Journal of
J.Neurol. 220, 71--76 (1979)
tqeurology ~) by Springer-Verlag 1979
Surveys of Progress On the Mechanism of Sudden Death with Subarachnoid Hemorrhage G. Parizel Department of Medicine, Middelheim Hospital, Lindendreef. 2, B-2020 Antwerp, Belgium
Summary. The mechanism of death in some patients with subarachnoid hemorrhage is cardiac arrhythmia. Prevention of cardiac arrhythmias by suitable drugs might save the life of patients whose brain is still good. Key words: Subarachnoid hemorrhage - Cardiac arrhythmias-Death sudden. Zusammenfassung. Als Ursache fiir den Tod in manchen Fallen von Subarachnoidalblutung muB eine Herzrhythmusst6rung angesehen werden. Eine Prophylaxe von Arrhythmien durch entsprechende Medikamente kann das Leben mancher dieser Patienten, deren Him noch funktionsttichtig w~ire, retten.
Mortality in patients with subarachnoid hemorrhage and especially sudden death, in spite of advances in diagnosis and treatment, remains distressingly high. Sudden death due to subarachnoid hemorrhage is also not uncommon; it accounts for 4--5% of all natural sudden deaths. In a series of autopsy-proven cases of subarachnoid hemorrhage only 40% had survived long enough to reach hospital and more than half of these died shortly after admission [10, 50]. Until recently it seemed logical to attribute the death of these patients to their central nervous system (CNS) lesions. However in a number of patients dying of subarachnoid hemorrhage remarkably few lesions of the CNS were found. This paucity of specific lesions in the CNS makes one speculate about other possible mechanism to explain the death of these patients. We have recently shown that life-threatening cardiac arrhythmias can occur in patients with subarachnoid hemorrhage [43]. When not promptly recognized and treated (which is unfortunately usually the case outside the hospital) these cardiac arrhythmias may welt be the cause of death especially of those patients in whom postmortem examination discloses only minimal CNS lesions. The relation between cardiac complications and CNS lesions has been known for quite some time. 0340-5354/79/0220/0071/$01.20
72
G. Parizel
Abnormalities of the electrocardiogram in patients with CNS diseases were first described in 1947 [6]. Numerous reports have confirmed these findings since then [1, 3, 6, 11, 13, 17, 18, 20, 22--24, 29, 30, 37, 39, 44, 47, 49, 51,55, 60, 62]. The pertinent ECG changes found in patients with CNS lesions, and especially subarachnoid hemorrhage, are abnormalities of the ST-T deflections: large upright or deeply inverted T waves, prolongation of the Q-T interval and prominent U waves. These ECG abnormalities often resemble those of ischemic heart disease and can sometimes be so pronounced as to suggest myocardial infarction [3,9,44]. This confusion could have unfortunate therapeutic consequences such as the administration of anticoagulants. The frequency, timing and duration of these ECG abnormalities have not been sufficiently documented. In our experience ECG changes can occur as late as 8 days after the first clinical manifestation of subarachnoid hemorrhage. There have been conflicting reports with regards to the question whether these ECG abnormalities are related to structural changes in the myocardium or not. Subendocardial hemorrhage, as well as microscopic lesions, have been described in patients dying of subarachnoid hemorrhage [7, 8]. These findings have been confirmed in experimental animals. There is now sufficient clinical evidence that the cardiac abnormalities found in patients with subarachnoid hemorrhage are not a fortuitous coincidence. Numerous studies have been undertaken in order to reproduce these clinical findings in the experimental animal. Experimental evidence indicates that both the sympathetic and parasympathetic nervous systems are implicated in the production of myocardial lesions following intracranial lesions. Electrical stimulation of the vagus nerve produces myocardial damage which can be prevented by the administration of atropine [33]. Similarly intravenous administration of acetylcholine produces focal myocardial necrosis or frank infarction. There is also evidence that lesions similar to those found with subarachnoid hemorrhage can be produced in the myocardium by intravenous administration of cathecholamines in the experimental animal [48,57]. Similar lesions have been demonstrated in patients treated with intravenous infusions of norepinephrine for shock [57]. Necrosis of the myocardium has also been described in patients dying of phaeochromocytoma [59]. Cardiotoxic effects of electrical stimulation of the stellate ganglia producing subendocardial hemorrhage and focal myocardial necrosis have also been described [27]. The experimental production of intracranial hemorrhage in animals has also produced myocardial damage [5, 25,41]. Other interventions in the experimental animal such as head trauma [26], intraventricular air insufflation, hypothalamic stimulation [16] can produce similar myocardial damage [58,45,28]. Striking electrocardiographic changes simulating myocardial infarction have also been observed in patients who had undergone bilateral carotid endarterectomy [2]. Numerous experiments have also shown the relation in the experimental animal between intracranial lesions and cardiac arrhythmias. Cardiac arrhythmias have been observed after the production of experimental subarachnoid hemorrhage in animals. Cardiac arrhythmias have also been produced by rapid changes of intracranial pressure [52]. Administration of atropine and vagotomy eliminated or prevented these arrhythmias.
On the Mechanism of Sudden Death with Subarachnoid Hemorrhage
73
Electrical stimulation of several cartical and subcortical areas has been shown to produce cardiac arrhythmias some of which are comparable to those seen in our patients [14, 21,32, 34, 35, 52]. Both the sympathetic and parasympathetic nervous system seem to play an important part in the production of the cardiac arrhythmias in these experimental procedures [15]. In spite of the numerous reports on the ECG changes and the numerous animal experiments scarcely any attention was paid to the occurrence of serious disturbances of cardiac rhythm in patients with subarachnoid hemorrhage prior to our report [43]. In 1973 we described two patients with subarachnoid hemorrhage who both presented life-threatening ventricular arrhythmias. Their ECG showed the typical abnormalities described for this condition. Prompt recognition and treatment of these arrhythmias was life-saving. It is also significant that both patients had an initial syncope and that no neurological abnormalities apart from the meningeal signs were found [43]. A whole range of cardiac arrhythmias has been described by different investigators in their animal experiments: premature ventricular beats, nodal rhythm; A-V block, ventricular tachycardia and fibrillation, pre-excitation pattern. One of our patients also manifested several different arrhythmias. It "is evident that not one single mechanism is responsible for such widely different cardiac arrhythmias. Some of these are probably due to the intervention of the autonomic nervous system on the impulse formation and conduction of the heart and do not necessarily imply structural changes. On the other hand the prolongation of the Q-T interval of the ECG in these patients seems to be an important factor in the causation of life-threatening ventricular arrhythmias. We assume that prolongation of the Q-T interval certainly plays an important part in the production of the ventricular arrhythmias in patients with subarachnoid hemorrhage, The long Q-T interval is due to diffuse disturbances in the repolarization of the myocardium. This causes an unequal duration of the refractory period in the different myocardial fibers favoring the reentry phenomenon and the development of ventricular dysrhythmias. Recently attention has been drawn to a particular ventricular dysrhythmia occuring in patients with a long Q-T interval called "torsade de pointe" [31,40,46] which must be distinguished from the common forms of ventricular tachycardia or ventricular fibrillation for etiological, morphological and therapeutic reasons. This arrhythmia, which we proposed to call "ventricular fibrilloflutter" [46] has been seen in patients with subarachnoid hemorrhage [42, 43]. The criteria for diagnosis of ventricular fibrilloflutter are: -
-
-
-
long Q-T interval during normal ryhthm the QRS complexes of the arrhythmia appear to twist around the isoelectric line, hence the application "torsade de pointe" in French the arrhythmia is triggered by late ventricular extrasytoles the attacks are of variable duration. Often they are short spontaneously resolving and recurring. When of sufficiently long duration they produce syncope (this may be the explanation of the syncope frequently seen in patients with subarachnoid hemorrhage). in some cases the arrhythmia persists and degenerates into fatal ventricular fibrillation.
74
G. Parizel
W i t h r e g a r d to s u b a r a c h n o i d h e m o r r h a g e an a n a l o g y can be m a d e with m y o cardial infarction. In some victims o f m y o c a r d i a l infarction the d a m a g e o f the m y o c a r d i u m is so extensive t h a t they die o f p u m p failure a n d cardiogenic chock. T h e r a p y in these cases is usually o f no avail. O n the o t h e r h a n d patients with quite small m y o c a r d i a l infarctions die, not because of p u m p failure, b u t because o f fatal c a r d i a c a r r h y t h m i a s . We k n o w that p r e v e n t i o n by a n t i - a r r h y t h m i c drugs a n d the p r o m p t r e c o g n i t i o n a n d t r e a t m e n t o f these a r r h y t h m i a s has saved the lives of m a n y o f these patients whose hearts were t o o g o o d to die. In s o m e patients with s u b a r a c h n o i d h e m o r r h a g e the m e c h a n i s m o f d e a t h is the d e s t r u c t i o n o r c o m p r e s s i o n o f vital centers in the brain. O n the o t h e r h a n d there is often little o r no evidence o f focal b r a i n d a m a g e in patients dying f r o m suba r a c h n o i d h e m o r r h a g e . The m e c h a n i s m o f their deaths m a y well be the occurrence o f life t h r e a t e n i n g c a r d i a c a r r h y t h m i a s , If cerebral d a m a g e is present very little can be d o n e for the patient. O n the o t h e r h a n d n o t h i n g can be lost a n d certainly no h a r m is d o n e b y treating these patients in the same way as patients suffering f r o m a m y o c a r d i a l infarction. P r e v e n t i o n o f c a r d i a s a r r h y t h m i a s b y the a d m i n i s t r a t i o n o f suitable drugs such as a t r o p i n e a n d b e t a - b l o c k i n g drugs a n d p r o m p t recognition a n d t r e a t m e n t of lifet h r e a t e n i n g d i s t u r b a n c e s of the c a r d i a c r h y t h m might save the lives o f patients whose b r a i n is t o o g o o d to die.
References 1. Abildskov, J. A., Millar, K., Burgess, M. J., et al.: The electrocardiogram and the central nervous system. Prog. Cardiovasc. Dis. 13, 210--216 (1970) 2. Baur, H. R., Pierach, C. A.: Electrocardiographic changes after bilateral carotid endarterect, ny. N. Eng. J. Med. 290, 1121--1122 (1974) 3. Beard, E. F., Robertson, J. W., Robertson, R. C. L.: Spontaneous subarachnoid hemorrhage simulating acute myocardial infarction. Am. Heart J. 58,755--759 (1959) 4. Burch, G. E., Calcolough, H., Giles, T.: Intracranial lesions and the heart. Am. Heart J. 80, 574--575 (1970) 5. Butch, G. E., Sun, S. C., Calcolough, H., et al.: Acute myocardial lesions. Following experimentally induced intracranial hemorrhage in mice: A histological and histochemical study. Arch. Path. 84, 517--521 (1967) 6. Byer, E., Ashman, R., Toth, L. A.: Electrocardiograms with large, upright T waves and long Q-T intervals. Am. Heart J. 33,796--906 (1947) 7. Connor, R. C. R.: Myocardial damage secondary to brain lesions. Am. Heart J. 78, 145--148 (1969) 8. Connor, R. C. R.: Fuchsinophilic degeneration of myocardium in patients with intracranial lesions. Brit. Heart J. 32, 81--84 (1970) 9. Cropp, G. J., Manning, G. W.: Electrocardiographic changes simulating myocardial ischemia an infarction associated with spontaneous intracranial hemorrhage. Circulation 22, 25--38 (1960) 10. Dinning, T. A. R., Falconer, M. A.: Sudden or unexpected natural death due to ruptured intracranial aneurysms. Survey of 250 forensic cases. Lancet 1953 II, 799--801 11. Eisalo, A., Perasalo, J., Halonen, P. I.: Electrocardiographic abnormalities and some laboratory findings in patients with subarachnoid haemorrhage. Brit. Heart J. 34, 217--226 (1972) 12. Estanol, B. V., Marin, O. S.: Cardiac arrhythmias and sudden death in subarachnoid hemorrhage. Stroke 8, 382--386 (1975) 13. Fentz, V., Gormsen, J.: Electrocardiographic patterns in patients with cerebrovascular accidents. Circulation 25, 22--28 (1962)
On the Mechanism of Sudden Death with Subarachnoid Hemorrhage
75
t4. Fuster, J. M., Weinberg, S. J.: Bioelectric changes of the heart cycle induced by stimulation of diencephalic regions. Exp. Neurol. 2, 26--39 (1960) 15. Groover, M. E. Jr., Stout, C.: Neurogenic myocardial necrosis. Angiology 16, 180--186 (1965) 16. Hall, R., Sybers, H., Greenhoot, J., et al.: Myocardial changes after hypothalamic stimulation in the intact, conscious dog (abstract). Circulation 46 (Suppl.II), 2--118 (1972) 17. Hammermeister, K. Eo, Reichenbach, D. D.: QRS changes, pulmonary edema, and myocardial necrosis associated with subarachnoid hemorrhage. Am. Heart J. 78, 94--100 (1969) 18. Harrison, M. T., Gibb, B. H.: Electrocardiographic changes associated with a cerebrovascular accident. Lancet 1964 II, 429 19. Hawkins, W. E., Clower, B. R.: Myocardial damage after head trauma and simulated intracranial haemorrhage in mice: The role of the autonomic nervous system. Cardiovasc. Res. 5, 524--529 (1971) 20. Hersch, C.: Electrocardiographic changes in subarachnoid haemorrhage, meningitis, and intracranial space-occupying lesions. Brit. Heart J. 26, 785--793 (1964) 21. Hockman, C. H., Mauck, H. P. Jr., Hoff, E. C.: ECG changes resulting from cerebral stimulation. II. A spectrum of ventricular arrhythmias of sympathetic origin. Am. Heart J. 71,695--700 (1966) 22. Hoffbrand, B. I., Morgan, B. D. G.: Functional significance of electrocardiographic changes associated with subarachnoid haemorrhage. Lancet 1965 I, 844--845 23. Hugenholtz, P. G.: Electrocardiographic abnormalities in cerebral disorders. Report of six cases and review of the literature. Am. Heart J. 63, 451--460 (1962) 24. Hunt, D., McRae, C., Zapf, P.: Electrocardiographic and serum enzyme changes in subarachnoid hemorrhage. Am. Heart J. 77,479--488 (1969) 25. Hunt, D., Gore, L.: Myocardial lesions following experimental intracranial hemorrhage: Prevention with propranolol. Am. Heart J. 83,232--236 (1972) 26. Jacobson, S. A., Danufsky, P.: Marked electrocardiographic changes produced by experimental head trauma. J. Neuropath. Exp. Neurol. 13,462--466 (1954) 27. Klouda, M. A., Brynjolfsson, G.: Cardiotoxic effects of electrical stimulation of the stellate ganglia. Ann. NY Acad. Sci. 156,271--280 (1969) 28. Korteweg, G. C. J., Boeles, J. T. F., TenCate, J.: Influence of stimulation of some subcortical areas on electrocardiogram. J. Neurophysiol. 20, 100---107 (1957) 29. Koskelo, P., Punsar, S., Sipil~i,W.: Subendocardial haemorrhage and ECG changes in intracranial bleeding. Br. Med. J. 19641, 1479--1480 30. Kreus, K. E., Kemil~i,S. J., Takala, J. K.: Electrocardiographic changes in cerebrovascular accidents. Acta reed. Scand. 185, 327m334 (1969) 31. Krikler, D. M., Curry, P. V. L: Tosades de pointes, an atypical ventricular tachycardia. Brit. Heart J. 38, 117 (1976) 32. Manning, J. W., Cotten, M. de V.: Mechanism of cardiac arrhythmias induced by diencephalic stimulation. Am. J. Physiol. 203, 1120--1124 (1962) 33. Manning, G. W., Hall, G. E., Banting, F. G.: Vagal stimulation and the production of myocardial damage. Canad. Med. Assoc. J. 37, 314~318 (1937) 34. Mauck, H. P., Hockman, C. H., Hoff, E. C.: ECG changes after cerebral stimulation. 1. Anomalous atrioventricular excitation elicited by electrical stimulation of the mesencephalic reticular formation. Am. Heart J. 68, 98--101 (1964) 35. Mauck, H. P. Jr., Szumski, A. J., Fu, T.-C., et al.: The effect of acute hypoxia on cardiac dysrhytmias induced by mesencephalic stimulation. Am. Heart J. 87, 197--202 (1974) 36. Melville, K. L., Blum, B., Shister, H. E., et al.: Cardiac ischemic changes and arrhythmias induced by hypothalamic stimulation. Am. J. Cardiol. 12, 781--79I (1963) 37. Menon, I. S.: Electrocardiographic changes stimulating myocardial infarction in cerebrovascular accident. Lancet 1964 II, 433--434 38. McNoir, J. L., Clower, B. R., Sanford, R. A.: The effect of reserpine pretreatment on myocardial damage associated with simulated intracranial hemorrhage in mice. Europ. J. PharmacoL 9, 1--6 (1970) 39. Milar, K., Abildskov, J. A.: Notched T-waves in young persons with central nervous system lesions. Circulation 27, 597---603 (1968)
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40. Mott6, G., Coumel, P. H., Ablitol, G., Desertenne, F., Slama, R.: Le syndrome QT long et syncopes par torsade de pointe. Arch. Mal Coeur 6, 831 (1970) 41. Offerhaus, I., Van Gool, J.: Electrocardiographic changes and tissue catecholamines in experimental subarachnoid hemorrhage. Cardiovasc. Res. 3,433--440 (1969) 42. Oury, M.: Le ph6nom~ne de "tosade de pointe". Revue M~dicale de Liege 28, 221 (1973) 43. Parizel, G.: Life threatening arrhythmias in subarachnoid hemorrhage. Angiology 24, 17--21 (1973) 44. Pfister, C. W., de Panda, B.: Cerebral hemorrhage simulating acute myocardial infarction. Dis. Chest 42, 206--207 (1962) 45. Porter, R. W., Komikowa, K., Greenhoot, J.: Persistent electrocardiographic anormalities experimentally induced by stimulation of the brain. Am. Heart J. 64, 815--819 (1962) 46. Ranquin, R., Parizel, G.: Ventricular fibrilloflutter ("Torsade de pointe"): an established electrocardiographic and clinical entity. Angiology 28, 115--117 (1977) 47. Russell, A. S.: The association of subarachnoid haemorrhage with abnormal electrocardiogram and acute pulmonary edema. Guy's Hosp. Rep. 115, 463--474 (1966) 48. Schenk, E. A., Moss, A. J.: Cardiovascular effects of sustained norepinephrine infusions. II. Morphology. Circulation Research 13, 605--615 (1966) 49. Scott, R. C.Y: Electrocardiographic changes in intracranial hemorrhage. J. electrocardiol. 2, 193--196 (1969) 50. Secher-Hansen, E.: Subarachnoidal hemorrhage and sudden unexpected death. Acta neurol. Scand. 40, 115--130 (1964) 51. Shuster, S.: The electrocardiogram in subarachnoid haemorrhage. Brit. Heart J. 22,316--320 (1960) 52. Smith, M., Ray, C. T.: Cardiac arrhythmias, increased intracranial pressure and the autonomic nervous system. Chest 61 (Suppl.), 125--133 (1972) 53. Smith, M.: Ventricular bigeminy and quadrigeminy occurring in a case of subarachnoid hemorrhage. J. Electrocardiol. 5, 78--85 (1972) 54. Smith, R. P., Tomlinson, B. E.: Subendocardial hemorrhages associated with intracranial lesions. J. Path. 68, 327--334 (1954) 55. Srivastava, S. C., Robson, A. O.: Electrocardiographic abnormalities associated with subarachnoid haemorrhage. Lancet 1964 II, 431--433 56. Surawicz, B.: Electrocardiographic pattern of cerebrovascular accident. JAMA 197, 913-914 (1966) 57. Szakacs, J. E., Cannon, A.: Norepinephrine myocarditis. Am. J. Clin. Path. 30,425--434 (1958) 58. van Bogaert, A., Selosse, P.: R61e du lobe frontal c~r~bral dans la gen~se des r6actions cardiovasculaires et ~lectrocardiographiques de l'h~morragiem+ning~e. Arch. Mal Coeur 65, 351--359 (1972) 59. Van Viet, P. D., Burchell, H. B., Titus, J. L.: Focal myocarditis associated with pheochromocytoma. New Eng. J. Med. 274, 1102--1108 (1966) 60. Wasserman, F., Choquette, G., Cassinelli, R., et al.: Electrocardiographic observations in patients with cerebrovascular accidents. Am. J. Med. Sci. 231,502--510 (1956) 61. Weinberg, S. J., Fuster, J. M.: Electrocardiographic changes produced by localized hypothalamic stimulations. Ann. Int. Med. 53, 332--341 (1960) 62. Weintraub, B. M., MacHenry, L. C. Jr.: Cardiac abnormalities in subarachnoid hemorrhage: A resum6. Stroke 5, 384--392 (1974) Received July 27, 1978
J.Neurol. 220, 71--76 (1979)
tqeurology ~) by Springer-Verlag 1979
Surveys of Progress On the Mechanism of Sudden Death with Subarachnoid Hemorrhage G. Parizel Department of Medicine, Middelheim Hospital, Lindendreef. 2, B-2020 Antwerp, Belgium
Summary. The mechanism of death in some patients with subarachnoid hemorrhage is cardiac arrhythmia. Prevention of cardiac arrhythmias by suitable drugs might save the life of patients whose brain is still good. Key words: Subarachnoid hemorrhage - Cardiac arrhythmias-Death sudden. Zusammenfassung. Als Ursache fiir den Tod in manchen Fallen von Subarachnoidalblutung muB eine Herzrhythmusst6rung angesehen werden. Eine Prophylaxe von Arrhythmien durch entsprechende Medikamente kann das Leben mancher dieser Patienten, deren Him noch funktionsttichtig w~ire, retten.
Mortality in patients with subarachnoid hemorrhage and especially sudden death, in spite of advances in diagnosis and treatment, remains distressingly high. Sudden death due to subarachnoid hemorrhage is also not uncommon; it accounts for 4--5% of all natural sudden deaths. In a series of autopsy-proven cases of subarachnoid hemorrhage only 40% had survived long enough to reach hospital and more than half of these died shortly after admission [10, 50]. Until recently it seemed logical to attribute the death of these patients to their central nervous system (CNS) lesions. However in a number of patients dying of subarachnoid hemorrhage remarkably few lesions of the CNS were found. This paucity of specific lesions in the CNS makes one speculate about other possible mechanism to explain the death of these patients. We have recently shown that life-threatening cardiac arrhythmias can occur in patients with subarachnoid hemorrhage [43]. When not promptly recognized and treated (which is unfortunately usually the case outside the hospital) these cardiac arrhythmias may welt be the cause of death especially of those patients in whom postmortem examination discloses only minimal CNS lesions. The relation between cardiac complications and CNS lesions has been known for quite some time. 0340-5354/79/0220/0071/$01.20
72
G. Parizel
Abnormalities of the electrocardiogram in patients with CNS diseases were first described in 1947 [6]. Numerous reports have confirmed these findings since then [1, 3, 6, 11, 13, 17, 18, 20, 22--24, 29, 30, 37, 39, 44, 47, 49, 51,55, 60, 62]. The pertinent ECG changes found in patients with CNS lesions, and especially subarachnoid hemorrhage, are abnormalities of the ST-T deflections: large upright or deeply inverted T waves, prolongation of the Q-T interval and prominent U waves. These ECG abnormalities often resemble those of ischemic heart disease and can sometimes be so pronounced as to suggest myocardial infarction [3,9,44]. This confusion could have unfortunate therapeutic consequences such as the administration of anticoagulants. The frequency, timing and duration of these ECG abnormalities have not been sufficiently documented. In our experience ECG changes can occur as late as 8 days after the first clinical manifestation of subarachnoid hemorrhage. There have been conflicting reports with regards to the question whether these ECG abnormalities are related to structural changes in the myocardium or not. Subendocardial hemorrhage, as well as microscopic lesions, have been described in patients dying of subarachnoid hemorrhage [7, 8]. These findings have been confirmed in experimental animals. There is now sufficient clinical evidence that the cardiac abnormalities found in patients with subarachnoid hemorrhage are not a fortuitous coincidence. Numerous studies have been undertaken in order to reproduce these clinical findings in the experimental animal. Experimental evidence indicates that both the sympathetic and parasympathetic nervous systems are implicated in the production of myocardial lesions following intracranial lesions. Electrical stimulation of the vagus nerve produces myocardial damage which can be prevented by the administration of atropine [33]. Similarly intravenous administration of acetylcholine produces focal myocardial necrosis or frank infarction. There is also evidence that lesions similar to those found with subarachnoid hemorrhage can be produced in the myocardium by intravenous administration of cathecholamines in the experimental animal [48,57]. Similar lesions have been demonstrated in patients treated with intravenous infusions of norepinephrine for shock [57]. Necrosis of the myocardium has also been described in patients dying of phaeochromocytoma [59]. Cardiotoxic effects of electrical stimulation of the stellate ganglia producing subendocardial hemorrhage and focal myocardial necrosis have also been described [27]. The experimental production of intracranial hemorrhage in animals has also produced myocardial damage [5, 25,41]. Other interventions in the experimental animal such as head trauma [26], intraventricular air insufflation, hypothalamic stimulation [16] can produce similar myocardial damage [58,45,28]. Striking electrocardiographic changes simulating myocardial infarction have also been observed in patients who had undergone bilateral carotid endarterectomy [2]. Numerous experiments have also shown the relation in the experimental animal between intracranial lesions and cardiac arrhythmias. Cardiac arrhythmias have been observed after the production of experimental subarachnoid hemorrhage in animals. Cardiac arrhythmias have also been produced by rapid changes of intracranial pressure [52]. Administration of atropine and vagotomy eliminated or prevented these arrhythmias.
On the Mechanism of Sudden Death with Subarachnoid Hemorrhage
73
Electrical stimulation of several cartical and subcortical areas has been shown to produce cardiac arrhythmias some of which are comparable to those seen in our patients [14, 21,32, 34, 35, 52]. Both the sympathetic and parasympathetic nervous system seem to play an important part in the production of the cardiac arrhythmias in these experimental procedures [15]. In spite of the numerous reports on the ECG changes and the numerous animal experiments scarcely any attention was paid to the occurrence of serious disturbances of cardiac rhythm in patients with subarachnoid hemorrhage prior to our report [43]. In 1973 we described two patients with subarachnoid hemorrhage who both presented life-threatening ventricular arrhythmias. Their ECG showed the typical abnormalities described for this condition. Prompt recognition and treatment of these arrhythmias was life-saving. It is also significant that both patients had an initial syncope and that no neurological abnormalities apart from the meningeal signs were found [43]. A whole range of cardiac arrhythmias has been described by different investigators in their animal experiments: premature ventricular beats, nodal rhythm; A-V block, ventricular tachycardia and fibrillation, pre-excitation pattern. One of our patients also manifested several different arrhythmias. It "is evident that not one single mechanism is responsible for such widely different cardiac arrhythmias. Some of these are probably due to the intervention of the autonomic nervous system on the impulse formation and conduction of the heart and do not necessarily imply structural changes. On the other hand the prolongation of the Q-T interval of the ECG in these patients seems to be an important factor in the causation of life-threatening ventricular arrhythmias. We assume that prolongation of the Q-T interval certainly plays an important part in the production of the ventricular arrhythmias in patients with subarachnoid hemorrhage, The long Q-T interval is due to diffuse disturbances in the repolarization of the myocardium. This causes an unequal duration of the refractory period in the different myocardial fibers favoring the reentry phenomenon and the development of ventricular dysrhythmias. Recently attention has been drawn to a particular ventricular dysrhythmia occuring in patients with a long Q-T interval called "torsade de pointe" [31,40,46] which must be distinguished from the common forms of ventricular tachycardia or ventricular fibrillation for etiological, morphological and therapeutic reasons. This arrhythmia, which we proposed to call "ventricular fibrilloflutter" [46] has been seen in patients with subarachnoid hemorrhage [42, 43]. The criteria for diagnosis of ventricular fibrilloflutter are: -
-
-
-
long Q-T interval during normal ryhthm the QRS complexes of the arrhythmia appear to twist around the isoelectric line, hence the application "torsade de pointe" in French the arrhythmia is triggered by late ventricular extrasytoles the attacks are of variable duration. Often they are short spontaneously resolving and recurring. When of sufficiently long duration they produce syncope (this may be the explanation of the syncope frequently seen in patients with subarachnoid hemorrhage). in some cases the arrhythmia persists and degenerates into fatal ventricular fibrillation.
74
G. Parizel
W i t h r e g a r d to s u b a r a c h n o i d h e m o r r h a g e an a n a l o g y can be m a d e with m y o cardial infarction. In some victims o f m y o c a r d i a l infarction the d a m a g e o f the m y o c a r d i u m is so extensive t h a t they die o f p u m p failure a n d cardiogenic chock. T h e r a p y in these cases is usually o f no avail. O n the o t h e r h a n d patients with quite small m y o c a r d i a l infarctions die, not because of p u m p failure, b u t because o f fatal c a r d i a c a r r h y t h m i a s . We k n o w that p r e v e n t i o n by a n t i - a r r h y t h m i c drugs a n d the p r o m p t r e c o g n i t i o n a n d t r e a t m e n t o f these a r r h y t h m i a s has saved the lives of m a n y o f these patients whose hearts were t o o g o o d to die. In s o m e patients with s u b a r a c h n o i d h e m o r r h a g e the m e c h a n i s m o f d e a t h is the d e s t r u c t i o n o r c o m p r e s s i o n o f vital centers in the brain. O n the o t h e r h a n d there is often little o r no evidence o f focal b r a i n d a m a g e in patients dying f r o m suba r a c h n o i d h e m o r r h a g e . The m e c h a n i s m o f their deaths m a y well be the occurrence o f life t h r e a t e n i n g c a r d i a c a r r h y t h m i a s , If cerebral d a m a g e is present very little can be d o n e for the patient. O n the o t h e r h a n d n o t h i n g can be lost a n d certainly no h a r m is d o n e b y treating these patients in the same way as patients suffering f r o m a m y o c a r d i a l infarction. P r e v e n t i o n o f c a r d i a s a r r h y t h m i a s b y the a d m i n i s t r a t i o n o f suitable drugs such as a t r o p i n e a n d b e t a - b l o c k i n g drugs a n d p r o m p t recognition a n d t r e a t m e n t of lifet h r e a t e n i n g d i s t u r b a n c e s of the c a r d i a c r h y t h m might save the lives o f patients whose b r a i n is t o o g o o d to die.
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