title: Reverse remodeling and enhanced adrenergic reserve from passive external support in experimental dilated heart failure.
abstract: OBJECTIVE
  We sought to test the efficacy of a passive elastic containment device to reverse chronic chamber remodeling and adrenergic down-regulation in the failing heart, yet still maintaining preload reserve.
  
  
  BACKGROUND
  Progressive cardiac remodeling due to heart failure is thought to exacerbate underlying myocardial dysfunction. In a pressure-volume analysis, we tested the impact of limiting progressive cardiac dilation by an externally applied passive containment device on both basal and adrenergic-stimulated function in failing canine hearts.
  
  
  METHODS
  Ischemic dilated cardiomyopathy was induced by repeated intracoronary microembolizations in six dogs. The animals were studied before and three to six months after surgical implantation of a thin polyester mesh (cardiac support device [CSD]) that surrounded both cardiac ventricles. Pressure-volume relations were measured by a conductance micromanometer catheter.
  
  
  RESULTS
  Long-term use of the CSD lowered end-diastolic and end-systolic volumes by -19 +/- 4% and -22 +/- 8%, respectively (both p < 0.0001) and shifted the end-systolic pressure-volume relation to the left (p < 0.01), compatible with reverse remodeling. End-diastolic pressure and chamber diastolic stiffness did not significantly change. The systolic response to dobutamine markedly improved after CSD implantation (55 +/- 8% rise in ejection fraction after CSD vs. -10 +/- 8% before CSD, p < 0.05), in conjunction with a heightened adenylyl cyclase response to isoproterenol. There was no change in the density or affinity of beta-adrenergic receptors. Diastolic compliance was not adversely affected, and preload-recruitable function was preserved with the CSD, consistent with a lack of constriction.
  
  
  CONCLUSIONS
  Reverse remodeling with reduced systolic wall stress and improved adrenergic signaling can be achieved by passive external support that does not generate diastolic constriction. This approach may prove useful in the treatment of chronic heart failure.
authors.affiliation: Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
authors.forename: W Federico
authors.initials: WF
authors.lastname: Saavedra
authors.forename: Richard S
authors.initials: RS
authors.lastname: Tunin
authors.forename: Nazareno
authors.initials: N
authors.lastname: Paolocci
authors.forename: Takayuki
authors.initials: T
authors.lastname: Mishima
authors.forename: George
authors.initials: G
authors.lastname: Suzuki
authors.forename: Charles W
authors.initials: CW
authors.lastname: Emala
authors.forename: Pervaiz A
authors.initials: PA
authors.lastname: Chaudhry
authors.forename: Petros
authors.initials: P
authors.lastname: Anagnostopoulos
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
authors.forename: Hani N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: David A
authors.initials: DA
authors.lastname: Kass
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D003328:Coronary Thrombosis / Q000503:physiopathology; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy; D007091:Image Processing, Computer-Assisted; D023421:Models, Animal; D009200:Myocardial Contraction / Q000502:physiology; D011091:Polyesters; D019736:Prostheses and Implants; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D017725:Ventricular Pressure; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D011091:Polyesters; D004280:Dobutamine