HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/H2971    most recent 00571.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Costandi, P. N. Articles by Omens, J. H. Search for Related Content PubMed PubMed Citation Articles by Costandi, P. N. Articles by Omens, J. H.

Role of diastolic properties in the transition to failure in a mouse model of the cardiac dilatation

Departments of ¹Bioengineering and ²Radiology, University of California, San Diego, La Jolla, California

Submitted 1 June 2006 ; accepted in final form 7 July 2006

Although the physiological states of hypertrophic remodeling and congestive heart failure have been intensively studied, less is known about the transition from one to the other. The use of genetically engineered murine models of heart failure has proven valuable in characterizing the progression of remodeling and its ultimate decompensation to failure. Mice deficient in the cytoskeletal muscle LIM-only protein (MLP) are known to present with a clinical picture of dilated cardiomyopathy and transition to failure as adults. Longitudinal high-field magnetic resonance (MR) cardiac imaging provided a time course of remodeling where an improvement in ejection fraction and stroke volume (15- vs. 31-wk MLP^–/– mice; P < 0.0001) was temporally concurrent with an abrupt phase of end-diastolic chamber dilatation. Hemodynamic analysis conducted throughout that dilatation phase showed improved ratio of maximum first derivative of pressure to end-diastolic pressure (dP/dt_max/EDP; 15- vs. 31-wk MLP^–/– mice; P < 0.0005), ratio of minimum first derivative of pressure to EDP (dP/dt_min/EDP; 15- vs. 31-wk MLP^–/– mice; P < 0.003), and developed pressure (15- vs. 31-wk MLP^–/– mice; P < 0.0001) levels in the MLP^–/– mice. Computational modeling techniques were used to estimate the EDP volume relationship, revealing that although MLP hearts possess a stiffer stress-strain relation, chamber compliance increased as a function of dilatation. This detailed physiological characterization during a phase of rapid anatomical remodeling suggests that systolic function in the MLP^–/– mice may temporarily improve as a result of alterations in chamber compliance, which are mediated by dilatation. In turn, a balance may exist between exploiting the Frank-Starling mechanism and altering chamber compliance that maintains function in the absence of hypertrophic growth. Though initially compensatory, this process may exhaust itself and consequently transition to a maladaptive course.

magnetic resonance imaging; finite element modeling

This article has been cited by other articles:

				K. M. Shioura, D. L. Geenen, and P. H. Goldspink Assessment of cardiac function with the pressure-volume conductance system following myocardial infarction in mice Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2870 - H2877. [Abstract] [Full Text] [PDF]