Klatt, Niklas, Scherschel, Katharina ORCID: 0000-0002-3237-140X, Schad, Claudia, Lau, Denise, Reitmeier, Aline, Kuklik, Pawel, Muellerleile, Kai, Yamamura, Jin, Zeller, Tanja, Steven, Daniel, Baldus, Stephan, Schaeffer, Benjamin, Jungen, Christiane, Eickholt, Christian ORCID: 0000-0002-5458-9688, Wassilew, Katharina ORCID: 0000-0002-8683-465X, Schwedhelm, Edzard, Willems, Stephan and Meyer, Christian (2016). Development of nonfibrotic left ventricular hypertrophy in an ANG II-induced chronic ovine hypertension model. PHYSIOL. REP., 4 (17). HOBOKEN: WILEY. ISSN 2051-817X

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Abstract

Hypertension is a major risk factor for many cardiovascular diseases and leads to subsequent concomitant pathologies such as left ventricular hypertrophy (LVH). Translational approaches using large animals get more important as they allow the use of standard clinical procedures in an experimental setting. Therefore, the aim of this study was to establish a minimally invasive ovine hypertension model using chronic angiotensin II (ANG II) treatment and to characterize its effects on cardiac remodeling after 8weeks. Sheep were implanted with osmotic minipumps filled with either vehicle control (n=7) or ANG II (n=9) for 8weeks. Mean arterial blood pressure in the ANG II-treated group increased from 87.4 +/- 5.3 to 111.8 +/- 6.9mmHg (P=0.00013). Cardiovascular magnetic resonance imaging showed an increase in left ventricular mass from 112 +/- 12.6g to 131 +/- 18.7g after 7weeks (P=0.0017). This was confirmed by postmortem measurement of left ventricular wall thickness which was higher in ANG II-treated animals compared to the control group (18 +/- 4mm vs. 13 +/- 2mm, respectively, P=0.002). However, ANG II-treated sheep did not reveal any signs of fibrosis or inflammatory infiltrates as defined by picrosirius red and H&E staining on myocardial full thickness paraffin sections of both atria and ventricles. Measurements of plasma high-sensitivity C-reactive protein and urinary 8-iso-prostaglandin F-2 were inconspicuous in all animals. Furthermore, multielectrode surface mapping of the heart did not show any differences in epicardial conduction velocity and heterogeneity. These data demonstrate that chronic ANG II treatment using osmotic minipumps presents a reliable, minimally invasive approach to establish hypertension and nonfibrotic LVH in sheep.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Klatt, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scherschel, KatharinaUNSPECIFIEDorcid.org/0000-0002-3237-140XUNSPECIFIED
Schad, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lau, DeniseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reitmeier, AlineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuklik, PawelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muellerleile, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yamamura, JinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeller, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steven, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baldus, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaeffer, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jungen, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eickholt, ChristianUNSPECIFIEDorcid.org/0000-0002-5458-9688UNSPECIFIED
Wassilew, KatharinaUNSPECIFIEDorcid.org/0000-0002-8683-465XUNSPECIFIED
Schwedhelm, EdzardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Willems, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-264036
DOI: 10.14814/phy2.12897
Journal or Publication Title: PHYSIOL. REP.
Volume: 4
Number: 17
Date: 2016
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 2051-817X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CARDIOVASCULAR MAGNETIC-RESONANCE; ANGIOTENSIN-II; 8-ISO-PROSTAGLANDIN F2-ALPHA; CARDIAC FIBROSIS; HEART-FAILURE; PRESSURE; SHEEP; INFLAMMATION; REGRESSION; DISEASEMultiple languages
PhysiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26403

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