Carotid sinushypersensitivity

Research Paper Clinical Autonomic Research 2, 389-392 (1992)

CAROTID sinus reflex hypersensitivity is a known cause of syncope in humans. The condition is characterized by cardioinhibition and vasodepression, each to varying degrees. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersensitivity. This study reports on the extent of sym- pathoinhibition measured directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hypersensi- tivity. Carotid massage elicited asystole, hypotension and complete inhibition of muscle sympathetic nerve activity. Carotid massage during atrioventricular pacing produced similar sympathoinhibition, but with minimal hypoten- sion. Therefore, sympathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position in this patient. Further investigations are required to elucidate the relation of sympathoinhibi- tion to hypotension in patients with carotid sinus hyper- sensitivity in the upright position.

Key words: Syncope, Sympathetic nervous system, Asystole, Carotid baroreflex

Sympathoinhibi t ion and hypotension in carotid sinus hypersensitivity

M i c h a e l L. S m i t h , PhD cA'•, K e n n e t h A. E l lenbogen, MD and D w a i n L. Eckberg, MD

Departments of Medicine and Physiology, Hunter Holmes McGuire Department of Veterans Affairs Medical Center and Medical College of Virginia, 1201 Broad Rock Blvd., Richmond, Virginia 23249, USA.

*Present Address: Division of Cardiology, Case Western Reserve University, 2074 Abington Road, Cleveland, Ohio 44106, USA.

CACorresponding Author

Introduction Carotid sinus reflex hypersensitivity is a re-

cognized cause of paroxysmal dizziness and syncope. This condition may be primarily cardioin- hibitory (sinus slowing or atrioventricular block), vasodepressor (hypotension with minimal cardiac slowing), or mixed cardioinhibitory and vasode- pressor. >4 In the mixed form, significant sinus slowing and hypotension occur with carotid massage, and significant hypotension persists when atrioventricular pacing is performed. The extent and importance of sympathoinhibition has not been determined in patients with carotid sinus hypersen- sitivity. We report on the extent of sympathoinhibi- tion measured directly during carotid massage with and without atrioventricular sequential pacing, in a patient with symptomatic carotid sinus reflex hyper- sensitivity.

Materials and Methods Studies were performed in one patient with

carotid sinus reflex hypersensitivity and five control subjects. Each subject gave written informed consent for this protocol which was approved by the committees for human research of the Medical College of Virginia and the Hunter Holmes McGuire Department of Veterans Affairs Medical Center.

A 65-year-old man with carotid sinus reflex hypersensitivity was evaluated for cardioinhibitory and vasodepressor manifestations of carotid sinus

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hypersensitivity. His symptoms included par- oxysmal dizziness and syncope associated with changes in head position, but not exertion or posture. The surface and intracardiac electrocardio- gram, brachial arterial pressure and efferent muscle sympathetic nerve activity s were measured contin- uously during right or left carotid massage for 8-10 s. Baseline data were collected during a 1 min control period prior to each carotid massage. Muscle sympathetic nerve activity is characterized by a pulse synchronous burst pattern during sinus rhythm. Changes in both burst incidence or amplitude reflect changes in total sympathetic activity. Left carotid massage was repeated with and without atrioventricular sequential pacing at cycle lengths of 500 and 600 ms. To help distinguish the contribution of sympathoinhibition and brady- cardia to the resulting hypotension, pacing was initiated in separate trials before (Fig. 1B, left panel) and after (Fig. 1B, right two panels) the onset of carotid massage. Carotid massage was repeated in triplicate for each condition. Five patients, without heart failure or previous myocardial infarction, referred for diagnosis of supraventricular tachy- cardia (age = 48-69 years) were studied as control subjects for carotid massage.

Results Control subjects. Figure 1A is a sample illustration of the modest responses to carotid massage in a control subject. Sympathetic responses varied from

Clinical Autonomic Research.vol 2-1992 389

M. L. Smith, K. A . Ellenbogen and D. L. Eckberg

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FIG. 1. Sample tracings of surface electrocardiogram, brachial arterial pressure and muscle sympathetic neurogram during left carotid massage in a control subject (panel 1A) and the study subject with and without atrioventricular pacing (panel 1B). Solid bars indicate periods of carotid massage. Arrows indicate periods of atrioventricular pacing. Middle panel illustrates pacing initiated after onset of carotid massage at a cycle length of 600 ms. Right panel illustrates pacing initiated prior to onset of carotid massage at a cycle length of 500 ms. Please note that two deflections in the sympathetic neurogram are artifacts (indicated by the extraordinary rate of deflection); these occur at 24 s in the middle panel of 1B and at 22 s of the right panel in lB.

modest increases to modest decreases during massage. In this group of control subjects, carotid massage produced moderate sinus cycle length slowing (mean 4- SE = 107 .4- 133 ms) and systolic pressure reduction (mean = - 7 + 4 mmHg). The peak change of sympathetic nerve activity during massage reflected a decrease from 7.1-t-1.3 bursts/10 s to 2.5 _ 3.2 bursts/10 s.

Patient with carotid sinus rejqex hypersensitivity. Results of left carotid message are summarized in Table 1. Left carotid massage without pacing produced sustained asystole (lasting 6 s before an escape beat occurred), a dramatic decrease in arterial pressure (systolic decreased from 144mmHg to below 60mmHg) and frank sympathoinhibition from 9.0 bursts/10 s to 0 bursts/10 s (Figure 1B, left panel). Pacing without carotid massage produced small increases of arterial pressure and moderate decreases of sympathetic nerve activity (Table 1, control data). Left carotid massage followed by atrioventricular pacing begun 3-5 s after the onset of asystole (Fig. 1B, middle panel) resulted in an initial abrupt fall in arterial pressure during asystole

(from 140/72 mmHg to 60 mmHg) followed by a rebound to near baseline levels during pacing (135/75 mmHg). Pacing prior to carotid massage resulted in a systolic pressure increase of 7--12

Table 1. Effects of left carotid massage and atrioventricular pacing on R-R interval, systolic pressure and muscle sympathetic nerve activity

No pacing Pacing cycle length

500 ms 600 ms

Control R-R interval (ms) 1120 500 600 Systolic pressure (mmHg) 144 151 155 Sympathetic nerve activity 9.1 3.0 2.5 (bursts/10 s)

Carotid Massage R-R interval (ms) asystole 500 600 Systolic pressure (mmHg) 57 135 141 Sympathetic nerve activity 0 0 0 (bursts/10 s)

Sympathetic nerve activity was recorded from efferent fibres of the peroneal nerve supplying muscle vasculature. Control pacing data are responses without carotid massage.

390 Clinical Autonomic Research.vol 2.1992

Carotid sinus hypersensitivity

mmHg followed by a decrease of 14-20 mmHg during carotid massage (Fig. 1B, right panel). Carotid massage produced frank and sustained sympathoinhibition regardless of pacing (Fig. 1B, all panels). Right carotid massage produced significant slowing of sinus cycle length (maximum slowing of 240-320ms), decreases of arterial pressure (maximum fall of 12-19mmHg) and decreases of sympathetic nerve activity (from 9.0 bursts/10 s to 1.3 bursts/10 s).

Discussion

Normal human responses to carotid baroreceptor st imulation include moderate cardiac slowing, evanescent sympathoinhibition and small decreases of arterial pressure, s'6 Our control subjects responded to carotid massage in a similar manner as normal subjects. In the patient with carotid sinus reflex hypersensitivity, left carotid massage pro- duced sustained ventricular asystole and frank inhibition of muscle sympathetic nerve activity; however, the sympathoinhibition was associated with only a small arterial pressure decrease when atrioventricular pacing accompanied carotid massage. Carotid massag e on the right side produced significant, but less profound responses (that is, asystole did not occur). Previous reports have shown that carotid sinus reflex hypersensi- tivity is commonly present on one side alone. 7'8 In this patient, the hypersensitivity appeared to be present on both sides, but was more pronounced on the left side.

These data suggest that in this patient, sympathoinhibition alone did not contribute importantly to hypotension during carotid sinus stimulation. Since sympathoinhibition is a normal response to carotid sinus stimulation, we speculate that sympathoinhibition occurs in most cases of carotid sinus hypersensitivity. However, our data suggest that the extent of vasodepression is dependent on factors other than the presence or absence of sympathoinhibition alone.

Three possible explanations are highlighted below. First, the extent of sympathoinhibition in different beds will determine in part the extent of hypotension. We show that sympathoinhibition in muscle vasculature of the legs contributed mini- mally to the hypotension in this patient. Sym- pathoinhibition in the splanchnic and renal vasculature may play a more important role since more than 25% of resting cardiac output is directed to these areas. Second, the background level of sympathetic nerve activity may influence the hypotensive effects of carotid sinus stimulation. Almquist and colleagues 3 found that infusion of a-adrenergic agonists reduced the hypotensive effects of carotid massage in hypersensitive patients.

The patient in our study had very high baseline sympathetic nerve activity (91 bursts/100 heart beats). Conditions in which sympathetic nerve activity is chronically elevated are associated with down-regulation of adrenergic receptors and impaired vasoconstrictor re-sponses. - n Thus, chronically high sympathetic nerve activity could be associated with altered norepinephrine kinetics or subnormal a-adrenergic receptor responsiveness which could influence the hypotensive outcome of carotid sinus stimulation.

Finally, body position (supine vs. upright) may determine the dependence of arterial pressure on vascular resistance. At rest, sympathetic nerve activity and vascular resistance may be 'relatively' low, such that reductions in sympathetic nerve activity and vascular resistance do not result in profound changes in arterial pressure. In the upright position, sympathetic nerve activity is augmented and vascular resistance is increased; hence, reductions in each variable may produce significantly greater decreases in arterial pressure than in the supine position. For example, epidural anaesthesia produces mild hypotension in the supine position, but profound hypotension with modest (30 °) upright tilting. 12 Patients with carotid sinus reflex hypersensitivity usually experience symptoms only in the upright position; therefore, it is possible that the sympathoinhibition we observed contributes significantly to hypotension in the upright position. This would be consistent with recent observations in a patient with the vasode- pressor form of carotid sinus hypersensitivity. 13

In conclusion, we report on a patient with carotid sinus reflex hypersensitivity who responded to carotid massage with asystole, inhibition of muscle sympathetic nerve activity and hypotension. The hypotension elicited by carotid massage during atrioventricular pacing was mild, despite marked sympathoinhibition. Hence, in this patient, sym- pathoinhibition did not contribute importantly to the hypotension during carotid massage in the supine position. These findings are provocative, but cannot be construed to represent the response of all patients with carotid sinus hypersensitivity. How- ever, these data do support speculation regarding the mechanisms of hypotension in carotid sinus

hypersensitivity which is worthy of further investigation.

R e f e r e n c e s

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2. Morley CA, Perrins E J, Grant P, Chan SL, McBrien D J, Sutton R. Carotid sinus syncope treated by pacing: analysis of persistent symptoms and the role of atrioventricular sequential pacing. Br Heart J 1982; 47:411418.

3. Almquist A, Gornick C, Benson DW, Dunnigan A, Benditt DG. Carotid sinus hypersensitivity: evaluation of the vesodepressor component. Circulation 1985; 71: 927-936.

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M. L. Smith, K. A . Ellenbogen and D. L. Eckberg

4. Stryjer D, Friedensohn A, Schlesinger Z. Carotid sinus hypersensitiv- ity: diagnosis of vasodepressor type in the presence of cardioinhibi- tory type. PACE 1982; 5: 793-800.

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11. Wilson JR, Frey M J, Mancini DM, Ferraro N, Jones, R. Sympathetic vasoconstriction during exercise in ambulatory patients with left ventricular failure. Circulation 1989; 79:1021-1027.

12. Ecoffey C, Edouard A, Pruszczynski W, Taly E, Samii K. Effects of epidural anesthesia on catecholamines, renin activity, and vaso- pressin changes induced by tilt in elderly men. Anesthesiol 1985; 62: 294-297.

13. Mathias C J, Armstrong E, Browse N, Chaudhuri KR, Eneroldson P, Ross-Russell R. Value of non-invasive continuous blood pressure monitoring in the detection of carotid sinus hypersensitivity. Clin Aut Res 1991 ; 1 : 157-1 59.

ACKNOWLEDGEMENTS. This research was supported by National Heart, Lung and Blood Institute grants HL-07556 and HL-22296.

Received 24 August 1992; accepted with revision 24 October 1992.

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