Carotid baroreceptor stimulation improves cardiac performance and reverses ventricular remodelling in canines with pacing-induced heart failure

Abstract

AimsCarotid baroreceptor stimulation (CBS) has potential protective effects on chronic heart failure (CHF). The aim of our study was to investigate the effects of CBS on more detailed aspects of ventricular remodelling and the underlying mechanisms in a CHF canine model. Main methodsTwenty-four beagles were randomised into Con (n = 8), CHF (n = 8), and CHF-CBS (n = 8) groups. The CHF and CHF-CBS groups underwent 6 weeks of rapid ventricular pacing (RVP) at 250 beats per minute to establish a CHF model. Concomitant CBS was delivered together with RVP in the CHF-CBS group. Key findingsRVP for 6 weeks caused typical heart failure in the CHF group. CBS significantly reversed the decrease in the high-frequency heart rate variability component and increase in low-frequency/high-frequency ratio induced by RVP. CBS significantly reduced cardiac dilation, improved left ventricle ejection fraction, and inhibited the increase in natriuretic peptide mRNA expression of LV tissue. CBS alleviated collagen volume fraction and reduced protein expression of transforming growth factor β1, matrix metallopeptidase 2, and matrix metallopeptidase 9, as well as decreased the percentage of TUNEL-positive nuclei and protein expression of Caspase-3 in LV tissue. The intracellular PKA signalling pathway and cardiac inflammation of LV tissue were upregulated in the CHF group, and markedly inhibited by CBS. SignificanceOur study found that CBS improved cardiac performance and reversed ventricular remodelling in CHF canines by rebalancing the autonomic nervous system; the suppression of the intracellular PKA signalling pathway and cardiac inflammation might underly the mechanisms.