Evaluation of myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP)

To evaluate the myocardial uptake of beta-methyl-(123I)-iodophenylpentadecanoic acid (123I-BMIPP), nineteen patients with ischemic heart disease including left ventricular hypertrophy (mean age 63 +/- 7.8, 14 males and 5 females) underwent BMIPP myocardial scintigraphy. Myocardial uptake (MU) of BMIPP to the total injected dose was calculated from anterior view of the planar image in all subjects, and was compared with plasma glucose (BS), triglyceride (TG), and free fatty acid (FFA). It was also compared with left ventricular mass (LVM) calculated with echocardiography. MU was not related to BS, TG, and FFA, however had the positive correlation with LVM (r = 0.676, p < 0.01). Myocardial uptake per left ventricular mass (MU/LVM) had the negative correlation with LVM (r = -0.671, p < 0.01). Further studies for the significance of MU/LVM will be required.     

Iodine-123 metaiodobenzylguanidine cardiac imaging to identify and localize vasospastic angina without significant coronary artery narrowing

OBJECTIVES: We assessed the ability of iodine-123 metaiodobenzylguanidine (MIBG) imaging to identify and localize coronary spasm and determined the most useful method of MIBG analysis in vasospastic angina without significant coronary narrowing. BACKGROUND: Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in patients with sporadic attacks. MIBG imaging has recently been proposed as a useful tool for detecting vasospastic angina. METHODS: Normal limits of both visual and quantitative analysis of two-dimensional polar maps (bull's-eyes) for MIBG imaging were at first established in 59 normal subjects. For optimal criteria of visual analysis, we established regional differences in abnormal MIBG defect scores. An abnormal region of the bull's-eye was defined as an area > 2 SD below normal. An abnormal regional washout rate was defined as < 0%. Using these criteria, we prospectively evaluated 104 patients with suspected vasospastic angina. Visual, bull's-eye and regional washout rate analyses were compared for overall detection of the disease and for individual vessel involvement. RESULTS: Overall sensitivity by these methods was 30%, 42% and 76%, respectively. Washout rate analysis showed a significantly higher sensitivity than the other two methods. Specificity was 78%, 72% and 87%, respectively. The sensitivity of detecting spasm-induced coronary artery with washout rate analysis was 82% for the left anterior descending (LAD), 76% for the right (RCA) and 69% for the circumflex (Cx) coronary arteries. The sensitivity of visual analysis was 29%, 15% and 35%, respectively; that for bull's-eye analysis was 34%, 54% and 41%, respectively. Washout rate analysis showed a significantly higher sensitivity for LAD spasm than for the other two methods and a higher sensitivity for RCA and Cx spasms than for visual analysis. CONCLUSIONS: Regional washout rate analysis of MIBG imaging is a highly accurate technique for determining the presence and location of coronary artery spasm.     

Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency

The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases [44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases] using a flow cytometer. 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases.     

Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency

A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.     

Use of 123I-BMIPP single-photon emission tomography to estimate areas at risk following successful revascularization in patients with acute myocardial infarction

PURPOSE: To determine the frequency and nature of intraoperative complications of endocapsular phacoemulsification cataract surgery. SETTING: Dalcross Private Hospital and the Departments of Ophthalmology, Concord Hospital and Prince of Wales Hospital, Sydney, Australia. METHODS: This prospective study included the first 1000 cases of planned endocapsular phacoemulsification cataract surgery performed by an experienced surgeon. A standardized proforma was completed at the time of surgery. Data recorded included pre-existing ocular abnormalities, duration of surgery, nuclear sclerosis grade, and intraoperative complications. RESULTS: Major complications comprised posterior capsule tears with vitreous loss (1.4%), isolated posterior capsule tears (0.7%), and zonulysis (0.1%). Minor complications included anterior capsule tears (3.8%), iris prolapse (0.6%), and ciliary body incision (0.2%). There was a significant trend toward complications as the nuclear sclerosis grade increased. The incidence of major complications was 9.3% in the first 150 cases and 0.9% in the last 850. This represents a relative risk of 9.9 (95% confidence interval 4.2 to 23.0) of a major complication occurring in the first 150 compared with the later 850 cases. CONCLUSION: The frequency of major and minor complications fell sharply after the first 150 operations and was maintained. This study may provide a guide for beginning phacoemulsification surgeons and a basis for experienced surgeons to compare their performance outcomes.     

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.     

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy

Injury of the normal central nervous system is a major concern in the radiotherapy of brain tumors, but the pathogenesis of injury remains poorly understood. Modulation of the production of growth factors is associated with ischemia and traumatic injury in the central nervous system. Ionizing radiation has been shown to induce basic fibroblast growth factor in endothelial cells and in cells of a human breast carcinoma cell line. The inducibility of basic fibroblast growth factor after irradiation and its potential role in the recovery response of the central nervous system led us to investigate the effects of radiation on the expression of this growth factor in primary cultures of normal rat type 1 astrocytes. Astrocyte monolayers were exposed to ionizing radiation (1 to 10 Gy). Northern blot analysis revealed that doses of 2 to 10 Gy markedly reduced the expression of basic fibroblast growth factor as early as 1 h after irradiation, and that it remained below levels in unirradiated cells for at least 24 h. The effect was not associated with astrocyte cytotoxicity, and it appears to have some specificity for basic fibroblast growth factor since the levels of mRNA coding for ciliary neurotrophic factor and glial fibrillary acidic protein were not affected.     

The relationship between discrepant areas on 201TlCl/123I-BMIPP myocardial scintigraphy, local wall motion, and glucose metabolism in patients with myocardial infarction

In order to clarify the significance of the discrepancy between myocardial blood flow and fatty acid metabolism on 201TlCl/123I-BMIPP SPECT after acute myocardial infarction, we examined 52 patients (278 segments) with their first acute myocardial infarction using two-dimensional echocardiography and FDG-PET. Patients with Tl/BMIPP discrepancy in the acute stage showed higher FDG accumulation than those without Tl/BMIPP discrepancy. In the chronic stage, however, there was no significant difference between both groups. Patients with Tl/BMIPP discrepancy in the chronic stage had lower wall motion scores than those without Tl/BMIPP discrepancy. Significant improvement of the wall motion score was recognized in patients who showed Tl/BMIPP discrepancy in the acute stage. Patients were classified into stenosis and non-stenosis groups by the presence of significant stenosis on coronary angiography in the chronic stage. In the stenosis group, the Tl/BMIPP discrepancy did not show much change from the acute to chronic stage, but there was a significant decrease in the non-stenosis group. It was concluded that 201TlCl/123I-BMIPP myocardial SPECT is useful for predicting future improvement of wall motion and determining the residual ischemia in the chronic stage based on the presence or absence of this discrepancy.     

Reproducibility of spasm in patients with long-term remission of vasospastic angina by medical treatment

No single musculoskeletal disorder has generated more passionate discussion than bone osteonecrosis. Surprisingly, its physiopathogenesis remains largely unknown despite in-depth studies. Its treatment is still debated, and its wide range of clinical manifestations which vary from totally asymptomatic to the catastrophic event of irreversible epiphyseal collapse remains a fascinating question for the clinicians (1-4). Magnetic Resonance (MR) imaging has given a large tribute to the discussion during the last decade by allowing detection of marrow infarcts at a presymptomatic period of the disease, thus providing data on its natural history. Unfortunately, MR imaging has also contributed to increase the confusion among various epiphyseal disorders. The aim of the current paper is to provide an overview of the current knowledge of imaging features by stressing accepted data and delineating blind areas.     

123I-MIBG myocardial imaging in hypertensive patients: abnormality progresses with left ventricular hypertrophy

An active component of the sex pheromone system of the yellowish elongate chafer, Heptophylla picea was identified by GC-EAD. Mass spectral data and hydrogenation revealed that the active compound was a hexadecadien-4-olide. It was not possible to determine the double bond positions by direct DMDS derivatization of the pheromone, but partial hydrogenation (diimide) followed by DMDS derivatization showed that the double bonds were located in positions 7 and 15. FTIR (tracer) of the pheromone corroborated the lactone structure (1772 cm-1) and showed a band characteristic of a terminal double bond at 3073 cm-1, and one of a double bond in the cis-configuration at 3002 cm-1. Chiral resolution of the pheromone, after hydrogenation, demonstrated that the natural lactone had the (R)-stereochemistry. Synthetic (R,Z)-7,15-hexadecadien-4-olide, prepared from L-malic acid in 14 steps, was identical to the natural product in MS, IR, retention times and biological activity. This is the first fatty acid derivative compound found as a sex pheromone of a Melolonthinae species and as far as biosynthesis is concerned this is the most complex pheromone constituent of a scarab species.     

Prediction of functional recovery and prognosis in patients with acute myocardial infarction by 123I-BMIPP and 201Tl 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 whether 123I-BMIPP and 201Tl myocardial SPECT are of use in predicting the prognosis and ventricular function after acute myocardial infarction (AMI). Patients with uncomplicated first AMI underwent resting 123I-BMIPP and 201Tl 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 scorebetween 123I-BMIPP and 201Tl 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, resting 123I-BMIPP and 201Tl myocardial SPECT performed in the subacute phase of AMI were shown to be useful in predicting prognosis and ventricular function for patient management.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

Increased serotonin release across the coronary bed during a nonischemic interval in patients with vasospastic angina

BACKGROUND: Platelet activation and coagulation abnormality have been observed during coronary spasm. It is crucial whether platelet activation occurs even during a nonischemic period. HYPOTHESIS: This study was designed to determine whether platelets might be activated across the coronary bed during a nonischemic interval in patients with vasospastic angina. METHODS: Plasma levels of serotonin, 6-keto-prostaglandin F1 alpha, and catecholamines in the aorta and the coronary sinus were simultaneously measured in 16 patients with vasospastic angina and 13 control patients with nonischemic heart disease. RESULTS: None of these patients showed myocardial ischemia during sampling. The difference in transcardiac plasma levels of serotonin in patients with vasospastic angina was significantly higher than that in controls (1.48 +/- 1.08 ng/ml vs. 0.07 +/- 0.12 ng/ml, respectively, p < 0.001). Coronary sinus plasma norepinephrine levels in these two groups were almost the same (204.8 +/- 110.8 pg/ml vs. 190.4 +/- 131.6 pg/ml, respectively). The ratio of 6-keto-prostaglandin F1 alpha in the coronary sinus and the aorta was not different between the two groups (1.17 +/- 0.96 in patients with vasospastic angina vs. 1.15 +/- 0.68 in controls). CONCLUSIONS: These data suggest that platelet activation across the coronary bed should be ascribed to endothelial dysfunction. Lack of compensatory enhancement of prostacyclin production might be concerned with dysfunction of coronary endothelial cells in these patients.     

Evaluation of myocardial perfusion and fatty acid uptake using a single injection of iodine-123-BMIPP in patients with acute coronary syndromes

The purpose of this study was to clarify the possibility of simultaneous evaluation of myocardial perfusion and fatty acid metabolism using a single injection of 123I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with acute coronary syndromes. METHODS: Thirty patients with unstable angina pectoris (UAP group) and 15 patients with acute myocardial infarction (MI group) were studied. BMIPP dynamic SPECT was performed 2 min after the injection of BMIPP (185 MBq), and images were obtained every 3 min for 15 min with a three-head gamma camera. Conventional BMIPP SPECT was also performed 30 min after the injection. Serial BMIPP and resting 201TI images were compared. RESULTS: A 201TI-BMIPP mismatch between 30-min BMIPP and resting 201TI images was observed in 27 of 30 patients in the UAP group and 8 of 15 patients in the MI group, respectively. However, a 201TI-BMIPP mismatch between early (2-5-min) BMIPP and resting 201TI images was observed in only 2 of 30 patients in the UAP group and in only 2 of 15 patients in the MI group, respectively. The kappa statistics of tracer uptake between early BMIPP and resting 201TI images showed good concordance in UAP (kappa = 0.823) and MI (kappa = 0.765) groups, respectively. These results indicated that initial distribution of BMIPP reflects myocardial perfusion in patients with acute coronary syndromes. CONCLUSION: Myocardial perfusion and fatty acid metabolism can be evaluated simultaneously using a single injection of BMIPP, when images are taken soon (2-5 min) and long after the injection in patients with acute coronary syndromes.     

Evaluation of long-term prognosis in patients with heart failure: is cardiac imaging with iodine-123 metaiodobenzylguanidine useful?

The effect of cardiac sympathetic activity on long-term prognosis in patients with heart failure was evaluated by cardiac imaging with iodine-123 metaiodobenzylguanidine (123I-MIBG) in 46 patients admitted for the first episode of heart failure (idiopathic dilated cardiomyopathy: 18, ischemic heart disease: 10, hypertensive heart disease: 7, valvular heart disease: 4, others: 7). Cardiac imaging was performed with 123I-MIBG and thallium-201 (201Tl) at rest on separate days before discharge. Using whole body imaging, the ratio of cardiac uptake of the isotope to total injected dose was calculated (percentage uptake). The cardiac uptake ratio of 123I-MIBG (percentage uptake of 123I-MIBG divided by percentage uptake of 201Tl) and percentage washout of 123I-MIBG from the heart over 3 hours were calculated as scintigraphic parameters. Cardiac events were defined as cardiac death or deterioration of heart failure requiring readmission. Scintigraphic parameters, clinical parameters, left ventricular function obtained by echocardiography and neurohumoral parameters were compared between the event group and event-free group. During the follow-up period of 26.9 +/- 13.9 (7.1-53.8 months), cardiac events developed in 14 patients (cardiac death in 10 and deterioration of heart failure in 4; 30%). Univariate analysis showed uptake ratio and washout rate of 123I-MIBG, percentage uptake of 201Tl, New York Heart Association class at discharge, fractional shortening of the left ventricle, serum norepinephrine and atrial natriuretic peptide levels differed significantly between the two groups. Cox proportional-hazard analysis showed that the uptake ratio was an independent predictor of cardiac events (p < 0.0001). When a cut-off point in the uptake ratio equal to or less than 0.50 and age equal to or more than 65 years old were included in the Cox proportional-hazard analysis instead of actual numbers, relative risks of cardiac events by each index were 31.2 (95% confidence interval, 3.9 to 247.6; p = 0.001) and 4.2 (p = 0.025), respectively. These data suggest that cardiac uptake of 123I-MIBG is a strong and independent predictor of long-term prognosis in patients with heart failure.     

Chlamydia pneumoniae infection in patients with myocardial infarct and angina pectoris

In a prospective open study we investigated Chlamydia pneumoniae infections in 36 consecutively admitted patients: 26 males, mean age 53.4 yr, range 36-70 yr, 10 females mean age 57.7 yr, range 47-70 yr, suffering myocardial infarction (24 acute, 2 previous) or angina pectoris (10). Antibody serum levels were measured by the immunefluorescent method and they were as follows: negative 5, low 12, medium/high 11, chronic infection 5, recent infection 3. The 3 cases considered as recent infections are described in detail.     

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with 123I-BMIPP and 201Tl

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method (TEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included. 201Tl cross-talk into the 123I acquisition window (group 1, n = 30) and 123I cross-talk into the 201Tl window (group 2, n = 41) were studied. In group 1, 123I images were first obtained (single-isotope images), followed by 201Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual 123I-BMIPP/201Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.     

Insulin resistance associated with compensatory hyperinsulinemia as an independent risk factor for vasospastic angina

BACKGROUND: It is generally believed that coronary artery spasm plays an important role in the progression of obstructive coronary artery disease. Since insulin resistance together with hyperinsulinemia plays an important role in the pathogenesis of coronary atherosclerosis, we investigated the association of hyperinsulinemia and insulin resistance with vasospastic angina (VAP). METHODS AND RESULTS: The study population consisted of 60 patients with VAP and 42 control subjects (62 subjects with normal glucose tolerance and 40 with impaired glucose tolerance). Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method for nondiabetic, normotensive, nonobese subjects (16 control subjects, 16 obstructive coronary artery disease patients, and 16 VAP patients). Compared with the control group, the 2-hour insulin area (area under the plasma insulin concentration-time curve) during a 75-g oral glucose tolerance test was significantly higher in both VAP groups with normal and impaired glucose tolerance. A high frequency of vasospastic angina was observed in subjects with clustered risk factors for insulin resistance syndrome, suggesting a close association of VAP with this syndrome. In stepwise discriminant analysis, the 2-hour insulin area was significantly associated with VAP independent of other risk factors. SSPG level in VAP was about twofold over control, indicating the presence of insulin resistance in patients with VAP. However, no differences were found between patients with VAP and obstructive coronary artery disease with respect to mean SSPG level. CONCLUSIONS: SSPG level was significantly elevated in patients with VAP and obstructive coronary artery disease compared with control subjects. This indicates that hyperinsulinemia is secondary to insulin resistance, both of which are thought to play important roles as risk factors for VAP in the early atheromatous lesion and in the future development of occlusive lesions when chronically present.     

Fasting and nonfasting iodine-123-idophenylpentadecanoic acid myocardial SPECT imaging in coronary artery disease

Iodine-123-labeled idophenylpentadecanoic acid (IPPA) metabolic imaging has been shown to be clinically useful for the identification of myocardial viability in patients with coronary artery disease and left ventricular dysfunction. Imaging is usually performed under fasting conditions since nonfasting conditions may affect myocardial uptake of 123I-IPPA. The purpose of this study was to examine the impact of dietary condition on 123I-IPPA metabolic imaging. METHODS: Forty patients with stable coronary artery disease underwent, in randomized order and on separate days, 123I-IPPA SPECT myocardial imaging under fasting and nonfasting conditions. Patients were injected with 123I-IPPA (4-5 mCi) at rest with imaging performed at 4 (initial) and 30 (delay) min. For each image (initial and delay images), 10 segments were analyzed by three experienced observers without knowledge of patient identity or dietary condition using a 5-point grading system (O = no uptake to 4 = normal uptake). A summed global score was obtained for each image by adding the scores for all 10 segments. Image quality was assessed using a 3-point grading system. RESULTS: Visual agreement for normal and abnormal segments between fasting and nonfasting conditions was 82% (kappa = 0.63). There were no significant differences in the summed global scores for both conditions. Image quality was equivalent for both conditions in 65% of cases and superior under the nonfasting condition in 25% of cases. CONCLUSION: Image quality as well as the presence, location and severity of defects are similar under fasting and nonfasting conditions with 123I-IPPA. Therefore, fasting is not necessary before 123I-IPPA SPECT imaging for the assessment of myocardial viability.