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Biomedical subjects

R Nohara

Publications and source records attributed to R Nohara.

At least 19 recordsLinked to original sources

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

Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid analog.

The clinical usefulness of single-photon tomography using both a beta-methyl-branched fatty acid analog, 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) and 201TI was assessed in 4 normal subjects and 28 patients with myocardial infarction. A homogeneous distribution of the tracer in the left ventricular myocardium was observed in each normal subject. BMIPP uptake was decreased compared to 201TI (discordant) in 17/28 patients (61%) and in 49/196 myocardial segments (25%). Such discordant BMIPP uptake was observed more often in areas of acute myocardial infarction (59% at less than or equal to 4 wk versus 31% at greater than 4 wk after onset) (p less than 0.01) and areas supplied with revascularized arteries (74% for revascularized versus 28% for nonrevascularized areas) (p less than 0.01). In addition, the discordant BMIPP uptake was seen more often in the segments exhibiting a wall motion score lower than the perfusion score (46%) in comparison to segments showing a similar decrease in both the wall motion and perfusion scores (12%) (p less than 0.01). Thus, BMIPP imaging may play a major role in increasing our understanding of the relationship between perfusion and wall motion, particularly in patients with acute myocardial infarction and those who received revascularization therapy.

Fatty Acids

Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate.

Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of beta-oxidation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65 +/- 5 vs 100 +/- 29 bpm, p less than 0.05 and 119 +/- 12 vs 144 +/- 16 mmHg, p less than 0.01, respectively). The clearance half time and the residual fraction were significantly decreased (23.4 +/- 2.6 vs 15.8 +/- 2.3 min and 67.0 +/- 2.5 vs 58.6 +/- 4.0%, P less than 0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that beta-oxidation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium.

Adult

Evaluation and clinical use of early washout ratio of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation using ring-type emission computed tomography.

Using newly developed ring-type emission computed tomography (SPECT), we investigated the washout ratio (WR) of T1-201 in the myocardium quantitatively with fast dynamic scanning after infusion of dipyridamole (0.57 mg/kg), and assessed the feasibility of early WR as a marker to detect coronary artery disease. Twenty-three patients with and 8 patients without coronary artery disease had serial SPECT images obtained every 5 min for 45 min and at 180 min after dipyridamole and subsequent T1-201 injection. The best appropriate transaxial slice was selected for WR analysis. Most appropriate diagnostic time was 25 min after infusion of T1-201 (WR-25). Normal WR-25 was 7.1 +/- 4.0%, 5.9 +/- 3.1% and 7.1 +/- 2.3% at the septum, anterior and lateral wall, respectively. Sensitivity, specificity and accuracy to identify coronary stenosis greater than 50% with a usage of abnormal WR-25, defined as WR-25 less than (mean of normals--1SD) in each region of inferest of the left ventricle (LV), were 96%, 100% and 97%, respectively. These results were better than those achieved by visual analysis (sensitivity 78%, specificity 100%, accuracy 84%). In patients with single as well as multivessel disease, the regional accuracy in assessing stenosis of more than 50% in the left anterior descending artery (LAD) and left circumflex artery (LCX) by WR-25 was 94% and 83%, respectively, which was significantly better than using visual methods (LAD 72% and LCX 50%; p less than 0.05). Thus, evaluation of early washout ratios (WR-25) after dipyridamole injection is a valuable method to increase sensitivity in assessing regional myocardial perfusion abnormality and is helpful in detection of ischemic heart disease, even with multivessel disease.

Adult

Effects of cardiac sympathetic nervous system on the stunned myocardium experimental study with 123I-metaiodobenzylguanidine.

123I-Metaiodobenzylguanidine (123I-MIBG) uptake in the stunned myocardium was investigated in open chest dogs. 123I-MIBG is a tracer taken up in presynaptic adrenergic vesicles and reflects the function of the myocardial sympathetic nervous system. This study revealed that in the stunned myocardium without infarct, 123I-MIBG uptake was normal up to 40 minutes of ischemia and that exogenous noradrenaline improved deteriorated regional wall motion with increased uptake of 123I-MIBG. However, uptake of 123I-MIBG per flow decreased with infarct in ischemic areas, and it showed a linear relation with regional wall motion. Thus, in the absence of infarction 123I-MIBG is a tracer to differentiate stunning from more severe ischemia with persistent wall motion abnormality. Normal uptake and storage of 123I-MIBG in the stunned condition suggests that catecholamine release or second effector mechanism may relate to the mechanism.

3-Iodobenzylguanidine

[Value of fatty acid imaging using 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) to assess viability of infarcted myocardium].

To evaluate clinical value of a new fatty acid imaging tracer, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP), 27 patients with myocardial infarction (MI) underwent BMIPP imaging at rest. The results were compared with those of thallium-201 imaging and contrast ventriculography. Of 100 hypoperfused segments on thallium-201 imaging, 34 segments (34%) showed lower BMIPP uptake than thallium-201, and remaining 66 segments showed similar distribution of those tracers. This discrepancy was more often observed in a patients with acute or subacute stages of MI (less than 4 weeks from onset) than those with chronic stage of MI (greater than 4 weeks) (75% vs. 47%; p less than 0.005). In addition, in the patients with chronic stage of MI, the regional wall motion abnormality was less severe in those showing discrepant BMIPP uptake than those showing concordant distribution (the wall motion score: 1.33 +/- 0.62 vs. 0.63 +/- 0.99; p less than 0.05). Furthermore, redistribution on stress thallium-201 imaging was more often observed in than those showing concordant distribution (12%) than those showing concordant distribution (12%) (p less than 0.005). These preliminary study indicates that discrepant distribution of BMIPP and thallium-201 may be often observed, particularly in recent MI and those showing less wall motion abnormality and redistribution on stress thallium-201 imaging. Thus, the combined study of BMIPP and thallium-201 has a potential for assessing tissue viability in patients with MI.

Adult

[Comparison of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile and 201Tl SPECT imaging for evaluation of coronary artery disease].

To evaluate clinical value of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile (MIBI) imaging for assessing coronary artery disease (CAD), 99mTc-MIBI SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours redistribution in 27 patients suspected with CAD. The sensitivities for detecting CAD patients were 94% (17/18) by both studies. The specificities were 71% (5/7) by 99mTc-MIBI and 57% (4/7) by 201Tl (p = NS). The sensitivities for detecting stenosed coronary arteries (greater than or equal to 75% stenosis) were also similar between 99mTc-MIBI (78%) and 201Tl (74%) (p = NS). The similar specificity values were obtained by 99mTc-MIBI (84%) and by 201Tl (82%) (p = NS). The patterns of abnormality (normal, ischemia and scar) were similar between 99mTc-MIBI and 201Tl images in 22 of the 25 cases (88%) and 117 of the 125 segments (94%). However, these patterns were occasionally different particularly in patients who received PTCA or CABG. Thus, 99mTc-MIBI SPECT imaging seems to be as accurate as 201Tl SPECT imaging for the detecting and evaluating CAD.

Adult

[Definitive myocardial blood flow evaluated by contrast echocardiography: experimental and A-C bypass flow studies].

We evaluated the feasibility of a new method for calculating definitive myocardial flow using contrast echocardiography in canine experiments and in patients who had undergone ACBG surgery. The principle for calculating flow was based on Kety-Schmidt method using time-intensity curve analysis between the epicardial and endocardial aspect. Inlet and outlet flows were hypothesized at the epicardium and endocardium, respectively. Analysis of time-contrast-intensity curves between the epicardium and endocardium, the difference of the area to the saturated point between epicardium and pericardium (A), and the saturated value (H) theoretically lead to the equation: Flow = 100 x (H/A) (Kety-Schmidt) in a 100-gram myocardium. No factors of intensity and time were included. Using this equation, the flow in 7 experimental canine and the flow of 9 patients who had ACBG surgery were compared to the electromagnetic flow. In the canine experiments, the left circumflex coronary artery was dissected free and was connected with contrast injector, a magnetic flowmeter and pneumatic occluder, proximal to distal in this order. Flow was controlled either by the occluder or drugs (papaverin and dipyridamole). Manually-agitated contrast media were injected rapidly (1 ml/2.5 sec), and M-mode echocardiographic recordings were densitometrically translated into time-intensity curves. Thirty-eight trials in 7 dogs showed close correlations (r = 0.901) between the electromagnetic flow and contrast echo flow. For the patients with ACBG, M-mode contrast echo recordings were made using transesophageal echo during the operations with contrast injections via the bypass grafts. Analysis of time-intensity curves was made and recorded in the same way as during the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[A bull's eye subtraction polar map for assessing thallium redistribution (1). Comparison with quantitative redistribution].

A new bull's eye subtraction polar (BS) map has been developed for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT studies. BS map was created after subtraction of a normalized stress bull's eye polar map from a normalized delayed polar map in 10 normal subjects and 33 patients with coronary artery disease to compare BS map with qualitative redistribution scores. The BS map showed less than 15% in all of the 50 segments in the normal subjects. Of 27 segments exhibiting persistent defect without redistribution, the BS map showed less than 10% in 20 segments (74%) and 10-15% in 6 segments (22%). On the other hand, of 34 segments exhibiting redistribution, the BS map showed greater than or equal to 15% in 25 segments (74%) and 10-15% in the remaining 9 segments (26%). Thus, significant redistribution was evident in the areas showing greater than or equal to 10-15% on the BS map. We conclude that the BS map is valuable for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT imaging.

Adult

Simple quantification of regional myocardial uptake of fluorine-18-deoxyglucose in the fasting condition.

Quantitative measurement of myocardial uptake of fluorine-18-deoxyglucose (FDG) is required for assessing tissue viability in the fasting state due to suppressed FDG uptake in the normal myocardium. A simple FDG uptake index (% dose per 100 ml tissue) has been introduced to compare with the fractional FDG uptake in 21 patients who underwent serial arterial blood sampling (14 under fasting and 7 under post-prandial conditions) and to measure the normal range in each myocardial segment in the study of 10 normal subjects (all in the fasting condition). Since the integral of plasma FDG values correlated with the body-weight corrected injected FDG dose (r = 0.82), an excellent correlation was observed between the FDG uptake index and the fractional FDG uptake (r = 0.98) in the fasting condition. In addition, the FDG uptake index correlated well with the regional metabolic rate of glucose calculated with the Patlak graphic analysis (r = 0.99). But this correlation was different in the postprandial condition and in the fasting condition in diabetic patients. In the study of normal subjects, the FDG uptake index was slightly higher in the lateral and inferior segments, as compared to the septal and anterior segments (p less than 0.05, each). We conclude that the FDG uptake index is considered as a simple and reliable parameter for quantitative assessment of myocardial FDG uptake in the nondiabetic patients in the fasting condition. Since its uptake was heterogeneous, FDG uptake should be carefully evaluated for assessing myocardial viability by comparing normal values in each segment.

Blood Glucose

Metabolic activity in the areas of new fill-in after thallium-201 reinjection: comparison with positron emission tomography using fluorine-18-deoxyglucose.

Reinjection of thallium-201 after recording the 3-hr delayed scan often demonstrates improvement in areas of persistent abnormalities. To determine the metabolic activity of these areas, the changes seen on stress/redistribution/reinjection thallium SPECT were compared with PET using fluorine-18-fluorodeoxyglucose (FDG) in 18 patients with coronary artery disease. Of 48 segments showing no redistribution on the delayed scan, the reinjection scan identified new fill-in in 20 segments (42%), all of which demonstrated FDG uptake. In contrast, only 7 of the 28 segments (25%) showing no fill-in after reinjection were PET viable (p less than 0.01). Eleven patients had coronary bypass graft surgery after the radionuclide study. The majority of the segments showing redistribution (87%) and new fill-in after reinjection (65%) improved in wall motion, whereas only eight segments (25%) without new fill-in improved after surgery. Of those without new fill-in, two segments showing PET ischemia improved in wall motion, whereas the remaining six segments showing PET scar did not improve after surgery. Thus, the segments showing new fill-in after reinjection are PET viable myocardium. However, reinjection thallium imaging still underestimates the extent of tissue viability compared to PET imaging.

Coronary Circulation

Regional wall thickening of left ventricle evaluated by gated positron emission tomography in relation to myocardial perfusion and glucose metabolism.

Regional wall thickening was assessed by electrocardiographically gated positron emission tomography (ECG-gated PET) in 26 patients with coronary artery disease. The standardized percent count increase from end-diastole to end-systole (S-percent Cl) was calculated as an index of wall thickening. The S-percent Cl was 77.8% +/- 28.9% in the segments with normal perfusion at rest, 51.9% +/- 29.5% in those with mild hypoperfusion, and 32.8% +/- 30.9% in those with severe hypoperfusion (p less than 0.001, each). Among the segments with resting hypoperfusion, the S-percent Cl was 38.9% +/- 31.5% in those without stress-induced ischemia and 48.7% +/- 30.9% in those with ischemia (p less than 0.05). Furthermore, among resting severe hypoperfusion, the S-percent Cl was 23.0% +/- 23.9% in the segments without fluorine-18-fluorodeoxyglucose (FDG) uptake and 37.8 +/- 32.9% in those with FDG uptake (p less than 0.05). These results suggest that stress-induced ischemia and FDG accumulation correlated with wall thickening. Thus, quantitative analysis of regional wall thickening seems to be useful for combined analysis of regional function, perfusion and metabolism in coronary patients.

Adult

Effects of nifedipine on cardiac function in patients with coronary artery disease evaluated with ambulatory radionuclide monitoring.

The effects of nifedipine on left ventricular function were evaluated in 17 patients with coronary artery disease with an ambulatory radionuclide detector (VEST). Hemodynamic data were recorded continuously at rest and during upright bicycle ergometer exercise before and 30 minutes after 10 mg of oral nifedipine administration. The heart rate increased and the resting systolic blood pressure decreased significantly with nifedipine. The end-diastolic and end-systolic volumes during exercise were significantly reduced and EF increased during exercise after nifedipine administration. These salutary hemodynamic responses of nifedipine appear to be beneficial for patients with effort angina pectoris.

Aged