Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptakein rabbit myocardium

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial im aging was introduced for the evaluation of myocardial sympathetic nerve fun ction. Two uptake mechanisms for MIBG have so far been identified: uptake t ype I, a saturable, energy-dependent mechanism, and uptake type II, a non-s aturable, energy-independent mechanism. We incubated isolated rabbit myocar dial tissue samples with I-123-MIBG in order to assess the uptake character istics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardi al uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% after 1 h, i.e. a concentration gradient of 10, i n a thermo-independent manner within a concentration range from 1.5 to 1500 mu M. This indicates an unsaturable uptake process in the tested concentra tions. Preincubation with the following drugs caused a significant inhibito ry effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprol ol, labetalol and clomipramine. According to our findings, the uptake mecha nism seems to be an unspecific process, but the concentration gradient of 1 0 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to cla rify the nature of the myocardial MIBG uptake mechanism.