Sympathetic Response to Ventricular Extrasystolic Beats in Hypertension and Heart Failure

Abstract

Abstract-Provoked premature ventricular contractions (PVCs) evoke, in concomitance with an early and late blood pressure fall and overshoot, an early sympathoexcitation and a later period of sympathoinhibition, respectively. The present study was designed to examine whether in healthy subjects this is the case for spontaneous PVCs. Because of their pathophysiological relevance for arrhythmogenesis, it was also designed to determine whether the sympathetic responses are different from those seen in essential hypertension and congestive heart failure. In 14 untreated mild essential hypertensives (EH; age, 53.8Ϯ2.6 years; meanϮSEM), 20 untreated congestive heart failure patients (CHF; age, 56.7Ϯ2.5 years; New York Heart Association class, II or III), and 16 age-matched healthy subjects (control) in Lown class ϽII, we evaluated the blood pressure (Finapres), heart rate (ECG), and muscle sympathetic nerve traffic (MSNA; by microneurography) responses to isolated monofocal PVCs. MSNA, quantified as bursts/100 heart beats, was significantly increased in EH (57.8Ϯ3.8, PϽ0.05) and CHF patients (77.7Ϯ4.0, PϽ0.01) compared with controls (44.6Ϯ4.4). In controls, the PVC-induced blood pressure fall and overshoot were accompanied by a sympathoexcitation (144.2Ϯ14%), followed by a period of sympathoinhibition (average duration, 12043Ϯ985 ms). The responses were similar in EH but not in CHF, in whom the magnitude of the sympathoexcitation and particularly the duration of the subsequent sympathoinhibition were strikingly reduced (average reduction, Ϫ46.1 and Ϫ72.8%, respectively). The most important factor accounting for this reduction appeared to be an altered baroreflex response to the PVC-induced BP changes. These data demonstrate that the MSNA responses to spontaneous PVCs are similar in controls and EH but markedly impaired in CHF, presumably because of the baroreflex alteration. This may represent an important factor for the genesis of the life-threatening ventricular arrhythmias that characterize CHF. Key Words: arrhythmia Ⅲ heart failure Ⅲ sympathetic nervous system Ⅲ baroreflex M icroneurographic recording of efferent postganglionic sympathetic nerve traffic to the skeletal muscle district (MSNA) has shown that in healthy humans, premature ventricular contractions (PVCs) induced by programmed ventricular stimulation evoke profound modifications in neural adrenergic discharge. 1 These modifications include (1) an enhancement in the amplitude and duration of the sympathetic burst immediately after the PVC and (2) a subsequent period of sympathetic silence, followed by the restoration of the normal pattern of adrenergic discharge. 1 With the exception of 2 studies 2,3 (in which the early sympathoexcitatory responses to spontaneous PVCs were evaluated in 9 patients affected by congestive heart failure [CHF]), no information exists as to whether the MSNA behavior characterizing provoked PVCs is also shared by the spontaneous ones. Furthermore, it is unknown whether the sympathetic responses to PVCs seen in healthy subjects d...

Heart Rate Turbulence: Standards of Measurement, Physiological Interpretation, and Clinical Use

“…The post-VPC drop of diastolic blood pressure initiates a surge of muscle sympathetic nerve activity, which is immediately followed by a period of sympathetic silence (27)(28)(29)(30)(31). The magnitude of this burst, which cannot be observed earlier than at the time of the first post-VPC beat, provokes noradrenaline release in perivascular sympathetic endings, leading to an increase of peripheral vascular resistance.…”

Sympathetic Nervous System Activation in Human Heart Failure

“…Independent, but complementary, methods provide additional evidence that arterial baroreflex control of sympathetic nerve activity is relatively intact in HF. Key observations include: 1) preserved MSNA pulse-synchronicity (37); 2) immediate reflex augmentation of MSNA burst amplitude and duration in response to the long diastolic period following a ventricular ectopic complex (18,38), with subsequent post-extrasystolic suppression of MSNA proportional to the diastolic pressure overshoot (39); 3) MSNA tracks reflexively pulsus alternans (37); 4) reflex reductions in MSNA when diastolic pressure rises modestly upon left or biventricular pacing (40); 5) similar inhibition of MSNA by aortic and ventricular mechanoreceptor stimulation in subjects with normal and impaired ventricular systolic function (41); 6) similar reflex increases in TNES in patients and control subjects with nitroprusside infusion to achieve comparable baroreceptor unloading (42); and 7) similar gain, in subjects with and without HF, of the cross-spectral transfer function between BP (stimulus) and MSNA (response) across all frequency bands (35).…”

Sympathetic and baroreflex function in hypertensive or heart failure patients with ventricular arrhythmias

“…Supine blood pressure was measured three times with a mercury sphygmomanometer, the first and fifth Korotkoff sounds having been taken to identify systolic and diastolic values, respectively. Beat-to-beat blood pressure was measured by a finger photoplethysmographic device (Finapres 2300; Ohmeda, Englewood, Colorado, USA) capable of providing accurate and reproducible systolic and diastolic values [12][13][14]. The beat-to-beat heart rate was measured by a cardiotachometer triggered by the R-wave of an EKG lead.…”

“…Plasma renin activity and plasma norepinephrine were assessed by radioimmunoassay and high-pressure liquid chromatography [15,16], respectively, from a blood sample taken from an antecubital vein. Multiunit recording of efferent postganglionic muscle sympathetic nerve traffic was obtained from a microelectrode directly inserted in the right or left peroneal nerve posterior to the fibular head [12][13][14]. The microelectrode was made of tungsten and had a diameter of 200 ìm in the shaft, tapering to 1-5 ìm at the level of the uninsulated tip.…”

“…Integrated nerve activity was monitored by a loudspeaker, displayed on a storage oscilloscope (model 511A; Tektronix, The Netherlands), and recorded together with the blood pressure, heart rate and respiratory rate on an ink polygraph. The muscle nature of the nerve traffic was assessed according to the criteria outlined in previous studies [12][13][14], and the recording was considered acceptable if the signal-tonoise ratio exceeded a value of 3 [12][13][14]. Under baseline conditions, muscle sympathetic nerve traffic was quantified as bursts incidence over time (bursts/ min) and corrected for heart rate values (bursts/ 100 heartbeats).…”