A Rare Case of Recurrent Vasodepressive Attacks of 2-Hours Duration: Analysis of the Mechanism by Muscle Sympathetic Nerve Activity Recording

Transcription

1 Clin. Cardiol. 12, (1989) A Rare Case of Recurrent Vasodepressive Attacks of 2-Hours Duration: Analysis of the Mechanism by Muscle Sympathetic Nerve Activity Recording A. YATOMI, M.D., A. IGUCHI, M.D., K. UEMURA, M.D., N. SAKAMOTO, M.D., s. IWASE, M.D., T. MANO, M.D. Third Department of Internal Medicine, Nagoya University School of Medicine, and Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan Summary: Muscle sympathetic nerve activity was recorded in a 57-year-old male patient suffering from severe hypotensive attacks with bradycardia for 10 years. Continuous blood pressure recording demonstrated frequent drastic falls in pressure. Disappearance and reappearance of muscle sympathetic nerve activity coincided with the onset and termination of attacks. Awakening from sleep or emotional and/or cardiovascular stress seems to trigger hypotension. Cardiac pacemaker was not useful in limiting the attack, because right ventricular pacing caused abrupt falls in both blood pressure and heart rate. Key words: orthostatic hypotension, vasodepressive syncope, muscle sympathetic nerve activity Introduction Orthostatic hypotension and vasovagal or vasodepressive syncope are well known conditions which induce sudden falls of blood pressure. Since Bradbury and Eggleston collected sufficient data to describe orthostatic hypotension as a syndrome, many facts have been clarified about its functional causes. Several permanent and often progressive neurologic disorders are known to interfere with necessary reflexes and orthostatic blood pressure control. Vasodepressive syncope is a common type of syncope and various mechanisms have been postulated as explanations Address for reprints: Nobuo Sakamoto, M.D. Third Department of Internal Medicine Nagoya University School of Medicine 65 Tsuruma-cho Showa-ku, Nagoya 466, Japan Received: June 14, 1988 Accepted with revision: October 14, 1988 of the characteristic association of hypotension and bradycardia. The patient in our study of severe recurrent longstanding hypotensive attacks has some characteristics in common with those observed in patients with orthostatic hypotension in sudden fall of blood pressure. However, this case must represent a different condition from orthostatic hypotension because hypotensive attacks occur even when he assumes a supine position and compensatory mechanism never works for longer than 2 hours. Rather, the observation that hypotension always accompanies bradycardia should be noted for its resemblance to vasodepressive syncope. To gain some insight into the mechanism of hypotensive attacks lasting more than 2 hours, we recorded the patient s muscle sympathetic nerve activity. Methods and Results After informed consent had been obtained from the patient, heart rate, blood pressure, muscle sympathetic nerve activity, respiration curve, and plethysmography of the left thigh were continuously recorded for 9 hours. The 57-year-old patient was hospitalized because of recurrent attacks of syncope. He had been well until 10 years before, when he experienced the first attack of hypotension with bradycardia. Thereafter, he had attacks of severe hypotension with bradycardia once or twice daily. He has wide swings in blood pressure (Figs. 1 and 2) and attacks occur suddenly without any prodromal symptom. Attacks have no close correlation to circadian rhythm, posture, micturition, coughing, or swallowing. Within a few seconds heart rate falls from to beatdmin, and systolic blood pressure from to mmhg. During attacks, he is forced to lie down and assume Trendelenburg s position. The onset of severe attack is sometimes accompanied by profuse sweating over his upper trunk. An episode lasts for 1 to 2 hours, and recovery is spontaneous and complete within one minute, without any neurological deficit,

2 A. Yatomi et al. : Muscle sympathetic activity in a vasodepressive case 165 Blood sampling for catecholamines y1-.--??p ~ A i h A 4. LA -- * * SS se 01 sg 70 r u) 60 f jb 3fip)pv\%wLyFJmr ++h 4 J-A;?-.;~+-#+ 1o:oo 11:oo 12:oo l:oo 2:OO 3:OO 3:OO 4:OO :OO 7:20 A.M. P.M. FIG 2 Blood pressure and heart rate record. The patient felt FIG. 1 Blood pressure and heart rate recorded with an automated drowsy after 3:OO. Arrows indicate timing of blood sampling for sphygmomanometer. Note the frequent variations in systolic and diastolic pressure during and after lunch (12:25-12:55) and during insertion of the second needle (1: 15-2:07) to resume muscle sympathetic nerve activity recording. catecholamines. Blood pressure and heart rate decreased synchronously with blood collection or speaking to the patient. At 4:49 a long attack began without any known triggering event. It lasted for more than 2 hours, ending at 7: P4.4 Resting levels of catecholamines on admission were normal. Plasma TS, T4, renin activity (in the morning on supine position), and aldosterone were normal. Urine 24-h excretion of 17-oxyhemoglobin corticosteroids and 17- ketosteroids were also normal. Blood gas analysis was normal even during an attack. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain revealed no abnormality. Electroencephalography during an attack showed nonspecific change. Standard 12-lead electrocardiogram revealed sinus bradycardia. Echocardiogram did not show cardiac abnormalities. Bedside testing of autonomic function demonstrated normal response during attack-free periods; systolic overshoot during Valsalva s maneuver. Parented administration of a-adrenergic agonist (etifermine HCl), 6-adrenergic agonist (isoproterenol), dopamine, and cholinergic muscarinic antagonist (atropine sulfate) was useful in limiting the attack, but none of the drugs per 0s proved effective. On temporary cardiac pacing at rates of 60,90, and 100 beatsimin, blood pressure fell after a few beats of pacing, with concomitant bradycardia, which made the patient anxious and made continuation of pacing impossible (Fig. 3). Even more interesting was that blood pressure and heart rate fell temporarily when the physicians merely announced the start of pacing (Fig. 3, arrowheads). For recording of muscle sympathetic nerve activity, the patient was asked to lie down on a tilting bed during the examination. Blood samples were collected from an indwelling catheter in a cephalic vein and plasma catecholamines were determined with high-performance liquid chromatography with electrochemical detector (Table I). A tungsten microelectrode (tip diameter lpm and impedance 3-5 Ma) was inserted at 1O:OO A.M. into the muscle nerve fascicle of the tibial nerve in the right popliteal fossa as described el~ewhere.~ Muscle sympathetic nerve activity was identified by four criteria: (1) efferent activity from the muscle nerve fascicle, (2) spontaneous and pulsesynchronous rhythmic bursts, (3) modulation by respiration, increasing activity during inspiration and decreasing during expiration and, (4) marked accentuation by Valsalva s maneuver. The sympathetic nerve signals were passed through a high impedance input preamplifier (WP Instruments DAMdA) and monitored on a cathode ray oscilloscope (Tektronizd 113). The arterial blood pressure was measured at intervals of 1 to 10 minutes using an autosphygmomanometer (Nippon Colin BP-203NP). The electrocardiogram and respiration were also monitored (Nihon Kohden MZE-6100). All data were recorded continuously from 1O:OO to 7:20 P.M. in a multichannel tape recorder (Sony-Magnescale KS-616U). From 1O:OO A.M. to 12:OO P.M., blood pressure and heart rate were stable. Brief falls of blood pressure were Announcement v Cardiac pacing o 0 2:OO 2:30 3:OO FIG. 3 Blood pressure and heart rate recorded during cardiac pacing. Note the fall of blood pressure and heart rate in synchrony with cardiac pacing or even the mere announcement of the commencement of the procedure. o n

3 1 66 Clin. Cardiol. Vol. 12, March 1989 TABLE I Plasma catecholamine levels at rest and during hypotensive attack No." Sampling time Epinephrine (pg/ml) Norepinephrine (pg/ml) 1 12: : : : : : : : "Numbering of sampling times is the same as in Figs. 1 and 2. observed during and after lunch (12:25-12:55), when the patient was allowed to sit up and the needle was removed, and during insertion of the second needle to resume muscle sympathetic nerve activity recording (1 : 15-2:07). The patient, on a tilting bed, complained of sleepiness and occasionally took short naps. Fall in blood pressure occurred frequently, especially when the examiner told the patient, while he was dozing, that blood samples would be collected. On blood collections at 3:06 and 4: 15, both blood pressure and heart rate fell (Fig. 2). At 4:50, while the patient was talking with the examiner, blood pressure and heart rate suddenly began to fall and did not recover for 2 hours. Figure 4 depicts polygraphic recording of muscle sympathetic nerve activity and other circulation-related factors for a brief attack at 2:21. Muscle sympathetic nerve activity bursts suddenly disappeared, blood pressure and heart rate decreased, and decrease and stagnation of blood flow caused by vasodilation followed 20 s later. Regular respiration ceased at the onset of the attack. Suppressed muscle sympathetic nerve activity bursts reappeared after 3 minutes and the attack terminated. A long attack of 2 hours duration (Fig. 2) showed the same pattern of disappearance and reappearance of muscle sympathetic nerve activity, in synchrony with the onset and termination of the attack (data not shown). Discussion From clinical evidence the patient's condition might be classified as vasodepressive reaction, but we could not find 1 23/75 86/54 Blood pressure 1 min FIG, 4 Muscle sympathetic nerve activity (MSA) recorded during a brief hypotensive attack. From top to bottom: plethysmography of left thigh, instantaneous heart rate, respiration, integrated muscle sympathetic nerve activity, and blood pressure. Muscle sympathetic nerve activity disappeared at the onset of the attack, followed by hypotension and bradycardia. Muscle sympathetic nerve activity reappeared at the end of attack.

4 A. Yatomi et al.: Muscle sympathetic activity in a vasodepressive case 167 any similar case of a 2-hour attack in a survey of the literature. This is an extremely rare case. One of our main findings is the pattern of muscle sympathetic nerve activity disappearance at the onset and reappearance at the termination of the attack; the same, except for the duration of the attack, as observed by Wallin et al.' in the case of vasodepressive syncope caused by glossopharyngeal neuralgia. They introduced the method of muscle sympathetic nerve activity recording in the sympathetic fibers of the peroneal muscle for analysis of vasodepressive reaction and noted an abrupt cessation of electrical activity at the onset of the syncope. In a study of vasodepression cases, Epstein et al6 reported that, in addition to hypotension and bradycardia, an invariable finding was dilatation of the resistant vessel of skeletal muscles. It has not been made clear whether vasodepressor hypotension is associated with a pattern of mixed sympathetic withdrawal and activation, or predominantly with sympathetic withdnwal. If the attack is due to vagal stimulation alone, then subjects with vasodepressor response should show greater increases than normal in plasma norepinephrine levels because hypotension stimulates reflex sympathetic nervous activity7 and low cardiac output increases plasma norepinephrine and epinephrine levels. * However, the vasodepressor subjects reportedly have decreased plasma norepinephrine levelsg and the same norepinephrine decrease during the attack was observed in our patient (Table I). Therefore, withdrawal of sympathetic nervous activity probably combined with an increase in vagal nervous activity to cause vasodepressive hypotension. On the other hand, sympathetic nervous activity temporarily augmented just before the onset of the attack and sweating is caused by sympathetic cholinergic activation. These studies and the muscle sympathetic nerve activity recordings in our patient suggest that attacks of hypotension with bradycardia are induced by vasodepressive reaction with sympathetic withdrawal. The major remaining question is what is the triggering factor? Pain and emotional stress seem to be closely related to the initiation of an attack. Fluctuations in blood pressure during the second needle insertion could be a vasovagal response to pain because it was more difficult and took more time to achieve than the first insertion. Blood collection of only 10 ml would not per se initiate hypotensive attack, but it is possible that it causes emotional stress. On cardiac pacing, fear response caused by the announcement of the start of the procedure may have triggered vasodepressive hypotension. The falls in blood pressure and heart rate immediately after cardiac pacing can be explained by cessation of sympathetic outflow, resulting in vasodilation. The combination of peripheral vasodilation and the powerful contractions of the heart could be the mechanism triggering hypotension. This is compatible with the hypothesis of the activation of left ventricular receptors in vasovagal syncope proposed by Oberg and ThorCn.Io In addition to pain- and fear-invoked responses, a very suggestive observation was that speaking to the patient, with or without blood collection, when he felt drowsy on the tilting bed seemed to induce brief attacks. Judging from the fact that attacks frequently occurred soon after waking in the morning or afternoon, it seems likely that sympathetic stimulation with a background of parasympathetic predominance cause imbalance of sympathetic and parasympathetic tones, resulting in vasodepressive attack. Brevetti et al. I 1 reported the relationship between blood pressure, sleep, and waking through 24-h continuous blood pressure recording in patients with orthostatic hypotension. They observed that blood pressure rises progressively in the early hours of the morning before waking and abruptly falls at the moment of arousal, which they considered a paradoxical response of blood pressure to activation of the sympathetic nervous system. For our patient, we consider that at the moment of arousal his sympathetic nervous tone is increased, but reactive parasympathetic activity overcomes the sympathetic activity to initiate an attack. Once an attack occurs, nerve impulses coming from the upper center of blood pressure regulation, namely the cerebral cortex, the limbic system, and the hypothalamus, may continue to stimulate the vasomotor center in the medulla oblongata to activate vagal tone and simultaneously inhibit sympathetic outflow to the heart and peripheral vessels for 2 hours. Termination of the attack seems to result from the inhibiting discharges having worn off, because the patient has a lengthy attack only after 10 hours or so have passed after the preceding long attack. The fact that attacks began suddenly 10 years ago suggests that some cerebrovascular accident occurred at that time which produced no other neurological deficit; however, we have no evidence for this on the CT or MRI examination, and if this is so, how this incident could cause disorders continuously stimulating the vasodepressor center remains unknown. We presume emotional stimuli, in the broad sense of the word, to be the triggering factor for hypotensive attack in our patient. However, usually we are not able to predict exactly what emotional stimulus will trigger an attack; certain emotional stresses trigger a hypotensive attack at certain times but not at other times. This leads us to another consideration: an attack had already begun at 12: 10, reflexogenic sympathetic activity, as shown by the increased heart rate at 12:20, maintained normal blood pressure and heart rate for more than 4 hours, but this effort failed at last at 4:49, causing a long attack. Possibly, after 12: 10, the vasomotor center might be vulnerable to various stimuli such as sitting, blood collection, or talking. These hypotensive events do not contradict our hypothesis, but the primary triggering factor at 12: 10 still remains to be solved. Acknowledgrnen t We wish to thank the patient for his cooperation, and Dr. Naito, Dr. Yanagisawa, Dr. Kurimoto, and Dr. Goshi-

5 168 Clin. Cardiol. Vol. 12, March 1989 ma for providing clinical information and Miss Satake for preparing the manuscript. References 1. Bradbury S, Eggleston C: Postural hypotension: A report of three cases. Am Heart J 1, 73 (1925) 2. Shy DM, Drager GA: A neurological syndrome associated with orthostatic hypotension: A clinical-pathologic study. Arch Neurot 2, 511 (1960) 3. Lewis T: Vasovagal syncope and carotid sinus mechanism. Br Med J 1, 873 (1932) 4. Kachi T, Iwase S, Mano T, Saito M, Kunimoto M, Sobue I: Effect of L-threo-hydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome. Neurology (Cleveland) 38, 1091 (1988) 5. Wallin BG, Westerberg CE, Sundlof G: Syncope induced by glossopharyngeal neuralgia: Sympathetic outflow to muscle. Neurology (Cleveland) 34, 522 (1984) 6. Epstein SE, Stampfer M, Beiser GD: Role of the capacitance and resistant vessels in vasovagal syncope. Circulation 37, 524 ( 1968) 7. Wallin BG: Sympathetic activity in human extremity nerves and its relationship to plasma norepinephrine. In Norepinephrine. (Eds. Ziegler MG, Lake CR). Williams and Wilkins, Baltimore (1984) Ziegler MG, Milano AJ, Hull E: The catecholaminergic response to stress and exercise. In Catecholamines in Psychium'c and Neurologic Disorders. Butterworth, Boston (1985) Ziegler MG, Echon C, Wilner KD, Specho P, Lake CR, McCuthen JA: Sympathetic nervous withdrawal in the vasodepressor (vasovagal) reaction. J Auton New Sysr 17,273 (1986) 10. Oberg B, Thordn P: Increased activity in left ventricular responses during hemorrhage or occlusion of caval veins in the cat-a possible cause of the vasovagal reaction. Acfa Physiol Scand 85, 164 (1972) 11. Brevetti G, Chiaroello M, Bonaduce D, Carmnico V, Breglio R: 24-hour blood pressure recording in patients with orthostatic hypotension. Clin Cardiol 8, 406 (1985)