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ABSTRACT: Two types of hemodynamic overload, pressure and volume overload, result in morphologically distinct types of cardiac remodeling. We explored the possibility that distinct hemodynamic overload may differentially activate the signal transduction pathway.
Pressure and volume overload were induced by thoracic aortic banding and carotid-jugular shunt formation in rabbits, respectively. Phosphorylation activities of mitogen-activated protein (MAP) kinase families, Akt, and signal transducer and activator of transcription (STAT) 3 in the left ventricular myocardium were determined by Western blotting using phospho-specific antibodies and were compared between hypertrophied hearts by pressure and volume overload.
Pressure and volume overload produced concentric and eccentric cardiac hypertrophy in rabbits, respectively. In pressure-overloaded hearts, extracellular signal-regulated kinase (ERK) 1/2, p38 MAP kinase, and STAT3 were transiently activated prior to hypertrophic changes. In contrast, activation of ERK1/2, but not p38 MAP kinase and STAT3, was observed only at 12 weeks after shunt surgery. Pressure overload evoked short and biphasic activation of Akt at 15 min and 1 day after aortic banding. In contrast, volume overload induced sustained activation of Akt from 1 day to 1 week. Concordant phosphorylation of downstream targets of Akt, glycogen synthase kinase-3beta (GSK-3beta) and p70 ribosomal S6 kinase (p70(S6K)), in response to Akt activation was observed at 15 min after pressure overload. However in volume-overloaded hearts, phosphorylation of GSK-3beta and p70(S6K) was observed at 6 weeks and at 6 and 12 weeks, respectively, and was not coincident with Akt activation. These findings suggest that phosphorylation of GSK-3beta and p70(S6K) is regulated by an alternative pathway other than Akt in volume-overloaded hearts.
Pressure and volume overload-induced cardiac hypertrophy is associated with distinct patterns of activation of signal transduction pathways. These data may suggest that stimulus-specific heterogeneity in the signaling pathway plays a role in determining the type of cardiac hypertrophy.
Archiv für Kreislaufforschung 10/2004; 99(5):328-37. · 7.35 Impact Factor
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ABSTRACT: The peroxisome proliferator-activated receptor (PPAR) alpha is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPARalpha and fatty acid oxidation enzymes in volume-overloaded rabbit hearts.
Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. (125)I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by beta-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPARalpha and fatty acid oxidation enzymes were examined by Western blotting.
Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0.06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by beta-oxidation was faster than the sham-control hearts (P < 0.05). However, protein levels of PPARalpha and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits.
These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPARalpha and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli.
European Journal of Clinical Investigation 03/2004; 34(3):176-81. · 3.02 Impact Factor
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ABSTRACT: Increased cardiovascular mortality is an unresolved problem in patients with chronic renal failure. Cardiac hypertrophy is observed in the majority of patients with chronic renal failure undergoing haemodialysis. However, the mechanisms, including signal transduction pathways, responsible for cardiac hypertrophy in renal failure remain unknown. We examined the subcellular localization of protein kinase C (PKC) isoforms and phosphorylation activities of 3 mitogen-activated protein (MAP) kinase families in hypertrophied hearts of progressive renal injury rat model by subtotal nephrectomy (SNx). We also examined the effects of a novel angiotensin II type-1 receptor antagonist, CS-866, on the PKC translocation, MAP kinase activity and cardiac hypertrophy in SNx rats. The left ventricle/body weight ratios were significantly larger in SNx rats than in sham rats at 1, 2, and 4 weeks after surgery. The translocation of PKCalpha and epsilon isoforms to membranous fraction was observed in SNx rat hearts at 1, 2, and 4 weeks after surgery. Activation of extracellular signal regulated kinase (ERK) 1/2, but not p38 MAP kinase and c-Jun N-terminal kinase (JNK), was observed at 1 and 2 weeks after surgery. Angiotensin II receptor blockade with CS-866 (1 mg kg-1 day-1) prevented cardiac hypertrophy, PKC translocation and ERK1/2 activation in SNx rats without significant changes in blood pressure. These data suggest that PKC and ERK1/2 are activated by an angiotensin II receptor-mediated pathway and might play an important role in the progression of cardiac hypertrophy in renal failure.
European Journal of Clinical Investigation 03/2004; 34(2):85-93. · 3.02 Impact Factor
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T Arimoto, Y Takeishi,
A Fukui,
H Tachibana,
N Nozaki,
O Hirono,
H Yamaguchi,
M Itoh,
T Miyamoto,
H Takahashi,
A Okada,
K Takahashi,
I Kubota
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ABSTRACT: 123I-metaiodobenzylguanidine (123I-MIBG) is useful for assessment of the severity and prognosis of patients with chronic heart failure (CHF). To examine 123I-MIBG kinetics in the early phase soon after tracer injection, we performed dynamic single photon emission computed tomography (SPECT) in 76 patients with CHF and 17 control subjects. The consecutive 15 images of 2 min-dynamic SPECT were acquired for 30 min after injection. From 0 to 4 min, a significant amount of radioactivity existed in the blood pool, thus we calculated washout rate of 123I-MIBG from 4 to 30 min (%WR-E). Patients were followed up with an end-point of cardiac death or re-hospitalization for 16 months (6-30 months). As the NYHA functional class advanced, %WR-E increased (control, NYHA class I, II, and III: 9 +/- 4%, 10 +/- 5%, 12 +/- 5%, and 17 +/- 5%*, respectively, *p < 0.01 vs. all other groups). Significant correlation was found between %WR-E and conventional WR from 30 min to 240 min (r = 0.606, p < 0.0001). %WR-E was positively correlated with left ventricular end-diastolic dimension (r = 0.372, p < 0.01) and was inversely correlated with left ventricular fractional shortening (r = -0.316, p < 0.02). The normal upper limit of %WR-E was defined as mean + 2SD value of 17 control subjects (17.1%). Patients with abnormally rapid %WR-E levels had a higher cardiac event rate than those with normal %WR-E levels (57% vs. 12%, p < 0.0001). These data suggest that washout rate of 123I-MIBG in the early phase from 4 min to 30 min (%WR-E) reflects cardiac sympathetic nervous integrity and is useful to evaluate the severity and prognosis of patients with CHF. The present results indicate a potential role of dynamic SPECT in shortening the 123I-MIBG imaging protocol.
Annals of Nuclear Medicine. 01/2004;
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S Yamauchi, Y Takeishi,
O Minamihaba,
T Arimoto,
O Hirono,
H Takahashi,
T Miyamoto,
J Nitobe,
N Nozaki,
H Tachibana,
T Watanabe,
A Fukui,
I Kubota
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ABSTRACT: This study aimed to examine whether angiotensin-converting enzyme (ACE) inhibition improved cardiac fatty acid metabolism in patients with congestive heart failure (CHF). Myocardial 123I-beta-methyl-iodophenylpentadecanoic acid (123I-BMIPP) imaging was performed in 25 patients with CHF and in 10 control subjects. Myocardial 123I-BMIPP images were obtained 30 min and 4 h after tracer injection. The heart-to-mediastinum (H/M) ratio of 123I-BMIPP uptake and the washout rate of 123I-BMIPP from the myocardium were calculated. Patients were given enalapril for 6 months, and 123I-BMIPP imaging was repeated. H/M ratios on early and delayed images were lower in CHF patients than in normal controls (P<0.01). The washout rate of 123I-BMIPP from the myocardium was faster in CHF patients than in controls (P<0.01). As the severity of the New York Heart Association (NYHA) functional class increased, the H/M ratio decreased and the washout rate increased. The washout rate of 123I-BMIPP was inversely correlated with left ventricular fractional shortening (R=-0.62, P<0.01). ACE inhibition with enalapril increased the H/M ratio on delayed images (P<0.05) and reduced the washout rate of 123I-BMIPP (P<0.05) in CHF patients. These data suggest that: (1) angiotensin II-mediated intracellular signalling activation may be a possible mechanism for the decreased myocardial uptake and enhanced washout of 123I-BMIPP in heart failure patients; and (2) the improvement in fatty acid metabolism by ACE inhibition may represent a new mechanism for the beneficial effect of this therapy in heart failure.
Nuclear Medicine Communications 08/2003; 24(8):901-6. · 1.40 Impact Factor
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O Minamihaba, Y Takeishi,
O Hirono,
S Yamauchi,
T Arimoto,
A Fukui,
M Okuyama,
N Nozaki,
H Akiyama,
K Fatema,
T Miyamoto,
H Takahashi,
S Fujiwara,
A Okada,
K Takahashi,
I Kubota
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ABSTRACT: The aim of the present study was to examine whether Doppler tissue imaging demonstrated comparable diagnostic performance for the detection of viable myocardium compared to myocardial perfusion imaging with Tc hexakis-2-methoxyisobutylisonitrile (MIBI). We studied 30 patients with old myocardial infarction who underwent percutaneous transluminal coronary angioplasty (PTCA). Myocardial single photon emission computed tomography (SPECT) with Tc-MIBI and two-dimensional echocardiography were carried out within 7 days before PTCA. We measured regional Tc-MIBI uptake for each myocardial segment from SPECT and peak systolic velocity and a ratio of regional pre-ejection period to regional ejection time (PEP/ET) from pulsed Doppler tissue imaging. Biplane left ventriculography was performed before interventional procedures and repeated 3 months after PTCA. Myocardial viability was determined when wall motion was improved at least one grade after PTCA. The peak systolic velocity was positively correlated with regional Tc-MIBI uptake (R =0.59, P<0.01). The PEP/ET demonstrated inverse correlation with Tc-MIBI uptake ( R=-0.59, P<0.01). Peak systolic velocity of viable segments was higher than that of non-viable segments ( P<0.05). The PEP/ET was lower in viable segments than in non-viable segments ( P<0.05). Peak systolic velocity and PEP/ET demonstrated high diagnostic accuracy for detecting viable myocardium compared with Tc-MIBI perfusion imaging (80% and 79% vs 90%). These data indicate that measurements of regional peak systolic velocity and PEP/ET by Doppler tissue imaging are useful for evaluating myocardial viability quantitatively and provide helpful information for a clinical judgment in an interventional strategy.
Nuclear Medicine Communications 01/2003; 23(12):1197-204. · 1.40 Impact Factor
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ABSTRACT: BACKGROUND: Reverse redistribution and rapid washout of 99mTc-sestamibi are observed in patients with acute myocardial infarction and may indicate viable myocardium. However, the clinical significance of this phenomenon has not been rigorously examined in other cardiac diseases. Thus, we investigated whether reverse redistribution and washout of 99mTc-sestamibi could be used in the diagnosis and follow-up of patients with coronary spastic angina.
METHODS: Thirty patients diagnosed as coronary spastic angina were examined. During coronary arteriography, spasm was induced by provocation test with ergonovine, and only total or subtotal occlusion was considered positive. Myocardial perfusion tomography was obtained 45 min (early) and 3 hr (delayed) after 99mTc-sestamibi injection. Segmental defect score was visually graded from 0 (normal) to 4 (defect), and a total defect score was determined as the sum of defect scores for all segments. Washout rate of 99mTc-sestamibi from the myocardium was calculated for each segment. After medical treatment with calcium antagonists and nitrates for 3 months, 99mTc-sestamibi imaging was repeated.
RESULTS: Out of 30 patients, on the early images 17 (57%) patients demonstrated decreased 99mTc-sestamibi uptake in spastic segments; on the other hand, 24 (80%) patients did decreased 99mTc-sestamibi uptake in spastic segments on delayed images. Total defect scores in delayed images were higher than those in early images (6.9 +/- 0.3 vs. 3.6 +/- 0.4, p < 0.01). Reverse redistribution of 99mTc-sestamibi was observed in 17 out of 30 patients (57%) with coronary spastic angina. Washout rate of 99mTc-sestamibi from spastic segments was higher than that from non-spastic segments (16 +/- 2% vs. 11 +/- 5%, p < 0.01). After medical treatment, washout rate from spastic segments was decreased to 10 +/- 4 (p < 0.01), and left ventricular ejection fraction was increased from 63 +/- 8% to 73 +/- 4% (p < 0.01).
CONCLUSION: Rapid washout of 99mTc-sestamibi was observed in patients with coronary spastic angina and might indicate that the ability of myocyte to retain the tracer was impaired due to repetitive brief ischemia by coronary spasm. The early and delayed 99mTc-sestamibi imaging provides useful information for the diagnosis and responses to the treatment in patients with coronary spastic angina.
Annals of Nuclear Medicine. 01/2003;
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S Fujiwara, Y Takeishi,
O Hirono,
A Fukui,
M Okuyama,
S Yamaguchi,
M Ito,
K Kaneko,
T Shishido,
T Miyamoto,
K Yuki,
T Miyashita,
K Takahashi,
O Minamihaba,
H Tomoike,
S Yamauchi,
K Fatema
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ABSTRACT: Reverse redistribution (RR) of 99mTc-sestamibi is observed after direct percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI). The purpose of this study was to clarify the functional characteristics of myocardial segments with RR after direct PTCA in AMI. Thirty patients with AMI who had undergone direct PTCA were examined. Myocardial perfusion tomography with 99mTc-sestamibi and low dose dobutamine echocardiography were performed within 2 weeks of the onset. The 99mTc-sestamibi images were obtained 1 and 3 h after tracer administration. The left ventricle was divided into nine segments, and regional 99mTc-sestamibi uptake and clearance were quantitatively evaluated in each segment. RR was defined as a decrease in 99mTc-sestamibi uptake of >10% on 3 h delayed images compared with the 1 h early images. The left ventricle in the echocardiographic images was also divided into nine segments corresponding to the scintigraphic images, and regional wall motion was assessed in the resting condition as the baseline and during dobutamine administration (5-10 microg x kg(-1) x min(-1)). Out of a total of 270 myocardial segments, 111 segments were perfused by the culprit coronary artery and were defined as ischaemic segments. There were 25 segments with RR and 86 segments without RR in the ischaemic myocardium. Enhanced clearance of 99mTc-sestamibi was observed in ischaemic segments with RR (P<0.001). Echocardiography demonstrated that 24 out of 25 segments with RR and 61 out of 86 segments without RR had wall motion abnormalities. Dobutamine infusion improved wall motion in 20 (83%) of the 24 dysfunctional segments with RR and 33 (54%) of the 61 dysfunctional segments without RR (P<0.02). These findings suggest that RR indicates reversible functional abnormalities associated with preserved contractile reserve in response to dobutamine. The early and delayed imaging of 99mTc-sestamibi provides useful information regarding the residual viability of the dysfunctional myocardium in AMI patients.
Nuclear Medicine Communications 11/2001; 22(11):1223-30. · 1.40 Impact Factor
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ABSTRACT: The present study examined the role of calcineurin in insulin-like growth factor (IGF)-1-induced hypertrophy in primary cultures of adult rat ventricular myocytes (ARVM), prepared from the ventricles of 14-16-week-old male Sprague-Dawley rats. The effects of several humoral factors, including phenylephrine, angiotensin II, endothelin-1, IGF-1 and interleukin-6, on the morphology of ARVM were studied. Myocyte surface area was significantly increased by IGF-1 (2,268 +/- 571 to 3,018 +/- 836 microm2, p < 0.01), but not by other humoral factors. This hypertrophic effect of IGF-1 was blocked by genistein (tyrosine kinase inhibitor), PD98059 (MEK inhibitor). These findings suggest that IGF-1 produces ARVM hypertrophy by a tyrosine kinase-MEK mediated pathway as has been reported in neonatal cardiomyocytes. IGF-1-mediated ARVM hypertrophy was also attenuated by cyclosporine A (calcineurin inhibitor), and staurosporine and chelerythrine (protein kinase C inhibitors). IGF-1 markedly increased calcineurin activity (8.7 +/- 1.2 to 98.0 +/- 54.3 pmol x h(-1) mg(-1), p < 0.01), and this activation was completely blocked by pre-treatment with cyclosporine A (8.5 +/- 11.4pmol x h(-1) x mg(-1), p < 0.01) and chelerythrine (2.3 +/- 2.7 pmol x h(-1) mg(-1), p < 0.01). It appears that IGF-1 activates calcineurin by a protein kinase C-dependent pathway. Increased mRNA expression of atrial natriuretic factor by IGF-1 was inhibited by cyclosporine A (p < 0.01). The findings indicate that IGF-1 induces ARVM hypertrophy by protein kinase C and calcineurin-related mechanisms. The fact that elevated calcineurin activity and induced atrial natriuretic factor mRNA expression by IGF-1 were blocked by cyclosporine A further supports the hypothesis that calcineurin is critically involved in IGF-1-induced ARVM hypertrophy.
Japanese Circulation Journal 10/2001; 65(9):815-9.
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ABSTRACT: Volume overload results in eccentric cardiac hypertrophy, but it is still unknown how this mechanical overload modulates the inotropic response to exogenous Ca2+ or adenylyl cyclase stimulation. Inotropic responsiveness in vivo and the levels of gene expression of Ca2+ signaling proteins were studied in rabbit hearts hypertrophied as a result of volume overload at 4 and 12 weeks after arteriovenous shunt formation. In sham-operated control rabbits, left ventricular (LV)+dP/dt was augmented in response to graded doses of CaCl2. Dose-related changes of LV+dP/dt to CaCl2 were attenuated significantly in shunt rabbits with volume overload. Forskolin dose-dependently augmented LV+dP/dt in sham rabbits, which was also attenuated significantly in rabbits with volume overload. The mRNA levels of dihydropyridine receptor, Na+/Ca2+ exchanger, sarcoplasmic reticulum Ca2+-ATPase, and ryanodine receptor decreased significantly at 4 and 12 weeks in the volume-overload rabbits compared with the sham rabbits, but the mRNA levels of phospholamban and calsequestrin remained unchanged. Chronic volume overload alters contractile responsiveness to Ca2+ or adenylyl cyclase stimulation, and downregulation of steady state mRNA levels of Ca2+ signaling proteins might be, at least in part, related to this pathologic process.
Japanese Circulation Journal 12/2000; 64(11):861-7.
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ABSTRACT: 123I-15-(p-iodophenyl)-9-R,S-methylpentadecanoic acid (9-MPA) has recently been developed as a tracer for myocardial fatty acid uptake. The aim of this study, which was performed as part of a phase III clinical trial of 9-MPA, was to test the usefulness of 9-MPA for the assessment of myocardial viability in patients with acute coronary syndrome (ACS).
Fifteen patients with ACS who had undergone direct percutaneous transluminal coronary angioplasty were examined. Myocardial SPECT with 9-MPA and 99mTc-sestamibi and low-dose dobutamine echocardiography were performed within 2 wk after onset. The 9-MPA images were obtained 10 and 60 min after tracer administration, and sestamibi imaging was begun 60 min after the injection. The left ventricle was divided into 9 segments, and 9-MPA and sestamibi uptake were scored from 0 (normal) to 3 (no activity) in each segment. Lower uptake of 9-MPA than of sestamibi was defined as a mismatch. Myocardial segments showing improvement in wall motion during low-dose dobutamine infusion (5-10 microg/kg/ min) were considered viable.
The 9-MPA images were of high quality for all patients. Myocardial uptake of 9-MPA was lower in ischemic myocardium than in nonischemic myocardium (58.2%+/-14.2% versus 91.9%+/-6.5%, P<0.0001). Clearance of 9-MPA from ischemic myocardium was slower than that from nonischemic myocardium (10.2%+/-11.7% versus 19.1%+/-5.9%, P<0.01). A mismatch was seen in 10 of 15 patients, and 18 of 20 (90%) mismatched segments were defined as viable by dobutamine echocardiography. Conversely, 18 of 20 (90%) matched segments did not show any improvement in function during dobutamine stimulation (P<0.0001). Uptake of 9-MPA in nonviable segments was lower than that in dysfunctional but viable segments (P<0.05), and 9-MPA clearance from nonviable segments was slower than that from viable segments (P<0.05).
The imaging characteristics of 9-MPA for SPECT are excellent, allowing noninvasive assessment of myocardial fatty acid uptake. Myocardial imaging with 9-MPA may reveal impaired fatty acid uptake in dysfunctional but viable myocardium and thus provide useful information for clinical decision making in ACS.
Journal of Nuclear Medicine 12/1999; 40(12):1999-2006. · 6.38 Impact Factor
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ABSTRACT: An increase of 99mTc-sestamibi uptake in the myocardium during exercise was defined as a response rate, and the feasibility of a response rate for detecting coronary artery disease (CAD) was tested. Eighty-seven patients with suspected CAD had myocardial perfusion imaging with 99mTc-sestamibi during exercise and at rest. A dose of 370 MBq of 99mTc-sestamibi was injected at the maximal level of exercise, and a myocardial image was obtained 90 min later (exercise image). Then, 740 MBq of 99mTc-sestamibi was administered at rest, and myocardial imaging was repeated (rest image). The exercise and rest images were corrected for physical decay and injected doses, and the exercise image was subtracted from the rest image to obtain the corrected rest image. A response rate was calculated as follows: (exercise image-corrected rest image)x100/corrected rest image (%). The global response rates of 20 patients without significant coronary stenosis (< or =50%) were higher than those of 67 patients with significant coronary stenosis (81+/-33% and 50+/-28%, p<0.01). Global response rates were correlated with the maximal rate pressure products during exercise (r=0.56, p<0.01) and delta rate pressure products (r=0.53, p<0.01). Regional response rates in myocardial areas perfused by stenotic coronary arteries of < or =50%, 75%, 90% and 99-100% were 60+/-24%,* 56+/-33%,* 40+/-23%* and 30+/-23%,* respectively, (*p<0.01 vs without significant coronary stenosis). The response rates decreased as the severity of coronary artery stenosis advanced, and distinguished between coronary stenoses of graded severity. Accordingly, the response rate from myocardial perfusion imaging with 99mTc-sestamibi may provide complementary information to the conventional inspection with myocardial tomography regarding the severity of CAD.
Japanese Circulation Journal 09/1998; 62(8):592-8.
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ABSTRACT: The aim of this study was to clarify the relationship between cardiac sympathetic nervous activity assessed by 123I-MIBG imaging and exercise capacity in patients with congestive heart failure. The subjects were 24 patients with heart failure (NYHA class II to III) and 7 normal controls. A dose of 148 MBq of 123I-MIBG was administered intravenously, and 5-min anterior planar images were obtained 20 min (early) and 4 h (delayed) after the injection of 123I-MIBG. Regions of interest were placed over the left ventricle and mediastinum, and the heart-to-mediastinum ratio (H/M ratio) was calculated as a fraction of the mean counts per pixel in the heart divided by those in the mediastinum. The washout rate from the myocardium was determined by: (early counts delayed counts) x 100/early counts (%). Treadmill exercise tests were performed using a ramp method within 1 week of the 123I-MIBG studies. During exercise, expired gas was analysed, and peak VO2 and VO2 at the anaerobic threshold (ATVO2) were measured. A significant linear correlation was found between the H/M ratio on delayed 123I-MIBG images and exercise duration (r = 0.48, P < 0.05), peak VO2 (r = 0.49, P < 0.05) and ATVO2 (r = 0.56, P < 0.01). The washout rate of 123I-MIBG was inversely correlated with exercise duration (r = -0.45, P < 0.05), peak VO2 (r = -0.51, P < 0.01), and ATVO2 (r = -0.50, P < 0.05). In conclusion, enhanced cardiac sympathetic nervous activity relates to exercise intolerance in patients with congestive heart failure. The non-invasive assessment of cardiac sympathetic nervous activity by 123I-MIBG can predict exercise capacity in human heart failure.
Nuclear Medicine Communications 06/1998; 19(5):451-6. · 1.40 Impact Factor
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ABSTRACT: The purpose of this study was to determine the biodistribution of 99mTc-tetrofosmin during intravenous infusion of adenosine triphosphate (ATP) and to evaluate the potential diagnostic value of myocardial tomography with 99mTc-tetrofosmin during ATP infusion for the detection of coronary artery disease.
Myocardial 99mTc-tetrofosmin imaging with ATP infusion and coronary arteriography were performed on 65 patients with suspected coronary artery disease. ATP was infused intravenously at a rate of 0.16 mg/kg/min for 5 min, and 370 MBq of 99mTc-tetrofosmin was injected 3 min after the start of ATP infusion. Myocardial SPECT imags were obtained 60 min later. Then, 740 MBq of 99mTc-tetrofosmin was administered at rest, and myocardial SPECT was repeated. Regional uptakes of 99mTc-tetrofosmin were scored from 4, normal, to 0, no activity. Serial 5-min planar images were obtained in the anterior projection at 15, 30, 45 and 60 min after the 99mTc-tetrofosmin injection in 10 patients. Heart-to-lung and heart-to-liver count ratios were defined from the serial planar images.
Adverse effects of ATP infusion were mild and transient. A heart-to-lung ratio after ATP infusion was high even at 15 min (3.40 +/- 0.33) and gradually increased with time. A heart-to-liver ratio after ATP was 0.53 +/- 0.40 at 15 min and increased with time. A heart-to-liver ratio reached 0.99 +/- 0.25 (p < 0.01) after 45 min and 1.32 +/- 0.36 (p < 0.01) after 60 min. The sensitivity and specificity for detecting coronary artery disease by myocardial SPECT with ATP were 89% (39/44) and 86% (18/21), respectively.
This study shows the favorable biodistribution of 99mTc-tetrofosmin after intravenous infusion of ATP. A one-day imaging protocol of 99mTc-tetrofosmin tomography with ATP is feasible and has high diagnostic accuracy for coronary artery disease.
Journal of Nuclear Medicine 04/1998; 39(4):582-6. · 6.38 Impact Factor
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ABSTRACT: The aim of this study was to clarify the clinical implications of decreased myocardial uptakes of 123I-labeled beta-methyl-p-iodophenyl-pentadecanoic acid (123I-BMIPP) in patients with unstable angina.
Fatty acid metabolic imaging with 123I-BMIPP was performed in 20 patients with unstable angina during the pain-free state. Regional uptakes of 123I-BMIPP were scored semiquantitatively, and clinical characteristics and angiographic findings were compared between the patients with the normal and abnormal 123I-BMIPP images.
There were 9 patients with normal and 11 patients with abnormal 123I-BMIPP images. Severe coronary stenosis exceeding 90% (91% compared with 44%, p < 0.05) and 99% (82% compared with 0%, p < 0.01) and collateral opacification (36% compared with 0%, p < 0.05) were more frequently observed in patients with abnormal 123I-BMIPP images than in those with normal images. Percutaneous transluminal coronary angioplasty or coronary artery bypass grafting was performed in 22% of patients with normal 123I-BMIPP images and in 82% of patients with abnormal 123I-BMIPP images (p < 0.01).
Fatty acid metabolic imaging with 123I-BMIPP can determine the functional severity of coronary artery disease and is helpful for a clinical judgment in interventional treatment.
Journal of Nuclear Medicine 09/1997; 38(9):1407-11. · 6.38 Impact Factor
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ABSTRACT: Radioiodinated metaiodobenzylguanidine (123I-MIBG), an analog of norepinephrine, has been used to assess cardiac sympathetic nerve activity. Decreased myocardial accumulation and enhanced washout of 123I-MIBG have been reported in patients with congestive heart failure (CHF). The purpose of this study was to determine whether angiotensin converting enzyme (ACE) inhibition reduced 123I-MIBG release and improved cardiac 123I-MIBG accumulation in patients with CHF.
Twenty-nine patients receiving conventional treatment for CHF, New York Heart Association (NYHA) functional class 2-3, were studied. Nineteen patients received additional treatment with enalapril, an ACE inhibitor, and 10 patients who were treated with conventional therapy alone were defined as a control group. Iodine-123-MIBG imaging and echocardiography were performed on all patients before treatment and repeated after 9.1 +/- 3.0 mo of treatment. Images were obtained 30 min and 4 hr after injection of 123I-MIBG, and a heart to mediastinum (H/M) ratio was defined to quantify cardiac 123I-MIBG uptake as a fraction of the mean counts per pixel in the heart divided by those in the mediastinum. The washout rate of 123I-MIBG from the heart was calculated as follows: (early counts - delayed counts)/early counts x 100(%).
In patients with enalapril group, the H/M ratio of 123I-MIBG was increased after treatment (early image: 1.60 +/- 0.22 vs. 1.73 +/- 0.28, p < 0.05, delayed image: 1.63 +/- 0.28 vs. 1.82 +/- 0.33, p < 0.01). The washout rate of 123I-MIBG was reduced from 38% +/- 11% to 30% +/- 12% after treatment (p < 0.01). However in the conventional therapy group, the H/M ratios in the early and delayed images (early image: 1.58 +/- 0.31 vs. 1.52 +/- 0.23, delayed image: 1.49 +/- 0.27 vs. 1.49 +/- 0.25) and the washout rate (34% +/- 8% vs. 33% +/- 7%) remained unchanged after treatment. In patients with an increased H/M ratio of enalapril group (n = 13), a left ventricular ejection fraction increased from 48% +/- 12% to 55% +/- 9% (p < 0.01) after treatment.
ACE inhibition reduces cardiac 123I-MIBG release and thus lowers cardiac sympathetic nerve activity. Iodine-123-MIBG may be helpful in evaluating the therapeutic effects of ACE inhibition on the cardiac sympathetic nervous system in patients with CHF.
Journal of Nuclear Medicine 07/1997; 38(7):1085-9. · 6.38 Impact Factor
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ABSTRACT: Iodine-123-BMIPP kinetics under high glucose levels were examined. The feasibility of 123I-BMIPP imaging after oral glucose loading for the detection of impaired fatty acid metabolism was tested in patients with coronary artery disease.
Fatty acid metabolic imaging with 123I-BMIPP was performed on 29 patients in the fasting state and repeated after oral glucose loading. Myocardial SPECT images were obtained 20 min and 4 hr after the injection of 123I-BMIPP. Myocardial uptake of 123I-BMIPP was calculated by a Ishii-Macintyre method and the clearance of 123I-BMIPP from the myocardium was determined as (early counts-delayed counts) x 100/early counts. Regional accumulation of 123I-BMIPP was scored semiquantitatively from 0 (normal) to 4 (no activity), and the sum of regional scores in each patient was defined as a total defect score (TDS).
Total myocardial uptake of 123I-BMIPP was 1.7% +/- 0.4% in the fasting state and 1.6% +/- 0.3% after oral glucose loading (p < 0.05). Iodine-123-BMIPP clearance from the myocardium was faster after glucose loading than in the fasting state (27% +/- 8% versus 11% +/- 6%, p < 0.01). After glucose loading, 123I-BMIPP clearance was faster in the ischemic myocardium (defined as areas perfused by stenosed coronary artery exceeding 90%) than in the nonischemic myocardium (33% +/- 8% versus 25% +/- 9%, p < 0.05). TDS in the ischemic myocardium increased from 1.8 +/- 0.4 in the fasting state to 2.1 +/- 0.4 after glucose loading (p < 0.01). The sensitivity for detecting coronary stenosis exceeding 90% increased from 55% (11/20) in the fasting state to 75% (15/20) after glucose loading without a loss of specificity (78%, 7/9).
Oral glucose loading enhanced the detection of areas with impaired fatty acid metabolism due to coronary artery narrowing. Iodine-123-BMIPP imaging with oral glucose loading may be a new approach for the noninvasive diagnosis of coronary artery disease.
Journal of Nuclear Medicine 02/1997; 38(2):175-80. · 6.38 Impact Factor
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ABSTRACT: Exercise thallium-201 (201T1) single photon emission computed tomography (SPECT) has been used to detect potential ischaemia in the left ventricular myocardium but not in the right ventricle. The purpose of this study was to establish the clinical usefulness of a right ventricular polar map of 201T1 SPECT for visualisation of exercise-induced right ventricular ischaemia.
Myocardial 201T1 SPECT was obtained immediately after treadmill exercise in 97 patients with suspected coronary artery disease. A region of interest was placed over the right ventricle (RV) on post-stress transaxial images. Short axis images of this region were generated and reconstructed as a bull's eye polar map. Normal ranges of RV 201T1 uptake were determined in 12 patients with normal coronary arteries. Scintigraphic criteria for identifying RV perfusion abnormality were derived from 25 patients with right coronary artery (RCA) stenosis greater than 75%. These criteria were applied to 60 consecutive patients with suspected coronary artery disease.
Perfusion defects in the RV were larger in patients with proximal RCA stenosis than in those with distal RCA stenosis (mean (SD) 28 (16)% v 6 (5)%, P < 0.001). The sensitivity and specificity of the RV polar map for the detection of proximal RCA stenosis were 67% (8/12) and 98% (47/48), respectively. RV perfusion defects became undetectable in 9 patients who had successful percutaneous transluminal coronary angioplasty to a proximal RCA lesion.
A right ventricular polar map display was useful for visualising exercise-induced right ventricular ischaemia.
Heart (British Cardiac Society) 01/1997; 77(1):40-5. · 4.22 Impact Factor
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ABSTRACT: The aim of this study was to assess the relation of plasma substrate concentration to 123I-beta-methyliodophenyl-pentadecanoic acid (123I-BMIPP) kinetics in the myocardium and to test the application of 123I-BMIPP imaging to patients with diabetes mellitus (DM) and/or hyperlipidemia (HL). 123I-BMIPP imaging was performed on 78 patients with suspected coronary artery disease, 22 with HL, 11 with DM, 12 with HL and DM, and 33 with neither HL or DM. Significant coronary stenosis (defined as > or = 50% of luminal diameter) was documented in 49 patients. After an overnight fast, blood samples were drawn for blood glucose, insulin, cholesterol, triglycerides and free fatty acid levels. Then, 148 MBq 123I-BMIPP was injected intravenously and flushed rapidly with saline. Data were obtained for 60s in a standard anterior projection in list mode, at a rate of 1 frame per second. Myocardial single photon emission tomographic (SPET) images were obtained 20 min and 4 h post-injection. The myocardial uptake of 123I-BMIPP was calculated using the Ishii-MacIntyre method. Regional accumulation of 123I-BMIPP was scored semi-quantitatively from 0 (normal) to 4 (no activity), and the sum of regional scores in each patient was defined as the total defect score (TDS). Myocardial uptake and clearance of 123I-BMIPP had no relation to the levels of blood glucose, insulin, cholesterol, triglycerides or free fatty acids. Myocardial uptake and clearance of 123I-BMIPP, TDS and the sensitivity of detecting significant coronary stenosis were not significantly different between the four groups of patients. We conclude that 123I-BMIPP can be used to detect impaired fatty acid metabolism in patients with diabetes mellitus and/or hyperlipidaemia.
Nuclear Medicine Communications 09/1996; 17(8):675-80. · 1.40 Impact Factor
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ABSTRACT: A pattern of reverse redistribution (RR) has not been documented in myocardial 99mTc-sestamibi imaging. The purpose of the study was to clarify the time-related changes in myocardial distribution of 99mTc-sestamibi in patients with acute myocardial infarction.
Myocardial SPECT with 99mTc-sestamibi was performed in 27 patients with acute myocardial infarction within 1 wk after the onset. Twenty-three patients received direct percutaneous transluminal coronary angioplasty (PTCA) and 4 patients did not. Myocardial images were obtained 1 hr (early) and 3 hr (delayed) after the injection of 99mTc-sestamibi. Regional myocardial uptake of 99mTc-sestamibi was scored from 4 (normal) to 0 (no activity), and the RR pattern was defined as a decrease of more than 1 in the regional score at the 3-hr delayed images. Regional myocardial uptake and clearance of 99mTc-sestamibi was also assessed quantitatively. Coronary arteriography and left ventriculography were performed 1 mo later.
Out of 22 patients with successful PTCA, RR of 99mTc-sestamibi was observed in 15 patients (68%). Persistent defects (PD) were seen in 12 patients (7 patients with successful PTCA, 1 patient with unsuccessful PTCA, and 4 patients who did not receive angioplasty). In patients with RR, regional uptake of 99mTc-sestamibi in the area of myocardial infarction decreased from 54% +/- 10% in the early images to 43% +/- 8% in the delayed images (p < 0.01). Technetium-99m-sestamibi clearance from the myocardium was faster in the infarct area than in the normal area (26% +/- 7% versus 9% +/- 6%, p < 0.01). Coronary arteriography performed 1 mo later revealed that the patency of the infarct related artery was 100% (15/15) in patients with RR and 50% (6/12) in those with PD (p < 0.01). The extent and severity of a wall motion abnormality were less in patients with RR than in those with PD (extent: 24 +/- 10 versus 36 +/- 9 chord, p < 0.01; severity: -2.7 +/- 0.4 versus -3.4 +/- 0.6 s.d./chord, p < 0.01).
The RR of 99mTc-sestamibi was observed in 68% of patients after successful direct PTCA and was associated with the accelerated clearance of 99mTc-sestamibi from the myocardium. The presence of RR in 99mTc-sestamibi imaging indicates the patency of the infarct-related artery and predicts the preserved left ventricular function.
Journal of Nuclear Medicine 09/1996; 37(8):1289-94. · 6.38 Impact Factor
