Clenbuterol administration with pressure overload in rats increased LV mass index by 66.1% versus 49.7% with banding alone, while preserving LV function and reducing fibrosis.
Does clenbuterol or thyroxine improve LV function and structure in Sprague-Dawley rats with pressure-overload cardiac hypertrophy?
In a rat model of pressure overload, clenbuterol induced cardiac hypertrophy with preserved left ventricular function, reduced fibrosis, and maintained SERCA2a expression compared to pressure overload alone.
Absolute Event Rate: 66.1% vs 49.7%
Background Appropriate cardiac hypertrophy (CH) is necessary in several clinical settings, such as pulmonary artery banding in the two-stage arterial switch operation for transposition of the great arteries. Pressure-overload CH, however, produces ventricular dysfunction due to structural and molecular changes. The β 2 -adrenergic receptor agonist clenbuterol has been shown to induce CH without such adverse effects to the rat heart. This study was performed to determine its effects on left ventricular (LV) function, structure, and gene expression in pressure-overload CH. Methods and Results Sprague-Dawley rats were assigned to one of four groups: 1, sham-operated (n=15); 2, banding of ascending aorta (n=22); 3, banding+clenbuterol (n=18); and 4, banding+thyroxine (n=17). At the end of 3 weeks, groups 2, 3, and 4 showed an increase in LV mass index of 49.7±5.1%, 66.1±3.8%, and 47.6±4.6%, respectively, relative to group 1. A subgroup with severe CH (>50%) in group 2 was found to have significantly impaired developed pressure and diastolic relaxation and an increase in passive stiffness, with significantly reduced LV expression of sarcoplasmic reticulum Ca 2+ -ATPase2a (SERCA2a) mRNA and increased LV collagen concentration. In comparison, similarly hypertrophied animals in groups 3 and 4 demonstrated improved developed pressure, normal relaxation and diastolic stiffness with normal collagen concentration, and a greater abundance of SERCA2a mRNA. Conclusions Clenbuterol administration in conjunction with pressure overload produces a specific type of CH with preserved LV function. In addition, an increase in LV mass was associated with less fibrosis and greater expression of SERCA2a mRNA than banding alone.
Wong et al. (Tue,) conducted a other in Pressure-overload cardiac hypertrophy (n=72). Clenbuterol vs. Banding of ascending aorta alone was evaluated on Increase in left ventricular mass index relative to sham. Clenbuterol administration with pressure overload in rats increased LV mass index by 66.1% versus 49.7% with banding alone, while preserving LV function and reducing fibrosis.
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