MODULATION OF LEFT-VENTRICULAR IODINE-125-MIBG ACCUMULATION IN CARDIOMYOPATHIC SYRIAN-HAMSTERS USING THE RENIN-ANGIOTENSIN SYSTEM

Genetically inbred cardiomyopathic hamsters were examined to investiga te the mechanism of reduced myocardial accumulation of metaiodobenzylg uanidine (MIBG) in the cardiomyopathic heart. Methods: Bio 14.6 Syrian hamsters (hypertrophic stage: n = 15, early heart failure stage: n = 17) and control F1b strain golden hamsters (n = 36) were injected with 296 kBq of [I-125] MIBG and killed 30 min or 4 hr later. Thirty-three of these hamsters were pretreated with 10 mg/kg of desipramine to det ermine non-neuronal MIBG accumulation. To evaluate the nonexocytotic M IBG release from nerve endings, desipramine was administered to four B io 14.6 hamsters 15 min after [I-125]MIBG injection. To determine the role of the activated renin-angiotensin system (RAS) in MIBG washout f rom sympathetic nerve terminals in cardiomyopathy at early heart failu re stage, 10 mg/kg/day cilazapril, an angiotensin-converting enzyme in hibitor, was given orally to 7 controls and 16 cardiomyopathic hamster s for 16 wk. Results: In the absence of desipramine pretreatment, left ventricular [I-125]MIBG accumulation 4 hr after injection was 0.376% +/- 0.015 %kg dose/g (mean +/- s.e.m.) in the hypertrophic hamsters (v ersus 0.418 +/- 0.019 in controls of the same age; ns), and 0.195 +/- 0.025 in early heart failure hamsters. Treatment with cilazapril parti ally restored MIBG accumulation in the Bio 14.6 hamsters but did not a ffect the controls. Conclusion: Decreased [I-125]MIBG accumulation in cardiomyopathic hamsters during the early heart failure stage is cause d by neuronal release which is partially modulated by the activated RA S.