Absence of Parasympathetic Control of Heart Rate After Human Orthotopic Cardiac Transplantation

Arrowood, James A.; Minisi, Anthony J.; Goudreau, Evelyne; Davis, Annette B.; King, Anne

doi:10.1161/01.cir.96.10.3492

Cited by 54 publications

(28 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mildly elevated global resting flow in transplant recipients is attributed to a higher RPP which is mostly because of higher heart rate as a consequence of lack of vagal tone from atrial parasympathetic denervation. 25 This finding is consistent with The observation of regionally heterogeneous restoration of sympathetic innervation, which occurs predominantly in the basal anteroseptal wall ( Figure 2B) and increases with time after transplantation, is consistent with several previous studies. 5,6,8,9 The novelty of this study is that intraindividual comparison of the kinetics of EPI, HED, and PHEN in transplant recipients suggests molecular differences in the recovery of subcellular mechanisms (catecholamine uptake, vesicular storage, and enzymatic degradation) required for normal catecholamine handling in cardiac presynaptic sympathetic nerve terminals.…”

Section: Discussionsupporting

confidence: 94%

Mechanistic Insights into Sympathetic Neuronal Regeneration

Bravo

Lautamäki

Carter

et al. 2015

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

T he sympathetic nervous system plays a key role in maintaining the homeostasis and integrity of the cardiovascular system. It is impaired in the natural course of various cardiovascular diseases, where imbalance contributes to electromechanical instability and progression of heart failure.1-3 Regeneration of impaired innervation, however, may also occur. See Clinical PerspectiveThe transplanted heart is a unique model in this regard. After transplantation, the heart becomes denervated because of surgical disruption of the extracardiac sympathetic nerve fibers at the base of the heart. However, this process is not complete as the intrinsic cardiac network or ganglia of the transplanted heart has the potential to function independently in the absence of central neuronal inputs. 4 Various studies have shown that the intrinsic cardiac nervous system becomes partly reinnervated by extracardiac sympathetic efferent neurons with time after transplantation. [5][6][7][8] This has been associated with improved left ventricular (LV) performance and exercise capacity after heart transplantation 9 and with improved regulation of myocardial perfusion 10 and substrate utilization.11 Studies evaluating the presence, extent, and functional consequences of restored extracardiac sympathetic innervation, however, have typically used only a single tracer to determine catecholamine uptake and washout. This provides only a snapshot of nerve terminal integrity and does Background-Post-transplant reinnervation is a unique model to study sympathetic neuronal regeneration in vivo. The differential role of subcellular mechanisms of catecholamine handling in nerve terminals has not been investigated. Methods and Results-Three different carbon-11-labeled catecholamines were used for positron emission tomography of transport (C-11 m-hydroxyephedrine, HED), vesicular storage (C-11 epinephrine, EPI), and metabolic degradation (C-11 phenylephrine). A 2-day protocol was used, including quantification of myocardial blood flow by N-13 ammonia.Resting myocardial blood flow and EPI, HED and phenylephrine retention were homogeneous in healthy volunteers (n=7). Washout was only observed for phenylephrine (T 1/2 49±6 min). In nonrejecting, otherwise healthy heart transplant recipients (>1 year after surgery, n=10), resting myocardial blood flow was also homogenous. Regional catecholamine uptake of varying degrees was observed in the anterior left ventricular wall and septum. Overall, 24±19% of left ventricle showed HED uptake levels comparable with healthy volunteers, whereas it was only 8±7% for EPI (P=0.004 versus HED). Phenylephrine washout was not different from healthy volunteers in the area with restored EPI and HED retention (T 1/2 41±7 min; P>0.05), but was significantly enhanced in the EPI/HED mismatch area (T 1/2 36±8 min; P=0.008), consistent with inefficient vesicular storage and enhanced metabolic degradation. Conclusions-Regeneration of subcellular components of sympathetic nerve terminal function does not occur simultaneously.In the rein...

show abstract

Section: Discussionsupporting

confidence: 94%

Mechanistic Insights into Sympathetic Neuronal Regeneration

Bravo

Lautamäki

Carter

et al. 2015

Circ: Cardiovascular Imaging

View full text Add to dashboard Cite

show abstract

“…5). In previous human studies it has also been shown that patients undergoing heart transplantation had lower heart frequency early after the heart transplantation than before (Arrowood et al, 1995;Arrowood et al, 1997;Marconi et al, 2002). Similar observations were noted after surgical sympathectomy in the rat (Hansson et al, 1998).…”

Section: Physiological Response After Treatmentsupporting

confidence: 67%

Receptor binding occurrence and plasma levels of natriuretic peptides in response to sympathectomy

Hansson

2005

Microsc. Res. Tech.

View full text Add to dashboard Cite

In the present investigation the relationship between the sympathetic nervous system and the endocardial levels of receptor binding sites for natriuretic peptides and the plasma content of atrial natriuretic peptide were analyzed in rats. In order to destruct the cardiac sympathetic nerve terminals, chemical sympathectomy with 6-hydroxydopamine was made in parallel with intravenous measurements of blood pressure and heart frequency. By use of immunohistochemical and enzyme-linked-immunosorbent techniques the expression of tyrosine hydroxylasepositive sympathetic nerve terminals and plasma levels of pro-atrial natriuretic peptide were determined, respectively. The occurrence of receptor binding sites for natriuretic peptides was examined by in vitro receptor autoradiography. In contrast to the marked occurrence of natriuretic peptide receptor binding sites seen in the ventricular endocardium of control rats, the sympathectomized rats exhibited a decreased number of binding sites for natriuretic peptides in the endocardium of both the right and left chambers. Interestingly, this was found in parallel with a significant decrease of systolic and diastolic blood pressure and increased plasma levels of pro-atrial natriuretic peptide in the treated group of rats. These findings, together with those in previous studies, give support to an idea that one part of the blood pressure-decreasing effects, seen in patients treated with b-adrenergic blockade, might be through a reduction of the natriuretic clearance receptor C, then giving rise to increased levels of atrial natriuretic peptide. Microsc. Res. Tech. 67:90-99, 2005. V

show abstract

“…17 However, it is likely that reappearance of a link between LF oscillations in RR and MSNA is indicative of a cardiac sympathetic reinnervation in our patients, because, first, LF oscillations in RR induced by sinusoidal neck suction in heart transplant recipients are attenuated by ␤-blockade but are not affected by atropine, 1 and, second, all of our patients had undergone standard cardiac transplantation, and cardiac reinnervation is primarily sympathetic rather than vagal in this condition. 3,4 Limited HF oscillations in RR can be induced by nonautonomic mechanisms, such as atrial stretch induced by changes in venous return. 1 Our observation of comparable HF oscillations in RR after an average of 5 and 138 months after transplantation additionally emphasizes that this component is unlikely to be mediated by the autonomic nervous system in cardiac transplant patients.…”

Section: Discussionmentioning

confidence: 99%

“…These LF oscillations are a marker of functional sympathetic reinnervation of the sinus node, because they increase in amplitude during sinusoidal neck suction and are attenuated by ␤-blockade. 1 Reinnervation has been demonstrated mainly for sympathetic efferents 1,[3][4][5][6] and is of clinical importance, because it is accompanied by partial restoration of the heart-rate response to exercise. 7 Previous studies in control subjects and patients with cardiac transplants have demonstrated that direct recordings of sympathetic nerve traffic (muscle sympathetic nerve activity [MSNA]) exhibit LF and HF oscillatory components almost identical to those present in heart-rate variability.…”

mentioning

confidence: 99%

Differential Characteristics of Neural Circulatory Control

et al. 2001

View full text Add to dashboard Cite

Background-Reappearance of low-frequency (LF) (Ϯ0.10 Hz) oscillations in RR interval (RR) after cardiac transplantation is indicative of sympathetic efferent reinnervation. We hypothesized that restored LF oscillations in RR in heart transplant recipients (HTRs) are linked to oscillations in muscle sympathetic nerve traffic (MSNA). Methods and Results-RR, RR variability, and MSNA were recorded 5Ϯ2 months (nϭ7, short-term HTRs) and 138Ϯ8 months (nϭ7, long-term HTRs) after heart transplantation and compared with matched hypertensive patients (nϭ7). A coherence function determined the coupling between LF oscillations in MSNA and RR. RR variance did not differ between short-term and long-term HTRs. However, LF variability was only 1Ϯ0.5 ms 2 in the short-term HTRs but was 15Ϯ8 ms 2 in the long-term HTRs (PϽ0.05). Normalized LF variability was also higher in the long-term HTRs (40Ϯ14 normalized unites) versus the short-term HTRs (6Ϯ3 normalized united, PϽ0.05) but did not differ from the LF variability of the hypertensive patients. Long-term HTRs were taking less cyclosporine (PϽ0.01) but had higher MSNA than the short-term HTRs (62Ϯ7 versus 31Ϯ7 burst/min, respectively, PϽ0.05). Coherence between LF oscillations in MSNA and RR was similar in the long-term HTRs (0.59Ϯ0.11) and the hypertensive patients (0.60Ϯ0.07) and was 3-fold greater than in the short-term HTRs (0.20Ϯ0.06, PϽ0.05). Conclusions-Cardiac reinnervation after long-term heart transplantation is characterized by a restoration of the coherence between LF oscillations in RR and MSNA. Higher MSNA in long-term than in short-term HTRs suggests that time elapsed after cardiac transplantation may be a major determinant of sympathetic excitation in heart transplant recipients.

show abstract

Absence of Parasympathetic Control of Heart Rate After Human Orthotopic Cardiac Transplantation

Abstract: These data suggest that parasympathetic influences on donor heart rate are absent in the majority of patients up to 96 months after cardiac transplantation.

Cited by 54 publications

References 24 publications

Mechanistic Insights into Sympathetic Neuronal Regeneration

Mechanistic Insights into Sympathetic Neuronal Regeneration

Receptor binding occurrence and plasma levels of natriuretic peptides in response to sympathectomy

Differential Characteristics of Neural Circulatory Control

Contact Info

Product

Resources

About