High-dose simvastatin normalized renal sympathetic nerve activity in rabbits with pacing-induced chronic heart failure (21.1% vs 39.4% in CHF controls).
Does simvastatin improve autonomic neural control in an experimental rabbit model of heart failure?
High-dose simvastatin normalizes sympathetic outflow and reflex regulation in an experimental rabbit model of heart failure, suggesting a non-lipid-lowering mechanism for statin benefits in CHF.
Absolute Event Rate: 21.1% vs 39.4%
BACKGROUND: HMG-CoA reductase inhibitors (statins) have been shown to beneficially affect outcomes in chronic heart failure (CHF). We hypothesized that statins exert effects on autonomic function, as assessed by plasma norepinephrine levels, direct recordings of renal sympathetic nerve activity (RSNA), and baroreflex function. METHODS AND RESULTS: Normolipidemic CHF rabbits were treated with simvastatin or vehicle. CHF was induced by continuous ventricular pacing at 320 to 340 bpm for 3 weeks. Two to 3 days after instrumentation of the rabbits with renal nerve electrodes and arterial and venous catheters, blood samples and RSNA recordings were obtained in the conscious state. Baroreflex function was assessed after administration of sodium nitroprusside and phenylephrine. Mean baseline RSNA (+/-SEM) in normal rabbits was 19.3+/-3.8%; in CHF rabbits, 39.4+/-2.9% (P<0.05); in CHF rabbits on low-dose (0.3 mg x kg(-1) x d(-1)) simvastatin, 39.8+/-8.3% (P<0.05); and in CHF rabbits on high-dose simvastatin (3 mg x kg(-1) x d(-1)), 21.1+/-4.5% (P=NS). Similar data were observed for plasma norepinephrine. In CHF rabbits treated with 3 mg x kg(-1) x d(-1) simvastatin, baroreflex regulation of heart rate to transient hypotension with sodium nitroprusside was normalized by 66% compared with CHF controls. CONCLUSIONS: These are the first data showing that non-lipid-lowering statin effects include a normalization of sympathetic outflow and reflex regulation in CHF. The precise neural and cellular pathways involved in these responses need further clarification. This finding may have important implications for the treatment of CHF and progression of the disease process.
Pliquett et al. (Mon,) conducted a other in Chronic heart failure (experimental). Simvastatin vs. Vehicle (CHF controls) was evaluated on Mean baseline renal sympathetic nerve activity (RSNA). High-dose simvastatin normalized renal sympathetic nerve activity in rabbits with pacing-induced chronic heart failure (21.1% vs 39.4% in CHF controls).