Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model

Dennis H. Lau, Lorraine MacKenzie, Arumuga Rajendram, Peter J. Psaltis, Douglas R. Kelly, Peter Spyropoulos, Yuan Zhang, Santosh A. Olakkengil, Christine H. Russell, Anthony G. Brooks, Randall J. Faull, David A. Saint, Darren J. Kelly, M. Mohan Rao, Stephen G. Worthley, Prashanthan Sanders

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective. The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. Methods. 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73±28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. Results. In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107±12 to 169±27, diastolic BP: 71±10 to 118±29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7±0.5 vs 2.1±0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9±4.9 vs 15.7±2.8g, p=0.003; left atrial, LA: 35.5±6.7 vs 20.9±4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9±6.8 vs 28.7±6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1±3.6 vs 31.6±3.0%, p=0.001) while LV function was relatively preserved (42.3±4.7 vs 46.4±4.1%, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. Conclusions. The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.

LanguageEnglish
Pages119-125
Number of pages7
JournalBlood Pressure
Volume19
Issue number2
DOIs
Publication statusPublished - 1 Jan 2010

Keywords

  • Animal models
  • Cardiac remodeling
  • Hypertension
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Lau, D. H., MacKenzie, L., Rajendram, A., Psaltis, P. J., Kelly, D. R., Spyropoulos, P., ... Sanders, P. (2010). Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model. Blood Pressure, 19(2), 119-125. https://doi.org/10.3109/08037050903576767
Lau, Dennis H. ; MacKenzie, Lorraine ; Rajendram, Arumuga ; Psaltis, Peter J. ; Kelly, Douglas R. ; Spyropoulos, Peter ; Zhang, Yuan ; Olakkengil, Santosh A. ; Russell, Christine H. ; Brooks, Anthony G. ; Faull, Randall J. ; Saint, David A. ; Kelly, Darren J. ; Rao, M. Mohan ; Worthley, Stephen G. ; Sanders, Prashanthan. / Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model. In: Blood Pressure. 2010 ; Vol. 19, No. 2. pp. 119-125.
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abstract = "Objective. The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. Methods. 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60{\%} ({"}one kidney-one clip{"}, 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73±28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. Results. In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107±12 to 169±27, diastolic BP: 71±10 to 118±29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7±0.5 vs 2.1±0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9±4.9 vs 15.7±2.8g, p=0.003; left atrial, LA: 35.5±6.7 vs 20.9±4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9±6.8 vs 28.7±6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1±3.6 vs 31.6±3.0{\%}, p=0.001) while LV function was relatively preserved (42.3±4.7 vs 46.4±4.1{\%}, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. Conclusions. The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.",
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author = "Lau, {Dennis H.} and Lorraine MacKenzie and Arumuga Rajendram and Psaltis, {Peter J.} and Kelly, {Douglas R.} and Peter Spyropoulos and Yuan Zhang and Olakkengil, {Santosh A.} and Russell, {Christine H.} and Brooks, {Anthony G.} and Faull, {Randall J.} and Saint, {David A.} and Kelly, {Darren J.} and Rao, {M. Mohan} and Worthley, {Stephen G.} and Prashanthan Sanders",
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Lau, DH, MacKenzie, L, Rajendram, A, Psaltis, PJ, Kelly, DR, Spyropoulos, P, Zhang, Y, Olakkengil, SA, Russell, CH, Brooks, AG, Faull, RJ, Saint, DA, Kelly, DJ, Rao, MM, Worthley, SG & Sanders, P 2010, 'Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model', Blood Pressure, vol. 19, no. 2, pp. 119-125. https://doi.org/10.3109/08037050903576767

Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model. / Lau, Dennis H.; MacKenzie, Lorraine; Rajendram, Arumuga; Psaltis, Peter J.; Kelly, Douglas R.; Spyropoulos, Peter; Zhang, Yuan; Olakkengil, Santosh A.; Russell, Christine H.; Brooks, Anthony G.; Faull, Randall J.; Saint, David A.; Kelly, Darren J.; Rao, M. Mohan; Worthley, Stephen G.; Sanders, Prashanthan.

In: Blood Pressure, Vol. 19, No. 2, 01.01.2010, p. 119-125.

Research output: Contribution to journalArticle

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T1 - Characterization of cardiac remodeling in a large animal "one-kidney, one-clip" hypertensive model

AU - Lau, Dennis H.

AU - MacKenzie, Lorraine

AU - Rajendram, Arumuga

AU - Psaltis, Peter J.

AU - Kelly, Douglas R.

AU - Spyropoulos, Peter

AU - Zhang, Yuan

AU - Olakkengil, Santosh A.

AU - Russell, Christine H.

AU - Brooks, Anthony G.

AU - Faull, Randall J.

AU - Saint, David A.

AU - Kelly, Darren J.

AU - Rao, M. Mohan

AU - Worthley, Stephen G.

AU - Sanders, Prashanthan

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N2 - Objective. The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. Methods. 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73±28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. Results. In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107±12 to 169±27, diastolic BP: 71±10 to 118±29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7±0.5 vs 2.1±0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9±4.9 vs 15.7±2.8g, p=0.003; left atrial, LA: 35.5±6.7 vs 20.9±4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9±6.8 vs 28.7±6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1±3.6 vs 31.6±3.0%, p=0.001) while LV function was relatively preserved (42.3±4.7 vs 46.4±4.1%, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. Conclusions. The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.

AB - Objective. The aim of this study is to characterize cardiac remodeling in a large animal model of hypertension. Methods. 23 sheep were subjected to unilateral nephrectomy followed by clamping of the remaining renal artery to 60% ("one kidney-one clip", 1K1C) 3 weeks later. Blood pressure (BP) was monitored invasively over 73±28 days. Cardiac function was assessed with magnetic resonance imaging and compared with 12 size-matched controls. Detailed atrial histopathological analysis was performed. Results. In the 1K1C animals, BP rose from baseline to reach a plateau by 4 weeks (systolic BP: 107±12 to 169±27, diastolic BP: 71±10 to 118±29 mmHg, both p< 0.0001); cardiac hypertrophy was significant when compared with controls with increased left ventricular weight [left ventricular (LV)/body wt: 2.7±0.5 vs 2.1±0.2 g/kg, p=0.01] as well as bi-atrial enlargement (right atrial, RA: 22.9±4.9 vs 15.7±2.8g, p=0.003; left atrial, LA: 35.5±6.7 vs 20.9±4.1g, p=0.0003); cardiac magnetic imaging demonstrated significantly increased LA volumes (end-diastolic volume: 42.9±6.8 vs 28.7±6.3 ml, p< 0.0001) and reduced LA ejection fraction (24.1±3.6 vs 31.6±3.0%, p=0.001) while LV function was relatively preserved (42.3±4.7 vs 46.4±4.1%, p=0.1); degeneration and necrosis of atrial myocytes were evident with increased atrial lymphocytic infiltration and interstitial fibrosis. Conclusions. The ovine 1K1C model produces reliable and reproducible hypertension with demonstrable cardiac end-organ damage.

KW - Animal models

KW - Cardiac remodeling

KW - Hypertension

KW - Magnetic resonance imaging

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