Prinzmetal’s Variant Angina Associated With Subarachnoid Hemorrhage: A Case
Report
Yoshifumi
Toyama, M.D., F.I.C.A., Hiromitsu Tanaka, M.D., F.I.C.A., Kohji Nuruki, M.D., and Tetsuya Shirao, M.D. KAGOSHIMA,
JAPAN
Abstract
panied
Prinzmetal’s variant of angina occurred in a 48-year-old man who sustained two attacks of subarachnoid hemorrhage within 10 days. The first anginal pain started at the same time that the second cerebrovascular accident developed, but subsequent anginal episodes were not accompanied by other symptoms or signs that indicated new development of subarachnoid hemorrhage. Twelve days later, when nuchal rigidity was fairly improved, the episodes of chest pain ended. A vasospasm of the large coronary arteries—probably due to the derangement of the autonomic nervous system caused by subarachnoid hemorrhage—was presumed to contribute to the occurrence of the variant angina. Based on this case and on review of the literature, we propose that coronary arterial spasm is one of several causes of the cardiac changes seen in subarachnoid
ment
at about same time
by
ST seg-
elevation, and it is frequently
asso-
ciated with arrhythmias. Recent clinical studies 3-13 have shown that the most likely mechanism of Prinzmetal’s angina is recurrent coronary arterial spasm with or without coronary stenotic lesions. Since the first description of Byer et a1.14 in 1947, a number of reports on the cardiac changes in patients with subarachnoid hemorrhage have been published. The cardiac changes thus far reported include electrocardiographic alterations, cardiac arrhythmias, myocardial damage, and pulmonary edema.15-17 It has been suggested that the increased or altered autonomic nervous activity caused by subarachnoid hemorrhage produces these cardiac abnormalities.15-17 It seems very worthwhile to determine whether Prinzmetal’s angina and subarachnoid hemorrhage occur at the same time in a patient, because such an association may explain the underlying mechanism of cardiac abnormalities in patients with subarachnoid hemorrhage. This paper presents what to our knowledge is the first report of a patient in whom Prinzmetal’s angina occurred in association with subarachnoid hemorrhage.
hemorrhage. Introduction A variant form of angina pectoris, described by Prinzmetal et al. in 19591 and 1960,~ is characterized by chest pain at rest or during ordinary daily activity. It often occurs in a cyclic pattern accom-
Case Report From the First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, and the Section of Neurosurgery, Nampoo Hospi-
A 48-year-old male office worker was admitted to the hospital on June 20, 1973, because of a persistent headache
tal, Kagoshima, Japan.
211
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
212 and vomiting. He had previously been in rather good health, except for borderline hypertension of a few years’ duration. But on the night before admission, when returning from a lavatory, he complained of nausea and weakness, and shortly thereafter he fell unconscious. His face became pale, with saliva oozing from the lips, but no convulsion was noted. There was no history of trauma. After about thirty minutes, he regained consciousness with poor response. Left upper monoparesis was observed at that time by his family physician. His blood pressure was 220/ 120 mm Hg, his pulse was 66/minute and regular, and respirations were 20/ minute. He was treated with hemostatic agents and sedatives. On the morning of his admission, he developed a generalized headache accompanied by vomiting. Because administration of chlorpromazine and analgesics was not effective, he was transferred to the hospital. Physical examination on admission revealed a well-nourished and normally responsive man. His pulse was 60/minute and regular, and his blood pressure was 164/100 mm Hg. Examination of the heart was normal. Neurologic examination was negative except for a marked nuchal rigidity. Left upper monoparesis was no longer noted. Complete blood count and urinalysis were normal. Serum potassium, serum sodium, serum chloride, blood urea nitrogen, and serum creatinine were all within normal limits. Serum cholesterol was 198 mg/dl, and serum triglyceride was 94 mg/dl. Chest x-ray and skull films were unremarkable. Cerebral angiograms disclosed an aneurysm of the right internal carotid artery and an aneurysm of the right anterior cerebral artery (Figure 1 ). A lumbar puncture revealed grossly bloody cerebrospinal fluid. An electrocardiogram showed sinus bradycardia at a rate of 55, and a PQ interval of 0.18
seconds. No ST segment or T wave changes were found (Figure 2). The patient was kept in bed, and his clinical course was satisfactory and uncomplicated until the ninth hospital day. Then at midnight he suddenly experienced a stubborn headache, left precordial pain, and difficultly in breathing. The former symptom persisted until the next morning, but the latter abated spontaneously in a few minutes. A specimen of arterial blood taken immediately after the onset of the headache showed that the oxygen saturation was 95%, the partial pressure of oxygen 95 mm Hg, and the partial pressure of carbon dioxide 40 mm Hg. Nuchal rigidity was aggravated and a lumbar puncture also revealed grossly bloody fluid, indicating that a second subarachnoid hemorrhage had occurred. After that night, he began to have repeated episodes of left precordial pain without headache early every morning between 2:00 and 4:00 AM. He had previously never experienced chest pain. An electrocardiogram taken during an attack of precordial pain showed marked elevation of the ST segment and highvoltage R waves in leads II, III, and aVF. Reciprocal ST segment depression was also noted in leads I and aVL. The elevation of the ST segment gradually returned to the baseline as the pain decreased (Figure 3). Several electrocardiograms taken while the chest pain was absent disclosed no remarkable changes. Serum glutamic oxaloacetic transaminase and lactic dehydrogenase levels, determined on several occasions, were all normal. The anginal attacks’ were not precipitated by any emotional stress or bodily motions. The pain was relieved in a few minutes by sublingual administration of isosorbide dinitrate. Coronary arteriography and operative resection of the aneurysms were not per-
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
213
FIG. 1. Cerebral angiogram showing an aneurysm of the aneurysm of the right anterior cerebral artery (1).
formed in accordance with the patient’s wishes. He was successfully treated with hemostatic agents and pentaerythritol tetranitrate. Twelve days later, when nuchal rigidity was fairly improved, the episodes of a chest pain ended. The patient completely recovered from all symptoms and was discharged on the 40th day of hospitalization. During 4 years of follow-up he has been asymptomatic. Discussion The patient reported here has the following clinical characteristics: (1) a variant form of angina pectoris that began almost concurrently with the recurrence of subarachnoid hemorrhage; (2) this
right
internal carotid artery
(T)
and
an
angina became less severe and later disappeared as the symptoms and signs of subarachnoid hemorrhage improved; and (3) the anginal attacks did not occur either before the recurrence of subarachnoid hemorrhage or after improvement of the latter condition. Therefore, it seems reasonable to think that Prinzmetal’s angina in this patient may have been caused by the second episode of subarachnoid hemorrhage. This thought prompted us to survey the literature on the cardiac changes in subarachnoid
hemorrhage. Electrocardiographic changes seen in subarachnoid hemorrhage include prolonged QTc or QU intervals; elevated or depressed ST segments; deeply inverted
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
214
FIG. 2.
Electrocardiogram
upright T or broad TU fusion waves; large positive or negative U waves; Q waves in both limb and precordial leads; a marked increase in the amplitude of the U wave in postextrasystolic beats; and notched or bifid T waves.18 Among these ECG changes, ST segment elevation is relatively infreor
tall
quent and is minimal
gree.19- 24
or
moderate in de-
on
admission.
The time course of ST segment elevation has not been fully documented. 23 We are aware of only one report describing episodic ST elevation in a patient with subarachnoid hemorrhage. In 1975 Goldman et a1.25 reported the case of a 65-year-old woman with fatal subarachnoid hemorrhage due to a posterior-inferior cerebral artery aneurysm. The patient had short and transient episodes of
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215
’
FIG. 3. Serial electrocardiograms (lead II) taken during an attack of precordial pain. At the onset of pain, marked elevation of ST segment, increased voltage of R wave, and high T wave are apparent. The ST segment elevation returned gradually to the baseline in 3 minutes when precordial pain disappeared. The increased R and T waves have also disappeared 3 minutes after the onset of pain.
and
several occasions. Continuous ECGs taken during such an episode demonstrated complete heart block with marked ST elevation which returned to normal probably in a few minutes. She was unable to re-
bradycardia
hypotension
on
to questions about pain. Therefore the clinical features and the ECG changes described in Goldman’s paper are in accordance with those of variant angina, except for anginal pain. It seems reasonable to assume that the patho-
spond
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
216 in Goldman’s patient was similar to that in Prinzmetal’s angina, because the episodic ST elevation with or without pain is probably one of the characteristic ECG findings in this form of
physiology
angina. 4,9,26,27 Considerable progress has been made in studies of the underlying mechanism of Prinzmetal’s form of angina. Prinzmetal et a1.1.2 had already postulated that the attacks were precipitated by spasm of a
single, narrowed, large
coronary artery. Later it was shown by coronary arteriography that recurrent arterial spasm of a large coronary artery might be responsible for the attacks of the variant angina.3-5.’-13 In 1973, Oliva et a].’
demonstrated spontaneously occurring spasm of the right coronary artery whose location and severity were not constant. The patient was a woman with recurrent attacks of variant angina. Recently, Yasue et al. 21,11 observed that the attack in patients with a variant form of angina pectoris was precipitated by the administration of propranolol, methacholine, or epinephrine, but not by isoproterenol, and that it was suppressed by the administration of atropine and phenoxybenzamine. They also demonstrated that severe spasm of the coronary artery occurred in association with ST segment elevation during the attack precipitated by the combined administration of epinephrine and propranolol.ll They concluded that severe spasm of a large coronary artery mediated by alphaadrenergic receptors was responsible for the attack of Prinzmetal’s angina. Although this is still controversia1,13 it seems probable that coronary arterial spasm mediated by the autonomic nervous system plays a major role in producing the attack, at least in some patients with variant angina. Therefore the results with our patient and Goldman’s patient25 seem to show that coronary arterial spasm mediated by the autonomic nervous system may
in
patients with subarachnoid hemorrhage. The cardiac changes in patients with subarachnoid hemorrhage have been attributed to the derangement of the autonomic nervous system.31-34 Hunt et a1.35 found that myocardial lesions seen in experimental intracranial hemorrhage were prevented by propranolol. However, the exact mechanism through which the cardiac changes are caused by the derangement of the autonomic nervous system in subarachnoid hemorrhage is still unknown. Some investigators32,36 proposed that the myocardial necrosis seen in patients with subarachnoid hemorrhage was due to release of catecholamines from adrenergic nerve endings in the heart. The arrhythmias observed in subarachnoid hemorrhage seem to be result from nonuniformity in the rate of repolarization of cardiac cells,37 the direct effect of catecholamine or acetylcholine released from the nerve endings of sympathetic or parasympathetic nerves, or cardiac myocardial damage32,36,38 probably induced by catecholamine. We propose that coronary arterial spasm, mediated by the derangement of the autonomic nervous system, may be one of several causes of cardiac changes in subarachnoid hemorrhage. The coronary arterial spasm may result in transient ST elevation with reciprocal ST depression, with (variant angina) or without complaints of anginal pain, or in acute myocardial infarction.39-41 Arrhythmias, including ventricular ones and conduction disturbances, may also occur under such circumstances. It has been suggested that coronary arterial constriction can be caused by electrical stimulation of the central nervous system in experimental animals.42 Because the ST changes of variant angina or of the related pathophysiology are transient in nature, continuous monitoring of the ECG is undoubtedly essential for managing such patients with suboccur
some
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217
.
arachnoid hemorrhage. The monitoring can also make clear the occurrence of such pathophysiology in subarachnoid hemorrhage. The treatment of patients with subarachnoid hemorrhage and episodic ST elevation due to coronary arterial spasm should be directed toward reducing the spasm; that is, they should be treated with alpha-blocking agents, nitroglycerine, the so-called Ca-antagonistic inhibitors, or a combination of two or more of these drugs. Alpha-blocking agent may alleviate the coronary arterial spasm which is likely to be mediated by alpha-receptors.43 Nitroglycerine causes prolonged vasodilation of large coronary arteries in animals.44,45 It also relieves both the pain and the spasm of the coronary artery, as has been documented by coronary arteriograph y3 - 5,7- 9, 11 or at the time of coronary surgery.’ Newly developed Ca-antagonistic inhibitors, such as verapamil, nifedipine, and diltiazem, are reported to have a potent effect in dilating coronary arteries through their Ca-antagonistic inhibitory action on vascular smooth muscle.46 Endo et al. 17 reported excellent results when using nifedipine to halt attacks of variant angina, and Mueller and Gunther48 reported a case in which nifedipine was effective in relieving attacks of Prinzmetal’s angina unresponsive to conventional therapy. Further studies are needed to detail both the pathophysiology and the management of cardiac changes in subarachnoid hemorrhage. The authors are grateful to Dr. V. J. Ferrans and Professor T. Kanehisa for their helpful review of the manuscript. We thank Miss Y. Taniyama for secretarial assistance.
Hiromitsu Tanaka, M.D., F.I.C.A. First Department of Internal Medicine
Faculty of Medicine Kagoshima University, Usuki-cho 1208-1
Kagoshima, 890, Japan
References
1. Prinzmetal, M., Kennamer, R., Merliss, R., et Angina pectoris. I. A. variant form of angina pectoris. Preliminary report. Am. J. al.:
27: 375, 1959. Med., 2. Prinzmetal, M., Ekmekci, A., Kennamer, R., et al.: Variant form of angina pectoris. Previously undelineated syndrome. J.A.M.A., 174: 1794, 1960. 3. Dhurandhar, R. W., Watt, D. L., Silver, M. D., et al.: Prinzmetal’s variant form of angina with arteriographic evidence of coronary arterial spasm. Am. J. Cardiol., 30: 902, 1972. 4. Cheng, T. O., Bashour, T., Kelser, G. A., et al.: Variant angina of Prinzmetal with normal coronary arteriograms. A variant of the variant. Circulation, 47: 476, 1973. 5. Oliva, P. B., Potts, D. E., Pluss, R. G.: Coronary arterial spasm in Prinzmetal angina. Documentation by coronary arteriography. N. Engl. J. Med., 288: 745, 1973. 6. MacAlpin, R. N., Kattus, A. A., Alvaro, A. B.: Angina pectoris at rest with preservation of exercise capacity. Prinzmetal’s variant angina. Circulation, 47: 946, 1973. 7. Hart, N. J., Silverman, M. E., King, S. B.: Variant angina pectoris caused by coronary artery spasm. Am. J. Med., 56: 269, 1974. 8. Gaasch, W. H., Adyanthaya, A. V., Wang, V. H., et al.: Prinzmetal’s variant angina: Hemodynamic and angiographic observations during pain. Am. J. Cardiol., 35: 683, 1975. 9. Maseri, A., Mimmo, R., Chierchia, S., et al.: Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest, 68: 625, 1975. 10. Endo, M., Hirosawa, K., Kaneko, N., et al.: Prinzmetal’s variant angina. N. Engl. J. Med., 294: 252, 1976. 11. Yasue, H., Touyama, M., Kato, H., et al.: Prinzmetal’s variant form of angina as a manifestation of alpha-adrenergic receptor-mediated coronary artery spasm: Documentation by coronary arteriography. Am. Heart J., 91: 148, 1976. 12. Higgins, C. B., Wexler, L., Silverman, J. F., et al.: Clinical and arteriographic features of Prinzmetal’s variant angina: Documentation of etiologic factors. Am. J. Cardiol., 37: 831, 1976. 13. Meller, J., Pichard, A., Dack, S.: Coronary arterial spasm in Prinzmetal’s angina: A proved hypothesis. Am. J. Cardiol., 37: 938, 1976. 14. Byer, E., Ashman, R., Toth, L. A.: Electrocardiograms with large, upright T waves and long Q-T intervals. Am. Heart J., 33: 796, 1947. 15. Weintraub, B. M., McHenry, L. C.: Cardiac abnormalities in subarachnoid hemorrhage: A resumé. Stroke, 5: 384, 1974. 16. Weidler, D. J.: Myocardial damage and cardiac arrhythmias after intracranial hemor-
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rhage. A critical review. Stroke, 5: 759, 1974. Estanol, B. V., Marin, O. S. M.: Cardiac arrhythmias and sudden death in subarachnoid hemorrhage. Stroke, 6: 382, 1975. Smith, M.: Ventricular bigeminy occurring in a case of subarachnoid hemorrhage. J. Elec-
trocardiol., 5: 78, 1972. 19. Shuster, S.: The electrocardiogram in subarachnoid haemorrhage. Br. Heart J., 22:
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431, 1964. 22. Kreus, K. E., Kemilä, S. J., Takala, J. K.: Electrocardiographic changes in cerebrovascular accidents. Acta Med. Scand., 185: 327, 1969. 23. Abildskov, J. A., Millar, K., Burgess, M. J., et al.: The electrocardiogram and the central nervous system. Prog. Cardiovasc. Dis., 13: 210, 1970. 24. Eisalo, A., Perasalo, J., Halonen, P. I.: Electrocardiographic abnormalities and some laboratory findings in patients with subarachnoid haemorrhage. Br. Heart J., 34: 217, 1972. 25. Goldman, M. R., Rogers, E. L., Rogers, M. C.: Subarachnoid hemorrhage. Association with unusual electrocardiographic changes. J. A. M. A., 234: 957, 1975. 26. Guazzi, M., Fiorentini, C., Polese, A., et al.: Continuous electrocardiographic recording in Prinzmetal’s variant angina pectoris. A report of four cases. Br. Heart J. 32: 611, 1970. 27. Gorfinkel, H. J., Inglesby, T. V., Lansing, A. M., et al.: ST-segment elevation, transient left-prosterior hemiblock, and recurrent ventricular arrhythmias unassociated with pain. A variant of Prinzmetal’s anginal syndrome. Ann. Intern. Med., 79: 795, 1973. 28. Guazzi, M., Olivari, M. T., Polese, A., et al.: Repetitive myocardial ischemia of Prinzmetal type without angina pectoris. Am. J. Cardiol., 37: 923, 1976. 29. Yasue, H., Touyama, M., Shimamoto, M., et al.: Role of autonomic nervous system in the pathogenesis of Prinzmetal’s variant form of angina. Circulation, 50: 534, 1974. 30. Yasue, H., Touyama, M., Tanaka, S., et al.: Prinzmetal’s angina: Atropine suppression. Ann. Intern. Med., 80: 553, 1974. 31. Cropp, G. J., Manning, G. W.: Elec-
trocardiographic changes simulating
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46.
myo-
cardial ischemia and infarction associated with spontaneous intracranial hemorrhage. Circulation, 22: 25, 1960. 32. Hammermeister, K. E., Reichenbach, D. D.: QRS changes, pulmonary edema, and myocardial necrosis associated with subarachnoid hemorrhage. Am. Heart J., 78: 94, 1969.
D., McRae, C., Zapf, P.:
trocardiographic
316, 1960. 20. Hersch, C.: Electrocardiographic changes in subarachnoid haemorrhage, meningitis, and intracranial space-occupying lesions. Br. Heart J., 26: 785, 1964. 21. Srivastava, S. C., Robson, A. O.: Electrocardiographic abnormalities associated with subarachnoid haemorrhage. Lancet, 2:
Elecenzyme changes in subarachnoid hemorrhage. Am. Heart J., 77: 479, 1969. Burch, G. E., Colcolough, H., Giles, T.: Intracranial lesions and the heart. Am. Heart J., 80: 574, 1970. Hunt, D., Gore, I.: Myocardial lesions following experimental intracranial hemorrhage : Prevention with propranolol. Am. Heart J., 83: 232, 1972. Greenhoot, J. H., Reichenbach, D. D.: Cardiac injury and subarachnoid hemorrhage. A clinical, pathological, and physiological correlation. J. Neurosurg., 30: 521, 1969. Han, J., Moe, C. K.: Nonuniform recovery of excitability in ventricular muscle. Circ. Res., 14: 44, 1964. Koskelo, P., Punsar, S., Sipilä, W.: Subendocardial haemorrhage and ECG changes in intracranial bleeding. Br. Med. J., 1: 1479, 1964. Khan, A. H., Haywood, L. J.: Myocardial infarction in nine patients with radiologically patent coronary arteries. N. Engl. J. Med., 291: 427, 1974. Ciraulo, D. A.: Recurrent myocardial infarction and angina in a woman with normal coronary angiograms. Am. J. Cardiol., 35: 923, 1975. Johnson, A. D., Detwiler, J. H.: Coronary spasm, variant angina, and recurrent myocardial infarctions. Circulation, 5: 947, 1977. Melville, K. I., Garvey, H. L., Shister, H. E., et al.: Central nervous system stimulation and cardiac ischemic changes in monkeys. Ann. N.Y. Acad. Sci., 156: 241, 1969. Levene, D. L., Freeman, M. R.: α-adrenoceptor-mediated coronary artery spasm. 236: 1018, 1976. J.A.M.A., Winbury, M. M., Howe, B. B., Hefner, M. A.: Effect of nitrates and other coronary dilators on large and small coronary vessels: A hypothesis for the mechanism of action of nitrates. J. Pharmacol. Exp. Ther., 168: 70, 1969. Cohen, M. V., Kirk, E. S.: Differential response of large and small coronary arteries to nitroglycerin and angiotensin. Autoregulation and tachyphyraxis. Circ. Res., 33: 445, 1973. Fleckenstein, A.: On the basic pharmacological mechanism of nifedipine and its relation to therapeutic efficacy, in The Third International Adalat® Symposium. New Therapy of Ischemic Heart Disease. Edited by A. D. Jatene, P. R. Lichtlen. Amsterdam and Oxford, Excerpta Medica, 1976, pp. 1-13. Endo, M., Kanda, I., Hosoda, S., et al.: Prinzmetal’s variant form of angina pectoris. Re-evaluation of mechanisms. Circulation, 52: 33, 1975. Muller, J. E., Gunther, S. J.: Nifedipine therapy for Prinzmetal’s angina. Circulation, 57 : 137, 1978.
33. Hunt,
47.
48.
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
and
serum
Report
Yoshifumi
Toyama, M.D., F.I.C.A., Hiromitsu Tanaka, M.D., F.I.C.A., Kohji Nuruki, M.D., and Tetsuya Shirao, M.D. KAGOSHIMA,
JAPAN
Abstract
panied
Prinzmetal’s variant of angina occurred in a 48-year-old man who sustained two attacks of subarachnoid hemorrhage within 10 days. The first anginal pain started at the same time that the second cerebrovascular accident developed, but subsequent anginal episodes were not accompanied by other symptoms or signs that indicated new development of subarachnoid hemorrhage. Twelve days later, when nuchal rigidity was fairly improved, the episodes of chest pain ended. A vasospasm of the large coronary arteries—probably due to the derangement of the autonomic nervous system caused by subarachnoid hemorrhage—was presumed to contribute to the occurrence of the variant angina. Based on this case and on review of the literature, we propose that coronary arterial spasm is one of several causes of the cardiac changes seen in subarachnoid
ment
at about same time
by
ST seg-
elevation, and it is frequently
asso-
ciated with arrhythmias. Recent clinical studies 3-13 have shown that the most likely mechanism of Prinzmetal’s angina is recurrent coronary arterial spasm with or without coronary stenotic lesions. Since the first description of Byer et a1.14 in 1947, a number of reports on the cardiac changes in patients with subarachnoid hemorrhage have been published. The cardiac changes thus far reported include electrocardiographic alterations, cardiac arrhythmias, myocardial damage, and pulmonary edema.15-17 It has been suggested that the increased or altered autonomic nervous activity caused by subarachnoid hemorrhage produces these cardiac abnormalities.15-17 It seems very worthwhile to determine whether Prinzmetal’s angina and subarachnoid hemorrhage occur at the same time in a patient, because such an association may explain the underlying mechanism of cardiac abnormalities in patients with subarachnoid hemorrhage. This paper presents what to our knowledge is the first report of a patient in whom Prinzmetal’s angina occurred in association with subarachnoid hemorrhage.
hemorrhage. Introduction A variant form of angina pectoris, described by Prinzmetal et al. in 19591 and 1960,~ is characterized by chest pain at rest or during ordinary daily activity. It often occurs in a cyclic pattern accom-
Case Report From the First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, and the Section of Neurosurgery, Nampoo Hospi-
A 48-year-old male office worker was admitted to the hospital on June 20, 1973, because of a persistent headache
tal, Kagoshima, Japan.
211
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
212 and vomiting. He had previously been in rather good health, except for borderline hypertension of a few years’ duration. But on the night before admission, when returning from a lavatory, he complained of nausea and weakness, and shortly thereafter he fell unconscious. His face became pale, with saliva oozing from the lips, but no convulsion was noted. There was no history of trauma. After about thirty minutes, he regained consciousness with poor response. Left upper monoparesis was observed at that time by his family physician. His blood pressure was 220/ 120 mm Hg, his pulse was 66/minute and regular, and respirations were 20/ minute. He was treated with hemostatic agents and sedatives. On the morning of his admission, he developed a generalized headache accompanied by vomiting. Because administration of chlorpromazine and analgesics was not effective, he was transferred to the hospital. Physical examination on admission revealed a well-nourished and normally responsive man. His pulse was 60/minute and regular, and his blood pressure was 164/100 mm Hg. Examination of the heart was normal. Neurologic examination was negative except for a marked nuchal rigidity. Left upper monoparesis was no longer noted. Complete blood count and urinalysis were normal. Serum potassium, serum sodium, serum chloride, blood urea nitrogen, and serum creatinine were all within normal limits. Serum cholesterol was 198 mg/dl, and serum triglyceride was 94 mg/dl. Chest x-ray and skull films were unremarkable. Cerebral angiograms disclosed an aneurysm of the right internal carotid artery and an aneurysm of the right anterior cerebral artery (Figure 1 ). A lumbar puncture revealed grossly bloody cerebrospinal fluid. An electrocardiogram showed sinus bradycardia at a rate of 55, and a PQ interval of 0.18
seconds. No ST segment or T wave changes were found (Figure 2). The patient was kept in bed, and his clinical course was satisfactory and uncomplicated until the ninth hospital day. Then at midnight he suddenly experienced a stubborn headache, left precordial pain, and difficultly in breathing. The former symptom persisted until the next morning, but the latter abated spontaneously in a few minutes. A specimen of arterial blood taken immediately after the onset of the headache showed that the oxygen saturation was 95%, the partial pressure of oxygen 95 mm Hg, and the partial pressure of carbon dioxide 40 mm Hg. Nuchal rigidity was aggravated and a lumbar puncture also revealed grossly bloody fluid, indicating that a second subarachnoid hemorrhage had occurred. After that night, he began to have repeated episodes of left precordial pain without headache early every morning between 2:00 and 4:00 AM. He had previously never experienced chest pain. An electrocardiogram taken during an attack of precordial pain showed marked elevation of the ST segment and highvoltage R waves in leads II, III, and aVF. Reciprocal ST segment depression was also noted in leads I and aVL. The elevation of the ST segment gradually returned to the baseline as the pain decreased (Figure 3). Several electrocardiograms taken while the chest pain was absent disclosed no remarkable changes. Serum glutamic oxaloacetic transaminase and lactic dehydrogenase levels, determined on several occasions, were all normal. The anginal attacks’ were not precipitated by any emotional stress or bodily motions. The pain was relieved in a few minutes by sublingual administration of isosorbide dinitrate. Coronary arteriography and operative resection of the aneurysms were not per-
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
213
FIG. 1. Cerebral angiogram showing an aneurysm of the aneurysm of the right anterior cerebral artery (1).
formed in accordance with the patient’s wishes. He was successfully treated with hemostatic agents and pentaerythritol tetranitrate. Twelve days later, when nuchal rigidity was fairly improved, the episodes of a chest pain ended. The patient completely recovered from all symptoms and was discharged on the 40th day of hospitalization. During 4 years of follow-up he has been asymptomatic. Discussion The patient reported here has the following clinical characteristics: (1) a variant form of angina pectoris that began almost concurrently with the recurrence of subarachnoid hemorrhage; (2) this
right
internal carotid artery
(T)
and
an
angina became less severe and later disappeared as the symptoms and signs of subarachnoid hemorrhage improved; and (3) the anginal attacks did not occur either before the recurrence of subarachnoid hemorrhage or after improvement of the latter condition. Therefore, it seems reasonable to think that Prinzmetal’s angina in this patient may have been caused by the second episode of subarachnoid hemorrhage. This thought prompted us to survey the literature on the cardiac changes in subarachnoid
hemorrhage. Electrocardiographic changes seen in subarachnoid hemorrhage include prolonged QTc or QU intervals; elevated or depressed ST segments; deeply inverted
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
214
FIG. 2.
Electrocardiogram
upright T or broad TU fusion waves; large positive or negative U waves; Q waves in both limb and precordial leads; a marked increase in the amplitude of the U wave in postextrasystolic beats; and notched or bifid T waves.18 Among these ECG changes, ST segment elevation is relatively infreor
tall
quent and is minimal
gree.19- 24
or
moderate in de-
on
admission.
The time course of ST segment elevation has not been fully documented. 23 We are aware of only one report describing episodic ST elevation in a patient with subarachnoid hemorrhage. In 1975 Goldman et a1.25 reported the case of a 65-year-old woman with fatal subarachnoid hemorrhage due to a posterior-inferior cerebral artery aneurysm. The patient had short and transient episodes of
Downloaded from ang.sagepub.com at Bibliothekssystem der Universitaet Giessen on May 22, 2015
215
’
FIG. 3. Serial electrocardiograms (lead II) taken during an attack of precordial pain. At the onset of pain, marked elevation of ST segment, increased voltage of R wave, and high T wave are apparent. The ST segment elevation returned gradually to the baseline in 3 minutes when precordial pain disappeared. The increased R and T waves have also disappeared 3 minutes after the onset of pain.
and
several occasions. Continuous ECGs taken during such an episode demonstrated complete heart block with marked ST elevation which returned to normal probably in a few minutes. She was unable to re-
bradycardia
hypotension
on
to questions about pain. Therefore the clinical features and the ECG changes described in Goldman’s paper are in accordance with those of variant angina, except for anginal pain. It seems reasonable to assume that the patho-
spond
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216 in Goldman’s patient was similar to that in Prinzmetal’s angina, because the episodic ST elevation with or without pain is probably one of the characteristic ECG findings in this form of
physiology
angina. 4,9,26,27 Considerable progress has been made in studies of the underlying mechanism of Prinzmetal’s form of angina. Prinzmetal et a1.1.2 had already postulated that the attacks were precipitated by spasm of a
single, narrowed, large
coronary artery. Later it was shown by coronary arteriography that recurrent arterial spasm of a large coronary artery might be responsible for the attacks of the variant angina.3-5.’-13 In 1973, Oliva et a].’
demonstrated spontaneously occurring spasm of the right coronary artery whose location and severity were not constant. The patient was a woman with recurrent attacks of variant angina. Recently, Yasue et al. 21,11 observed that the attack in patients with a variant form of angina pectoris was precipitated by the administration of propranolol, methacholine, or epinephrine, but not by isoproterenol, and that it was suppressed by the administration of atropine and phenoxybenzamine. They also demonstrated that severe spasm of the coronary artery occurred in association with ST segment elevation during the attack precipitated by the combined administration of epinephrine and propranolol.ll They concluded that severe spasm of a large coronary artery mediated by alphaadrenergic receptors was responsible for the attack of Prinzmetal’s angina. Although this is still controversia1,13 it seems probable that coronary arterial spasm mediated by the autonomic nervous system plays a major role in producing the attack, at least in some patients with variant angina. Therefore the results with our patient and Goldman’s patient25 seem to show that coronary arterial spasm mediated by the autonomic nervous system may
in
patients with subarachnoid hemorrhage. The cardiac changes in patients with subarachnoid hemorrhage have been attributed to the derangement of the autonomic nervous system.31-34 Hunt et a1.35 found that myocardial lesions seen in experimental intracranial hemorrhage were prevented by propranolol. However, the exact mechanism through which the cardiac changes are caused by the derangement of the autonomic nervous system in subarachnoid hemorrhage is still unknown. Some investigators32,36 proposed that the myocardial necrosis seen in patients with subarachnoid hemorrhage was due to release of catecholamines from adrenergic nerve endings in the heart. The arrhythmias observed in subarachnoid hemorrhage seem to be result from nonuniformity in the rate of repolarization of cardiac cells,37 the direct effect of catecholamine or acetylcholine released from the nerve endings of sympathetic or parasympathetic nerves, or cardiac myocardial damage32,36,38 probably induced by catecholamine. We propose that coronary arterial spasm, mediated by the derangement of the autonomic nervous system, may be one of several causes of cardiac changes in subarachnoid hemorrhage. The coronary arterial spasm may result in transient ST elevation with reciprocal ST depression, with (variant angina) or without complaints of anginal pain, or in acute myocardial infarction.39-41 Arrhythmias, including ventricular ones and conduction disturbances, may also occur under such circumstances. It has been suggested that coronary arterial constriction can be caused by electrical stimulation of the central nervous system in experimental animals.42 Because the ST changes of variant angina or of the related pathophysiology are transient in nature, continuous monitoring of the ECG is undoubtedly essential for managing such patients with suboccur
some
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217
.
arachnoid hemorrhage. The monitoring can also make clear the occurrence of such pathophysiology in subarachnoid hemorrhage. The treatment of patients with subarachnoid hemorrhage and episodic ST elevation due to coronary arterial spasm should be directed toward reducing the spasm; that is, they should be treated with alpha-blocking agents, nitroglycerine, the so-called Ca-antagonistic inhibitors, or a combination of two or more of these drugs. Alpha-blocking agent may alleviate the coronary arterial spasm which is likely to be mediated by alpha-receptors.43 Nitroglycerine causes prolonged vasodilation of large coronary arteries in animals.44,45 It also relieves both the pain and the spasm of the coronary artery, as has been documented by coronary arteriograph y3 - 5,7- 9, 11 or at the time of coronary surgery.’ Newly developed Ca-antagonistic inhibitors, such as verapamil, nifedipine, and diltiazem, are reported to have a potent effect in dilating coronary arteries through their Ca-antagonistic inhibitory action on vascular smooth muscle.46 Endo et al. 17 reported excellent results when using nifedipine to halt attacks of variant angina, and Mueller and Gunther48 reported a case in which nifedipine was effective in relieving attacks of Prinzmetal’s angina unresponsive to conventional therapy. Further studies are needed to detail both the pathophysiology and the management of cardiac changes in subarachnoid hemorrhage. The authors are grateful to Dr. V. J. Ferrans and Professor T. Kanehisa for their helpful review of the manuscript. We thank Miss Y. Taniyama for secretarial assistance.
Hiromitsu Tanaka, M.D., F.I.C.A. First Department of Internal Medicine
Faculty of Medicine Kagoshima University, Usuki-cho 1208-1
Kagoshima, 890, Japan
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