title: Ventricular structure and function in aged dogs with renal hypertension: a model of experimental diastolic heart failure.
abstract: BACKGROUND
  Heart failure (HF) with normal ejection fraction (diastolic HF [DHF]) usually occurs in elderly patients with hypertension. The presence and significance of altered systolic and diastolic ventricular function in DHF is increasingly controversial. Our objective was to develop a clinically relevant large-animal model to better understand the pathophysiology of DHF.
  
  
  RESULTS
  Ventricular structure and function were characterized in young control (YC group; n=6), old control (OC group; n=7), and old dogs made hypertensive by renal wrapping (experimental DHF [ExDHF] group; n=8). The ExDHF group was associated with normal left ventricular (LV) volume, increased LV mass, and myocardial fibrosis. LV relaxation was impaired in ExDHF (tau=53+/-6 ms) compared with OC (tau=35+/-3 ms; P<0.05) and YC (tau=33+/-6 ms; P<0.05) dogs. The percent diastole at which relaxation is complete was increased in ExDHF (116+/-30%) compared with OC (69+/-8%; P<0.05) and YC (35+/-5%; P<0.05) dogs. The coefficient of LV diastolic stiffness was similar in OC, YC, and ExDHF dogs. Diastolic pressures increased dramatically in response to increases in blood pressure. End-systolic LV stiffness was enhanced in ExDHF dogs and after load enhancement of myocardial performance was maintained. Arterial stiffness was increased in ExDHF dogs.
  
  
  CONCLUSIONS
  Aged dogs with chronic hypertension exhibit LV hypertrophy and fibrosis with impaired LV relaxation but no increase in the coefficient of LV diastolic stiffness. LV systolic and arterial stiffness are increased, which may exacerbate load-dependent impairment of relaxation and contribute to increased filling pressures with hypertensive episodes. This model mimics many of the structural and functional characteristics described in the limited studies of human DHF and provides insight into the pathogenesis of DHF.
authors.affiliation: Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minn 55905, USA.
authors.forename: Vijaya K
authors.initials: VK
authors.lastname: Munagala
authors.forename: Chari Y T
authors.initials: CY
authors.lastname: Hart
authors.forename: John C
authors.initials: JC
authors.lastname: Burnett
authors.forename: Donna M
authors.initials: DM
authors.lastname: Meyer
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Redfield
mesh_terms: D000375:Aging; D000818:Animals; D003971:Diastole; D004285:Dogs; D005355:Fibrosis; D006333:Heart Failure / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D006977:Hypertension, Renal / Q000150:complications* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology; D018583:Pliability; D013599:Systole
references.citation: Heart. 2002 Feb;87(2):121-5
references.pmid: 11796546
references.citation: Heart. 2002 Jan;87(1):29-31
references.pmid: 11751660
references.citation: Circulation. 2002 Mar 26;105(12):1503-8
references.pmid: 11914262
references.citation: J Card Fail. 2002 Oct;8(5):279-87
references.pmid: 12411978
references.citation: JAMA. 2002 Nov 6;288(17):2144-50
references.pmid: 12413374
references.citation: Circulation. 2003 Feb 11;107(5):656-8
references.pmid: 12578861
references.citation: Circulation. 2003 Feb 11;107(5):714-20
references.pmid: 12578874
references.citation: J Hypertens. 2003 Sep;21(9):1737-45
references.pmid: 12923407
references.citation: N Engl J Med. 2004 May 6;350(19):1953-9
references.pmid: 15128895
references.citation: J Clin Invest. 1978 Dec;62(6):1296-1302
references.pmid: 748380
references.citation: Circulation. 1985 May;71(5):994-1009
references.pmid: 3986986
references.citation: Circulation. 1988 Jun;77(6):1203-12
references.pmid: 3286035
references.citation: Circulation. 1991 May;83(5):1676-84
references.pmid: 1827056
references.citation: Am J Physiol. 1991 Jul;261(1 Pt 2):H70-6
references.pmid: 1858932
references.citation: Circ Res. 1992 Jan;70(1):9-19
references.pmid: 1345778
references.citation: Ann Biomed Eng. 1992;20(1):41-62
references.pmid: 1562104
references.citation: Circulation. 1992 Jun;85(6):2326-8
references.pmid: 1317276
references.citation: Circ Res. 1993 Apr;72(4):795-806
references.pmid: 8095187
references.citation: Circulation. 1993 Oct;88(4 Pt 1):1893-906
references.pmid: 8403335
references.citation: Am J Cardiol. 1995 Oct 1;76(10):702-5
references.pmid: 7572629
references.citation: Am J Physiol. 1997 Nov;273(5 Pt 2):H2406-14
references.pmid: 9374778
references.citation: Basic Res Cardiol. 1998;93 Suppl 1:108-16
references.pmid: 9833138
references.citation: J Am Coll Cardiol. 1999 Jan;33(1):267-72
references.pmid: 9935040
references.citation: Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):793-8
references.pmid: 10639159
references.citation: Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H698-705
references.pmid: 10710336
references.citation: Curr Cardiol Rep. 2000 Sep;2(5):461-9
references.pmid: 10980915
references.citation: Cardiol Clin. 2000 Aug;18(3):571-86
references.pmid: 10986590
references.citation: Circulation. 2000 Sep 19;102(12):1388-93
references.pmid: 10993857
references.citation: N Engl J Med. 2001 Jan 4;344(1):17-22
references.pmid: 11136955
references.citation: Circulation. 2001 Jul 10;104(2):215-20
references.pmid: 11447089
references.citation: Circulation. 2001 Aug 14;104(7):779-82
references.pmid: 11502702
references.citation: J Pharmacol Exp Ther. 2001 Sep;298(3):1161-6
references.pmid: 11504815
references.citation: J Am Coll Cardiol. 2001 Sep;38(3):796-802
references.pmid: 11527636
references.citation: Circulation. 2002 Mar 12;105(10):1195-201
references.pmid: 11889013