Evidence for Functional Sympathetic Reinnervation of Left Ventricle and Coronary Arteries After Orthotopic Cardiac Transplantation in Humans

Burke, M. Nicholas; McGinn, Andrew L.; Homans, D. C.; Christensen, Betsy V.; Kubo, Spencer H.; Wilson, Robert F.

doi:10.1161/01.cir.91.1.72

Cited by 80 publications

(42 citation statements)

References 22 publications

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“…However, considering the anatomy of the cardiac autonomic nervous system only the postganglionic parasympathetic cells were eliminated by the endocardial RF-ablation. The sensory and sympathetic postganglionic cells are far from the heart and were preserved whereas the sympathetic and sensory fibres eliminated by RF have the capacity of recovery similar to that observed in post-transplantation patients [19].…”

Section: Sympathetic and Sensory Denervationsupporting

confidence: 56%

“Cardioneuroablation” – new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation

et al. 2005

EP Europace

230

277

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Cardiac neuroablation is a new technique for management of patients with dominantly adverse parasympathetic autonomic influence. The technique is based on radiofrequency (RF) ablation of autonomic connections in the three main ganglia around the heart. Their connections are identified by Fast-Fourier Transforms (FFTs) of endocardial signals: sites of autonomic nervous connections show fractionated signals with FFTs shifted to the right. In contrast, normal myocardium without these connections does not show these features. RF-ablation is thought to inflict permanent damage on the parasympathetic autonomic influence because its cells are adjacent to the heart whereas sympathetic cells are remote. Twenty-one patients with a mean age of 48 years, neurally mediated reflex syncope in six, functional high grade atrioventricular block in seven and sinus node dysfunction in 13 (there is overlap between the second and third groups) were treated. Follow-up for a mean of 9.2 months demonstrated success in all cases with relief of symptoms. No complications occurred.

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Section: Sympathetic and Sensory Denervationsupporting

confidence: 56%

“Cardioneuroablation” – new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation

et al. 2005

EP Europace

230

277

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“…This finding is in good agreement with previous studies with i.v. tyramine in healthy volunteers (Scriven et al 1984) and also with studies in patients where intracoronary injection of tyramine resulted in a significant increase of peak dP/dt (Burke et al 1995).…”

Section: Methodological Considerationsmentioning

confidence: 91%

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Schäfers¹,

Poller

Pönicke

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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This study aimed firstly to compare the in vivo cardiovascular effects of exogenously administered and of endogenously released noradrenaline; secondly to characterize the adrenoceptors mediating these responses; thirdly to assess the influence of parasympathetic tone on the cardiovascular effects of noradrenaline. In two randomised placebo-controlled studies, healthy, young, male volunteers received intravenous (i.v.) infusions of noradrenaline at six incremental doses of 10-160 ng/kg/min and-in order to release endogenous noradrenaline-tyramine at four incremental doses of 5-20 micrograms/kg/min. Noradrenaline and tyramine were administered in the absence and presence of alpha 1-adrenoceptor blockade with doxazosin (2 mg p.o.), alpha 2-adrenoceptor blockade with yohimbine (15 mg p.o.), selective beta 1-adrenoceptor blockade with bisoprolol (15 mg p.o.) and muscarinic receptor blockade with atropine (1.5 micrograms/kg i.v. loading dose followed by 0.15 microgram/kg/min by i.v. infusion). Vasoconstrictor effects were assessed by measurement of diastolic blood pressure (Pdiast) and myocardial effects by measurement of systolic time intervals, namely the duration of electromechanical systole corrected for heart rate (QS2c). I.v. noradrenaline increased Pdiast (delta max 17 mmHg) and this was nearly completely suppressed by doxazosin but only slightly blunted by yohimbine. Noradrenaline also slightly shortened QS2c (delta max -22 ms), and this was potentiated by both doxazosin and yohimbine and completely blocked by biosprolol. I.v. tyramine reduced Pdiast (delta max -7 mmHg), which was not affected by alpha 1-adrenoceptor blockade, and profoundly shortened QS2c (delta max -104 ms) which was significantly correlated with a marked increase in systolic blood pressure (Psyst) (delta max 57 mmHg). The shortening of QS2c and the rise in Psyst were not influenced by alpha-adrenoceptor blockade but were antagonized by bisoprolol. Atropine potentiated the blood pressure rise and the shortening of QS2c induced by i.v. noradrenaline and converted the fall in Pdiast induced by i.v. tyramine into an increase. Thus the cardiovascular effects of exogenous noradrenaline are mainly characterized by alpha 1-adrenoceptor-mediated vasoconstriction and the actions of endogenous noradrenaline (released by i.v. tyramine) by beta 1-adrenoceptor-mediated positive inotropic effects. The rise in Psyst with i.v. tyramine most likely reflects positive inotropism and not a vascular "pressor' response.

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“…The small number of subjects did not allow us to establish any difference in the leptin-heart rate relationship early compared with late after heart transplantation. Partial autonomic reinnervation may occur in long-standing heart transplant recipients, 19,20 although this is not invariable. 21,22 Overall, the data suggest that functional reinnervation, if it occurs, is mediated by relatively small numbers of sympathetic or parasympathetic neurons.…”

Section: Winnicki Et Al Leptin and Heart Rate In Transplanted Heartsmentioning

confidence: 99%

Independent Association Between Plasma Leptin Levels and Heart Rate in Heart Transplant Recipients

et al. 2001

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Background-Leptin, the protein product of the ob gene, has been linked to a faster heart rate in animal and human studies.The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. Methods and Results-We studied 32 male patients (mean age, 56.5Ϯ9.3 years; range, 41 to 74 years) after orthotopic heart transplantation. All subjects underwent a physical examination, anthropometric measurements, blood chemistry analysis, and office blood pressure measurements. A blood sample was collected from each subject while fasting. In univariate analysis, heart rate was related to leptin levels (rϭ0.47, Pϭ0.007) but heart rate was not related to systolic or diastolic blood pressure, mean arterial pressure, body mass index, or catecholamines. Leptin levels were only strongly associated with heart rate and body mass index (rϭ0. 73, PϽ0.0001). In multivariate analysis, heart rate was independently and positively associated with leptin levels (Fϭ2.61, Pϭ0.017). We also observed a strong, independent association between leptin levels and body mass index (Fϭ5.8, PϽ0.00001). Conclusions-We show an independent association between leptin levels and heart rate in heart transplant recipients. We speculate that this may be due, in part, to a direct effect of leptin on heart rate, conceivably mediated through cardiac leptin receptors. Key Words: leptin Ⅲ heart rate Ⅲ transplantation H eart rate is emerging as an important cardiovascular risk factor, and it may predict the development of sustained hypertension. 1 Autonomic neural and humoral mechanisms contribute to the control of heart rate. Leptin, the 167 amino acid product of the ob gene, 2 has also been linked to cardiovascular risk. 3,4 Animal studies show that chronic leptin infusion increases heart rate and blood pressure. 5,6 High leptin levels are linked to poor prognosis in the setting of myocardial infarction. 4 In human studies, plasma leptin levels correlate strongly with heart rate, most strikingly during sleep. [7][8][9] The effects of leptin on heart rate are presumably mediated by the central effects of leptin as it modulates autonomic neural control of the heart. 5,6 However, there is emerging evidence that leptin may have direct, non-neural effects on cardiovascular function. Leptin receptors or their mRNA have been detected in blood vessels and in the heart. 10 -13 The interaction between leptin and heart rate in the denervated heart is not known. Therefore, we studied the relationship between plasma leptin levels and heart rate in heart transplant recipients. Methods SubjectsWe studied 32 male patients (aged 56.5Ϯ9.3 years; range, 41 to 74 years). Subjects were selected across a broad spectrum of time intervals after transplantation (mean time after transplantation, 56Ϯ8 months; range, 1 to 132 months). Acute rejection, significant graft vasculopathy (stenoses Ն50%), and impaired systolic function were excluded by endomyocardial ...

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Evidence for Functional Sympathetic Reinnervation of Left Ventricle and Coronary Arteries After Orthotopic Cardiac Transplantation in Humans

Cited by 80 publications

References 22 publications

“Cardioneuroablation” – new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation

“Cardioneuroablation” – new treatment for neurocardiogenic syncope, functional AV block and sinus dysfunction using catheter RF-ablation

Influence of adrenoceptor and muscarinic receptor blockade on the cardiovascular effects of exogenous noradrenaline and of endogenous noradrenaline released by infused tyramine

Independent Association Between Plasma Leptin Levels and Heart Rate in Heart Transplant Recipients

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