–71.[ISI][Medline]
12. Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet 1994; 343:435–9.[ISI][Medline]
13. Bull GM. Meterological correlates with myocardial and cerebral infarction and respiratory disease. Br J Prev Soc Med 1973; 27:108–13.[ISI][Medline]
14.
Jakovljevic D, Salomaa V, Sivenius J, Tamminen M, Sarti C, Salmi K, Kaarsalo E, Narva V, Immonen-Räihä P, Torppa J, Toumilehto J. Seasonal variation in the occurrence of stroke in a Finnish adult population. The FINMONICA stroke register. Stroke 1996; 27:1774–9.
15. Seretakis D, Lagiou P, Lipworth L, Signorello LB, Rothman KJ, Trichopoulos D. Changing seasonality of mortality from coronary heart disease. JAMA 1997; 278:1012–14.[Abstract]
16. Brennan PJ, Greenberg G, Miall WE, Thompson SF. Seasonal variation in arterial blood pressure. Br Med J 1982; 285:919–23.
17. Gordon DJ, Hyde J, Trost DC. Cyclic seasonal variation in plasma lipids and lipoprotein levels: The lipid research clinics coronary primary prevention trial placebo group. J Clin Epidemiol 1988; 41:679–89.[ISI][Medline]
18. Meade TW, Ruddock V, Stirling Y, Chakrabarti R, Miller GJ. Fibrinolytic activity, clotting factors, and long term incidence of ischemic heart disease in the Northwick Park Heart Study. Lancet 1993; 342:1076–9.[ISI][Medline]
19. Cook NS, Ubben D. Fibrinogen as a major risk factor in cardiovascular disease. Trends Pharmacol Sci 1990; 11:444–51.[Medline]
20. Miller GJ, Wikes HC, Meade TW, Bauer KA, Barzegar S, Rosenberg RD. Haemostatic changes that constitute the hypercoagulable state. Lancet 1991; 338:1079.[ISI][Medline]
21. Woodhouse PR, Khaw KT, Plummer M. Seasonal variation of blood pressure and its relationship to ambient temperature in an elderly population. J Hypertens 1993; 11:1267–74.[ISI][Medline]
22. Robinson D, Bevan EA, Hinohara S, Takahashi T. Seasonal variation in serum cholesterol levels: evidence from the UK and Japan. Atherosclerosis 1992; 95:15–24.[ISI][Medline]
23. Meade TW, North WRS, Chakrabarti RR, Stirling Y, Haines I, Thompson SG. Haemostatic function and cardiovascular death: early results from a prospective study. Lancet 1980; I:1050–4.
24. Stout RW, Crawford V. Seasonal variation in fibrinogen concentrations among elderly people. Lancet 1991; 338:9–13.[ISI][Medline]
25. Deklunder G, Rivolier J, Gazes G. Psychobiological study of 3 groups of subjects performing a polar expedition. In: Bond N, Siddle D, eds. Psychobiology: issues and applications. North Holland, Elsevier, 1989:381–97.
26.
Leblanc J, Cote'J, Jobin M, Labrie D. Plasma catecholamines and cardiovascular response to cold and mental activity. J Appl Physiol 1979; 47:1207–11.
27.
Wilkerson J, Raven P, Bolduan N, Norvath S. Adaptations in man's adrenal function in response to acute cold stress. J Appl Physiol 1974; 36:183–9.
28. Leblanc J. Factors affecting cold acclimation and thermogenesis in man. Med Sci Sport Exerc 1988; 20:193–6.
29.
Raven P, Niki I, Dahms T, Horvath S. Compensatory cardio-vascular responses during an environmental cold stress (5 °C). J Appl Physiol 1979; 29:417–21.
30.
Bittel J. Heat debt as an index for cold adaptation in men. J Appl Physiol 1987; 62:1627–34.
31. Horvath S, Spurr G, Hutt B, Hamilton L. Metabolic cost of shivering. J Appl Physiol 1955; 8:595–602.
32.
De Servi S, Mussini A, Angoli L. Effects of cold stimulation on coronary haemodynamics during exercise in patients with coronary artery disease. Eur Heart J 1985; 6:239–46.
33.
Keatinge WR, McIlroy MB, Goldfien A. Cardiovascular responses to ice-cold showers. J Appl Physiol 1964; 19:1145–50.
34. Delius W, Hagbarth KE, Hongell A, Wallin BG. Manoeuvres affecting sympathetic outflow in human skin nerves. Acta Physiol Scand 1972; 84:177–86.[ISI][Medline]
35. Hiramatsu K, Yamada T, Katakura M. Acute effects of cold on blood pressure, renin-angiotensin-aldosterone system, catecholamines and adrenal steroids in men. Clin Exp Pharmacol Physiol 1984; 11:171–9.[ISI][Medline]
36.
Johnson DG, Hayward JS, Jacobs TP, Collis ML, Eckerson JD, Williams RH. Plasma norepinephrine responses of man in cold water. J Appl Physiol 1977; 43:216–20.
37. Hassi J, Rintamaki H, Ruskoaho H, Leppäluoto J, Vuolteenaho O. Plasma levels of endothelin-1 and atrial natriuretic peptide in men during a 2-hour stay in a cold room. Acta Physiol Scand 1991; 142:481–5.[ISI][Medline]
38. Rowell LB. Cardiovascular adjustment to thermal stress. In: Shepherd JD, Abboud FM, Geiger SR, eds. Handbook of Physiology, sect 2, vol III, part 2. Bethesda, American Physiological Society, 19??:967–1023.
39. Uehlinger DE, Weidmann P, Gnaedinger MP, Shaw S, Lang RE. Depressor effects and release of atrial natriretic peptide during norepinephrine or angiotensin II infusion in man. J Clin Endocrinol Metab 1986; 63:669–94.[Abstract]
40. Hammel HT, Elsner RW, Lange Andersen K, Scholander PF, Coon CS, Medina A, Strozzi L, Milan FA, Hock RJ. Thermal and metabolic responses of the Alacaluf Indians to moderate cold exposure. Ladd AFB, AK: Wright Air Develop Div. (Tech Rep 60–63) 1960.
41.
Irving L, Lange Andersen K, Elsner R, Hildes JA, Loyning Y, Nelms JD, Peyton LJ, Waley RD. Metabolism and temperature of Arctic Indian men during a cold night. J Appl Physiol 1960; 15:635–44.
42.
Hart JS, Sabean HB, Hildes JA, Depocas F, Hammel HT, Lange-Andersen K, Irving L, Foy G. Thermal and metabolic responses of coastal Eskimos during a cold night. J Appl Physiol 1962; 17:953–60.
43.
Scholander PF, Hammel HT, Lange-Andersen K, Loyning Y. Metabolic acclimation to cold in man. J Appl Physiol 1958; 12:1–8.
44.
Adams T, Heberling EJ. Human physiological responses to a standardized cold stress as modified by physical fitness. J Appl Physiol 1958; 13:226–30.
45.
Hammel HT, Elsner RW, Le Messurier DH, Andersen HT, Milan FA. Thermal and metabolic responses of the Australian Aborigenes to moderate cold in summer. J Appl Physiol 1959; 14:605–15.
46.
Davies TRA, Johnston DR. Seasonal acclimatization to cold in man. J Appl Physiol 1961; 16:231–4.
47.
Skreslett S, Aarefjord A. Acclimatization to cold in man induced by frequent scuba diving in cold water. J Appl Physiol 1968; 24:177–81.
48. Hammel HT, Hildes JA, Jackson DC, Andersen HT. Thermal and metabolic responses of the Kalahari Bushmen to moderate cold exposure at night. Ladd AFB, AK 1962: Arctic Aeromed Lab (Techn Rep 62–44).
49. Elsner RW, Bolstad A. Thermal and metabolic responses to cold exposure of Andean Indians native to high altitudes. Ladd AFB, AK 1963: Arctic Aeromed Lab, Tech Rep AAL-tor-62-64.
50.
Leblanc J. Evidence and meaning of acclimatization to cold in man. J Appl Physiol 1956; 9:395–398.
51. Brück K, Baum E, Schennicke HP. Cold adaptive modifications in man induced by repeated short term cold exposures and during a 10 day and night cold exposure. Pfuegers Arch 1976; 363:123–33.
52.
Lange-Andersen K, Loyning Y, Nelms JD, Wilson O, Fox RH, Bolstad A. Metabolic and thermal response to a moderate cold exposure in nomadic Lapps. J Appl Physiol 1960; 15:649–53.
53. Hong SK. Comparison of diving and non-diving women of Korea. Federation Proc 1963; 22:831–3.[ISI][Medline]
54. Boutelier C, Livingstone SD, Bougues L, Reed LD. Thermoregulatory changes to cold in pre-acclimated and non-acclimated men following an arctic winter stay. In: Koll Stool II. Canada, Univ. of Toronto Press, 1982; B1–B19.
55.
Golden F, Tipton MJ. Human adaptation to repeated cold immersions. J Physiol 1988; 396:349–63.
56. Bittel J. The different types of general cold adaptation in man. Int J Sports Med 1992; 13:S172–6.
57.
Jansk
L, 
rámek P, avlíková J, Ulin B, Janáková H, Hork K. Change in sympathetic activity, cardiovascular functions and plasma hormone concentrations due to cold water immersion in men. Eur J Appl Physiol 1996; 74:148–52.
58.
Radomski MW, Boutelier C. Hormone response of normal and intermittent cold-preadapted humans to continuous cold. J Appl Physiol 1982; 53:610–16.
59. Leblanc J. Adaptation of men to cold. In: Wang LCH, Hudson JW, eds. Strategies in cold. New York, Academic Press, 1978:695–715.
60.
Heldmaier G. Cold adaptation by short daily cold exposures in the young pig. J Appl Physiol 1974; 36:163–8.
61.
Slee J. Habituation and acclimatization of sheep to cold following exposures of varying length and severity. J Physiol 1972; 227:51–70.
62.
Budd GN, Warhaft N. Urinary excretion of adrenal steroids, catecholamines and electrolytes in man, before and after acclimatization to cold in Antarctica. J Physiol 1970; 210:799–80.
63. Boutelier C, Bouges L, Timbal J. Technique rapide d'acclimatement de l'homme au froid. Med Aeronaut Spat Med Subaquat Hyperbare 1977; 16:172–6.
64. Keatinge WR, Evans M. The respiratory and cardiovascular response to immersion in cold and warm water. Q J Exper Physiol 1961; 46:83–94.
65. Golden F, Tipton MJ. Human adaptation to repeated cold immersions. J Physiol 1988; 396:349–63.
66. Glaser EM, Griffin JP. Changes of habituation induced by lesions and stimulation of the brain in rats. J Physiol 1961; 155:54–5.
67. Griffin JP. The role of frontal areas of the cortex upon habituation in men. Clin Sci 1963; 24:127–34.[ISI][Medline]
68. Glaser EM, Hall MS, Whittow GC. Habituation to heating and cooling of the same hand. J Physiol 1959; 146:152–64.
69. De Lorenzo F, Kadziola Z, Kakkar VV. Sympathetic activation and myocardial ischaemia- A role for cold adaptation? Clin Sci 1999; 96:663–4.[Medline]
70. Muza SR, Young AJ, Sawka MN, Bogart JE, Pandolf KB. Respiratory and cardiovascular responses to cold stress following repeated cold water immersion. Undersea Biomed Res 1988; 15:165–78.[ISI][Medline]
71.
Leblanc J, Dulac S, Cote J, Girard B. Autonomic nervous system and adaptation to cold in man. J Appl Physiol 1975; 39:181–6.
72.
De Lorenzo F, Kadziola Z, Mukherjee M, Saba N, Kakkar VV. Haemodynamic responses and changes of haemostatic risk factors in cold adapted humans. Q J Med 1999; 92:509–13.
73. Knapp RM, Chiu AT, Reilly TM. Effects of recombinant plasminogen activator inhibitor type 1 on fibrinolysis in vitro and in vivo. Thrombosis Res 1990; 59:309–17.[ISI][Medline]
74. Hamsten A. The haemostatic system and coronary heart disease. Thrombosis Res 1993; 70:1–38.[ISI][Medline]
75. Bowie EJW. The role of von Willebrand factor in thrombosis. In: Poller L, Thomson JM, eds. Thrombosis and its management. London, Churchill Livingstone, 1993:134–40.
76. De Lorenzo F, Mukherjee M, Sherwood R, Kadziola Z, Kakkar VV. Central cooling effects in patients with hypercholesterolemia. Clin Sci 1998; 95:213–17.[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Sher, F. De Lorenzo, and Z. Kadziola Seasonal variation in coronary heart disease and seasonal mood changes QJM, June 1, 2000; 93(6): 385 - 387. [Full Text]
|
|
|
|
|
|
T.Q. CHENG Seasonal variation in CHD QJM, March 1, 2000; 93(3): 197 - 198. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||