Stephen L. Wasmund

Effect of Atrial Fibrillation and an Irregular Ventricular Response on Sympathetic Nerve Activity in Human Subjects

Background—Although the hemodynamic changes associated with atrial fibrillation (AF) have been extensively studied, the neural changes remain unclear. We hypothesized that AF is associated with an increase in sympathetic nerve activity (SNA) and that the irregular ventricular response contributes to this state of sympathoexcitation. Methods and Results—In 8 patients referred for an electrophysiological study, SNA, blood pressure (BP), central venous pressure (CVP), and heart rate were recorded during 3 minutes of normal sinus rhythm (NSR) and 3 minutes of induced AF. In 5 of 8 patients who converted to NSR, right atrial (RA) pacing was performed for 3 minutes in atrial pacing triggered by ventricular sensing mode triggered by playback of an FM tape previously recorded from the right ventricle during AF (RA-irregular) and atrial pacing inhibited by atrial sensing mode at a rate equal to the mean heart rate obtained during AF (RA-regular). SNA data were expressed as percentage of baseline during NSR. SNA increased in all 8 patients during induced AF compared with NSR (171±40% versus 100%, respectively;P <0.01). This was associated with a trend for a decrease in BP and an increase in CVP (P =0.02). Similarly, SNA was significantly higher during RA-irregular pacing compared with RA-regular pacing (124±24% versus 91±20%, respectively;P =0.03). BP and CVP were not significantly different between the 2 pacing modes. Conclusions—Induced AF results in a significant increase in SNA, which is in part attributable to the irregular ventricular response. Our findings suggest that restoring NSR or regularity might be beneficial, particularly in patients with heart failure.

Serotonin Reuptake Inhibitor (Paxil) Does Not Prevent the Vasovagal Reaction Associated With Carotid Sinus Massage and/or Lower Body Negative Pressure in Healthy Volunteers

Background—The purpose of this study was to assess the effect of the serotonin reuptake inhibitor paroxetine hydrochloride (Paxil, SmithKline Beecham) on cardiovascular reflexes. We hypothesized that Paxil prevents neurally mediated syncope (NMS) by attenuating the sympathoinhibition and vagotonia associated with a vasovagal reaction. Methods and Results—In a double-blind randomized study, 25 healthy subjects with a positive response to either carotid sinus massage (CSM) or lower body negative pressure (LBNP) received Paxil (20 mg/d) or placebo for 6 weeks. Arterial baroreflex sensitivity (BRS), muscle sympathetic nerve activity (SNA), baroreflex control of SNA, blood pressure, and heart rate responses to CSM and LBNP were measured at baseline and at 6 weeks. Nineteen subjects completed the study (Paxil, n=9; placebo, n=10). In the Paxil group, BRS decreased significantly compared with baseline (15.8±4.0 ms/mm Hg versus 11.0±2.6 ms/mm Hg, P =0.05); however, all 9 subjects continued to have a positive response to LBNP with presyncope. Paxil did not attenuate the sympathoinhibition or vagotonia associated with a positive LBNP response and had no significant effect on baroreflex control of SNA. In the control group, no significant change in BRS was noted compared with baseline. Seven out of 9 subjects who had a positive LBNP response at baseline had a repeat positive LBNP response, and the subject with a positive CSM at baseline had a negative response at 6 weeks. Conclusions—Paxil decreases arterial BRS but does not prevent the presyncope associated with LBNP. The effect of Paxil on the autonomic reflexes in patients with neurally mediated syncope remains unclear.

Baroreflex Gain Predicts Blood Pressure Recovery During Simulated Ventricular Tachycardia in Humans

BACKGROUND Despite similar degrees of left ventricular dysfunction and similar tachycardia or pacing rate, blood pressure (BP) response and symptoms vary greatly among patients. Sympathetic nerve activity (SNA) increases during sustained ventricular tachycardia (VT), and the magnitude of this sympathoexcitatory response appears to contribute to the net hemodynamic outcome. We hypothesize that the magnitude of sympathoexcitation and thus arterial baroreflex gain is an important determinant of the hemodynamic outcome of VT. METHODS AND RESULTS We evaluated the relation between arterial baroreflex sympathetic gain and BP recovery during rapid ventricular pacing (VP) in patients referred for electrophysiological study. Efferent postganglionic muscle SNA, BP, and central venous pressure (CVP) were measured in 14 patients during nitroprusside infusion and during VP at 150 (n=12) or 120 (n=2) bpm. Arterial baroreflex gain was defined as the slope of the relationship of change in SNA to change in diastolic BP during nitroprusside infusion. Recovery of mean arterial pressure (MAP) during VP was measured as the increase in MAP from the nadir at the onset of pacing to the steady-state value during sustained VP. Arterial baroreflex gain correlated positively with recovery of MAP (r=0.57, P=0.034). No significant correlation between ejection fraction and baroreflex gain (r=0.48, P=0.08) or BP recovery (r=0.41, P=0.15) was found. When patients were separated into high versus low baroreflex gain, the recovery of MAP during simulated VT was significantly greater in patients with high gain. CONCLUSIONS These data strongly suggest that arterial baroreflex gain contributes significantly to hemodynamic stability during simulated VT. Knowledge of baroreflex gain in individual patients may help the clinician tailor therapy directed toward sustained VT.

Increased sympathetic activity after atrioventricular junction ablation in patients with chronic atrial fibrillation.

OBJECTIVES The aim of this study was to determine the changes in sympathetic nerve activity (SNA) after atrioventricular junction (AVJ) ablation in patients with chronic atrial fibrillation (AF). BACKGROUND Polymorphic ventricular tachycardia (PMVT) has been reported after AVJ ablation in patients paced at a rate of < or =70 beats/min. We hypothesized that AVJ ablation results in sympathetic neural changes that favor the occurrence of PMVT and that pacing at 90 beats/min attenuates these changes. METHODS Sympathetic nerve activity, 90% monophasic cardiac action potential duration (APD90), right ventricular effective refractory period (ERP) and blood pressure measurements were obtained in 10 patients undergoing AVJ ablation. Sympathetic nerve activity was analyzed at baseline and during and after successful AVJ ablation for at least 10 min. Data were also collected after ablation at pacing rates of 60 and 90 beats/min. The APD90 and ERP were measured before and after AV block during pacing at 120 beats/min. RESULTS Sympathetic nerve activity increased to 134 +/- 16% of the pre-ablation baseline value (p < 0.01) after successful AVJ ablation plus pacing at 60 beats/min and decreased to 74 +/- 8% of baseline (p < 0.05) with subsequent pacing at 90 beats/min. Both APD90 and ERP increased significantly. CONCLUSIONS 1) Ablation of the AVJ followed by pacing at 60 beats/min is associated with an increase in SNA. 2) Pacing at 90 beats/min decreases SNA to or below the pre-ablation baseline value. 3) Cardiac APD and ERP increase after AVJ ablation. The increase in SNA, along with the prolongation in APD, may play a role in the pathogenesis of ventricular arrhythmias that occur after AVJ ablation.

High-frequency ventricular ectopy can increase sympathetic neural activity in humans

BACKGROUND Sudden cardiac death is usually caused by ventricular arrhythmias and in many cases, is preceded by frequent ventricular ectopy. It is known that ectopic beats cause transient increases in sympathetic nerve activity (SNA). OBJECTIVE Because high SNA is known to be arrhythmogenic, we hypothesized that high rates of ectopy increase SNA, thereby creating a milieu that favors development of ventricular tachycardia and/or fibrillation. METHODS This study measured muscle SNA, coronary sinus catecholamine, and arterial pressure during graded rates of ventricular ectopy (from 4:1 to 1:1, sinus to ectopic beat ratio) in a total of 21 patients referred for electrophysiologic testing. RESULTS Both muscle SNA and coronary sinus norepinephrine increased significantly with increased ectopy frequency (P < .05). Moreover, the change in muscle SNA correlated significantly with the change in coronary sinus norepinephrine levels (r = .72, P < .001). CONCLUSION These data demonstrate that sympathoexcitation evoked by high rates of ventricular ectopy can contribute to a state of elevated SNA both in peripheral tissues and within the heart. This altered autonomic state may contribute to an increased susceptibility to life-threatening tachyarrhythmias in patients with high rates of ectopy.

Sympathoexcitation is attenuated during low level lower body negative pressure in subjects who develop pre-syncope

Abstract. The purpose of this study was to compare the hemodynamic and sympathetic nerve activity (SNA) responses to graded lower body negative pressure (LBNP) in healthy subjects with either a positive (n = 24, SNA in 8) or a negative (n = 18, SNA in 6) LBNP response. A positive LBNP response was defined as an abrupt drop in systolic blood pressure associated with a decrease in heart rate and/or a decrease in SNA. All positive responses were accompanied by symptoms common to pre-syncope, defined as lightheadedness, diaphoresis, tunnel vision and/or nausea. If subjects tolerated 30 minutes of LBNP, this was considered a negative response. Comparisons were made between baseline, −10 mmHg (low-level LBNP) and −60 mmHg (high-level LBNP). Baseline SNA and arterial baroreflex sensitivity were not different between the 2 groups. However, subjects with pre-syncope had a significantly attenuated SNA response during low-level LBNP (p < 0.05) compared to subjects who did not experience pre-syncope. The hemodynamic data during high-level LBNP were similar until the occurrence of pre-syncope. Pre-syncope was preceded by a significant decrease in heart rate and SNA. Our findings suggest that subjects with LBNP induced pre-syncope might have an impairment in the cardiopulmonary baroreflex gain function in the setting of a preserved arterial baroreflex gain.

Do vestibular otolith organs participate in human orthostatic blood pressure control

We hypothesized that vestibular otolith organ stimulation contributes to human orthostatic responses. Twelve subjects underwent three 60 degrees upright tilts: (1) with the neck flexed from 0 degrees to 30 degrees relative to the body during 60 degrees tilt, such that the head moved from horizontal to 90 degrees above horizontal (0 to 1 Gz otolith stimulation); (2) with the head and body aligned, such that they tilted together to 60 degrees (0 to 0.87 Gz otolith stimulation); and (3) with the neck flexed 30 degrees relative to the body during supine conditions, and the neck then extended to -30 degrees during 60 degrees body tilting, such that the head remained at 30 degrees above horizontal throughout body tilting (constant 0.5 Gz otolith stimulation). All three tilt procedures increased thoracic impedance, sympathetic nerve activity (N = 8 of 12), arterial pressure, and heart rate relative to supine conditions (all P < 0.04). Within the first 20 s of tilt, arterial pressure increased most obviously in the 0 to 1 Gz otolith condition. Thoracic impedance tended to increase more in otolith-constant conditions, but no dependent variable differed significantly between tilt conditions, and no significant time x tilt interactions emerged. Otolith inputs may contribute to early transient adjustments to orthostasis. However, lack of significant main effects of tilt condition and time x tilt interactions suggests that potential otolith effects on the variables we studied are relatively subtle and ephemeral, or that other mechanisms compensate for a lack of change in otolith input with orthostasis.

Selective parasympathetic denervation following posteroseptal ablation for either atrioventricular nodal reentrant tachycardia or accessory pathways

Baroreflex gain and coronary sinus norepinephrine and epinephrine levels were measured before and immediately after radiofrequency ablation in the posteroseptal region in 9 patients with atrioventricular nodal reentrant tachycardia or posteroseptal accessory pathways. Arterial baroreflex gain was significantly reduced after radiofrequency ablation (p = 0.046), whereas coronary sinus epinephrine and norepinephrine levels did not change significantly compared with preablation levels.

The acute effect of atrioventricular pacing on sympathetic nerve activity in patients with normal and depressed left ventricular function

Although modest elevations in pacing rate improve cardiac output and induce reflex sympathoinhibition, the threshold rate above which hemodynamic perturbations induce reflex sympathoexcitation remains unknown. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressures (MAP) and sympathetic nerve activity (SNA) were measured during normal sinus rhythm (NSR) and atrioventricular (AV) sequential pacing in 25 patients. Pacing was performed at 100, 120, and 140 beats/min with an AV interval of 100 ms. Patients were divided into two groups based on normal or abnormal left ventricular ejection fraction (LVEF): group 1 (n = 11; mean LVEF, 55%) and group 2 (n = 14; mean LVEF, 31%). In group 1, relative to NSR, SBP decreased an average of 2%, 3%, and 8% at 100, 120, and 140 beats/min (P < 0.001), respectively. DBP and MAP increased 9%, 15%, and 15% (P = 0.001) and 3%, 6%, and 5% [P = not significant (NS)], respectively. In group 2, SBP reductions were even greater, with an average decrease of 4%, 8%, and 16% (P < 0.001). Whereas DBP increased 9%, 9%, and 8% at 100, 120, and 140 beats/min (P = NS), MAP increased 3% and 2% at 100 and 120 beats/min but decreased 3% at 140 beats/min (P = 0.001). SNA recordings were obtained in 11 patients (6 in group 1 and 5 in group 2). In group 1, SNA decreased during all rates, with a mean 21% reduction. In group 2, however, SNA decreased at 100 and 120 beats/min (49% and 38%) but increased 24% at 140 beats/min. Patients with depressed LVEF exhibited altered hemodynamic and sympathetic responses to rapid sequential pacing. The implications of these findings in device programming and arrhythmia rate control await future studies.

Poor baroreflex gain is a marker of heightened sympathetic activity post-tachycardia termination in humans

Abstract.We hypothesized that sympathetic nerve activity (SNA) remains elevated after tachycardia termination in patients with low baroreflex gain (BRG), and decreased to or below baseline in patients with high BRG. In a cohort of patients who participated in a previously published study [3], BRG, SNA, blood pressure, and central venous pressure were measured immediately after the termination of simulated tachycardia. While the hemodynamic responses following tachycardia termination were similar in both groups, SNA remained elevated in patients with low BRG compared to a decrease below baseline levels in patients with high BRG (p = 0.04). Increased sympathetic activity following tachycardia termination could be arrhythmogenic and might play a role in the genesis of recurrent ventricular arrhythmias following tachycardia termination.