Volume overload left ventricular hypertrophy: effects on coronary microvascular reactivity in rabbits

Abstract

The mechanisms controlling the coronary vascular responses of vessels perfusing the left ventricular (LV) myocardium that is hypertrophied from chronic volume overload are unclear. We hypothesised that endothelial function is compromised, and receptor-mediated contraction is exacerbated, in coronary resistance vessels from rabbits with LV hypertrophy compared to controls. The mitral valve of 10 rabbits was damaged surgically to cause mitral regurgitation and chronic volume overload, resulting in LV hypertrophy (LV hypertrophy rabbits). Echocardiographic assessment at 12 weeks verified that mitral regurgitation was present in LV hypertrophy but not sham-operated, weight-and agematched animals (control rabbits; n = 17). Percentage increases from weeks 0 to 12 in LV cross-sectional area (47 f 7 % vs. 2 f S%), LV volume (47 f 14% vs. 7 f 10%) and LV mass (27 f 4% vs. 3 f 6%), were greater (all P < 0.05) in LV hypertrophy vs. control rabbits, respectively. At 12 weeks, coronary resistance vessel (-130 pm, internal diameter) reactivity was evaluated using wire myography. Endothelium-dependent (i.e. acetylcholine, 10-8-10-5 M) and -independent (i.e. sodium nitroprusside, 10-9-104 M) relaxation, and receptor-mediated vasocontraction (i.e. endothelin-1, 10-"-10-7 M) were similar between groups. However, tension development in response to nitric oxide synthase inhibition (lo4 M NG-monomethyl-carginine) was greater (P < 0.05) in LV hypertrophy compared to control rabbits. These results indicate that while coronary resistance vessel function is similar between groups, our estimate of basal nitric oxide production is greater in vessels from LV hypertrzophy than control rabbits. Experimental Physiology (2001) 86.6,725-732. Left ventricular (LV) hypertrophy is an important risk factor for cardiac mortality and morbidity (Sheridan et al. 1993). Concentric LV hypertrophy develops to compensate for increased ventricular wall stress resulting from chronic pressure overload caused by, for example, aortic stenosis or systemic hypertension (pressure overload LV hypertrophy) while eccentric LV hypertrophy results from long-term volume overload caused by, for example, aortic or mitral regurgitation (volume overload LV hypertrophy) (Chilian, 1987).

Prognostic Value of Coronary Flow Reserve in Patients with Dialysis-Dependent ESRD

“…However, consistent evidence from experimental animals and humans suggests that endothelium-dependent or -independent coronary vasodilatory function is not affected by volume overload. [19][20][21] Finally, our sample size limited the number of confounding variables that we could adjust for in our multivariable Cox survival analyses and may have limited our power to detect weak associations of baseline characteristics with global CFR.…”

Longitudinal assessment of endothelial function in the microvasculature of mice in-vivo

“…In animal studies, this is carried out by intra-vital microscopy, or more commonly by ex-vivo wire myography, which allows investigators to examine functional responses and vascular reactivity of isolated resistance arteries (Shafaroudi et al, 2005). This technique has been utilized successfully in vessels from various species (Argyle and McGrath, 2000;Arribas et al, 1997;Docherty et al, 2001;Jones et al, 2003;Symons et al, 2001), including transgenic models (Eichhorn et al, 2009;Sainsbury et al, 2004), and in pathological disease states (Sharifi et al, 1998). A major limitation of using such methodology is that animals need to be culled in order to harvest the required vascular tissue.…”

Accuracy of the Electrocardiograph in Detecting Cardiac Left Ventricular Hypertrophy in Pediatric Patients with Aortic Valve Disease

“…Aortic stenosis refers to a narrowing of the aortic valve, resulting in greater resistance (by Laplace's law) faced by the left ventricle. Over time, this can translate into a maladaptive burden and an increased afterload upon the left ventricle, leading to the development of LVH as a compensatory mechanism [6,12]. These ventricular modifications may be detected through voltage changes -the 12-lead electrocardiogram (ECG) is an important tool in preliminary detection of left ventricular voltage changes.…”

“…These mechanical stresses placed on the heart may be pressure or volume-mediated [6]. Pressure-induced hypertrophy induces concentric hypertrophy (thickening of cardiac muscle without dilatation), while volumemediated hypertrophy is termed eccentric hypertrophy, or left ventricular dilatation (LVD) [6]. The difference between these forms of hypertrophy stems from the addition of sarcomeric units added in series (eccentric) or in parallel (concentric) [2].…”

“…LVH typically arises as a compensatory mechanism against a chronic increase in cardiac workload, though neurochemical and hormonal stimuli have also been implicated, including mediators such as cardiotrophin -1 and parathyroid hormone [3][4][5]. These mechanical stresses placed on the heart may be pressure or volume-mediated [6]. Pressure-induced hypertrophy induces concentric hypertrophy (thickening of cardiac muscle without dilatation), while volumemediated hypertrophy is termed eccentric hypertrophy, or left ventricular dilatation (LVD) [6].…”