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Biomedical subjects

R Nohara

Publications and source records attributed to R Nohara.

At least 91 records · Page 5Linked to original sources

Technetium-99m-pyrophosphate uptake as an indicator of myocardial injury without infarct.

UNLABELLED: Technetium-99m-pyrophosphate (PYP) is bound to calcium in necrotic myocardium and has been used clinically to evaluate myocardial infarction. Technetium-99m-PYP is also reported to accumulate in myocardium with unstable angina pectoris and it is speculated that severe ischemia with noninfarcted tissue may also increase uptake of 99mTc-PYP. In this paper, 99mTc-PYP uptake was determined in various models of myocardial ischemia of short duration to examine its applicability to the assessment of myocardial viability. METHODS: In 23 open-chest dogs under anesthesia, models of ischemia-reperfusion of the left anterior descending artery (LAD) subjected to ischemia for 10, 30 or 60 min were produced. Wall motion was examined by echocardiography and myocardial blood flow was calculated using colored microspheres. Technetium-99m-PYP was injected after each ischemic intervention and reperfusion. RESULTS: Technetium-99m-PYP showed 1.18 +/- 0.009 in the uptake ratio (ischemic area/normal area) following 10-min ischemia (11 dogs). The uptake ratio following 30-min ischemia (8 dogs) showed a significantly higher increase than that following 10-min ischemia (4.09 +/- 1.75; p < 0.05), permitting in vivo and ex vivo imaging. After 60-min ischemia resulting in infarction (4 dogs), 99mTc-PYP uptake of the ischemic area showed an uptake ten times that of the normal area (transmural: 12.2 +/- 2.9, epicardium: 7.5 +/- 1.9, endocardium: 16.8 +/- 4.1). CONCLUSIONS: These findings indicate that since 99mTc-PYP accumulates in injured myocardium, its concurrent use with blood flow imaging is useful for the assessment of severity of ischemia, injured area and myocardial viability.

Animals↗

Myocardial tomography using technetium-99m-tetrofosmin to evaluate coronary artery disease.

UNLABELLED: To assess the clinical value of the 99mTc-labeled myocardial perfusion agent, 99mTc-tetrofosmin, the findings of stress and rest myocardial tomography were compared with those of stress and 3-hr delayed 201Tl tomography and coronary arteriography. METHODS: Twenty-five patients who had coronary arteriography were studied with both stress tetrofosmin and 201Tl tomography. RESULTS: The image quality of tetrofosmin was superior to that of 201Tl despite a shorter acquisition time. Both the tetrofosmin and 201Tl studies were quite sensitive to detect coronary artery disease (100% and 95%, respectively) (p = ns). The two studies showed similar sensitivity (75% and 73%) and specificity (80% and 77%, respectively) for the detection of significant (> or = 75% diameter) coronary artery stenosis. Stress distribution of tetrofosmin tended to be slightly higher than that of 201Tl (% uptake: 63.3% +/- 13.5% versus 60.4% +/- 12.2%, p = 0.0006; uptake score: 2.33 +/- 1.03 versus 2.22 +/- 1.07, p = 0.007), indicating less defect contrast in the former. A high concordant rate (89%) of the stress perfusion score was observed between the two radiopharmaceuticals. Reversible perfusion abnormalities were observed to be similar between stress-rest tetrofosmin and stress-delayed 201Tl studies. CONCLUSIONS: Stress tetrofosmin perfusion tomography is a valuable method to detect coronary artery disease and to assess tissue viability with accuracy similar to that of stress 201Tl tomography.

Aged↗

[Comparative study of 201Tl-scintigraphic image and endomyocardial biopsy findings in patients with dilated cardiomyopathy].

201Tl-SPECT image was compared with the findings of endomyocardial biopsy in patients with dilated cardiomyopathies (DCM), and diagnostic value of 201Tl patchy pattern image for fibrosis with DCM was evaluated. Serial 22 patients diagnosed as DCM with endomyocardial biopsy findings were selected for this study (age: 50 +/- 17 y.o., Male/Female = 17/5). Patchy pattern of 201Tl-SPECT image was visually classified to 4 stage according to the severity of inhomogeneous defect, and pathologic findings of fibrosis was also classified into 4 according to the severity of fibrosis (0: none, 1: mild, 2: moderate, 3: severe). Ejection fraction calculated from left ventriculography and end-diastolic dimension by echocardiography were also compared with 201Tl-SPECT image. Out of 22 patients, 21 patients (95%) showed fibrosis, and 18 patients (82%) showed patchy pattern with 201Tl-SPECT. Severity of patchy pattern was not in good relation to that of fibrosis (r = 0.374). 201Tl image was not related to the function nor dimension. Four autopsy studies revealed a good relation of macroscopic severity, spatial distribution of fibrosis and inhomogeneous 201Tl-defect pattern before death. Patchy pattern of 201Tl-SPECT image will show the myocardial fibrosis in patients with DCM, and is independent of the function. 201Tl-SPECT may show more clinically useful findings of spatial distribution and severity of fibrosis with focal myocardial biopsy.

Adolescent↗

[Evaluation of myocardial distribution of iodine-123 labeled metaiodobenzylguanidine (123I-MIBG) in normal subjects].

The normal pattern of the myocardial sympathetic innervation was studied in 15 subjects using gamma camera scintigraphy with iodine-123 labeled metaiodobenzylguanidine (123I-MIBG). Seven younger subjects (mean age 24.6 +/- 3.6) and eight older patients (mean age 60.9 +/- 8.4) with normal cardiac function were studied. Planar imaging was obtained at 15 minute and 3 hours, and SPECT was also performed 3 hours after injection of 111 MBq (3 mCi) of MIBG. The younger subjects showed higher the heart to mediastinum count ratio (2.91 +/- 0.25 vs. 2.67 +/- 0.34; p < 0.05) and higher inferior to anterior count ratio (1.19 +/- 0.15 vs. 0.97 +/- 0.13; p < 0.05) on the late scan. The bull's-eye polar map also differences in counts in the mid-inferior (p < 0.005), basal-inferior (p < 0.05) and mid-lateral sectors (p < 0.01). But there was no significant difference in MIBG washout rate from myocardium between two groups. These data suggest that there is a difference of the cardiac sympathetic innervation, with older subjects having fewer sympathetic nerve terminals, especially in inferior than younger subjects. We conclude that the age difference in sympathetic nerve function should be considered in the interpretation of MIBG scan.

3-Iodobenzylguanidine↗

Prognostic value of an increase in fluorine-18 deoxyglucose uptake in patients with myocardial infarction: comparison with stress thallium imaging.

OBJECTIVES: This study was undertaken to evaluate the prognostic value of an increase in fluorine (F)-18 deoxyglucose uptake compared with clinical, angiographic and stress thallium findings in patients with myocardial infarction. BACKGROUND: Positron emission tomography (PET) imaging using F-18 deoxyglucose has been applied to assess tissue viability in patients with coronary artery disease. We hypothesized that patients with a myocardial segment with augmented F-18 deoxyglucose uptake are at high risk for a future cardiac event. METHODS: One hundred fifty-eight consecutive patients with myocardial infarction referred for F-18 deoxyglucose PET and stress thallium scans were studied. Follow-up was obtained in 84 patients at a mean interval of 23 months to investigate prognostic implications of radionuclide studies. RESULTS: Seventeen patients had a cardiac event during the follow-up interval. Univariate analysis showed that an increase in F-18 deoxyglucose uptake was the best predictor of a future cardiac event (p = 0.0006), followed by the number of stenosed vessels (p = 0.008). In the multivariate analysis, when an increase in F-18 deoxyglucose uptake was entered into the model, only angiographic variables had an independent prognostic value, whereas no other radionuclide variables showed significant prognostic value. Among patients who did not show redistribution, a future cardiac event was observed more often in patients with than in those without an increase in F-18 deoxyglucose uptake (p < 0.05). CONCLUSIONS: Thus, an increase in F-18 deoxyglucose uptake seemed to be the best predictor of a future cardiac event among all clinical, angiographic and radionuclide variables in this study of stable patients with myocardial infarction. Even when a stress thallium-201 scan does not show redistribution, those patients who have an increase in F-18 deoxyglucose uptake in a PET study may be at risk for a future cardiac event, and these patients may need aggressive treatment to prevent a future cardiac event.

Aged↗

Oxidative metabolism in the myocardium in normal subjects during dobutamine infusion.

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

Acetates↗

Functional recovery after reperfusion is predicated on recovery of myocardial oxidative metabolism.

To test the hypothesis that recovery of myocardial oxidative metabolism (MVO2) is a necessary prerequisite for recovery of contractile function following reperfusion and to evaluate its dependency on the interval of antecedent ischemia before reflow, we evaluated 11 dogs serially for 4 weeks. Six dogs were subjected to prompt reperfusion (after 1 hour of coronary artery occlusion) and five were subjected to delayed reperfusion (after 4 hours of ischemia). Despite equivalent levels of myocardial blood flow with reperfusion, hearts subjected to prompt reperfusion had faster and more complete recovery of MVO2 (assessed by sequential positron emission tomography with [11C]acetate) and function (assessed by echocardiography) compared with dogs subjected to delayed reperfusion. Infarct size was diminished in dogs with prompt reperfusion. In all dogs, recovery of function with reperfusion was predicted and correlated with early recovery of MVO2 (r = 0.61, p < 0.04). The results demonstrate that prompt reperfusion is associated with more rapid and complete recovery of oxidative metabolism and function and support the hypothesis that the ability to metabolize substrate oxidatively is a necessary prerequisite for recovery of function.

Animals↗

Assessment of myocardial fatty acid metabolism with positron emission tomography at rest and during dobutamine infusion in patients with coronary artery disease.

The myocardial clearance rate of C-11 palmitate as an index of fatty acid oxidation was assessed by means of positron emission tomography (PET) at rest and during dobutamine infusion in seven normal subjects and 10 patients with coronary artery disease. In the normal subjects the clearance half time was homogeneous in the left ventricle at rest and uniformly shortened during dobutamine infusion. In the myocardium at risk, clearance half time tends to be longer in the segments with an abnormal Q wave on ECG, exhibiting regional wall motion abnormality, and supplied by severely stenosed coronary arteries, particularly during dobutamine infusion. These data indicate that fatty acid oxidation may be decreased in infarcted myocardium and associated with regional asynergy. Such an abnormality was most striking in those with severe coronary stenosis during dobutamine infusion. We conclude that PET with the use of C-11 palmitate at rest and during dobutamine is a useful means of identifying impaired fatty acid oxidation and decreased metabolic reserve in patients with coronary artery disease.

Carbon Radioisotopes↗

[Assessment of myocardial metabolic reserve with positron emission tomography and C-11 acetate].

Positron emission tomography (PET) with C-11 acetate allows noninvasive quantification of myocardial oxidative metabolism. To assess the myocardial metabolic reserve, clearance of C-11 acetate from the myocardium was measured with PET in 8 normal subjects at rest and during the infusion of dobutamine (inotropic agent) or dipyridamole (vasodilator). During dobutamine infusion, the clearance rate constant of C-11 acetate increased significantly (0.063 +/- 0.014 vs 0.109 +/- 0.016, p < 0.002) in good correlation with the rate-pressure product (r = 0.83). During dipyridamole infusion, myocardial acetate clearance also significantly increased (0.088 +/- 0.024, p < 0.05) in correlation with the rate-pressure product (r = 0.54). In normal myocardium, myocardial oxidative metabolism increased in response to increased work load with pharmacological stress. These findings suggest that PET with C-11 acetate and pharmacological stress may be a promising approach for the evaluation of metabolic reserve in patients with ischemic heart disease.

Acetates↗

[Three-dimensional assessment of myocardial blood flow and glucose metabolism using oblique-angle tomograms and polar map displays of cardiac PET images].

To evaluate clinical value of three-dimensional assessment of cardiac PET image, oblique-angle tomograms and polar map displays were reconstructed from transaxial PET images using 18F-2-fluoro-2-deoxyglucose and 13N-ammonia in 19 patients with coronary artery disease. Short-axis and vertical long-axis images enabled to evaluate extent and severity of perfusion abnormality easily in the anterior and inferior regions which were tangential in the transaxial images. Using polar map displays, perfusion/metabolism mismatch may be more easily assessed. Thus, semiquantitative analysis of ischemic and infarcted myocardium may be permitted with PET studies.

Aged↗

[Quantitative assessment of improvement in perfusion after coronary bypass grafting: assessed by thallium-201 bull's eye subtraction polar map method].

To assess redistribution (RD) and improvement in regional perfusion after coronary bypass grafting (CABG) on thallium-201 SPECT images quantitatively, the Bull's eye subtraction polar (BS) map was created. BS map was created after subtraction of a normalized bull's eye polar map from another normalized polar map. The quantitative assessment on this map was compared to the visual qualitative analysis in 23 patients (115 segments) who received CABG. All of the improved segments after CABG showed > or = 15% on the BS map. On the other hand, 60% of the non improved segments showed < 10% on the BS map. Furthermore, 67% of the RD segments showing > or = 15% on the BS map before CABG improved in perfusion by > or = 15% on the BS map after CABG. On the BS map, an excellent correlation was observed between the extent of redistribution before CABG and the extent of improvement after CABG. Thus, BS map permits quantitative assessment of improvement in perfusion on T1 SPECT imaging, and this technique seems to be valuable for predicting improvement in perfusion after CABG.

Adult↗

[Evaluation of coronary artery disease by 99mTc-PPN1011: comparison with 201Tl imaging and ventricular function].

To evaluate clinical value of 99mTc-1,2-bis[bis (2-ethoxyethyl)phosphino]ethane(99mTc-PPN1011) imaging for assessing coronary artery disease (CAD), 99mTc-PPN1011 SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours in 24 patients with CAD. The sensitivities for detecting CAD were 100% (21/21) by 99mTc-PPN1011 SPECT and 95% (20/21) by 201Tl SPECT. The sensitivities for detecting stenosed coronary arteries (> or = 75% stenosis) were similar between 99mTc-PPN1011 (68%) and 201Tl (66%). The similar specificity values were obtained by 99mTc-PPN1011 (80%) and 201Tl (77%). The patterns of abnormality (normal, ischemia and scar) were concordant between 99mTc-PPN1011 and 201Tl images in 20 of the 24 cases (83%) and 106 of the 120 segments (88%). In the simultaneous analysis of cardiac function by first pass radionuclide angiography with 99mTc-PPN1011, there was good correlation between left ventricular ejection fraction and perfusion score at rest (r = 0.70) and exercise (r = 0.80). The degrees of abnormality between perfusion and wall motion were similar in 56 of 66 segments (85%) at rest and 52 of 66 segments (79%) at exercise. We conclude that this agent is promising for the diagnosis and evaluation of coronary artery disease.

Aged↗

Clinical evaluation of cardiac function by ambulatory ventricular scintigraphic monitoring (VEST): validation and study of the effects of nitroglycerin and nifedipine in patients with and without coronary artery disease.

Global left ventricular function and ECGs were continuously monitored by radionuclide ambulatory ventricular function monitoring (VEST) and validated against multigated blood pool analysis (MUGA) and left ventriculography in 26 subjects (study 1). Ejection fraction by VEST (Y) showed good correlation with Y = 5.5 +/- 0.79 X (r = 0.91), Y = 1.7 +/- 0.86 X' (r = 0.91), and Y = 11.6 + 0.68 X" (r = 0.82) to sitting and supine MUGA and left ventriculography, respectively. In study 2 left ventricular function and ECGs were evaluated at rest and during exercise without any drug (control), with nitroglycerin, and with nifedipine in 21 patients with coronary disease (group I) and six normal subjects (group II). In group I abnormal ejection fraction responses (exercise increase less than or equal to 6%) during the control exercise period were found in 15 patients (71%), ST segment abnormalities in seven (33%), and chest pain in four (18%). Control exercise increased end-diastolic volume (100 to 112 +/- 8%) and end-systolic volume (53 +/- 15% to 63 +/- 22%) and decreased the ejection fraction (47 +/- 15% to 43 +/- 21%). The ejection fraction during exercise increased after nitroglycerin (50 +/- 22%) or nifedipine (54 +/- 21%) (p less than 0.05). In group II the ejection fraction was unchanged between rest and exercise with or without nitroglycerin or nifedipine. Thus combined radionuclide and ECG monitoring by VEST could detect changes in left ventricular function at rest and during exercise over a prolonged period and demonstrated that nitroglycerin and nifedipine improved cardiac function in the ischemic setting with an increased ejection fraction in the upright position.

Coronary Disease↗

Regional myocardial perfusion and glucose metabolism in experimental left bundle branch block.

BACKGROUND: Several authors have reported cases in which 201Tl scintigraphy demonstrated perfusion abnormality in the septum of patients with left bundle branch block (LBBB) and normal coronary arteriogram. The mechanism of this abnormality, however, remains to be clarified. METHODS AND RESULTS: To determine whether LBBB itself induces abnormal myocardial perfusion and ischemia and to elucidate its mechanism, we used an in vivo animal model. LBBB was induced by right ventricular pacing in 17 open-chest dogs. We examined myocardial perfusion and glucose uptake using 201Tl and 18F-labeled 2-fluoro-2-deoxy-D-glucose. 201Tl activity in the septum was reduced to 74.7 +/- 14.5% of its maximal activity, and mean activity was 86.5 +/- 5.3% in the free wall (p less than 0.05). 18F activity in the septum was also reduced compared with that in the free wall (67.4 +/- 12.1% versus 88.0 +/- 5.2%, p less than 0.05). Regional myocardial blood flow was significantly reduced in the septum compared with the free wall, averaging 0.53 +/- 0.18 ml/min/g versus 0.84 +/- 0.14 ml/min/g, respectively (p less than 0.01). Systolic thickening in the septum was reduced from 1.36 +/- 0.20 to 0.98 +/- 0.04 (p less than 0.01) after the induction of LBBB, and the intramyocardial pressure in the septum in diastolic phase, in which the major flow of left anterior descending coronary artery (LAD) exists, increased from 26.6 +/- 10.5 to 57.8 +/- 22.2 mm Hg (p less than 0.02). Mean aortic pressure, LAD flow, and lactate extraction rate showed no significant change. CONCLUSIONS: LBBB itself may reduce myocardial perfusion and glucose uptake in the septum because of impaired systolic thickening and augmented intramyocardial pressure in the septum; however, this is not necessarily related to septal ischemia.

Animals↗

Effect of diltiazem on stunned myocardium evaluated with 99mTc-pyrophosphate imaging in canine heart.

The effect of diltiazem on stunned myocardium was evaluated by measuring the myocardial uptake of 99mTc-PYP (pyrophosphate) in open chest experiments with dogs. Myocardial stunning was induced by a 30 min ischemic occlusion of the anterior descending coronary artery. Regional wall motion was monitored by echocardiography of the epicardium for 2 h during reperfusion. After a 30 min occlusion of the coronary artery, it was reperfused and 99mTc-PYP was injected, followed by 201Tl 2 h later. The ischemic area was defined by Evans blue dye, and the infarct area by TTC staining. No dogs showed infarcts or 201Tl defects in this study group. Five dogs of the control-1 group (C1, ischemic area = 19.1 +/- 3.2%) showed decreased regional wall motion during occlusion (15.5 +/- 3.5% of control), and a slow recovery from depressed motion after 2 h of reperfusion (20.3 +/- 9.3%) with uptake ratio (compared to the non-ischemic area uptake) of 99mTc-PYP (4.96 +/- 2.28). In contrast, both groups with diltiazem infusion (20 micrograms/kg/min), started either 30 min before ischemia (D1 = 5 dogs) or just after reperfusion (D2 = 5 dogs), showed significantly better recovery after 2 h of reperfusion (D1:115.4 +/- 36.0%, D2:109.2 +/- 44.2%) than C1 (p less than 0.05), D1 and D2 groups also showed suppressed 99mTc-PYP uptake ratio (D1:1.06 +/- 0.33, D2:2.34 +/- 2.05, p less than 0.05 vs C1) in spite of comparable ischemic area. Four dogs with small ischemic area (C2:5.3 +/- 5.0%) did not show increased 99mTc-PYP uptake (1.15 +/- 0.35), and regional wall motion after 2 h of reperfusion was 96.1 +/- 24.1% of the control value (p less than 0.05 vs C1). Thus, diltiazem was effective in enhancing the suppression of 99mTc-PYP uptake in the stunned myocardium, and similar results were obtained for small ischemic areas. The protective effect of diltiazem appears to be strongly related to the mechanism of 99mTc-PYP uptake.

Animals↗

Positron emission tomography--usefulness in assessing myocardial viability.

Positron emission tomography (PET) using N-13 ammonia and F-18 fluorodeoxyglucose (FDG) has been used to evaluate myocardial viability in comparison with thallium-201 single photon emission computed tomography (SPECT), and left ventricular wall motion in comparison with contrast ventriculography. Forty patients with anterior myocardial infarction underwent stress and delayed resting perfusion imaging using Tl-201 SPECT and ammonia PET, a glucose metabolism study using FDG PET, and wall motion assessment with left ventriculography. Out of a total of 600 segments of left ventricular imaging, SPECT demonstrated 197 fixed perfusion defects, 99 with redistribution on delayed imaging and 304 normal segments. Of 197 segments with fixed defects, 24 (12%) were normal and 71 (36%) ischemic according to PET criteria. Nineteen of 28 with infarction and all of 12 with non-Q wave infarction showed a viable myocardium. Left ventricular wall motion was significantly better in patients with normal PET findings compared with those with ischemia or scar on PET. Post-PTCA PET revealed improved ammonia PET in 6 of 11 patients but reduced FDG uptake was noted only in 3. These data suggests that Tl-201 SPECT significantly underestimates myocardial viability and that PET imaging is a promising tool for assessing the presence of salvaged myocardium.

Angioplasty, Balloon, Coronary↗

Viable myocardium identified by reinjection thallium-201 imaging: comparison with regional wall motion and metabolic activity on FDG-PET.

Reinjection thallium-201 scans were performed in 68 patients with coronary artery disease after the routine stress-delayed scans for more accurate identification of new fill-in. Following the stress and 3 hour delayed thallium-201 SPECT scans, 40 MBq (1.1 mCi) was injected at rest, and 10 min later, the reinjection SPECT scan was obtained. To determine whether the reinjection method can aid in identifying ischemic but viable myocardium, the thallium-201 findings were compared with regional wall motion on radionuclide ventriculography in 61 patients and with metabolic activity on positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) in 18 patients. The reinjection scan identified new fill-in which had not been shown on the stress-delayed scans in 6 of the 22 patients (27%) or in 29 of the 105 segments (28%). Regional wall motion was preserved more in the segments that exhibited new fill-in after reinjection (wall motion score = 1.64 +/- 1.29) than in those without new fill-in (score = 2.72 +/- 1.04) (p < 0.01). In the comparative study with FDG-PET, persistent FDG uptake was observed in all segments with new fill-in (20/20 segments: 100%); whereas, it was seen in only 7 of the 28 segments (25%) without new fill-in after reinjection (p < 0.05). We concluded that the segments having new fill-in after reinjection may represent ischemic but viable myocardium. Thus, the reinjection thallium-201 scan should be performed to identify ischemic myocardium which occasionally cannot be detected by the routine stress-delayed thallium-201 scans.

Adult↗