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Lithium carbonate in vasospastic disorders
Medical Hypotheses 9:
179-181, 1982
LITHIUM CARBONATE IN VASOSPASTIC DISORDERS Julian Lieb 41 Village Lane, Pethany, Connecticut 06525 ABSTRACT Abnormal thermoregulation is a hallmark of many vasospastic disorders. Lithium carbonate is capable of reversing hypothermia and may be of prophylactic value in vasospastic disorders. INTRODUCTION Recently, an association between migraine, Raynaud's phenomenon, and variant angina has been identified. (1). I propose that a common underlying mechanism could be a thermoregulatory disorder caused by a disturbance in prostaglandin synthesis, and that lithium carbonate could be a prophylactic agent for all three conditions.
HYPOTHESIS Exposure to cold temperature or to wind may accentuate or precipitate the symptoms of angina, and Raynaud's phenomenon is essentially a cold sensitivity disease. There is also good evidence of a disturbance of thermoregulation in migraine (2-3). Prostaglandins play an important role in thermoregulation (4) and are in turn influenced by ambient temperature (5). Cold appears to reduce thromboxane A2 (TXAZ) synthesis in blood vessels and Horrobin has proposed that in patients with Raynaud's phenomenon cold may lead to excessive synthesis of prostaglandins secondary to reduced TXA2 synthesis (6). Prostaglandin E has a potent vasodilator effect on cerebral blood vessels, and prostaglandin F2 alpha causes vasoconstriction of the arterioles in the internal carotid system (7). Injection of prostaglandins can cause headache in susceptible subjects (8) and in some patients migraine headache can be alleviated by prostaglandin synthesis inhibitors (9). There is also evidence of disturbed prostaglandin synthesis or metabolism in coronary artery disease (lo), angina (ll), and cardiac arrhythmias (12).
179
Lithium is effective prophylactically for some patients with vascular headaches (13~14~15) and 1 have reported remission of Raynaud's phenomenon in patients taking lithium (16). Competitive, always-pressed-for-time behavior, which has been termed Type A behavior, is associated with coronary artery disease (17). This pattern of behavior is characteristic of hypomanic individuals, which is one of the observations that led Voors to propose that lithium depletion could be a factor in atherosclerotic heart disease (18). CONCLUSION Lithium influences both thermoregulation and prostaglandin synthesis. It raises body temperature in manic depressives (19), it is capable of reversing hypothermia (20), and, by limiting the mobilization and conversion of dihomogammalinolenic acid it stabilizes prostaglandin El synthesis (21). Lithium is an effective remedy for such vasospastic disorders as cluster headache (13,14,15) and Raynaud's phenomenon (16). It is effective in many inflammatory and immune disorders that are characterized by unpredictable relapses and remissions (22). Thus, there is biochemical, epidemiological and clinical evidence to support the proposition that lithium may be of value in the prophylaxis of vasospastic disorders in general and of variant angina in particular.
REFERENCES 1.
Miller D, Waters DD, Warnica W et al. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med 304(13):763-766, 1981.
2.
Blau JN. Migraine: A vasomotor instability of the meningeal circulation. Lancet ii:1136-1139, 1978.
3.
Wahlberg P.
4.
Dingfelder JR, Brenner WE. The thermogenic activity of exogenous E and F prostaglandins in humans. Acta Obstet Gynecol Stand 57:35-40, 1978.
5.
Barney CC, Elizondo RS. Effect of ambient temperature on development of prostaglandin Bl in hyperthermia in the rhesus monkey. J Appl Physiol Resp Environ Exercise Physiol 44(5):751-758, 1978.
6.
Horrobin DF. Prostaglandins. Physiology, Pharmacology, and Clinical Significance. Montreal, Eden Press, p.197, 1978.
7.
Denton IC, White KP, Robertson JJ. The effects of prostaglandins El, Al, and F2 alpha on the cerebral circulation of dogs and monkeys. J Neurosurg 36:34-43, 1972.
8.
Carlson LA, Ekelund LG, Oro L. Clinical and metabolic effects of different doses of prostaglandin El in man. Acta Med Stand 183:423-430, 1968.
9.
Vardi Y, Rabey IM, Streifler M, et al. Migraine attacks. Alleviation by inhibitors of prostaglandin synthesis and action. Neurol 26:447-450, 1976.
Two types of migraine.
180
Lancet i:152-153, 1979.
10.
Dusting GH, Moncada S, Vane JR. Prostaglandins, their intermediates and precursors: Cardiovascular actions and regulatory roles in normal and abnormal circulatory systems. Prog Cardiovasc Dis 21(6):405-430, 1979.
11.
Tsuboi T, Hatano T, Nakatsuki K et al. Pharmacological evaluation of OP 1206, a prostaglandin El derivative, as an antianginal agent. Arch Int Pharmacodyn 247:89-102, 1980.
12.
Kelliher GJ, Lawrence T, Jurkiewicz N, Dix RK. Comparison of the effects of prostaglandins El and Al on coronary occlusion induced arrhythmia. Prostaglandins 2:163-177, 1979.
13.
Lieb J, Zeff A. Lithium treatment of chronic cluster headaches. Psychiat 133:556-558, 1978.
14.
Ekbom K. Lithium for cluster headache: Review of the literature and preliminary results of long-term treatment. Headache 21:132-139, 1981.
15.
Kudrow L. Lithium prophylaxis for chronic cluster headache. 15-18, 1977.
16.
Lieb J. Immunopotentiation and inhibition of herpes virus activation during therapy with lithium carbonate. Med Hypotheses 7:885-890, 1981.
17.
Friedman M, Rosenman RH. Association of specific overt behavior pattern J A M A 169:1286, 1959. with blood and cardiovascular findings.
18.
Voors AW. Does lithium depletion cause artherosclerotic heart-disease? Lancet ii:1337-1339, 1969.
19.
Mellerup ET, Widding A, Wildschiodz G, Rafaelson OJ. Lithium effect on temperature rhythm in psychiatric patients. Acta Pharmacol et Toxic01 42:125-129, 1978.
20.
Lieb J, Lombard D, Nazzaro A. Lithium treatment of hypothermia caused by electric shock. Med Hypotheses 6~769-772, 1980.
21.
Horrobin DF, Mtabaji JP, Manku MS, Karmazyn M. Lithium as a regulator of hormone-stimulated prostaglandin synthesis. In Johnson FN, Johnson F, eds. Lithium in medical practice. Baltimore, University Park Press, pp. 243-263, 1978.
22.
Horrobin DF, Lieb, J. A biochemical basis for the actions of lithium on behaviour and on immunity: Relapsing and remitting disorders of inflammation and immunity such as multiple sclerosis or recurrent herpes as manic-depression of the immune system. Med Hypotheses 7:891-905, 1981.
181
Brit J
Headache 17:
179-181, 1982
LITHIUM CARBONATE IN VASOSPASTIC DISORDERS Julian Lieb 41 Village Lane, Pethany, Connecticut 06525 ABSTRACT Abnormal thermoregulation is a hallmark of many vasospastic disorders. Lithium carbonate is capable of reversing hypothermia and may be of prophylactic value in vasospastic disorders. INTRODUCTION Recently, an association between migraine, Raynaud's phenomenon, and variant angina has been identified. (1). I propose that a common underlying mechanism could be a thermoregulatory disorder caused by a disturbance in prostaglandin synthesis, and that lithium carbonate could be a prophylactic agent for all three conditions.
HYPOTHESIS Exposure to cold temperature or to wind may accentuate or precipitate the symptoms of angina, and Raynaud's phenomenon is essentially a cold sensitivity disease. There is also good evidence of a disturbance of thermoregulation in migraine (2-3). Prostaglandins play an important role in thermoregulation (4) and are in turn influenced by ambient temperature (5). Cold appears to reduce thromboxane A2 (TXAZ) synthesis in blood vessels and Horrobin has proposed that in patients with Raynaud's phenomenon cold may lead to excessive synthesis of prostaglandins secondary to reduced TXA2 synthesis (6). Prostaglandin E has a potent vasodilator effect on cerebral blood vessels, and prostaglandin F2 alpha causes vasoconstriction of the arterioles in the internal carotid system (7). Injection of prostaglandins can cause headache in susceptible subjects (8) and in some patients migraine headache can be alleviated by prostaglandin synthesis inhibitors (9). There is also evidence of disturbed prostaglandin synthesis or metabolism in coronary artery disease (lo), angina (ll), and cardiac arrhythmias (12).
179
Lithium is effective prophylactically for some patients with vascular headaches (13~14~15) and 1 have reported remission of Raynaud's phenomenon in patients taking lithium (16). Competitive, always-pressed-for-time behavior, which has been termed Type A behavior, is associated with coronary artery disease (17). This pattern of behavior is characteristic of hypomanic individuals, which is one of the observations that led Voors to propose that lithium depletion could be a factor in atherosclerotic heart disease (18). CONCLUSION Lithium influences both thermoregulation and prostaglandin synthesis. It raises body temperature in manic depressives (19), it is capable of reversing hypothermia (20), and, by limiting the mobilization and conversion of dihomogammalinolenic acid it stabilizes prostaglandin El synthesis (21). Lithium is an effective remedy for such vasospastic disorders as cluster headache (13,14,15) and Raynaud's phenomenon (16). It is effective in many inflammatory and immune disorders that are characterized by unpredictable relapses and remissions (22). Thus, there is biochemical, epidemiological and clinical evidence to support the proposition that lithium may be of value in the prophylaxis of vasospastic disorders in general and of variant angina in particular.
REFERENCES 1.
Miller D, Waters DD, Warnica W et al. Is variant angina the coronary manifestation of a generalized vasospastic disorder? N Engl J Med 304(13):763-766, 1981.
2.
Blau JN. Migraine: A vasomotor instability of the meningeal circulation. Lancet ii:1136-1139, 1978.
3.
Wahlberg P.
4.
Dingfelder JR, Brenner WE. The thermogenic activity of exogenous E and F prostaglandins in humans. Acta Obstet Gynecol Stand 57:35-40, 1978.
5.
Barney CC, Elizondo RS. Effect of ambient temperature on development of prostaglandin Bl in hyperthermia in the rhesus monkey. J Appl Physiol Resp Environ Exercise Physiol 44(5):751-758, 1978.
6.
Horrobin DF. Prostaglandins. Physiology, Pharmacology, and Clinical Significance. Montreal, Eden Press, p.197, 1978.
7.
Denton IC, White KP, Robertson JJ. The effects of prostaglandins El, Al, and F2 alpha on the cerebral circulation of dogs and monkeys. J Neurosurg 36:34-43, 1972.
8.
Carlson LA, Ekelund LG, Oro L. Clinical and metabolic effects of different doses of prostaglandin El in man. Acta Med Stand 183:423-430, 1968.
9.
Vardi Y, Rabey IM, Streifler M, et al. Migraine attacks. Alleviation by inhibitors of prostaglandin synthesis and action. Neurol 26:447-450, 1976.
Two types of migraine.
180
Lancet i:152-153, 1979.
10.
Dusting GH, Moncada S, Vane JR. Prostaglandins, their intermediates and precursors: Cardiovascular actions and regulatory roles in normal and abnormal circulatory systems. Prog Cardiovasc Dis 21(6):405-430, 1979.
11.
Tsuboi T, Hatano T, Nakatsuki K et al. Pharmacological evaluation of OP 1206, a prostaglandin El derivative, as an antianginal agent. Arch Int Pharmacodyn 247:89-102, 1980.
12.
Kelliher GJ, Lawrence T, Jurkiewicz N, Dix RK. Comparison of the effects of prostaglandins El and Al on coronary occlusion induced arrhythmia. Prostaglandins 2:163-177, 1979.
13.
Lieb J, Zeff A. Lithium treatment of chronic cluster headaches. Psychiat 133:556-558, 1978.
14.
Ekbom K. Lithium for cluster headache: Review of the literature and preliminary results of long-term treatment. Headache 21:132-139, 1981.
15.
Kudrow L. Lithium prophylaxis for chronic cluster headache. 15-18, 1977.
16.
Lieb J. Immunopotentiation and inhibition of herpes virus activation during therapy with lithium carbonate. Med Hypotheses 7:885-890, 1981.
17.
Friedman M, Rosenman RH. Association of specific overt behavior pattern J A M A 169:1286, 1959. with blood and cardiovascular findings.
18.
Voors AW. Does lithium depletion cause artherosclerotic heart-disease? Lancet ii:1337-1339, 1969.
19.
Mellerup ET, Widding A, Wildschiodz G, Rafaelson OJ. Lithium effect on temperature rhythm in psychiatric patients. Acta Pharmacol et Toxic01 42:125-129, 1978.
20.
Lieb J, Lombard D, Nazzaro A. Lithium treatment of hypothermia caused by electric shock. Med Hypotheses 6~769-772, 1980.
21.
Horrobin DF, Mtabaji JP, Manku MS, Karmazyn M. Lithium as a regulator of hormone-stimulated prostaglandin synthesis. In Johnson FN, Johnson F, eds. Lithium in medical practice. Baltimore, University Park Press, pp. 243-263, 1978.
22.
Horrobin DF, Lieb, J. A biochemical basis for the actions of lithium on behaviour and on immunity: Relapsing and remitting disorders of inflammation and immunity such as multiple sclerosis or recurrent herpes as manic-depression of the immune system. Med Hypotheses 7:891-905, 1981.
181
Brit J
Headache 17: