Serial changes in BMIPP uptake in relation to thallium uptake in the rat myocardium after ischaemia

Several clinical studies have shown that iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) uptake is often lower than the uptake of perfusion tracers in patients with ischaemic heart disease. However, BMIPP accumulation may not decrease during the acute phase of a stunned myocardium in patients with acute coronary syndrome. We evaluated serial changes in BMIPP and perfusion tracer uptake in the myocardium after ischaemia. We performed a 20-min left coronary artery occlusion followed by reperfusion in male Wister rats. One hour after the reperfusion, echocardiography was performed. Intravenous injection of iodine-125 labelled BMIPP and thallium-201 was performed 1 day (acute group) and 5 days (subacute group) after the operation. To determine the myocardial distribution of ¹²⁵I-BMIPP and ²⁰¹Tl, dual-tracer autoradiography was conducted. We identified regions of interest in the anterolateral wall as an area at risk and in the inferoseptum as a remote control area. The anterolateral wall/inferoseptum ratio (A/I ratio) was calculated to compare the distributions of ¹²⁵I-BMIPP and ²⁰¹Tl. Coronary occlusion induced hypokinesia in the anterolateral region 1 h after the reperfusion. The A/I ratio of ¹²⁵I-BMIPP was significantly higher than that of ²⁰¹Tl in the acute group (1.01±0.15 vs 0.80±0.23, P<0.001). On the other hand, there was no significant difference between the A/I ratios of ¹²⁵I-BMIPP and ²⁰¹Tl in the subacute group (0.88±0.18 vs 0.85±0.18). Two rats showed a significantly lower A/I ratio of ¹²⁵I-BMIPP than ²⁰¹Tl in the subacute phase. These data suggest that BMIPP uptake is preserved despite a decrease in perfusion in the acute phase after ischaemia. In the subacute phase, on the other hand, BMIPP uptake is similar to or even lower than thallium uptake. Since BMIPP uptake may change with time after ischaemia, careful interpretation of BMIPP uptake after ischaemia is required in a clinical setting.     

Dynamic changes in cardiac fatty acid metabolism in the stunned human myocardium

BACKGROUND: The chronological changes or mechanisms in cardiac fatty acid metabolism under clinical conditions of hypoxia and ischemia have not been fully elucidated. 123-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) can be used with single photon emission computed tomography (SPECT) to evaluate myocardial fatty acid metabolism. We investigated chronological changes in energy metabolism in the stunned human myocardium by means of 123I-BMIPP myocardial SPECT. METHODS AND RESULTS: We conducted 123I-BMIPP myocardial SPECT in 10 patients with stunned myocardium during the acute, subacute and chronic phases after onset. The left ventricle was divided into 9 regions on SPECT, and the degree of abnormalities in each region was scored in four grades from normal (0) to defect (4). We also examined wash-out rates on BMIPP images. The scores on early BMIPP images in the acute, subacute and chronic phases were 5.6 +/- 1.8, 13.4 +/- 3.5 and 2.5 +/- 1.1, respectively, and the score was highest in the subacute phase (p < 0.001). Similarly, scores on the late images were 2.3 +/- 1.7, 18.3 +/- 4.5 and 4.7 +/- 2.6, respectively, and highest in the subacute phase (p < 0.001). The wash-out rates (normal: 18.2 +/- 2.1%) in the acute, subacute and chronic phases were 12.1 +/- 4.8%, 44.9 +/- 10.0% and 23.1 +/- 4.6%, respectively, with the value being lowest during the acute phase (p < 0.05), and highest during the subacute phase (p < 0.001). CONCLUSION: These results suggested that fatty acid metabolism in the stunned human myocardium changes dynamically over time.     

Kinetics of radioiodinated species in subcellular fractions from rat hearts following administration of iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (123I-BMIPP)

It is recognized that iodine-123-labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (¹²³IBMIPP) slowly washes out of the myocardium. The mechanism for the washout was investigated in normal rat hearts by analyses of the subcellular distribution and lipid classes based on the BMIPP metabolism. Rat hearts were excised at 1–120 min after intravenous injection of¹²³I-BMIPP. After counting the radioactivity, the hearts were digested with Nagarse and homogenized, and then fractionated into the cytosolic, mitochondrial, microsomal and crude nuclear fractions by centrifugations. The radioactivity of each fraction was counted, and the lipid classes were analysed by radio-thin-layer chromatographic and high-performance liquid chromatographic methods. The heart uptake of 1231-BMIPP was maximal at 5 min (6.81%±0.36% ID/g), and 41% of the radioactivity disappeared within 120 min. The myocardial radioactivity was immediately distributed into the cytosolic, mitochondrial, microsomal and crude nuclear fractions. The distribution (%) of each fraction was almost identical from 5 min through 120 min. The cytosolic fraction was always the major site of radioactivity deposition (60%), and the time-activity curve of the cytosolic fraction paralleled that of the whole heart throughout the 120-min study period. In the cytosolic fraction, most of the radioactivity was incorporated into the triglyceride class, and the rest was present in the free fatty acid, phospholipid (phosphatidylcholine) and diglyceride classes. In the mitochondrial fraction, the radioactivity was mostly incorporated into the phospholipid class (phosphatidylethanolamine), followed by free fatty acids. The final metabolite of¹²³I-BMIPP,¹²³I-p-iodophenylacetic acid (¹²³I-PIPA), initially appeared in the mitochondrial fraction as early as 1 min, and subsequently in the cytosolic fraction at 5 min. Another intermediary metabolite,¹²³I-p-iodophenyldodecanoic acid (¹²³I-PIPC₁₂), was found only in the mitochondrial fraction after 5 min. In conclusion, the slow washout kinetics of¹²³I-BMIPP from the myocardium mainly reflects the turnover rate of the triglyceride pool in the cytosol. The BMIPP metabolism, i.e. initial -oxidation followed by subsequent cycles of -oxidation, was confirmed in vivo. The participation of the mitochondria in the metabolism was also proven.     

Reduced 123I-BMIPP uptake implies decreased myocardial flow reserve in patients with chronic stable angina

Purpose Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. ¹²³I-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced ¹²³I-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate ¹²³I-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with ¹⁵O-water positron emission tomography (PET).Methods We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent ¹²³I-BMIPP single-photon emission computed tomography (SPECT) and ¹⁵O-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. ¹²³I-BMIPP uptake was evaluated as follows: score 0=normal, 1=slightly decreased uptake, 2=moderately decreased uptake, 3=severely decreased uptake, and 4=complete defect. ¹²³I-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR.Results The numbers of segments with ¹²³I-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93±0.25, 0.86±0.21, 0.97±0.30, and 0.99±0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76±1.29, 1.84±0.74, 1.37±0.39, and 1.08±0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01±1.38, 2.20±0.95, 1.44±0.22, and 1.10±0.26, respectively. As ¹²³I-BMIPP uptake declined, hyperemic MBF and MFR decreased.Conclusion In chronic stable angina without previous infarction, reduced ¹²³I-BMIPP uptake implies decreased MFR.     

Myocardial metabolism of 123I-BMIPP in a canine model with ischemia: implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.

123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. However, the reason of this mechanism remains unclear. METHODS: Using open-chest dogs under anesthesia, we made a system to release all the blood of the great cardiac vein outside without recirculation, if necessary. Left anterior descending artery (LAD) was occluded for 30 min after reperfusion. After the injection of BMIPP into LAD, blood samplings from the cardiac vein and abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chromatography (HPLC) in the efflux study. Thin-layer chromatography (TLC) technique was introduced in the tissue analytical study. RESULTS: Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, the early washout (8 min) of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early phase with ischemia. In tissue, the radioactivity was concentrated in the triglyceride pool even in the early phase, and in addition, BMIPP and alpha-oxidized metabolite significantly decreased in the early phase with ischemia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). CONCLUSION: These results show that backdiffusion of nonmetabolized BMIPP from the myocardium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an important role in myocardial perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.     

Prediction of functional recovery in acute myocardial infarction: Comparison between sestamibi reverse redistribution and sestamibi/BMIPP mismatch

Background  It has been known that Tc 99m sestamibi/iodine 123 betamethyliodophenylpentadecanoic (¹²³I-BMIPP) (sestamibi/BMIPP) mismatch is an indicator of viable myocardium in acute myocardial infarction (AMI). We have reported that reverse redistribution of sestamibi in AMI indicates the patency of infarct-related artery and a preserved left ventricular function in the chronic stage. In this study we investigated the relationship between reverse redistribution of sestamibi and sestamibi/BMIPP mismatch in patients with AMI. Methods  Twenty-three patients with AMI who received direct percutaneous transluminal coronary angioplasty underwent both BMIPP and sestamibi SPECT within 2 weeks after onset. Sestamibi images were obtained 1 hour (early) and 3 hours (delayed) after injection of sestamibi. BMIPP imaging was carried out 30 minutes after injection. The left ventricle was divided into 17 segments, and regional myocardial uptakes of the tracers in each segment were scored from 0 (normal) to 3 (no activity). A reverse redistribution pattern was defined as an increase of ≽1 in the regional score at the delayed images. More reduced BMIPP uptake than sestamibi uptake in each segment was determined as sestamibi/BMIPP mismatch. Contrast left ventriculography was performed soon after revascularization and repeated 1 month later. Results  Of 15 patients with sestamibi reverse redistribution, sestamibi/BMIPP mismatch was observed in 14 patients (93%), whereas mismatch was seen in only one of seven patients (14%) without reverse redistribution (p<0.01). In patients with sestamibi reverse redistribution, regional scores of BMIPP agreed with those of early and delayed images of sestamibi in 51 segments (46%) and in 92 segments (83%), respectively. In the chronic stage, both regional wall motion and left ventricular ejection fraction improved in patients with sestamibi reverse redistribution (wall motion score: 6.7±2.4 vs 2.7±2.1, p<0.01; ejection fraction: 56%±7% vs 64% ±8%, p<0.01), but not in those without reverse redistribution. Conclusion  Both reverse redistribution of sestamibi and sestamibi/BMIPP mismatch reflect the recovery of left ventricular function and thus imply myocardial viability in AMI. Because the presence of reverse redistribution of sestamibi agreed with that of sestamibi/BMIPP mismatch, additional BMIPP images can be replaced by the delayed images after a single injection of sestamibi. Supported in part by grants-in-aid for Scientific Research (nos. 08457200 and 08770488) from the Ministry of Education, Science and Culture, Japan.     

Prediction of cardiac events in patients with dilated cardiomyopathy using <Superscript>123</Superscript>I-BMIPP and <Superscript>201</Superscript>Tl myocardial scintigraphy

Objective Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, ¹²³I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using ¹²³I-BMIPP and ²⁰¹TI (Tl) myocardial scintigraphy. Methods Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. Results The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 × 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (χ² test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). Conclusions These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.     

Characterization of Japanese standards for myocardial sympathetic and metabolic imaging in comparison with perfusion imaging

Objective  The standard patterns of myocardial radiotracer distribution of ¹²³I-metaiodobenzylguanidine (MIBG) and ¹²³I-β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) should be defined in a Japanese population. The purpose of this study was to present and provide data on the characteristics of MIBG and BMIPP with respect to myocardial single photon emission computed tomography. Methods  The normal database included ¹²³I-MIBG and ¹²³I-BMIPP imaging and a ^99mTc-sestamibi/tetrofosmin myocardial perfusion study. The projection images were transferred by digital imaging and communications in medicine (DICOM) format and reconstructed and analyzed with polar maps. Results  The projection data from multiple centers were successfully transferred to a common format for SPECT reconstruction. When the average values were analyzed using a 17-segment model, MIBG uptake in the inferior and apical wall appeared to be slightly lower than anterior uptake (P < 0.05). The inferior and apical uptake of MIBG has a larger standard deviation (10.7 units in males, 12.6 units in females). BMIPP uptakes in the septal wall have higher than that of ^99mTc-tracer uptake (P < 0.05). Conclusion  Myocardial sympathetic nerve and metabolic scintigraphy data that were specific for the Japanese population were generated and found to be different from that of perfusion tracers. The normal database can serve as a standard for nuclear cardiology work conducted in Japan.     

Impairment of regional fatty acid uptake in relation to wall motion and thallium-201 uptake in ischaemic but viable myocardium: Assessment with iodine-123-labelled beta-methyl-branched fatty acid

In coronary artery disease, discrepancy in the uptake of thallium-201 and of methyl-branched fatty acid at rest has been described. The purpose of this study was to evaluate iodine-123 labelled beta-methylbranched fatty acid (BMIPP) myocardial uptake and wall motion at rest in segments with stress-induced ischaemia identified by stress²⁰¹Tl tomography in patients with chronic coronary artery disease.¹²³I-BMIPP myocardial tomography was performed at rest and was compared with the findings of exercise-reinjection²⁰¹Tl tomography in 45 patients with chronic coronary artery disease. Regional wall motion was evaluated by contrast left ventriculography in 36 patients. Among 237 segments with reversible²⁰¹Tl defects, equally decreased uptake on both reinjection²⁰¹Tl and BMIPP images was observed in 93 (39%), more severely decreased uptake of BMIPP in 118 (50%) and more severely decreased uptake of reinjection²⁰¹Tl in 26 (11%). On the other hand, among 90 segments with non-reversible²⁰¹Tl defects, each pattern was observed in 71 (79%), 6 (7%) and 13 (14%) segments, respectively. When comparing the ischaemic segments with and without more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl, wall motion was impaired to a greater extent in the segments with more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl [severe hypo- or dyskinesis was present in 64 (70%) of 91 segments and in 24 (22%) of 110 segments, respectively,P<0.005]. In patients with chronic coronary artery disease, resting fatty acid uptake was frequently more reduced than reinjection²⁰¹Tl in the segments with stress-induced ischaemia, while in most of the fixed perfusion defects BMIPP and reinjection²⁰¹Tl uptake decreased concordantly. In ischaemic myocardium, wall motion was impaired to a greater extent in those segments which showed more severely reduced uptake of BMIPP than of reinjection²⁰¹Tl. In ischaemic but viable myocardium, discordant BMIPP uptake less than reinjection²⁰¹Tl uptake may indicate metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities. In conclusion, the combination of resting BMIPP and stress-reinjection²⁰¹Tl imaging may provide information on metabolic alterations and wall motion abnormality at rest independent of perfusion abnormalities.     

Incremental predictive value of myocardial scintigraphy with<Superscript> 123</Superscript>I-BMIPP in patients with acute myocardial infarction treated with primary percutaneous coronary intervention

Purpose It is unclear whether ¹²³I-labelled -methyl iodophenyl pentadecanoic acid (¹²³I-BMIPP) myocardial scintigraphy adds further predictive value for future cardiac events compared with the variables obtained during cardiac catheterisation in patients with acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention (PCI). We therefore investigated whether ¹²³I-BMIPP imaging in patients with AMI treated by primary PCI was useful in predicting future cardiac events.Methods One hundred and fifty-nine patients with AMI who were treated with primary PCI and underwent left ventriculography (LVG) on admission underwent ²⁰¹Tl and ¹²³I-BMIPP myocardial scintigraphy. Scintigrams were visually classified, and the total defect score (TDS) was calculated. Major adverse cardiac events (MACE) were defined as cardiac death including sudden death, congestive heart failure and recurrence of acute coronary syndrome. Patients were followed up for a mean of 34.5 months (12–63 months).Results Twenty-six patients had MACE. Kaplan-Meier analysis indicated that patients with the top 50% of ¹²³I-BMIPP TDSs had a significantly higher rate of MACE (P=0.007). Patients with mismatch between ²⁰¹Tl and ¹²³I-BMIPP images also had significantly more MACE (P=0.02). In the prediction of MACE, the global chi-square value was 5.2 (P=0.001) based on LVEF (<45%) and the number of diseased vessels (two or three). Adding ¹²³I-BMIPP TDS and the mismatch improved the global chi-square value ( ²=7.2)Conclusion Myocardial scintigraphy using ²⁰¹Tl and ¹²³I-BMIPP predicts future cardiac events in patients with AMI treated with primary PCI, and provides additional predictive value compared with the variables obtained with cardiac catheterisation alone.     

Effect of exercise induced hyperlactatemia on the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid in normal volunteers

We have evaluated the biodistribution and metabolism of iodine-123-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) in the presence of increased lactate levels induced by short-term heavy exercise. Five healthy male subjects received 159 MBq (±13 MBq) ¹²³I-BMIPP at rest and a week later after they performed a maximal exercise test using a bicycle ergometer. Planar and tomographic images were obtained with a dual-head gamma camera up to 4 h after administration of the tracer. Multiple blood samples were taken at different time points for blood clearance, substrate concentration measurements and for HPLC analysis of metabolites. The exercise test did not alter plasma glucose and non-esterified fatty acid concentrations, but blood lactate increased from 1.12 mmol/l at rest to 9.26 mmol/l with maximal exercise. After exercise, BMIPP showed a significantly faster plasma clearance than at rest and the production of PIPA, the end metabolite of BMIPP oxidation, was reduced. Activity in the heart was similar after exercise and at rest on planar images 15 min after injection (4.83±0.50%ID vs 4.80±0.43%ID, P=NS), although the myocardium-to-cavity activity ratio, as determined on the SPET images 20 min after tracer injection, was slightly increased after the exercise test (4.20±0.63 vs 3.78±1.34 at rest, P=NS). Significantly increased activity was observed in a leg muscle region of interest after exercise (4.98±0.50%ID vs 3.93±0.44%ID at rest, P=0.02). Between early and late images, tracer washout from the myocardium increased from 20.72% at rest to 36.72% after exercise (P<0.05), but was unchanged for liver and leg muscles. The metabolic and physiological alterations induced by exercise do not degrade image quality of BMIPP scintigraphy. On the contrary, exercise-induced hyperlactatemia seems to enhance myocardium-to-cavity activity ratios on SPET images, although this effect does not reach statistical significance in this small group of normal subjects. These findings further support the robustness of BMIPP SPET in varied metabolic environments. Received 7 June and in revised form 7 August 1999     

Prognosis of hypertrophic cardiomyopathy: Assessment by123I-BMIPP (β-methyl-p-(123I)iodophenyI pentadecanoic acid) myocardial single photon emission computed tomography

¹²³I-BMIPP (β-methyl-iodophenyl pentadecanoic acid) has shown unique properties for potential use in assessing myocardial metabolism. Previous basic and clinical studies demonstrated that the disturbances of myocardial metabolism precede the occurrence of myocardial perfusion abnormalities by using²⁰¹Tl in hypertrophic myocardium. The present study was therefore undertaken to determine whether or not¹²³I-BMIPP myocardial SPECT is useful in predicting the prognosis of hypertrophic cardiomyopathy (HCM) in 65 patients in 6 facilities. There were 33 patients with non-obstructive HCM, 12 with obstructive HCM, 12 with apical HCM and 8 with dilated-phase HCM. Fasted patients at rest received an intravenous injection of 111 MBq of¹²³I-BMIPP. Twenty to thirty minutes later, myocardial SPECT was carried out. The BMIPP severity score (BMIPP SS) was evaluated semiquantitatively by using representative short axial SPECT images. We followed up the incidence of cardiac events for a mean period of 3.0 ± 0.6 years. Cardiac events occurred in 13 patients. Of these, 11 developed heart failure and 6 died (4 from heart failure and 2 from sudden death). The BMIPP SS in the dilated-phase HCM was significantly higher than that in the remaining HCM patients. The BMIPP SS for the survivors was significantly lower than that for the non-survivors. The BMIPP SS was particularly high in patients with fatal heart failure. Furthermore, there was a close negative correlation between the BMIPP SS and percent fractional shortening measured by echocardiography (r = ?0.49). Finally, the mortality over the three years increased according to the extent of the BMIPP SS. In conclusion, these results indicate that the BMIPP SS is useful in evaluating the severity of HCM. We conclude that¹²³I-BMIPP is a valuable metabolic tracer in predicting the outcome of HCM.     

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion

To assess the biventricular response of the clearance rate of carbon-11 acetate as an index of myocardial oxidative metabolism to increase in work-load, dynamic positron emission tomography was performed at rest and during dobutamine infusion in 14 normal subjects. The clearance rate constant (K_mono) of the left ventricular (LV) myocardium increased during dobutamine infusion (0.112±0.020 min^–1 vs 0.065±0.015 min^–1 at rest) (P<0.001) in proportion to the increase in the pressure-rate product. K_mono in the right ventricular (RV) myocardium also increased (0.080±0.018 min^–1 vs 0.034±0.013 min^–1 at rest) (P<0.001), with an excellent correlation with the LV K_mono (r=0.920). The fact that the increase in RV Kmono during dobutamine infusion was greater (158%±81%) than that in LV Kmono (79%±39%) (P < 0.005) indicates a greater increase in oxidative metabolism in the RV in response to inotropic stimulation in normal subjects. Correspondence to: N. Tamaki     

Heterogeneous myocardial distribution of iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in patients with hypertrophic cardiomyopathy

It has been proposed that iodine-123 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (¹²³I-BMIPP) is an agent for myocardial fatty acid metabolism in animal models. The aim of the present study was to determine whether alterations in fatty acid uptake and/or utilization in patients with hypertrophic cardiomyopathy (HCM) could be detected by ¹²³I-BMIPP. Myocardial imaging with ¹²³I-BMIPP and thallium-201 (²⁰¹Tl) was performed in 14 fasted patients. A dose of 111 MBq of ¹²³I-BMIPP was administered intravenously at rest, and myocardial emission computed tomography was obtained 20 min and 3 h after injection. The ²⁰¹Tl imaging was also performed within 1 week after the ¹²³I-BMIPP study. The regional myocardial uptake and clearance of ¹²³I-BMIPP and ²⁰¹Tl were assessed quantitatively. The myocardial distribution of ¹²³I-BMIPP was more heterogeneous than that of ²⁰¹Tl in patients with HCM. The myocardial uptake of ¹²³I-BMIPP was lower in the anteroseptal region of the left ventricle than in the posterolateral region (74% vs. 85%, P < 0.001). The anteroseptal wall showed a faster clearance of ¹²³I-BMIPP than the posterolateral wall (33% vs. 27%, P < 0.01). Both a decreased uptake and rapid clearance of ¹²³I-BMIPP were observed in the hypertrophied myocardium of the anteroseptal wall, where ²⁰¹Tl uptake was normal or even increased. Myocardial segments with a markedly increased thickness showed a lower uptake and faster clearance of ¹²³I-BMIPP than those with mild hypertrophy (uptake 73% vs. 82%, P < 0.05; clearance 30% vs. 25%, P < 0.05). Myocardial imaging with ¹²³I-BMIPP was thus applicable to patients with HCM for detecting myocardial regions with altered fatty acid metabolism.Supported in part by Grants-in-Aid for Scientific Research (nos. 02454259, 03268224) from the Ministry of Education, Science and Culture, Japan, a grant for Research on Cardiovascular Disease (1S-1) from the Ministry of Health and Welfare, Japan, and a grant from Uehara, Memorial Foundation. Offprint requests to: Y Takeishi     

Prediction of functional recovery and prognosis in patients with acute myocardial infarction by123I-BMIPP and201Tl myocardial single photon emission computed tomography: A multicenter trial

¹²³I-BMIPP [15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid] was developed for metabolic imaging with SPECT. A multicenter collaborative study was conducted on a large patient series to determine whether¹²³I-BMIPP and²⁰¹Tl myocardial SPECT are of use in predicting the prognosis and ventricular function after acute myocardial infarction (AMI). Patients with uncomplicated first AMI underwent resting¹²³I-BMIPP and²⁰¹Tl myocardial SPECT in the subacute phase after the onset of AMI. Of these, 167 patients who had been followed up for an average of 22 months were retrospectively reviewed to predict serious cardiac events and recurrent ischemia. In addition, the association between changes in radionuclide parameters and recurrent ischemia was investigated in Subgroup A (58 patients) who had repeated SPECT in the chronic phase. Furthermore, prediction of the ejection fraction (EF) was investigated in Subgroup B (94 patients) and Subgroup C (76 patients) in whom left ventriculography was performed at the time of discharge and 90 days or more after the onset, respectively. The prognosis was generally favorable, with 4 cases of cardiac death (2%), 3 of heart failure (2%), 4 of nonfatal reMI (2%), and 25 of recurrent ischemia (15%). The results of Cox multivariate regression analysis revealed a high probability of serious cardiac events in patients who were elderly (p = 0.04), who had 90% or more residual stenosis of the infarct-related artery (p = 0.09), and who had a high BMIPP defect score (p = 0.17). There was a high probability of recurrent ischemia in elderly patients (p = 0.10) who had multi-vessel disease (p = 0.03), but no association was found with radionuclide parameters in the subacute phase. In Subgroup A, however, the probability of recurrent ischemia tended to be high in patients with a large mismatch score between¹²³I-BMIPP and²⁰¹Tl in the subacute to chronic phase. An important observation was that the extent of BMIPP defect was more strongly correlated with EF at the time of discharge and 90 days or more after the onset than the extent of Tl defect (r = ?0.60 vs. r = ?0.47, and r = ?0.53 vs. r = ?0.43, respectively). In addition, multiple regression analysis showed that parameters related to the BMIPP defect were also better predictive factors of EF both at the time of discharge and 90 days or more after the onset. In conclusion, resting¹²³I-BMIPP and²⁰¹Tl myocardial SPECT performed in the subacute phase of AMI were shown to be useful in predicting prognosis and ventricular function for patient management.     

Involvement of pulmonary endothelial cell injury in the pathogenesis of pulmonary fibrosis: clinical assessment by 123I-MIBG lung scintigraphy

Purpose Pulmonary microvascular endothelial injury may be involved in the pathogenesis of pulmonary fibrosis (PF). The aim of this study was to evaluate the pulmonary vascular status in patients with PF by lung scintigraphic assessment of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG), which reflects latent endothelial cell lesions.Methods We assessed lung ¹²³I-MIBG kinetics and clinical indices in 23 PF patients and 16 controls. Mean uptake ratios of lung to mediastinum (L/M) were calculated in anterior planar images at 30 (early image) and 270 (delayed image) min after intravenous injection of ¹²³I-MIBG. The pulmonary mean washout rate (WR) of ¹²³I-MIBG was also calculated.Results The L/M ratio in early images, but not in delayed images, was significantly lower in the PF patients than in the controls (L/M_early 1.41±0.14 vs 1.53±0.10, p<0.01; L/M_delayed 1.28±0.10 vs 1.33±0.07, p=NS). WR was significantly reduced in the PF patients compared with the controls (28.6%±3.1% vs 34.2%±5.1%, p<0.001). In the study subjects (PF patients plus controls) there were significant relationships between lung WR of ¹²³I-MIBG and other diagnostic parameters for the severity of PF, such as vital capacity (r=0.625, p<0.0001), total lung capacity (r=0.691, p<0.0001), carbon monoxide diffusing capacity (r=0.622, p<0.0001), serum angiotensin-converting enzyme activity (r=0.422, p<0.01), carbohydrate antigen KL-6 levels (r=–0.495, p<0.01) and surfactant protein-D levels (r=–0.461, p<0.01). When control subjects were excluded, similar significant correlations were observed between WR and %TLC (r=0.508, p<0.05), DL_CO (r=0.593, p<0.01) and serum ACE activity (r=0.515, p<0.05) in the PF patients.Conclusion These results suggest that endothelial cell injury plays a significant role in the pathogenesis of PF, and that lung WR of ¹²³I-MIBG, which is a specific marker of endothelial damage, can serve as a novel diagnostic tool to evaluate the functional severity of PF.     

Recovery of impaired left ventricular function in patients with acute myocardial infarction is predicted by the discordance in defect size on123I-BMIPP and201TI SPET images

A discrepancy between myocardial perfusion defect and wall motion abnormalities is frequently found early after coronary reperfusion in patients with acute myocardial infarction. The purpose of this study was to assess recovery of impaired left ventricular function by reference to the discordance in defect size between myocardial fatty acid uptake and myocardial perfusion using combined single-photon emission tomographic (SPET) imaging early after coronary perfusion therapy. In 37 patients with acute myocardial infarction, iodine-123 15(p-iodophenyl)-3(R, S)-methylpentadecanoic acid (BMIPP) and thallium-201 SPET scans were performed early after coronary reperfusion. A severity score was determined from the extent of the imaging defect with each tracer. Left ventricular wall motion score (WMS) and ejection fraction (EF) were obtained at admission and at 4 weeks after the onset of infarction. In 32 of the 37 patients, discordance in defect sizes delineated with the two SPET studies was found during the acute stage. The severity score for BMIPP was larger than that for²⁰¹Tl during the acute stage (7.7±2.4 vs 4.4±2.5,P <0.001). There was a fair correlation between the severity score for BMIPP and WMS (r=0.82,P <0.0001), but a poor correlation between that for²⁰¹Tl and WMS. The extent of discordance in severity scores between BMIPP and²⁰¹Tl during the acute stage correlated well with the extent of the improvement in WMS (r=0.86,P <0.0001) and that of EF (r=0.85,P <0.0001). We conclude that the discordance in defect size on BMIPP and²⁰¹TI SPET images during the acute stage of infarction is an early predictor of the viability of the myocardium at risk of infarction.     

Fatty acid myocardial imaging using 123I-β-methyl-iodophenyl pentadecanoic acid (BMIPP): comparison of myocardial perfusion and fatty acid utilization in canine myocardial infarction (Occlusion and reperfusion model)

To evaluate the relationship between myocardial perfusion and fatty acid metabolism in canine myocardial infarction, 16 dogs were studied using thallium and ¹²³I--methyl-iodophenyl pentadecanoic acid (BMIPP). Eight dogs (group A) had left anterior coronary arterial occlusion (6 h ligation), 6 dogs (group B) had reperfusion (3 h ligation and 1 h reperfusion) and 2 dogs served as the normal control. Myocardial imaging with BMIPP was excellent, owing to its higher uptake and longer retention in myocardium and rapid blood disappearance in addition to diminished liver and lung uptake. The mean half time value which was generated from the BMIPP myocardial washout curve, was significantly larger in the reperfused myocardium. The gamma camera imaging showed uncoupling of BMIPP and thallium (BMIPP uptake greater than thallium uptake) in five dogs in group B. On the other hand, all dogs in group A had a persistent defect in BMIPP and thallium uptake. Our findings indicate that the combination of BMIPP and thallium for myocardial imaging supply different information about the zone of infarction and ischemia, which may be useful for the assessment of myocardial viability.     

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     

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model

Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with¹²⁵I-BMIPP, a branched fatty acid analog.Methods: SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of¹²⁵I-BMIPP and²⁰¹Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition,¹²⁵I-BMIPP uptake was corrected by²⁰¹Tl uptake (B/T).Results: The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p < 0.001). In SHR, this ratio increased up to 18 weeks (12 weeks; 0.266 ± 0.005, 18 weeks; 0.281 ± 0.006: mean ± SE, p < 0.05). The¹²⁵I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373 ± 0.212, 18 weeks; 1.380 ± 0.047: mean ± SE, p < 0.05). Such a difference in BMIPP uptake was more evident when BMIPP uptake was corrected by Tl uptake (B/T), but no regional difference or heterogeneity of BMIPP distribution was observed in the hypertrophie myocardium in SHR.Conclusion: A change in fatty acid metabolism with age was observed in association with myocardial hypertrophy in this hypertensive rat model, which was well demonstrated with¹²⁵I-BMIPP and²⁰¹Tl.