Abstract
Background
To evaluate cardiac sympathetic activity, a simple method should be developed to replace such complex methods as the spillover rate of tritiated norepinephrine (3H-norepinephrine) or microneurography of sympathetic nerve activity. The goal of this study is to evaluate cardiac sympathetic activities by analyzing the washout of I-123 meta-iodobenzylguanidine (123I-MIBG), a radiolabeled norepinephrine analogue, in Dahl salt-sensitive (DS) rats as it relates to the progression of hypertension.
Methods and Results
Dahl salt-resistant (DR) rats and DS rats were fed an 8% salt diet starting at age 5 weeks. Marked hypertension and cardiac hypertrophy developed in the DS rats, whereas DR rats remained normotensive. Then the time-activity curves of 123I-MIBG from 15 to 200 minutes were obtained from both DS and DR strains at ages 8, 11, and 13 weeks using dynamic scintigraphic analysis. We also examined the nonneuronal washout of 123I-MIBG using dynamic scintigraphic studies in desipramine pretreated normal rats. In the preliminary study with desipramine pretreatment, the majority of the nonneuronal 123I-MIBG washout occurred by 90 minutes after injection. Therefore the late-phase washout in the control rats was found to reflect the neuronal washout. We then applied exponential curve fitting to the time activity curves acquired in the 90- to 200-minute period after 123I-MIBG injection in both DR and DS rats. When we compared the coefficients of these washout curves in the DS and DR rats as an index of cardiac sympathetic activities, the coefficient values remained high during all stages in DS rats, whereas they decreased with age in DR rats.
Conclusion
Measurement of late-phase 123I-MIBG washout may be a useful tool for assessing the change in sympathetic activity in the progression of hypertension without the influence of extraneuronal washout of 123I-MIBG and left ventricular hypertrophy.
Similar content being viewed by others
References
Dae MW, Herre JM, O'Connel JW, Botvinick EH, Newman D, Munoz L. Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction. J Am Coll Cardiol 1991;17:1416–23.
Stanton MS, Tuli MM, Radtke NL, Heger JJ, Miles WM, Mock BH, et al. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using 123I-metaiodobenzylguanidine. J Am Coll Cardiol 1989;14:1519–26.
Dae MW, De Marco T, Botvinick EH, Ahearn T, Yee E, Huberty JP, et al. Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts: implications for clinical studies. J Nucl Med 1992;33:1444–50.
Glowniak JV, Turner FE, Gray LL, Palac RT, Lagunas-Solar MC, Woodward WR. Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive heart failure and cardiac transplants. J Nucl Med 1989;30:1182–91.
Sisson JC, Shapiro B, Meyers L, Mallette S, Mangner TJ, Wieland DM, et al. Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man. J Nucl Med 1987;28:1625–36.
Sisson JC, Wieland DM, Sherman P, Mangner TJ, Tobes MC, Jacques S. Metaiodobenzylguanidine as an index of the adrenergic nervous system integrity and function. J Nucl Med 1987;28:1620–4.
Dae MW, O'Connell JW, Botvinick EH, Chin MC. Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content. Cardiovasc Res 1995;30:270–80.
Jacques S, Tobes MC, Sisson JC, Baker JA, Wieland DM. Comparison of the sodium dependency of uptake of meta-iodobenzylguanidine and norepinephrine into cultured bovine adrenomedullary cells. Mol Pharmacol 1984;26:539–46.
Glowniak JV. Cardiac studies with metaiodobenzylguanidine: a critique of methods and interpretation of results. J Nucl Med 1995;36:2133–7.
Takatsu H, Uno Y, Fujiwara H. Modulation of left ventricular iodine-125 MIBG accumulation in cardiomyopathic Syrian hamsters using the renin-angiotensin system. J Nucl Med 1995;36:1055–61.
Takatsu H, Scheffel U, Fujiwara H. Sympathetic tone assessed by washout of iodine 125-labeled metaiodobenzylguanidine from the murine left ventricle—influence of immobilization stress and inhibition of the renin-angiotensin system. J Nucl Cardiol 1995;2:507–12.
Julius S. Autonomic nervous system dysregulation in human hypertension. Am J Cardiol 1991;67:3–7.
Julius S, Gudbrandsson T. Early association of sympathetic overactivity, hypertension, insulin resistance, and coronary risk. J Cardiovasc Pharmacol 1992;20(suppl 8):40–8.
Widimsky J, Fejfarova MH, Fejfar Z. Changes of cardiac output in hypertensive disease. Cardiologia 1957;31:381–9.
Messerli FH, Frohlich ED, Suarez DH, Reisin E, Dreskinski GR, Dunn EG, et al. Borderline hypertension: relationship between age, hemodynamics and circulating catecholamines. Circulation 1981;64:760–4.
Julius S, Conway J. Hemodynamic studies in patients with borderline blood pressure elevation. Circulation 1968;28:282–8.
Dahl LK, Heine M, Tassinari L. Effects of chronic salt ingestion: evidence that genetic factors play an important role in susceptibility to experimental hypertension. J Exp Med 1962;115:1173–90.
Dahl LK, Knudsen KD, Heine MA, Leitl GJ. Effects of chronic excess salt ingestion: modification of experimental hypertension in the rat by variations in the diet. Circ Res 1968;22:11–8.
Inoko M, Kihara Y, Morii I, Fujiwara H, Sasayama S. Transition from compensatory hypertrophy to dilated, failed left ventricles in Dahl salt-sensitive rats. Am J Physiol 1994;267:2471–82.
Mock BH, Tuli MM. Influence of specific activity on myocardial uptake of 123I-MIBG in rats. Nucl Med Commun 1988;9:663–7.
Tobes MC, Jacques S, Wieland DM, Sisson JC. Effect of uptake-one inhibitors on the uptake of norepinephrine and metaiodo-benzylguanidine. J Nucl Med 1985;26:897–907.
Mancia G, Grassi G, Parati G, Daffonchio A. Evaluating sympathetic activity in human hypertension. J Hypertens 1993;11(suppl 5):13–9.
Esler M, Jennings G, Komer P, Willett I, Dudley F, Hastings G, et al. Assessment of human sympathetic nervous system activity from measurement of norepinephrine turnover. Hypertension 1988;11:3–20.
Melet P, Valette H, Dubois-Rande JL, Moyse D, Duboc D, Done P, et al. Prognostic value of cardiac metaiodobenzylguanidine imaging in patients with heart failure. J Nucl Med 1992;33:471–7.
Nakajima K, Taki J, Tonami N, Hisada K. Decreased 123-I MIBG uptake and increased clearance in various cardiac diseases. Nucl Med Commun 1994;15:317–23.
Henderson EB, Kahn JK, Corbett JR, Jansen DE, Pippin JJ, Kulkarni P, et al. Abnormal I-123 metaiodobenzylguanidine myocardial washout and distribution may reflect myocardial adrenergic derangement in patients with congestive cardiomyopathy. Circulation 1988;78:1192–9.
Nakajo M, Shimabukuro K, Yoshimura H, et al. Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart. J Nucl Med 1986;27:84–9.
Rabinovitch MA, Rose CP, Schwab AJ, Fitchett DH, Honos GN, Stewart JA, et al. A method of dynamic analysis of iodine-123-metaiodobenzylguanidine scintigrams in cardiac mechanical overload hypertrophy and failure. J Nucl Med 1993;34:589–600.
Lurie KG, Dae MW, Dutton J, Velazquez-Roch SJ, O'Connell JW. Metaiodobenzylguanidine as an index of atrioventricular nodal adrenergic activity. J Nucl Med 1995;36:1096–101.
Genain CP, Reddy S, Ott C, Van Loon GR, Kotchen TA. Failure of salt loading to inhibit tissue norepinephrine turnover in prehypertensive Dahl salt-sensitive rats. Hypertension 1988;12:568–73.
Esler M, Jennings G, Bivano B, Lambert G, Hasking G. Mechanisms of elevated plasma noradrenaline in the cause of essential hypertension. J Cardiovasc Pharmacol 1986;8(suppl 5):39–44.
Esler M, Jennings G, Lambert G. Noradrenaline release and the pathophysiology of primary human hypertension. Am J Hypertens 1989; 2:140–6.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takatsu, H., Noda, T., Arai, M. et al. Washout of I-123 meta-iodobenzylguanidine for assessing cardiac sympathetic activity with progression of hypertension in Dahl salt-sensitive rats. J Nucl Cardiol 6, 204–210 (1999). https://doi.org/10.1016/S1071-3581(99)90081-8
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1016/S1071-3581(99)90081-8