Demonstrable Cardiac Reinnervation After Human Heart Transplantation by Carotid Baroreflex Modulation of RR Interval

Bernardi, Luciano; Bianchini, B; Spadacini, Giammario; Leuzzi, Stefano; Valle, Fernando Cano; Marchesi, E.; Passino, Claudio; Calciati, A; Viganò, Mario; Rinaldi, Mauro; Martinelli, Luigi; Finardi, G; Sleight, Peter

doi:10.1161/01.cir.92.10.2895

Cited by 145 publications

(253 citation statements)

References 24 publications

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“…As shown in the 15-fold magnified spectral window in the top right panel of Figure 3, after high-dose atropine all remaining power in the RR interval variability is condensed into the LF component, leading to high values of normalized LF power (see Table 2). These findings are similar to those noted by Bernardi and colleagues 27 after atropine administration in normal subjects and by Rimoldi et al 28 in studies in conscious dogs. Thus, an alternative conclusion is that the relative sympathetic predominance in RR modulation after high-dose atropine is evident from the marked increase in the normalized LF of RR variability and in the LF/HF ratio of RR variability.…”

Section: Effects Of High-dose Atropinesupporting

confidence: 92%

Central Vagotonic Effects of Atropine Modulate Spectral Oscillations of Sympathetic Nerve Activity

et al. 1998

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Background-Low-dose atropine causes bradycardia either by acting on the sinoatrial node or by its effects on central muscarinic receptors increasing vagal activity. Any central muscarinic effects of high-dose atropine on RR interval are masked by peripheral muscarinic blockade at the sinoatrial node, which causes tachycardia. Effects of central parasympathetic activation on sympathetic activity are not known. Methods and Results-Using power spectral analysis of RR interval, intra-arterial blood pressure, respiration, and muscle sympathetic nerve activity (MSNA), we examined the effects of both low (2 g/kg IV) and high (15 g/kg IV) doses of atropine. After low-dose atropine, RR increased by 9Ϯ1% (PϽ0.0001), the low-frequency (LF) component (in normalized units, NU) of RR variability decreased by Ϫ32Ϯ8%, and the high-frequency (HF) NU component increased (ϩ74Ϯ19%); hence, LF/HF of RR variability fell by 52Ϯ10% (all PϽ0.01). Although overall MSNA did not change, LF NU of MSNA decreased (Ϫ15Ϯ5%), HF NU of MSNA increased (ϩ31Ϯ3%), and LF/HF of MSNA fell (Ϫ41Ϯ8%) (all PϽ0.01). After high-dose atropine, LF NU of MSNA decreased (Ϫ17Ϯ12%), HF NU of MSNA increased (ϩ22Ϯ3%), and LF/HF of MSNA fell (Ϫ51Ϯ21%) (all PϽ0.02). Conclusions-Increasing central parasympathetic activity with low-dose atropine is associated with an increase in the HF and a decrease in the LF oscillations of both RR interval and MSNA variability. High-dose atropine similarly induces an increase in the HF and a decrease in the LF components of MSNA variability. Thus, central parasympathetic activation is able to modulate the oscillatory characteristics of sympathetic nerve traffic to peripheral blood vessels.

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Section: Effects Of High-dose Atropinesupporting

confidence: 92%

Central Vagotonic Effects of Atropine Modulate Spectral Oscillations of Sympathetic Nerve Activity

et al. 1998

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“…The baroreflexes contribute importantly to modulation of the LF component of cardiovascular variability. 17,18 Cardiac transplantation is accompanied by marked increases in baroreflex gain. 11 Figure 2.…”

Section: Discussionmentioning

confidence: 99%

Sympathetic Rhythmicity in Cardiac Transplant Recipients

Borne

Montano

Degaute³

et al. 1999

Circulation

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Background-Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, Ϯ0.1 Hz) and a high frequency (HF, Ϯ0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. Methods and Results-We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74Ϯ3) than either patients with heart failure (56Ϯ6) or normal subjects (40Ϯ4) (PϽ0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (PϽ0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (PϽ0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. Conclusions-Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.

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“…This group comprised 12 participants (5 men, 7 women, aged 54.7 ± 2.4 years), who had undergone orthotopic heart transplantation 34.7±4.9 months previously. These participants were part of a previously published study [27], documenting absent or only rudimentary renervation. As the protocol of that study also contained similar recordings (not used in the previous publication) to those for our patients with type 1 diabetes, they were included in the present study to test whether and to what extent an almost denervated heart could respond to interventions capable of increasing BRS.…”

Section: Study Populationmentioning

confidence: 99%

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

et al. 2009

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Aims/hypothesis Cardiac autonomic neuropathy is associated with increased morbidity and mortality rates in patients with type 1 diabetes. The prevalence of early autonomic abnormalities is relatively high compared with the frequency of manifest clinical abnormalities. Thus, early autonomic dysfunction could to some extent be functional and might lead to an organic disease in a subgroup of patients only. If this is true, manoeuvres such as slow deep-breathing, which can improve baroreflex sensitivity (BRS) in normal but not in denervated hearts, could also modify autonomic modulation in patients with type 1 diabetes, despite autonomic dysfunction.Methods We compared 116 type 1 diabetic patients with 36 matched healthy control participants and 12 hearttransplanted participants with surgically denervated hearts. Autonomic function tests and spectral analysis of heart rate and blood pressure variability were performed. BRS was estimated by four methods during controlled (15 breaths per minute) and slow deep-breathing (six breaths per minute), and in supine and standing positions. Results Conventional autonomic function tests were normal, but resting spectral variables and BRS were reduced during normal controlled breathing in patients with type 1 diabetes. However, slow deep-breathing improved BRS in patients with type 1 diabetes, but not in patients with surgically denervated hearts. Standing induced similar reductions in BRS in diabetic and control participants. Conclusions/interpretation Although we found signs of increased sympathetic activity in patients with type 1 diabetes, we also observed a near normalisation of BRS with a simple functional test, indicating that early autonomic derangements are to a large extent functional and potentially correctable by appropriate interventions.

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Demonstrable Cardiac Reinnervation After Human Heart Transplantation by Carotid Baroreflex Modulation of RR Interval

Abstract: The presence of baroreceptor-induced RR oscillations is evidence of functional, although incomplete, autonomic reinnervation.

Cited by 145 publications

References 24 publications

Central Vagotonic Effects of Atropine Modulate Spectral Oscillations of Sympathetic Nerve Activity

Central Vagotonic Effects of Atropine Modulate Spectral Oscillations of Sympathetic Nerve Activity

Sympathetic Rhythmicity in Cardiac Transplant Recipients

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

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