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Ventricular late potentials in familial amyloidotic polyneuropathy
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. (kardiologi)
2006 (English)In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 39, no 1, 57-62 p.Article in journal (Refereed) Published
Abstract [en]

It is well known that cytokines are highly involved in the disease process of rheumatoid arthritis (RA). Recently, targeting of neuropeptides has been suggested to have potential therapeutic effects in RA. The aim of this study was to investigate possible interrelations between five neuropeptides (bombesin/gastrin-releasing peptide (BN/GRP), substance P (SP), vasoactive intestinal peptide, calcitonin-gene-related peptide, and neuropeptide Y) and the three cytokines tumour necrosis factor (TNF)-alpha, IL-6, and monocyte chemoattractant protein-1 in synovial fluid of patients with RA. We also investigated possible interrelations between these neuropeptides and soluble TNF receptor 1 in serum from RA patients. Synovial fluid and sera were collected and assayed with ELISA or RIA. The most interesting findings were correlations between BN/GRP and SP and the cytokines. Thus, in synovial fluid, the concentrations of BN/GRP and SP grouped together with IL-6, and SP also grouped together with TNF-alpha and monocyte chemoattractant protein-1. BN/GRP and SP concentrations in synovial fluid also grouped together with the erythrocyte sedimentation rate. In the sera, BN/GRP concentrations and soluble TNF receptor 1 concentrations were correlated. These results are of interest because blocking of SP effects has long been discussed in relation to RA treatment and because BN/GRP is known to have trophic and growth-promoting effects and to play a role in inflammation and wound healing. Furthermore, the observations strengthen a suggestion that combination treatment with agents interfering with neuropeptides and cytokines would be efficacious in the treatment of RA. In conclusion, BN/GRP and SP are involved together with cytokines in the neuroimmunomodulation that occurs in the arthritic joint.

Place, publisher, year, edition, pages
2006. Vol. 39, no 1, 57-62 p.
Keyword [en]
Adult, Arthritis; Rheumatoid/*blood/immunology, Cytokines/*analysis/blood, Female, Gastrin-Releasing Peptide/*analysis/blood, Humans, Male, Middle Aged, Neuroimmunomodulation/physiology, Substance P/*analysis/blood, Synovial Fluid/*chemistry/immunology
URN: urn:nbn:se:umu:diva-13522DOI: doi:10.1016/j.jelectrocard.2005.06.106PubMedID: 16387053OAI: diva2:153193
Available from: 2007-07-04 Created: 2007-07-04 Last updated: 2012-06-21Bibliographically approved
In thesis
1. Cardiac arrhythmias and heart rate variability in familial amyloidotic polyneuropathy: A clinical study before and after liver transplantation
Open this publication in new window or tab >>Cardiac arrhythmias and heart rate variability in familial amyloidotic polyneuropathy: A clinical study before and after liver transplantation
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Familial amyloidotic polyneuropathy (FAP), found in the northernmost counties in Sweden, is a rare, lethal and inherited amyloidosis. The disease is caused by mutated transthyretin (TTR). The mutation is characterized by an exchange of valine for methionine at position 30 (ATTRVal30Met). FAP is characterised by progressive polyneuropathy affecting both the peripheral and autonomic nervous system (ANS). Cardiac arrhythmia and autonomic disturbances are common as well as gastrointestinal symptoms: such as constipation and diarrhoea.

Today, orthotopic liver transplantation (LTx) is the only treatment to stop the progression of FAP. The rationale for this is because 95% of TTR is synthesized by the liver, a liver transplantation should abolish the production of new mutated amyloidogenic TTR. The first liver transplantation for FAP was performed in Sweden 1990.

Heart complications and autonomic disturbances are common in FAP patients both before and after liver transplantation. The aim of the present study was three-fold: to determine whether liver transplantation affects the natural course of cardiac arrhythmias and cardiac autonomic function; to predict the risk of ventricular arrhythmias; and to elucidate heart rate variability (HRV) patterns by power spectrum analysis and Poincaré plots.

In total, ninety-seven Swedish FAP patients were included in the studies. The patients underwent 24-hours electrocardiography (Holter) recordings, and/or signal averaged electrocardiography (SAECG) and heart rate variability.

The study showed that many patients developed cardiac arrhythmias and conduction disturbances after LTx. Approximately 25 percent of patients were pacemaker treated after LTx. The SAECG recordings disclosed that many FAP patients had ventricular late potentials (LP) compared with healthy subjects, and that LP were associated with nonsustained ventricular arrhythmia. Analyses of heart rate variability (HRV) showed reduced autonomic function in the majority of patients. Some patients had high HRV with broadband power spectra and Poincaré graphs with a fan or complex pattern. These novel findings could be an indicator of ECG abnormalities (subtle atrial arrhythmia) in FAP patients instead of reflecting normal cardiac autonomic modulation. The HRV studies also showed that LTx preserves cardiac autonomic function in FAP.

In conclusion, cardiac arrhythmias, late potentials and reduced heart rate variability were common in Swedish patients with FAP, whether they underwent liver transplantation or not. The absence of LP may indicate a low risk for ventricular tachycardia in FAP patients.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2007. 65 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1116
National Category
urn:nbn:se:umu:diva-1407 (URN)978-91-7264-413-7 (ISBN)
Public defence
2007-11-16, Sal 933, Norrlands universitetssjukhus, Umeå, 13:00 (English)
Available from: 2007-10-26 Created: 2007-10-26 Last updated: 2009-05-25Bibliographically approved

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Wiklund, UrbanSuhr, Ole BJensen, Steen
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