[show abstract][hide abstract] ABSTRACT: To assess whether the variable impact of quantitative changes in myocardial collagen on left ventricular (LV) diastolic myocardial stiffness (myocardial k) and remodelling (increased volume intercept of diastolic pressure-volume relations) in LV hypertrophy (LVH) is associated with alterations in myocardial collagen cross-linking.
We evaluated myocardial collagen content (hydroxyproline concentrations [HPRO]) and the degree of myocardial collagen cross-linking (solubility to cyanogen bromide digestion) in 14-15- and 21-22-month-old spontaneously hypertensive rats (SHRs), and in aortic-banded rats with pressure overload hypertrophy (POH).
In rats with POH and in SHRs irrespective of age, increases in myocardial [HPRO] were noted. However, hypertensive rats differed in the material and geometric properties of the myocardium, and in qualitative aspects of fibrosis. In 14-15-month-old SHRs myocardial k (determined from diastolic stress-strain relations) and insoluble (cross-linked) [HPRO] were increased, but no LV remodelling or increases in myocardial soluble (non-cross-linked) [HPRO] were noted. In rats with POH, LV remodelling and increases in soluble myocardial [HPRO] occurred, but no increase in k or insoluble myocardial [HPRO] were observed. In 21-22-month-old SHRs, increases in k, soluble and insoluble myocardial [HPRO], as well as LV remodelling occurred.
Collagen cross-linking may determine the diverse relation that exists between increases in myocardial collagen concentrations and either myocardial stiffness or chamber remodelling in hypertension. These findings support the notion that fibrosis contributes to myocardial stiffness as well as LV dilatation in LVH, albeit an effect that is modulated by collagen quality.
Cardiovascular Research 04/2003; 57(3):632-41. · 5.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: It is uncertain whether chronic beta-adrenoreceptor (beta-AR)-activation in hypertension could initiate the progression from compensated left ventricular (LV) hypertrophy to pump dysfunction. It is also uncertain if this effect is through adverse LV remodeling (chamber dilatation with wall thinning and pump dysfunction) or intrinsic myocardial contractile dysfunction. We evaluated the effect of 5 months of isoprenaline (0.02 mg x kg(-1) x d(-1)) on hemodynamics, LV wall thickness, cavity size, and interstitial characteristics in spontaneously hypertensive rats (SHR) with compensated LV hypertrophy. In the absence of myocyte necrosis, changes in volume preload, pressure afterload, and heart rate or decreases in baseline systolic myocardial elastance (load independent measure of intrinsic myocardial contractility), ISO produced a right shift in LV diastolic pressure-volume (P-V) relations (chamber dilatation), a decrease in LV wall thickness despite a further increase in LV weight in SHR, LV pump dysfunction (right shift in LV systolic P-V relations), and deleterious interstitial remodeling (increments in total and noncrosslinked myocardial collagen concentrations). The isoprenaline-induced LV geometric, chamber performance, and interstitial changes were similar to alterations noted during decompensation in older SHR. In summary, in the absence of tissue necrosis and baseline intrinsic myocardial contractile dysfunction, chronic beta-AR activation induces interstitial and chamber remodeling and, hence, pump dysfunction. These data suggest that chronic sympathetic activation initiates the progression from compensated concentric LV hypertrophy in hypertension to cardiac dysfunction primarily through deleterious cardiac remodeling rather than intrinsic myocardial contractile dysfunction.