ABNORMALITIES OF CARDIAC SYMPATHETIC FUNCTION IN PACING-INDUCED HEART-FAILURE AS ASSESSED BY [I-123] METAIODOBENZYLGUANIDINE SCINTIGRAPHY

Background Increased activity of the sympathetic nervous system contri butes 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 inne rvation using [I-123]metaiodobenzylguanidine (MIBG) and compared this with left ventricular (LV) tissue norepinephrine concentration and myo cardial perfusion, assessed by Tl-201, in a canine model of heart fail ure. Methods and Results Planar and tomographic cardiac imaging was pe rformed for MIBG and Tl-201 in 23 dogs: 8 normal dogs (group 1) and 15 dogs with heart failure induced by right ventricular pacing at 250 be ats per minute either continuously for 3 weeks (group 2) or intermitte ntly for 7 weeks (group 3). Plasma and LV tissue norepinephrine concen trations were also measured. Scintigraphic studies in group 2 demonstr ated reduced cardiac MIBG activity at heart failure (0.17+/-0.04 versu s 0.29+/-0.05 counts per megabecquerel per pixel at baseline, mean+/-S D; P=.0001), whereas thallium activity was unchanged from baseline. Th is reduction in cardiac MIBG activity with heart failure was associate d with increased intraimage variability in the distribution of MIBG ac tivity (21+/-8% versus 13+/-7% at baseline, mean+/-SD; P=.0001). The M IBG heart-to-lung ratio was calculated for all groups to control for t he inhibitory effect that plasma norepinephrine has on the neuronal up take of MIBG. There was a positive correlation between LV tissue norep inephrine and the MIBG heart-to-lung ratio (r=.67; P<.001; n=22), for which the group 2 heart failure animals had the lowest values. No rela tion existed between plasma norepinephrine concentration and the MIBG heart-to-lung ratio. In addition, regional LV tissue norepinephrine co ncentration and MIBG activity were both lowest at the apex in normal ( group 1) and heart failure (group 2) dogs. The MIBG heart-to-lung rati o also correlated inversely with cardiac filling pressure (r= -.59; P< .05) and heart rate (r=-.65; P<.01) and positively with cardiac output (r=.53; P<.05). Conclusions Heart failure is associated with severe c ardiac adrenergic dysfunction manifested by reduced MIBG activity and increased heterogeneity in the LV distribution of MIBG. Furthermore, M IBG scintigraphy is a simple noninvasive method for assessing global a nd regional LV tissue norepinephrine levels.