123 I-MIBG scintigraphy in the assessment of heart failure prognosis and effectiveness of cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is one of the methods of treating patients with chronic heart failure, which can reduce the mortality rate of this group. Scintigraphic assessment of sympathetic myocardial innervation allows us to evaluate the heart failure prognosis and the effectiveness of interventional treatment. The method is based on use of the radiopharmaceutical 123 I-methiodiobenzylguanidine (123 I-MIBG), which is a structural analogue of norepinephrine and is able to selectively accumulate in the sympathetic nerve endings. This review includes a brief description of norepinephrine metabolism and pharmacokinetics of 123 I-MIBG in the sympathetic nerve ending, a brief description of the study methodology and the clinical significance of this method in patients with heart failure. Particular attention is paid to the possibilities of using this method in patients with severe chronic heart failure before and after CRT.

CO2asphyxia increases plasma norepinephrine in rats via sympathetic nerves

The objective of this study was to determine whether the plasma norepinephrine (NE) increase in rats exposed to CO2asphyxia was due to adrenal gland release or sympathetic nerve ending (SNS) release. Plasma NE was measured by high-performance liquid chromatography in hypertensive and normotensive rats using the following protocol: control session, CO2exposure, N2exposure, reserpine + CO2, and adrenalectomy + CO2. Four strains of male and female rats were used: spontaneously hypertensive rats, Wistar-Kyoto rats, and two congenic strains with different Y chromosomes. The same rats were used throughout the experiment ( n = 80). Blood pressure measured by aortic telemetry increased ∼50–60 mmHg in response to CO2in all strains. CO2increased NE 6–10× in all strains and both genders. N2produced a significant increase in NE (73% of CO2response). Reserpine significantly decreased (67%) plasma NE after CO2. Adrenalectomy did not significantly reduce the NE response to CO2. In conclusion, the increase in plasma NE after CO2was associated with SNS release and not adrenal medullary release, was mainly due to hypoxia, and was not a specific response to CO2.

Release of tritiated noradrenaline from perfused rat hearts by sympathomimetic amines

The hypothesis that the limiting factor controlling the noradrenaline-releasing activity of a sympathomimetic amine is the ability of the nerve ending to take up the amine, i.e. the affinity of the amine for the postulated amine carrier in the sympathetic nerve ending, was tested on perfused rat hearts labelled with tritiated noradrenaline (NA). Experiments were done to determine whether cocaine and desmethylimipramine (DMI) would block the releasing action of sympathomimetic amines (SMA) and to determine whether the ranking order of the releasing activity of a series of SMA corresponds to the order of affinity for the amine carrier as reported by Iversen. The releasing activity of NA was found to be a saturable process, reaching a maximum rate estimated to be 2.6% of the amount present in the heart per minute. In addition, cocaine and DMI competitively blocked the releasing activity of infused NA, adrenaline, and dopamine, but this inhibition could be overcome by increasing the dose of the SMA. The ranking order of releasing activity of this series of amines was l-noradrenaline, dopamine, l-adrenaline, p-tyramine, d-noradrenaline, d-adrenaline, l-isoproterenol, phenylethylamine, d-isoproterenol, which was approximately the same as their order of affinity for the amine carrier. Our results indicate that uptake by a membrane carrier is probably the limiting factor in the releasing activity of SMA which are catechols and have a β-OH group. However, those amines studied which do not have these structural properties, i.e. dopamine, tyramine, and phenylethylamine, are further limited in their releasing activity, possibly owing to a less rapid exchange at the binding site on the storage granule.