Myocardial Muscarinic Receptor Upregulation and Normal Response to Isoproterenol in Denervated Hearts by Familial Amyloid Polyneuropathy

Delahaye, Nicolas; Guludec, Dominique Le; Dinanian, S.; Delforge, Jacques; Slama, Michel; Sarda, Laure; Dollé, Frédéric; Mzabi, H.; Samuel, Didier; Adams, David; Syrota, A.; Merlet, Pascal

doi:10.1161/hc4901.100380

Cited by 48 publications

(17 citation statements)

References 38 publications

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“…23 On the other hand, vagal function is an important component of the efferent arm of the baroreflex that regulates BP by changing the HR. Delahaye et al 5 disclosed that cardiac autonomic denervation in FAP results in an upregulation of myocardial muscarinic receptors without any change in cardiac b-receptor responsiveness to catecholamine. Our FAP patients presented significantly reduced HRV as compared with controls, whereas the patients' BP overshoot levels were of larger magnitude.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism behind the disturbed hemodynamic responses has been suggested to be a parasympathetic dysfunction leading to myocardial muscarinic receptor upregulation. 5 The presence of parasympathetic dysfunction in FAP has been verified by findings of markedly reduced heart rate variability (HRV). [6][7][8][9] However, the pathophysiology of the hemodynamic responses to postural stress in FAP remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy

et al. 2010

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The pathophysiology of the hemodynamic responses to postural stress in familial amyloidotic polyneuropathy (FAP) remains to be elucidated. The aim of the study was to evaluate hemodynamic responses after tilt reversal in FAP. Systolic blood pressure (BP) and heart rate variability (HRV) were analyzed in the baseline, 701 upright position, and after tilt reversal in 15 FAP patients and 14 healthy controls. Beat-to-beat BP was recorded with a Finapres device. Maximum systolic BP after tilt reversal was increased with 22 ± 13 mm Hg in FAP patients as compared with baseline (BP overshoot), whereas controls showed a significantly lower BP overshoot (8 ± 6 mm Hg, Po0.001). In all states, total spectral power and the power of the low and high frequency components were all significantly lower than those of the controls (Po0.01). In a linear regression analysis adjusted for age, we found a significant inverse relation between BP overshoot and HRV (total spectral power, power of the low-frequency and high-frequency components) in all three states (standardized b between À0.74 to À0.53, Po0.01). Five FAP patients presented a trial arrhythmia precluding HRV analysis: four of those presented BP overshoots X12 mm Hg. BP overshoot may be a marker to assess the progression of cardiac autonomic dysfunction, especially as heart arrhythmia in many FAP patients prevent HRV analysis. In addition, assessment of the post-tilt BP reaction points to possible treatment modalities for orthostatic hypotension at least in the early stages of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy

et al. 2010

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“…[11][12][13][14] The values (32Ϯ17 pmol/mL tissue; nϭ156) were higher and more scattered than those previously obtained using the same 2-injection protocol in 5 volunteers (25Ϯ7 pmol/mL tissue; nϭ5). 11 These differences could be partially ascribed to the TACs being corrected for partial volume effects with the GTM method, whereas correction in previous studies were performed by taking into account the ventricle wall thickness and applying an experimental recovery factor; prior studies usually considered 1 large region covering the entire transaxial PET slice, whereas we included 3 short-axis slices and divided each of them into 6 regions.…”

Section: Technical Considerationsmentioning

confidence: 99%

“…This methodology allows for the absolute quantification of postsynaptic muscarinic receptors (muscarinic receptor density [Bmax] in pmol/mL tissue), but it requires a 3-injection protocol and complex mathematical modeling. 10,11 Because this approach appears difficult for clinical use, its application in patients has been very limited, [12][13][14] and no imaging studies have assessed LV muscarinic receptors in patients with MI.…”

Section: Editorial See P 353mentioning

confidence: 99%

Muscarinic Receptor Upregulation in Patients With Myocardial Infarction

Mazzadi

Pineau

Costes

et al. 2009

Circ: Cardiovascular Imaging

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Background-Despite the major role attributed to myocardial vagal activity in left ventricular arrhythmogenesis in chronic myocardial infarction, the impact of infarction on left ventricular muscarinic receptor density remains unknown. Methods and Results-Left ventricular muscarinic receptor density was measured in vivo by positron emission tomography using the specific antagonist [ 11 C]methylquinuclidinyl benzilate ([ 11 C]MQNB) in 11 patients 43Ϯ20 days after myocardial infarction and 9 healthy volunteers. The extent of myocardial damage was quantified by delayed contrast-enhanced MRI. Three short-axis slices from each subject were analyzed in matched positron emission tomography and MRI images. A 2-injection positron emission tomography protocol was used; [11 C]MQNB timeactivity curves were obtained in 6 regions per slice and fitted to a 3-compartment ligand-receptor model. Four classes of myocardial regions were considered: normal (in volunteers); remote, supplied by healthy or Ͻ70% diameter reduction arteries and without MRI signs of damage; potentially damaged, supplied by infarct-related or Ͼ70% diameter reduction arteries and without signs of damage; and damaged, with damage. The muscarinic receptor density in remote (67Ϯ30 pmol/mL tissue; nϭ86) and potentially damaged (71Ϯ30 pmol/mL tissue; nϭ42) regions of patients was higher than in normal regions of volunteers (32Ϯ17 pmol/mL tissue; nϭ156; PϽ0.001). The muscarinic receptor density in damaged regions (42Ϯ21 pmol/mL tissue; nϭ58) was reduced compared with remote and potentially damaged regions (PϽ0.001) but was not significantly different from normal regions in volunteers (Pϭ0.093). Conclusions-Vagal

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“…Another cause of the decrease in MIBG uptake may be a specific involvement of the autonomic system, as found by Delahaye et al in 2001. They used the PET tracer 11 C-methylquinuclidinyl benzilate (MQNB) and found a parasympathetic myocardial denervation with a very low increase in heart rate in patients after atropine injection compared with controls, and an upregulation of myocardial parasympathetic postsynaptic muscarinic receptors in response to the presynaptic denervation [17].…”

Section: I-mibgmentioning

confidence: 99%

Nuclear imaging in cardiac amyloidosis

Glaudemans

Slart

Zeebregts

et al. 2009

Eur J Nucl Med Mol Imaging

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Amyloidosis is a disease characterized by depositions of amyloid in organs and tissues. It can be localized (in just one organ) or systemic. Cardiac amyloidosis is a debilitating disease and can lead to arrhythmias, deterioration of heart function and even sudden death. We reviewed PubMed/Medline, without time constraints, on the different nuclear imaging modalities that are used to visualize myocardial amyloid involvement. Several SPECT tracers have been used for this purpose. The results with these tracers in the evaluation of myocardial amyloidosis and their mechanisms of action are described. Most clinical evidence was found for the use of 123 I-MIBG. Myocardial defects in MIBG activity seem to correlate well with impaired cardiac sympathetic nerve endings due to amyloid deposits. 123 I-MIBG is an attractive option for objective evaluation of cardiac sympathetic level and may play an important role in the indirect measurement of the effect of amyloid myocardial infiltration. Other, less sensitive, options are 99m Tc-aprotinin for imaging amyloid deposits and perhaps 99m Tc-labelled phosphate derivatives, especially in the differential diagnosis of the aetiology of cardiac amyloidosis. PET tracers, despite the advantage of absolute quantification and higher resolution, are not yet well evaluated for the study of cardiac amyloidosis. Because of these advantages, there is still the need for further research in this field.

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Myocardial Muscarinic Receptor Upregulation and Normal Response to Isoproterenol in Denervated Hearts by Familial Amyloid Polyneuropathy

Cited by 48 publications

References 38 publications

Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy

Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy

Muscarinic Receptor Upregulation in Patients With Myocardial Infarction

Nuclear imaging in cardiac amyloidosis

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