Affiliation:
1. From the Department of Veterans Affairs Medical Center (C.H.C., W.W.B., J.A.H., K.G.R., O.H.L.B.), Boston, Mass; Department of Medicine (C.H.C., W.W.B., O.H.L.B.), Tufts University School of Medicine, Boston, Mass; Department of Pathology (J.A.H.), Boston University School of Medicine, Boston, Mass; and Research Division (S.S.), Cleveland Clinic Foundation, Cleveland, Ohio.
Abstract
Background
Fibrosis is commonly found in association with cardiac hypertrophy and failure, but the relation of the connective tissue response to the development of impaired cardiac function remains unclear. We examined passive myocardial stiffness, active contractile function, and fibrosis in the spontaneously hypertensive rat (SHR), a model of chronic pressure overload in which impaired cardiac function follows a long period of stable hypertrophy.
Methods and Results
We studied the passive and active mechanical properties of left ventricular (LV) papillary muscles isolated from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) at the ages of 12 months and 20 to 23 months. Seven of 15 SHR between 20 and 23 months of age had findings consistent with heart failure (SHR-F). In comparison to preparations from WKY rats and nonfailing SHR (SHR-NF), papillary muscles from the SHR-F group demonstrated increased passive stiffness (central segment exponential stiffness constant,
k
cs
: SHR-F 95.6±19.8, SHR-NF 42.1±9.7, WKY rats 39.5±9.5 (mean±SD); SHR-F
P
<.01 versus SHR-NF, WKY rats). The increase in stiffness was associated with an increase in LV collagen concentration (SHR-F 8.71±3.14, SHR-NF 5.83±1.20, WKY rats 4.78±0.70 mg hydroxyproline/g dry LV wt; SHR-F
P
<.01 versus SHR-NF, WKY rats); an increase in interstitial fibrosis, as determined histologically (SHR-F 13.5±8.0%, SHR-NF 4.9±2.1%, WKY rats 3.6±0.8%; SHR-F
P
<.01 versus SHR-NF, WKY rats); and impaired tension development (SHR-F 3.18±1.27, SHR-NF 4.41±1.04, WKY rats 4.64±0.85 kdyne/mm
2
; SHR-F
P
<.05 versus SHR-NF;
P
<.01 versus WKY rats).
Conclusions
The development of heart failure in the aging SHR is associated with marked myocardial fibrosis, increased passive stiffness, and impaired contractile function relative to age-matched nonfailing SHR and nonhypertensive control animals. These data suggest that fibrosis or events underlying the connective tissue response are important in the transition from compensated hypertrophy to failure in the SHR.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Physiology (medical),Cardiology and Cardiovascular Medicine
Reference53 articles.
1. A mechanism of hypertrophy and wear of the myocardium
2. Cardiac function and morphology with aging in the spontaneously hypertensive rat
3. Bing OHL Wiegner AW. Myocardial mechanics in the spontaneously hypertensive rat: changes with age. In: Alpert NR ed. Perspectives in Cardiovascular Research Vol 7 Myocardial Hypertrophy and Failure. New York NY: Raven Press; 1983:281-291.
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