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Biomedical subjects

R Nohara

Publications and source records attributed to R Nohara.

At least 55 records · Page 3Linked to original sources

Fate of collateral vessels after successful coronary angioplasty in patients with effort angina.

OBJECTIVES: The purpose of the present study was to evaluate whether severe restenosis after percutaneous transluminal coronary angioplasty (PTCA) promotes collateral development and whether successful dilation regresses collateral vessels. BACKGROUND: It is well known that in the presence of severe coronary stenosis, native collateral arterioles mature to small coronary arteries with several layers of smooth muscle cells. However, it remains unclear whether well developed collateral vessels regress after removal of coronary stenosis. METHODS: The study group comprised 41 patients who underwent elective PTCA for effort angina due to single-vessel disease, followed by repeat PTCA to treat restenosis. We classified the patients into three groups depending on the change in baseline Thrombolysis in Myocardial Infarction (TIMI) flow grade of the ischemia-related artery at initial and repeat PTCA, and we compared the extent of ST segment elevation at 1 min of the first balloon inflation between the two procedures. The average interval from initial to repeat PTCA was 125 days. RESULTS: The three patient groups comprised group A, 12 patients with decreased flow grade because of severe coronary restenosis; group B, 12 patients with increased flow grade who had severe initial stenosis and relatively mild restenosis; and group C, 17 patients with unchanged flow grade. In the presence of comparable rate-pressure products at initial and repeat PTCA, patients in group A had significantly greater ST segment elevation (p < 0.01) at initial than at repeat PTCA (mean +/- SD 0.42 +/- 0.31 vs. 0.13 +/- 0.22 mV). In group B, ST segment elevation was significantly less at initial than at repeat PTCA (0.13 +/- 0.25 vs. 0.19 +/- 0.17 mV, p < 0.05), and in group C, it was comparable at the two procedures (0.37 +/- 0.32 vs. 0.35 +/- 0.33 mV, p = 0.50). CONCLUSIONS: These findings indicate that severe restenosis after PTCA promotes collateral development and that successful dilaton regresses collateral vessels during a relatively short period of time.

Aged↗

Heparin and exercise treatment in a patient with arteriosclerosis obliterans.

A 65-year-old man was admitted with a diagnosis of arteriosclerosis obliterans. He had a 3-month history of intermittent claudication of the right leg. Physical examination revealed absence of pulsation of the right posterior tibial artery. Contrast angiography of lower extremities showed several obstructive lesions below the right popliteal artery. As interventional and surgical approached were not indicated, the patient was treated with exercise with heparin pretreatment (5,000 IU). As a result, walk distance on a floor was increased from 400 m to 2,000 m, and repeat magnetic resonance angiography revealed increased flow to the right lower extremity. Thus, he was successfully treated with exercise and heparin pretreatment without any side effects.

Aged↗

Indium-111 antimyosin antibody imaging and thallium-201 imaging--a comparative myocardial scintigraphic study using single-photon emission computed tomography in patients with myocarditis and dilated cardiomyopathy.

Indium-111 antimyosin antibody imaging (a tracer of myocardial necrosis) and thallium-201 imaging (a tracer of myocardial perfusion) were compared in patients with myocarditis and dilated cardiomyopathy. The distribution of each tracer and antimyosin/thallium-201 overlapping were evaluated with single-photon emission computed tomography (SPECT). Scintigraphic data were classified into 5 patterns according to the distribution of both images and were compared with histologic findings of endomyocardial biopsy: AM-D, intense and diffuse antimyosin uptake and no perfusion abnormality (active myocarditis); AM-L, localized antimyosin uptake and no perfusion abnormality (active myocarditis); HM, no antimyosin uptake with or without perfusion abnormality (healed myocarditis); DCM-NH, diffuse antimyosin uptake and inhomogeneous thallium-201 uptake (dilated cardiomyopathy); DCM-PD, diffuse or localized antimyosin uptake and myocardial perfusion defect(s) (dilated cardiomyopathy). Patients with dilated-phase hypertrophic cardiomyopathy were frequently found in the DCM-PD group. Taken together, comparative antimyosin/thallium-201 SPECT images are useful for evaluating the activity of myocarditis and ongoing myocardial damage even in areas with no perfusion in patients with dilated cardiomyopathy.

Adult↗

Metabolism substrate with negative myocardial uptake of iodine-123-BMIPP.

UNLABELLED: Iodine-123-BMIPP is an iodinated methyl-branched-chain fatty acid. Low uptake of BMIPP relative to thallium or other perfusion tracer indicates metabolically damaged but viable myocardium (for example, ischemic but viable myocardium). In some cases, however, negative myocardial uptake of BMIPP is observed. The main purposes of this study were to assess the frequency of such BMIPP findings and to clarify metabolism of such cases by using PET. METHODS: Among the 1258 patients who underwent BMIPP scintigraphy, 11 patients (0.9%) showed negative myocardial uptake of BMIPP. Under fasting condition, PET using [11C]palmitate, 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and [11C]acetate was performed in nine of these 11 patients. RESULTS: Global myocardial uptake of [11C]palmitate, expressed as the standardized uptake value, was significantly lower in the patients than in control (3.62 +/- 0.44 versus 5.49 +/- 1.62; p < 0.01). However, the early phase clearance rate of [11C]palmitate and oxidative metabolism was not significantly different. In the fasting state, PET studies showed increased FDG accumulation in seven of nine patients (high group) and decreased accumulation in two patients (low group). In the high group patients, glucose metabolism in the fasting state was similar to that in the normal volunteers after glucose loading (Kcomplex: 0.050 +/- 0.016 versus 0.038 +/- 0.015; p = ns). However, low glucose metabolism was noted in the low group patients (Kcomplex: 0.007 and 0.005). CONCLUSION: Negative myocardial uptake of BMIPP is occasionally, but not often, observed. Global uptake of [11C]palmitate was decreased in these patient. The majority of these patients showed "metabolic switching" from normal free fatty acid metabolism to abnormally enhanced glucose metabolism in the fasting state. However, some patients showed decreases in both exogenous glucose utilization and free fatty acid uptake in the fasting state.

Acetates↗

Assessment of cardiac sympathetic function with iodine-123-MIBG imaging in obstructive sleep apnea syndrome.

UNLABELLED: Iodine-123-MIBG imaging has been used to evaluate myocardial sympathetic function in various cardiac diseases. In patients with obstructive sleep apnea syndrome (OSAS), increased sympathetic activity has been widely recognized, as assessed by measuring the plasma concentration and urinary excretion of catecholamines and by measuring muscle sympathetic nerve activity. However, these measurements are not specific indices of cardiac sympathetic function. Therefore, this study was undertaken to assess cardiac sympathetic function in patients with OSAS using MIBG cardiac scintigraphy. METHODS: This study consisted of 11 patients (10 men, 1 woman; mean age 43 +/- 16 yr) with a diagnosis of OSAS established by polysomnography, and 8 age-matched normal control subjects (7 men, 1 woman; mean age 45 +/- 18 yr). Early (15 min) and delayed (3 hr) planar images were taken after the injection of 111 MBq of [123I]MIBG. The mean counts of the whole heart and the mediastinum were obtained to calculate heart-to-mediastinum count ratios from the early images (H/Me) and from the delayed images (H/Md) and the myocardial washout rate (WR). Eight patients were restudied after 1 mo of nasal continuous positive airway pressure treatment. RESULTS: The H/Me and H/Md ratios were significantly lower in the patients than in the control subjects (H/Me, 2.49 +/- 0.32 versus 2.84 +/- 0.34, p = 0.0207; and H/Md, 2.33 +/- 0.30 versus 3.02 +/- 0.36, p = 0.0013). The WR was higher in the patients than in the control subjects (36.2 +/- 9.0% versus 23.6 +/- 4.9%, p = 0.0022). The H/Me and H/Md ratios in the patients were significantly correlated with the apnea-hypopnea index and the degree of hypoxemia during sleep. After treatment, H/Me and H/Md remained unchanged, but WR significantly recovered (from 34.9 +/- 10.4% to 26.3 +/- 7.7%, p = 0.0357). CONCLUSION: Cardiac sympathetic function and integrity are impaired in subjects with OSAS when compared with age-matched control subjects. MIBG cardiac imaging can be helpful in evaluating cardiac involvement and efficacy of therapy in OSAS.

3-Iodobenzylguanidine↗

Myocardial kinetics of iodine-123-BMIPP in canine myocardium after regional ischemia and reperfusion: implications for clinical SPECT.

UNLABELLED: To evaluate the clinical utility of 123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) for ischemic heart disease, we investigated the metabolic fate of 123I-BMIPP in canine models with mild and severe ischemia and evaluated the clinical utility of this tracer. METHODS: Using open-chest dogs under anesthesia, we assembled a system that would release all the blood from the great cardiac vein without recirculation, if necessary. After injection of BMIPP into the left anterior descending coronary artery, blood samplings from cardiac vein and abdominal aorta were performed for 10-min ischemia (mild ischemia, five dogs) and 30-min ischemia (severe ischemia, six dogs), after reperfusion and for normal controls (six dogs). The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated using high-performance liquid chromatography. RESULTS: Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged among three groups, the early washout (at 8 min) of radioactivity significantly increased (from 50% +/- 13% to 61% +/- 8%; p < 0.05) in severe ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP and alpha-oxidation, intermediate-oxidation and full-oxidation metabolites. For mild ischemia, these values were not significantly changed from the normal control, although the respective proportions of metabolites showed some variation. Lactate production after reperfusion on mild ischemia, which indicates the severity of ischemia, was closely correlated with the level of backdiffusion of BMIPP (r = -0.92) and the full-oxidation metabolite (r = 0.78). On the other hand, for severe ischemia, the level of backdiffusion of nonmetabolized BMIPP increased (from 25.1% +/- 8.0% to 34.7% +/- 8.7%; p < 0.05), and the full-oxidation metabolites decreased (from 21.4% +/- 10.9% to 14.8% +/- 7.3%). CONCLUSION: The metabolism of BMIPP was closely associated with the severity of myocardial ischemia. Thus, 123I-BMIPP might be a promising and sensitive radiopharmaceutical for the evaluation of ischemic heart disease.

Animals↗

Noninvasive assessment of myocardial viability by positron emission tomography with 11C acetate in patients with old myocardial infarction. Usefulness of low-dose dobutamine infusion.

BACKGROUND: When patients with severely depressed left ventricular function are treated, it is crucial to know in advance how much functional recovery is expected from coronary revascularization. METHODS AND RESULTS: We compared the results of 11C acetate positron emission tomography (PET) with dobutamine infusion with changes in regional wall motion evaluated by left ventriculography in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but viable myocardium (group A, n = 13) was separated from nonviable myocardium (group B, n = 15) by echocardiographic assessments of regional wall motion before and after successful coronary revascularization. 11C acetate PET was performed to characterize normalized myocardial blood flow and oxidative metabolism (the clearance rate constant, k mono). While the baseline k monos of the infarct areas of the two groups were different with overlap, the responses to dobutamine infusion were directionally different. In addition, relative perfusion by 11C acetate PET could predict recovery of left ventricular function as well as or better than dobutamine 11C acetate kinetics. The extent of the increase in k monos of the infarct area with dobutamine infusion correlated well (P < .01) with the degree of the increase in the percentage of systolic segment shortening in the infarct area (left ventriculography) after coronary revascularization. CONCLUSIONS: 11C acetate PET with dobutamine infusion can predict not only the reversibility of dysfunctioning myocardium after coronary revascularization but also the extent of improvement of regional wall motion in patients with old Q-wave infarction.

Acetates↗

Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina.

BACKGROUND: Collateral growth is induced by chemical signals from the ischemic myocardium. We hypothesized that angiogenic growth factors are produced by cardiac tissue; they are diffusible, more concentrated in pericardial fluids, and are increased by myocardial ischemia. METHODS AND RESULTS: With the use of an enzyme-linked immunosorbent assay, we measured the concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in pericardial fluids of 12 patients with unstable angina (group 1) and of 8 patients with nonischemic heart diseases (group 2). The levels of protein in pericardial fluids were quite comparable between the two groups (34 +/- 2 versus 32 +/- 4 mg/mL). The concentration of bFGF in pericardial fluids in group 1 was 2036 +/- 357 pg/mL, significantly (P < .001) higher than the 289 +/- 72 pg/mL in group 2. The amount of bFGF per milligram of protein was also significantly (P < .05) higher in group 1 than in group 2 (67 +/- 15 versus 12 +/- 4 pg/mg). The concentration of VEGF in pericandial fluids tended to be higher in group 1, but the difference was statistically insignificant (39 +/- 7 versus 22 +/- 6 pg/mL). The amount of VEGF per milligram of protein was 1.2 +/- 0.3 pg/mg in group 1, similar to the 0.8 +/- 0.4 pg/mg in group 2. CONCLUSIONS: This finding provides new evidence that bFGF plays an important role in mediating collateral growth in humans.

Aged↗

Patency of infarct-related artery. Effect of restoration of anterograde flow on vagal reflexes. ATRAMI (Automatic Tone and Reflexes After Myocardial Infarction) Investigators.

BACKGROUND: In post-myocardial infarction (MI) patients, the restoration of anterograde flow in the infarct-related artery (IRA) significantly improves survival. Limitation of infarct size and increased electrical stability of the myocardium are likely operating mechanisms for this beneficial effect. We tested the hypothesis that patency of the IRA may enhance vagal reflexes, a factor known to affect electrical stability of the infarcted myocardium. METHODS AND RESULTS: Analysis of angiographic data was performed in 359 of 1284 post-MI patients enrolled in a multicenter prospective study within 8 weeks after the index MI. All the patients underwent baroreflex sensitivity (BRS) assessment by the phenylephrine method. The BRS of the entire population averaged 8.2+/-5.5 ms/mm Hg and was significantly related to age but not to ejection fraction (EF). One-, two-, and three-vessel disease was present in 138, 96, and 99 patients, respectively, while no coronary stenosis was observed in 26. IRA patency was documented in 234 patients (65%), while in the remaining 125 (35%), the artery remained occluded. Patients with occluded IRAs had more extensive coronary disease (2 to 3 vessels, 71% versus 46%, P<.01) and more depressed left ventricular (LV) function (LVEF, 48+/-13% versus 53+/-12%, P<.001). Patency of the IRA was associated with higher BRS values (BRS, 8.9+/-5.8 versus 7.1+/-4.7 ms/mm Hg, P<.005) and with a lower incidence (9% versus 18% P<.02) of markedly depressed BRS (<3 ms/mm Hg), a condition suggested by preliminary studies to be associated with an increased risk of post-MI mortality. The association between IRA patency and BRS was more evident in anterior than in inferior MI. Multivariate regression analysis showed that age of the patient and patency of the IRA were the major independent determinants of BRS, while LVEF was weakly related to BRS and only when analyzed as a categorized variable. CONCLUSIONS: The presence of an open IRA is associated with higher baroreflex sensitivity, and this effect is largely independent of limitation of infarct size by IRA patency. These data offer new insights into the mechanisms by which coronary artery patency may affect cardiac electrical stability and survival.

Adult↗

Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction.

This study was undertaken to evaluate the prognostic value of iodine-123 labelled 15-iodophenyl-3-R,S-methyl pentadecanoic acid (BMIPP) imaging in patients with myocardial infarction. BMIPP is an iodinated methyl branched fatty acid analogue which is trapped in the myocardium with little washout, thereby reflecting fatty acid utilization in the myocardium. We previously reported that in patients with myocardial infarction, regions are often observed where reduced BMIPP uptake is seen relative to thallium-201 perfusion at rest. However, the clinical significance of such discordant BMIPP uptake remains unknown. Fifty consecutive patients with chronic myocardial infarction referred for stress thallium scan and coronary arteriography underwent BMIPP imaging at rest. Each patient was in a stable condition at the time of the radionuclide study. Follow-up was performed at a mean interval of 23 months to investigate the prognostic implications of the radionuclide studies. Nine patients had cardiac events during the follow-up period. Univariate analysis showed that the number of discordant BMIPP versus 201TL uptake segments was the best predictor of future cardiac events (P=0.0245), followed by the presence of discordant BMIPP uptake (P=0.0388) and the number of 201TL redistribution segments (P=0.0444). When all the clinical and radionuclide variables were analysed by Cox regression analysis, the presence of discordant BMIPP uptake was the best, and an independent, predictor of future cardiac events (chi 2=8.5) followed by the number of coronary stenoses on angiography (chi 2=3.9). These preliminary data suggest that decreased BMIPP uptake relative to 201TL is a valuable predictor of future cardiac events in patients with myocardial infarction. Areas with such discordant BMIPP uptake may contain jeopardized myocardium where fatty acid utilization has been severely suppressed relative to myocardial perfusion.

Aged↗

Comparative study of 201Tl-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy.

The objective of the present study was to characterize the production of 201Tl myocardial perfusion defects, the relation between the 201Tl multiple small defects and the myocardial damage indicated by myocardial fibrosis shown histopathologically in patients with dilated cardiomyopathy (DCM). Rest 201Tl scintigraphy was performed in thirty-seven patients with myocardial tissue fibrosis by endomyocardial biopsy, and without stenosis of the coronary artery. 201Tl myocardial SPECT images were visually classified into 4 grades according to the severity of inhomogeneous perfusion defects (IPD), 0: none, 1: slight, 2: moderate, 3: severe. 201Tl uptake, defect regions (DR), and coefficient of variation % (CV%) were also quantified by Bull's eye quantification in nineteen patients. During cardiac catheterization, three biopsy specimens were obtained from the lateral wall to the apical region of the left ventricle and the amount of fibrosis was assessed by means of light microscopic morphometry. The myocardial fibrosis was also classified into 4 grades by a point-counting method. Autopsy study was also assessed in six patients. 201Tl perfusion defects were observed in 35 (94.6%) patients, of whom 29 (78.4%) showed inhomogeneous perfusion defects. Twenty-four (64.9%) showed Stage 0 and 201Tl findings, and 21 (62.2%) had myocardial fibrosis in stage 1. Clinically, the correlation between the grades of the IPD, % 201Tl uptake, DR and CV% of myocardial uptake, which were calculated semiquantitatively by Bull's eye image, and the histological grades of fibrosis were also good (IPD vs. fibrosis: r = 0.7014; % 201Tl uptake vs. fibrosis: r = -0.6542; DR vs. fibrosis: r = 0.7027; CV% vs. fibrosis: r = 0.6985). The 201Tl SPECT findings were in close agreement with the severity of myocardial fibrosis confirmed by autopsy, but the grading of the IPD was not related to the ejection fraction or left ventricular diameter. It showed a higher rate of inhomogeneous 201Tl myocardial perfusion defects (78.4%) in patients with DCM. This result may contribute to the clinical evaluation of DCM or differentiation from other diseases. Furthermore, the grading of 201Tl inhomogeneous perfusion defects related to the myocardial fibrosis of left ventricular myocardium may contribute to speculation of the myocardial degenerative stage in clinical settings.

Adult↗

Limitation of infarct size with preconditioning and calcium antagonist (diltiazem): difference in 99mTc-PYP uptake in the myocardium.

UNLABELLED: Ischemic cell injury and the uptake mechanism of 99mTc-PYP (Pyrophosphate) were studied with preconditioning and calcium antagonist. METHOD: The coronary artery of an adult mongrel dog was clamped for 1 hour, followed by reperfusion and 99mTc-PYP injection. A control group (group C, n = 8), a group in which continuous drip infusion of diltiazem (10 mg/kg) (group D, n = 7), and a group preconditioned by six 5-minute clampings and perfusions before occlusion (group P, n = 6) were compared. RESULTS: Wall motion was fully recovered in group D but not in group P after 2 hours of reperfusion. The 99mTc-PYP uptake ratio showed a significant (p < 0.05) reduction in group D (11.5 : 3.6 compared with group C), but not in group P (11.5 : 9.1, p = 0.25). The infarct area was 1.2 +/- 0.6% of the left ventricle in group D, 1.3 +/- 0.4 in group P, and 6.4 +/- 1.0 in group C (p < 0.01 in groups D and P vs. group C). CONCLUSIONS: These findings suggest that preconditioning does not alleviate stunning, but it improves cell injury in spite of high uptake of 99mTc-PYP. Diltiazem protects from both stunning and cell injury, suggesting a different mechanism of myocardial protection from that of preconditioning.

Animals↗

Relation between preexistent coronary collateral circulation and the incidence of restenosis after successful primary coronary angioplasty for acute myocardial infarction.

OBJECTIVES: The purpose of this study was to test the hypothesis that the incidence of restenosis after primary percutaneous transluminal coronary angioplasty for acute myocardial infarction is largely influenced by the preexistent coronary collateral circulation to the infarct-related coronary artery. BACKGROUND: The occurrence of restenosis after coronary angioplasty is the most serious limitation of this procedure. However, prediction of restenosis is difficult. Severe preexistent stenosis of the infarct-related coronary artery causing the development of collateral circulation may result in a high frequency of restenosis. METHODS: The study group consisted of 152 consecutive patients undergoing primary coronary angioplasty within 12 h after the onset of a first acute myocardial infarction. Of this group, 124 patients were angiographically followed up during the convalescent period of infarction and were classified into two groups according to the extent of preexistent collateral circulation to the infarct-related coronary artery. RESULTS: Restenosis occurred in 26 (38%) of 69 patients with poor or no collateral circulation (group A) in contrast to 35 (64%) of 55 patients with good angiographic collateral circulation (group B, p < 0.005). The frequency of preinfarction angina was significantly lower (p < 0.05) in group A (26% [18 of 69]) than in group B (44% [24 of 55]). CONCLUSIONS: These findings indicate that the presence of well developed collateral circulation to the infarct-related coronary artery predicts a higher frequency of restenosis after primary coronary angioplasty. The difference in restenosis rates observed between the patients with and without good collateral circulation probably reflects the impact of underlying severity of stenosis on the long-term outcome after coronary angioplasty.

Aged↗

Myocardial metabolic changes in hypertrophic cardiomyopathy.

UNLABELLED: We evaluated myocardial blood flow, glucose and oxygen metabolism using PET in hypertrophic cardiomyopathy (HCM). METHODS: PET studies using 18F-fluorodeoxyglucose (FDG) and 11C-acetate were performed at rest in patients with HCM and normal subjects as a control group. The metabolic rate of glucose (MRGlu), K mono value as a marker of oxidative metabolism, and myocardial blood flow were estimated from serial dynamic FDG and 11C-acetate PET studies. RESULTS: Myocardial blood flow (%) did not differ significantly in hypertrophic and nonhypertrophic myocardium (90.3 +/- 3.1 versus 91.7 +/- 3.4). The MRGlu in hypertrophic myocardium, however, was lower than that of hypertrophic and normal myocardium (0.44 +/- 0.10 versus 0.52 +/- 0.15 and 0.53 +/- 0.15 mumole/min/g, respectively, p < 0.05). The K mono values were also lower in hypertrophic myocardium than in nonhypertrophic and normal myocardium (0.05 +/- 0.010 versus 0.066 +/- 0.0011 and 0.065 +/- 0.017 per min, respectively, p < 0.05). The %FDG/%perfusion values in hypertrophic myocardium did not differ significantly from those in nonhypertrophic myocardium (0.96 +/- 0.10 versus 1.02 +/- 0.07). CONCLUSION: Myocardial ischemia at rest is observed less frequently in patients with HCM. Impairment of oxidative and glucose metabolism may precede decreased blood flow. Primary metabolic impairment is considered to be dominant in hypertrophic myocardium.

Acetates↗

Evaluation of myocardial viability with iodine-123-BMIPP in a canine model.

UNLABELLED: The tracer 123I-BMIPP was examined for its ability to reflect myocardial lipid metabolism. Studies in mice indicate that myocardial BMIPP uptake correlates with ATP content. Details, however, of myocardial accumulation in the ischemic period with either infarct or ischemia are not well documented. METHODS: Sixteen adult mongrel dogs were investigated. The occluded left anterior descending artery (LAD) alone was reperfused to make the ischemic area, and the first diagonal branch of the LAD was kept occluded to make the infarct area. Regional wall motion was evaluated by echocardiography in the short-axial view from the epicardium. Tissue blood flow was calculated using nonradioactive colored microspheres. Changes in blood glucose levels, lipid levels and lactate extraction were examined in blood collected from the aorta and great cardiac vein (GCV). The ATP concentration and BMIPP count were determined by high-performance liquid chromatography and gamma-counter, respectively. RESULTS: Two hours after reperfusion, blood flow decreased to 20% +/- 5% in the infarct area and 64% +/- 9% in the ischemic area (p < 0.05), despite comparable wall-motion reduction (32% +/- 5% and 42% +/- 12% in the infarct and ischemic areas, respectively). BMIPP content and ATP concentration showed parallel reduction: 40% +/- 7% and 75% +/- 4% (p < 0.05) of BMIPP and 32% +/- 9% and 69% +/- 7% (p < 0.05) of ATP in the infarct and ischemic areas, respectively. The nonesterified fatty acid extraction, defined as flow x ([artery] - [GCV]), decreased to 87% +/- 5.6% during occlusion and 75% +/- 20.1% 2 hr after reperfusion, as compared with the control value. CONCLUSION: BMIPP uptake correlated well with lipid metabolism and tissue ATP levels and may prove useful in differentiating myocardial infarction from ischemia in the acute phase of ischemic episodes.

Adenosine Triphosphate↗

Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir.

UNLABELLED: To clarify the metabolic fate of 123I-(-p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in dysfunctional myocardium, a comparison between normal dogs and those with etomoxir administration was studied using an open-chest canine model. METHODS: Using open-chested dogs under anesthesia, we created a system to release all the blood in the great cardiac vein outside without recirculation, if necessary. Iodine-123-BMIPP was directly injected into the left anterior descending artery, its extraction, retention and washout rate in the early phase were calculated, and the metabolites in the myocardium were evaluated using a high-performance liquid chromatography. Moreover, these factors were compared between normal dogs and those pretreated with etomoxir, that creates a condition similar to ischemia. RESULTS: Although rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, early washout (8 min) of radioactivity significantly increased (49.6% +/- 13.3%-->70.5% +/- 10.7%, p < 0.05) with etomoxir. The levels of the full metabolite formed by complete oxidation of BMIPP decreased significantly with etomoxir (21.4% +/- 10.9%-->5.5% +/- 3.5%, p < 0.01). In addition, back diffusion of BMIPP increased (25.1% +/- 8.0%-->41.9% +/- 12.0%, p < 0.05) in the etomoxir-treated animals without affecting the levels of alpha-oxidation metabolite and the intermediate metabolites. CONCLUSION: BMIPP is very sensitive to etomoxir and is suitable for assessing mitochondrial dysfunction. Iodine-123-BMIPP might be a promising radiopharmaceutical for the evaluation of ischemic heart disease, cardiomyopathy and mitochondrial encephalomyopathy.

Animals↗

Generator-produced copper-62-PTSM as a myocardial PET perfusion tracer compared with nitrogen-13-ammonia.

UNLABELLED: The purpose of this study was to determine the suitability of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM) for estimating myocardial blood flow (MBF) over a wide range of flow by comparison with 13N-ammonia (13NH3). METHODS: PET studies using 62Cu-PTSM and 13NH3 were performed at rest and after pharmacological vasodilatation in 9 normal subjects and 13 patients with coronary artery disease (CAD). According to the microsphere method, values for the product of the extraction fraction and MBF (ExMBF) were calculated using both tracers. In static images, the percent uptake (normalized to the peak count) of each tracer was measured in patients with CAD. RESULTS: The myocardial tracer distribution in the normal subjects was significantly higher in the inferior wall in the 62Cu-PTSM studies and lower in the lateral wall in the 13NH3 studies. The ExMBF values showed linear correlation for both tracers in a low flow range. In a high flow range, however, the ExMBF values for 62Cu-PTSM were nonlinearly proportional to the increase of those for 13NH3 (y = 1.1 x -0.21x2, r = 0.81). The percent uptake for both tracers at baseline well correlated linearly (y = 10.4 + 0.88x, R = 0.91). After pharmacological vasodilatation underestimation of blood flow with 62Cu-PTSM was noted compared to that with 13NH3 at high flows (y = 31.8 + 0.63x, r = 0.76). CONCLUSION: These results suggest that the MBF estimates using 62Cu-PTSM in a low flow range may be as accurate as those with 13NH3. In a high flow range, however, the extraction fraction of 62Cu-PTSM is considered to be lower than that of 13NH3, and this may limit the estimation of MBF with 62Cu-PTSM after pharmacological vasodilatation.

Ammonia↗