PT  - JOURNAL ARTICLE
AU  - Dinko Susic
AU  - Edward D. Frohlich
TI  - Increased Collagen, Per Se, May Not Affect Left Ventricular Function in Spontaneously Hypertensive Rats
DP  - 2011 Sep 21
TA  - Ochsner Journal
PG  - 241--245
VI  - 11
IP  - 3
4099  - http://www.ochsnerjournal.org/content/11/3/241.short
4100  - http://www.ochsnerjournal.org/content/11/3/241.full
SO  - Ochsner J2011 Sep 21; 11
AB  - Background Left ventricular fibrosis is considered to be a major participant in the development of cardiac dysfunction in various conditions (hypertension, aging, etc). Because cardiac myocytes as well as blood supply may also be affected in these conditions, it is difficult to define quantitatively the role of fibrosis. We hypothesized that by inducing myocardial collagen accumulation by treatment with an inhibitor (doxycycline) of matrix metalloproteinases, which by itself should not affect cardiac myocytes, we might examine a more specific role of fibrosis in cardiac dysfunction.Methods Adult male spontaneously hypertensive rats were divided into 2 groups. The control group received no treatment; the second group was given doxycycline (30 mg/kg/day) for 6 months. Arterial pressure, pulse wave velocity, indexes of heart function (end-diastolic pressure, maximal rates of pressure rise and fall [dP/dtmax and dP/dtmin], diastolic time constant [Tau]), weight indexes, and myocardial collagen concentration were determined at the end.Results The results demonstrated that treatment with an inhibitor of matrix metalloproteinases induced significant accumulation of ventricular collagen, as indicated by increased ventricular hydroxyproline concentration (4.71 ± 0.12 mg/g vs 5.35 ± 0.17 mg/g in control and doxycycline groups, respectively). However, arterial pressure, aortic stiffness (pulse wave velocity), and left ventricular function were unaffected.Conclusions These findings suggest that moderate collagen accumulation does not by itself adversely affect cardiovascular function and that other changes in collagen properties (eg, formation of advanced glycation end-products) may be responsible for the adverse effects of myocardial fibrosis.