Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy

Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity.     

Value of iodine-123 metaiodobenzylguanidine scintigraphy in patients with vasospastic angina

To assess the presence and location of presynaptic myocardial sympathetic abnormality in patients with vasospastic angina, iodine-123 labelled metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET) was performed. Fifty patients suspected of having vasospastic angina pectoris were enrolled in the study. All patients underwent a provocative test with intracoronary ergonovine infusion during coronary angiography, in which 99%–100% obstructive spasm was defined as a positive result. Twenty-five patients were diagnosed as having vasospastic angina based on a positive provocative test. MIBG SPET was performed at 20 min and 3 h after administration of 111 MBq of MIBG. On early images, only 5 of 25 patients with vasospastic angina showed a mild reduction in MIBG uptake, whereas 3-h delayed images demonstrated MIBG abnormality in 20 patients (80%). The location of the MIBG abnormality was completely or partially consistent with the spastic coronary territory in 18 patients. On the other hand, only 4 of 25 patients (16%) with a negative provocative test demonstrated reduced MIBG uptake. Accordingly, positive and negative predictive values of MIBG SPET for the provocative test were 83% (20/24) and 81% (21/26) respectively. In conclusion, MIBG scintigraphy with SPET can permit the non-invasive detection and evaluation of suspected vasospastic angina. Received 16 July and in revised form 26 November 1997     

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42+/-12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36+/-0.26 versus 1.98+/-0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients.     

Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability

Familial amyloid polyneuropathy (FAP) is a rare and severe hereditary form of amyloidosis, due to nervous deposits of a genetic variant transthyretin produced by the liver and characterized by both sensorimotor and autonomic neuropathy. Left ventricular systolic dysfunction is rare, but conduction disturbances and sudden deaths can occur. The neurological status of the heart has not been elucidated, and an alteration of the sympathetic nerves may be involved. We studied 17 patients (42±12 years) before liver transplantation by iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy, heart rate variability analysis, coronary angiography, radionuclide ventriculography, rest thallium single-photon emission tomography (SPET) and echocardiography. Coronary arteries, left ventricular systolic function and rest thallium SPET were normal in all patients. Only mild evidence of amyloid infiltration was found at echocardiographic examination. Cardiac MIBG uptake was dramatically decreased in patients compared with age-matched control subjects (heart-to-mediastinum activity ratio at 4 h: 1.36±0.26 versus 1.98±0.35, P<0.001), while there was no difference in MIBG washout rate. Heart rate variability analysis showed a considerable scatter of values, with high values in four patients despite cardiac sympathetic denervation as assessed by MIBG imaging. The clinical severity of the polyneuropathy correlated with MIBG uptake at 4 h but not with the heart rate variability indices. Cardiac MIBG uptake and the heart rate variability indices did not differ according to the presence or absence of conduction disturbances. Patients with FAP have sympathetic cardiac denervation as assessed by MIBG imaging despite a preserved left ventricular systolic function and cardiac perfusion, without correlation with conduction disturbances. Results of the heart rate variability analysis were more variable and this technique does not seem to be the best way to evaluate the extent of cardiac sympathetic denervation in FAP patients. Received 19 October 1998 and in revised form 6 January 1999     

Septal penetration in iodine-123 metaiodobenzylguanidine cardiac sympathetic imaging using a medium-energy collimator

Background

Septal penetration of high-energy photons affects the estimation of the heart-to-mediastinum (H/M) ratio in cardiac ¹²³I-metaiodobenzylguanidine (MIBG) imaging, and the use of a medium-energy (ME) collimator has been shown to improve quantitative accuracy. We investigated the effect of septal penetration on the estimation of H/M ratios using an ME collimator.

Methods and Results

Point sources of ^99mTc and ¹²³I were imaged using various collimators, which indicated that the effect of high-energy photons with the ME collimator was relatively small but larger than that with the high-energy (HE) collimator. Four hours after ¹²³I-MIBG injection, 20 patients underwent planar anterior chest imaging by different methods in succession. The ME collimator gave lower H/M ratios (mean 2.52) than the HE collimator (2.57), indicating influence of septal penetration in the ME collimator; however, the difference was limited. Although narrowing the energy window from 20% (2.51) to 15% (2.54) increased the H/M ratios in imaging with the ME collimator, the difference was quite limited.

Conclusions

Septal penetration affects the estimation of the H/M ratios using an ME collimator; however, this influence is small and would not have clinical significance.     

Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus.

The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure >/=140 and/or diastolic blood pressure >/=90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55+/-11 vs 63+/-12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120+/-12 vs 145+/-16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1. 81+/-0.29 vs 2.27+/-0.20, respectively, P<0.01). During the follow-up period (18+/- 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%+/-16.87% vs 12.89%+/-11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences between the control group and non-survivors in terms of age (54+/-11 vs 73+/-11 years, respectively, P<0.01), H/M ratio (2. 27+/- 0.20 vs 1.64+/-0.36, respectively, P<0.01) and %WR (12. 89%+/-11.94% vs 42.52%+/-22.39%, respectively, P<0.01). In conclusion, cardiac sympathetic denervation using MIBG scintigraphy observed in hypertensive NIDDM patients, and was more profound in non-survivors. MIBG scintigraphy proved useful for the evaluation of NIDDM patients with new onset hypertension, and it was found that NIDDM patients with abnormalities on MIBG scintigraphy needed to be observe carefully.     

Investigation of the relationship between regression of hypertensive cardiac hypertrophy and improvement of cardiac sympathetic nervous dysfunction using iodine-123 metaiodobenzylguanidine myocardial imaging

Although many theories exist on the subject, the mechanisms responsible for a reduction of hypertensive cardiac hypertrophy in response to antihypertensive therapy are still unclear. In order to investigate the relationship between regression of hypertensive cardiac hypertrophy and cardiac nervous function, we studied ten patients with untreated essential hypertension (six men and four women, 62±12 years old). Both echocardiography and iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging were performed before and after antihypertensive therapy. Left ventricular mass (LVM) was significantly reduced in conjunction with the reduction of blood pressure following treatment. MIBG myocardial images showed that the heart-to-mediastinum activity ratio (H/M) was significantly increased while the washout ratio was significantly decreased. Patients were divided into two groups according to the ratio of the LVM values before and after therapy (LVM ratio). Patients with an LVM ratio of less than 0.75 were classified as group A and those with values higher than 0.75 as group B. Neither the change in blood pressure nor the length of treatment was significantly different between these two groups. On the other hand, both the increase in H/M and the decrease in the washout ratio were significantly greater in group A than in group B. These results indicate that an improvement in cardiac sympathetic nervous function may be related to the regression of hypertensive cardiac hypertrophy. Increasing the subject base in these studies and a more precise analysis of the relevance of the data obtained from MIBG myocadial images are recommended to clarify how changes in cardiac sympathetic nervous function relate to the regression of hypertensive cardiac hypertrophy.     

Use of iodine-123 metaiodobenzylguanidine scintigraphy to assess cardiac sympathetic denervation and the impact of hypertension in patients with non-insulin-dependent diabetes mellitus

The objectives of this clinical study using iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were (a) to evaluate cardiac sympathetic denervation in non-insulin-dependent diabetes mellitus (NIDDM) patients with and without hypertension and (b) to investigate the relation between cardiac sympathetic denervation and prognosis in NIDDM patients. We compared clinical characteristics and MIBG data [heart to mediastinum (H/M) ratio and % washout rate (WR)] in a control group and NIDDM patients with and without hypertension. MIBG scintigraphy was performed in 11 controls and 82 NIDDM patients without overt cardiovascular disease except for hypertension (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg). After MIBG examination, blood pressure was measured regularly in all NIDDM patients. There were significant differences between 65 normotensive and 17 hypertensive NIDDM patients with respect to age (55±11 vs 63±12 years, respectively, P<0.05), prevalence of diabetic retinopathy (12% vs 35%, respectively, P<0.05) and systolic blood pressure (120±12 vs 145±16 mmHg, respectively, P<0.001). The H/M ratio in hypertensive NIDDM patients was significantly lower than in the control group (1.81±0.29 vs 2.27±0.20, respectively, P<0.01). During the follow-up period (18± 12 months), 17 NIDDM patients newly developed hypertension after MIBG examination. There were no significant differences in their clinical characteristics compared with persistently normotensive or hypertensive NIDDM patients. %WR in patients with new onset hypertension was significantly higher than in the control group (30.88%±16.87% vs 12.89%±11.94%, respectively, P<0.05). Moreover, in these patients %WR correlated with duration from the date of MIBG scintigraphy to the onset of hypertension (r=-0.512, P<0.05). Five NIDDM patients died during the follow-up period (four newly hypertensive patients and one normotensive patient). There were significant statistical differences between the control group and non-survivors in terms of age (54±11 vs 73±11 years, respectively, P<0.01), H/M ratio (2.27± 0.20 vs 1.64±0.36, respectively, P<0.01) and %WR (12.89%±11.94% vs 42.52%±22.39%, respectively, P<0.01). In conclusion, cardiac sympathetic denervation using MIBG scintigraphy observed in hypertensive NIDDM patients, and was more profound in non-survivors. MIBG scintigraphy proved useful for the evaluation of NIDDM patients with new onset hypertension, and it was found that NIDDM patients with abnormalities on MIBG scintigraphy needed to be observe carefully. Received 1 April and in revised form 27 May 1999     

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p < 0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p < 0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p < 0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart.     

Evaluation of cardiac sympathetic neuronal integrity in diabetic patients using iodine-123 metaiodobenzylguanidine

Autonomic dysfunction is associated with increased mortality in diabetic patients. To evaluate the cardiac autonomic dysfunction in these patients, a prospective study was undertaken using iodine-123 metaiodobenzylguanidine (MIBG) single-photon emission tomography (SPET). The study groups consisted of ten diabetic patients with cardiac autonomic neuropathy (group 1) and six without autonomic neuropathy (group II). Autonomic nervous function tests, thallium scan, radionuclide ventriculographic data including ejection fraction and wall motion study, and 24-h urine catecholamine levels were evaluated.¹²³I-MIBG SPET was performed at 30 min and 4 h following injection of 3 mCi of¹²³I-MIBG in groups I and II and in normal subjects (n=4). On planar images, the heart to mediastinum (H/M) ratio was measured. Defect pattern and severity of MIBG uptake were qualitatively analysed on SPET. Compared with control subjects, diabetic patients had a reduced H/M ratio regardless of the presence of clinical autonomic neuropathy. There was no difference in H/M ratio between groups I and II. On SPET images, focal or diffuse defects were demonstrated in all patients in group I, and in five of the six patients in group II. The extent of defects tended to be more pronounced in group I than in group II. In conclusion, SU1-MIBG scan was found to be a more sensitive method than clinical autonomic nervous function tests for the detection of autonomic neuropathy in diabetes.     

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with ¹²³I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial 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, in a thermo-independent manner within a concentration range from 1.5 to 1500 μM. This indicates an unsaturable uptake process in the tested concentrations. Pre-incubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism. Received 1 September and in revised form 18 November 1999     

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial 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, in a thermo-independent manner within a concentration range from 1.5 to 1500 microM. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy.

Serial change of the metaiodobenzylguanidine iodine-123 (123I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and 123I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30-60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of 123I-MIBG did not differ significantly from that of the controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15-45 min) was significantly larger in DCM than in the controls (21.2% +/- 7.5% vs. 5.3% +/- 4.0%, P less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the 123I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease.     

Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy

Serial change of the metaiodobenzylguanidine iodine-123 (¹²³I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and ¹²³I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30–60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of ¹²³I-MIBG did not differ significantly from that of the controls. The washout of ¹²³I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15–45 min) was significantly larger in DCM than in the controls (21.2%±7.5% vs. 5.3%±4.0%, P <0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = –0.72 P < 0.05). For ²⁰¹TI, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the ¹²³I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease. Offprint requests to: K. Yamakado     

Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy

A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.     

Clinical value of lung uptake of iodine-123 metaiodobenzylguanidine (MIBG), a myocardial sympathetic nerve imaging agent, in patients with chronic heart failure

This study investigated the clinical value of I-123 MIBG pulmonary accumulation and washout in patients with chronic heart failure (CHF). Nineteen patients with CHF and 15 normal volunteers (NL) were included. The uptake ratio of heart to mediastinum (H/M), that of lung fields to mediastinum (L/M), and washout rate (WR) of the heart and lung fields were calculated in anterior planar images and compared with results of echocardiography and cardiac catheterization. In the CHF group, the lung uptake in delayed images increased and lung WR was decreased, suggesting pulmonary endothelial lesions. Furthermore, there was a negative correlation between right and left lung WR and pulmonary arterial diastolic pressure (PA(D)) and pulmonary arterial systolic pressure (PA(s)) in the CHF group. Since the WR of MIBG reflected PA, it may be used as an index of severity of cardiac dysfunction.     

Cilnidipine as an agent to lower blood pressure without sympathetic nervous activation as demonstrated by iodine-123 metaiodobenzylguanidine imaging in rat hearts

BACKGROUND: Administration of short-acting antihypertensive agents to patients with ischemic heart disease results in increased sympathetic nervous activity and is associated with worsened outcomes. Cilnidipine is an agent which blocks not only L-type calcium channels at the smooth muscle in the artery, but also N-type calcium channels at the presynaptic terminal. The goal of the present study was to determine the effect of cilnidipine on sympathetic nervous activity as on agent which blocks both L-type and N-type calcium channels at the presynaptic terminal, on sympathetic nervous activity in an experimental rat model using iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging. METHODS: Fourteen-week-old Wistar-Kyoto rats were divided into 3 separate groups: CTR group (control: distilled water administered), Nif group (nifedipine administered), or Cil group (cilnidipine administered). Agents were administered via a stomach tube, followed by injection of MIBG via the femoral vein. Systolic blood pressure (SBP) and heart rate (HR) were measured by tail-cuff plethysmography just prior to administration of antihypertensive drugs and 150 minutes later. Initial imaging (Ce) and delayed imaging (Cd) were defined as the sum of density counts in the region of interest created by adjusting to myocardial edge, and were corrected for both physical decay and weight. The myocardial washout rate (WR) was defined as the percent change in the count density from the initial to delayed images. RESULTS: Significant decreases in SBP were seen in the Nif group (from 132 +/- 3 mmHg to 85 +/- 5 mmHg, p < 0.0001) and the Cil group (from 128 +/- 4 mmHg to 92 +/- 7 mmHg, p = 0.0008), whereas no significant change in SBP was noted in the CTR group (from 123 +/- 5 mmHg to 127 +/- 3 mmHg). HR significantly increased in the Nif group (from 290 +/- 12/min to 378 +/- 14/min, p < 0.0001) but not in the CTR (from 278 +/- 3/min to 300 +/- 6/min) or Cil (from 291 +/- 6/min to 303 +/- 5/min) groups. WR was significantly greater in the Nif group (64.7 +/- 0.5%) when compared to the CTR (56.4 +/- 1.2%, p = 0.0031) or the Cil (55.4 +/- 2.2%, p = 0.0016) groups. CONCLUSION: In contrast to nifedipine, administration of cilnidipine did not result in increased myocardial sympathetic nervous activation.     

Clinical usefulness of iodine-123-MIBG scintigraphy for patients with neuroblastoma detected by a mass screening survey

The purpose of this study was to evaluate the usefulness in a clinical setting of iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy, planar and single photon emission computed tomography (SPECT) images, in patients with neuroblastoma as detected by a mass screening survey. METHODS: 123I-MIBG planar whole body images, and regional SPECT images of patients with neuroblastoma in 51 studies were reviewed. They were all detected by a mass screening survey performed in the 6th month after birth using vanil mandelic acid (VMA), and homovanillic acid (HVA) and the neuroblastoma had been confirmed by surgery. Scintigraphy was performed 24 hours after injection of 111 MBq of 123I-MIBG. We assessed the accuracy of the planar whole body images in order to demonstrate the extent of the lesion and the correlation between the degree and extent of the lesions of 123I-MIBG accumulation and clinical staging with tumor markers, such as urinary VMA, urinary HVA, serum neuron specific enolase (NSE) and serum lactate dehydrogenase (LDH). Additionally, we evaluated SPECT how useful supplemental SPECT might be in a clinical setting as compared with planar whole body images. RESULTS: 123I-MIBG planar whole body images revealed all 33 (100%) primary lesions, 4 of the 5 cases (80%) with liver metastasis, 3 of the 13 (23%) with lymph nodes metastasis and 1 of 3 (33%) with bone marrow infiltration. The extent and degree of accumulation correlated with the values of urinary VMA, urinary HVA and serum NSE. SPECT images helped to understand the positional relation in all cases and provided useful additional information for clinical staging in 7 cases. CONCLUSION: 123I-MIBG scintigraphy with planar and SPECT images is useful for evaluating patients with neuroblastoma, following detection by a mass screening survey.     

Increased myocardial uptake of iodine-123 metaiodobenzylguanidine on delayed images, compared with early images, in patients with multiple system atrophy

We present 2 interesting cases of multiple system atrophy in which increased myocardial iodine-123 metaiodobenzylguanidine uptake was observed on delayed images (3 hours after injection) compared with early images (15 minutes after injection). These findings have not been previously described. The duration of symptoms was less than 1 year in both these patients. The mechanism responsible for these findings is not clearly understood, but could be related to the pathophysiological changes in the early stage of multiple systemic atrophy.