Abnormalities of cardiac sympathetic function in pacing-induced heart failure as assessed by [123I]metaiodobenzylguanidine scintigraphy

Abstract

Background: Increased activity of the sympathetic nervous system contributes significantly to the pathophysiology of heart failure. However, cardiac efferent sympathetic function has not been well characterized in this disorder. In this study, we evaluated cardiac sympathetic innervation using [123I]metaiodobenzylguanidine (MIBG) and compared this with left ventricular (LV) tissue norepinephrine concentration and myocardial perfusion, assessed by 201Tl, in a canine model of heart failure. Methods and Results: Planar and tomographic cardiac imaging was performed for MIBG and 201Tl in 23 dogs: 8 normal dogs (group 1) and 15 dogs with heart failure induced by right ventricular pacing at 250 beats per minute either continuously for 3 weeks (group 2) or intermittently for 7 weeks (group 3). Plasma and LV tissue norepinephrine concentrations were also measured. Scintigraphic studies in group 2 demonstrated reduced cardiac MIBG activity at heart failure (0.17±0.04 versus 0.29±0.05 counts per megabecquerel per pixel at baseline, mean±SD; P=.0001), whereas thallium activity was unchanged from baseline. This reduction in cardiac MIBG activity with heart failure was associated with increased intraimage variability in the distribution of MIBG activity (21±8% versus 13±7% at baseline, mean±SD; P=.0001). The MIBG heart-to-lung ratio was calculated for all groups to control for the inhibitory effect that plasma norepinephrine has on the neuronal uptake of MIBG. There was a positive correlation between LV tissue norepinephrine and the MIBG heart-to-lung ratio (r=.67;P