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Biomedical subjects

R D Okada

Publications and source records attributed to R D Okada.

At least 19 recordsLinked to original sources

Relationship between septal perfusion, viability, and motion before and after coronary artery bypass surgery.

The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients.

Adult

Serial magnetic resonance imaging in patients following acute myocardial infarction.

The detection of serial changes in magnetic resonance (MR) signal intensity of the heart following acute myocardial infarction may provide a useful method of characterizing tissue healing. Fourteen patients with acute Q-wave infarction underwent T2-weighted, spin-echo cardiac imaging during hospitalization, followed by one or more additional MR studies (total 31) over a 6- to 27-wk period (mean: 3 mo). Visual assessment of the images demonstrated a gradual reduction in signal intensity and localization of the bright signal to the subendocardium of the infarction region over the three-mo study period. A quantitative measurement of signal intensity (infarction/normal myocardium) fell from 1.81 +/- 0.42 on the initial study to 1.34 +/- 0.37 (p less than 0.05) at a mean of 14 wk. Two patients had an increase in signal intensity on the follow-up study and both patients had been readmitted with acute coronary syndromes. In summary, characterization of changes in signal intensity may provide a useful method of assessing myocardial healing following acute myocardial infarction. Further studies are indicated to determine the prognostic significance of these parameters.

Female

Dipyridamole 201Tl scintigraphy in the evaluation of prognosis after myocardial infarction.

Dipyridamole 201Tl imaging has been proposed as an alternative to exercise ECG testing for the prehospital discharge evaluation of patients recovering from myocardial infarction. The rationale is that many postinfarction patients with exercise-induced ischemia experience later cardiac events, and the sensitivity of predischarge exercise ECG testing in patients with multivessel disease ranges from only 45% to 62%. In addition, several groups of investigators have shown the sensitivity of submaximum exercise 201Tl imaging to be less than ideal. This report summarizes the current status of dipyridamole 201Tl imaging in the period of 1-13 days after myocardial infarction. Although the number of studies performed to date is limited, the following conclusions can be drawn: dipyridamole 201Tl imaging after myocardial infarction was associated with no serious side effects, and those present could be quickly reversed with aminophylline; redistribution with dipyridamole 201Tl images definitely correlates with prognosis after uncomplicated myocardial infarction; dipyridamole 201Tl imaging is definitely useful in patients unable to exercise for a variety of reasons; and future studies are definitely indicated to further define the role of dipyridamole 201Tl imaging for assessing prognosis, especially in those patients undergoing interventional therapy after acute myocardial infarction.

Aged

Serial evaluation of right ventricular dysfunction associated with acute inferior myocardial infarction.

Right ventricular (RV) function was evaluated serially by multigated blood pool imaging in 18 patients with RV dysfunction associated with acute inferior myocardial infarction. Radionuclide ventriculograms were performed on all patients within 18 hours of chest pain and again at 10 days. In addition, 15 of 18 patients had rest and exercise radionuclide ventriculograms at 3 months. The mean resting right ventricular ejection fractions (RVEF) at admission, 10 days, and 3 months in these patients was 31.8 +/- 12.6% (SD), 46.9 +/- 11.2% (p less than 0.05), and 44.5 +/- 10.2% (p less than 0.05), while the left ventricular ejection fractions were 55.9 +/- 10.6%, 57.9 +/- 13.3%, and 53.1 +/- 11.2% (p = ns). The 3-month exercise radionuclide ventriculogram demonstrated an increase in RVEF greater than 5% in 6 of 15 patients. In eight catheterized patients, neither the location nor the severity of coronary artery narrowing nor the presence of collaterals correlated with the RV exercise response. Improvement in RV function over a 10-day interval following acute inferior myocardial infarction suggests the presence of significant reversible right ventricular dysfunction during the acute phase.

Cardiac Catheterization

Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole.

Technetium 99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) is a promising new myocardial perfusion imaging agent producing excellent rest images. Imaging, however, will need to be performed with exercise or dipyridamole to detect ischemia and to differentiate salvaged but still ischemic myocardium from scar. Accordingly, 12 dogs were given mild-to-moderate left circumflex coronary stenoses (group 2), and 10 dogs were given severe stenoses (group 3). In five control dogs (group 1), there was no stenosis. After an intravenous infusion of dipyridamole (0.08 mg/kg/min for 4 minutes), Tc-MIBI was injected into the right atrium. Over the next 4-hour study period, myocardial Tc-MIBI activities were continuously monitored in both the left anterior descending (LAD) (normal) and left circumflex (LCx) (ischemic) coronary artery (ischemic) zones using miniature cadmium telluride radiation detectors and serial gamma camera images were acquired when necessary. Tc-MIBI was rapidly taken up by nonischemic, mild-to-moderate, and severe ischemic myocardium. The initial myocardial uptake of Tc-MIBI was linearly related (r = 0.97) to regional myocardial blood flow at rates up to 2.0 ml/min/g. After the initial uptake, the mean 4-hour fractional myocardial clearance was similar between the control (0.09 +/- 0.03 [+/- SEM]) and group 2 (0.07 +/- 0.03) and group 3 (0.09 +/- 0.03) ischemic zones. Tc-MIBI blood clearance was rapid and biexponential with an initial fast clearance phase followed by a slow clearance phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

MRI detection of myocardial perfusion changes by gadolinium-DTPA infusion during dipyridamole hyperemia.

To detect abnormal regional myocardial coronary flow reserve, serial spin-echo MR tomograms of four control dogs and six with a partial balloon occlusion of the left anterior descending (LAD) coronary artery were acquired before and after dipyridamole infusion and during the paramagnetic effect of a bolus plus infusion of gadolinium-DTPA. Microsphere myocardial blood flow was measured for correlation with serial regional changes in MR signal intensity. Significant difference in gadolinium-enhanced MR signal intensity existed between the hypoperfused LAD and the hyperemic left circumflex perfusion beds (46 +/- 22% vs 78 +/- 29% above baseline, respectively; P less than 0.05). The percentage changes in gadolinium-enhanced MR signal and microsphere myocardial blood flow were significantly correlated (r2 = 0.93).

Animals

Kinetics of Tc-99m hexakis t-butyl isonitrile in normal and ischemic canine myocardium.

Hexakis 99mTc-tertiary butyl isonitrile (99mTc-TBI) was studied as a cardiac perfusion imaging agent in nine dogs with partial occlusion of the LAD. Thirty min after applying the stenosis, 99mTc-TBI was injected into the right atrium (RA) in five dogs and left atrium (LA) in four dogs. Normal and ischemic zone regional myocardial 99mTc-TBI activities were monitored continuously for 4 h. Dogs with LA injections had minimal and equivalent 4 h fractional clearance from the normal and ischemic zones. Dogs with RA injections had minimal, but significantly lower 4 h fractional 99mTc clearances in the ischemic zone (0.08 +/- 0.08) compared to the normal zone (0.16 +/- 0.07, P less than 0.05). The delayed ischemic zone clearance is probably due to the high initial lung uptake observed after RA injection. Despite the differences in clearance, this minimal amount of redistribution could not be detected on gamma camera images. The minimal myocardial washout and redistribution, and the 140 keV gamma make 99mTc-TBI a promising cardiac perfusion imaging agent.

Animals

The effect of dipyridamole on transmural blood flow gradients.

The effect of dipyridamole (DP) on subendocardial (ENDO) and subepicardial (EPI) blood flow in stenosed and normal regions was determined with radioactive microspheres before and after intravenous infusion of 0.08 mg/kg.min-1 of DP in two groups of dog hearts in situ. Group 1 (n = 6) had coronary stenoses that did not reduce distal perfusion at rest, but did attenuate hyperemic response, and group 2 (n = 6) had stenoses which reduced resting blood flow. In nonstenosed zones, a doubling in perfusion during DP infusion induced proportionate changes in ENDO and EPI flows (unchanged ENDO/EPI ratio) in group 1 hearts, but increased EPI more than ENDO flows in group 2 hearts (decreased ENDO/EPI ratio). In mildly stenosed regions, a 47 percent increase in perfusion during DP was associated with an increase in only EPI flow, which thereby reduced the ENDO/EPI ratio. In severely stenosed zones, the ENDO/EPI ratio was already significantly reduced at rest and a further reduction in ENDO flow during DP caused a significant decline in the ENDO/EPI ratio. Therefore, during pharmacologic vasodilation, a redistribution of coronary transmural flow occurs (relative ENDO to EPI steal) in non- and mildly stenosed regions while an absolute decrease or steal in ENDO flow was noted only in regions distal to more severe stenoses. These studies suggest that an interaction between the stenosis severity and vasodilation is a determining factor in ENDO/EPI ratios with dipyridamole.

Angina Pectoris

Serial changes in nuclear magnetic resonance relaxation times after myocardial infarction in the rabbit: relationship to water content, severity of ischemia, and histopathology over a six-month period.

To determine the serial changes in T1 and T2 relaxation times of myocardial infarction, and their relationship to observed changes in water content, regional myocardial blood flow, and histopathology, rabbits were studied at 14 time intervals ranging from 30 min to 6 months after coronary artery ligation. All values were compared to a control group. Hearts were subdivided into infarct and normal segments for measurement of blood flow, water content, and relaxation times (20-MHz spectrometer); other hearts were excised intact for histopathologic studies. T1 relaxation time of infarcted myocardium did not change significantly compared to control over the 6-month study period. T2 relaxation time increased (P less than 0.0001) at 3 days and returned to baseline by 2 months. Consonant with the increase in T2 of infarct, nuclear magnetic resonance (NMR) images at 3 days demonstrated an increase in signal intensity of infarct compared to surrounding normal myocardium. At 6 months, marked myocardial thinning was observed without changes in signal intensity. Changes in T2 of infarcted myocardium were not related to changes in water content or severity of ischemia, but correlated best with infarct healing and scar formation as detected on histopathology. In conclusion, the findings of this study indicate that T2 relaxation time of the infarcted myocardium increases markedly at 3 days and remains elevated for 2 months. These changes correlate best with the onset and progression of infarct healing. These data demonstrate the potential of T2-weighted NMR imaging for assessing healing patterns following ischemic myocardial injury.

Animals

Cardiac imaging and myocardial kinetics of technetium-tertiary butyl-isonitrile during dipyridamole-induced hyperemia.

UNLABELLED: To determine the myocardial kinetics of technetium-tertiary-butyl-isonitrile (Tc-TBI) during dipyridamole-induced hyperemia, the circumflex coronary arteries (LCX) of 15 dogs were partially occluded. Dipyridamole was then infused intravenously over 4 minutes, creating hyperemic flows in the anterior descending (LAD) coronary system. Tc-TBI was administered, then LAD and LCX regional myocardial Tc-TBI activities were continuously monitored with miniature detectors and gamma camera imaging over 3 hours. Microsphere-determined regional myocardial blood flows demonstrated an LCX/LAD flow ratio of 0.81 +/- 0.21 at rest and 0.45 +/- 0.24 (SD) during dipyridamole infusion. Three-hour fractional Tc-TBI clearance rates were minimal and were equal in the LAD (0.14 +/- 0.11) and LCX (0.13 +/- 0.12) zones (p = ns). Excellent gamma camera images, demonstrating the LCX defect, were obtained in all dogs. The correlation coefficient was 0.98 for regional myocardial blood flow vs initial Tc-TBI distribution. IN CONCLUSION: (1) Dipyridamole vasodilation unmasked coronary stenoses despite no flow disparities at rest. (2) The initial distribution of Tc-TBI is proportional to regional myocardial blood flow. (3) There is minimal washout and no redistribution into the initial defect over time, and thus image quality is stable over time. (4) Tc-TBI myocardial kinetics may be applicable to closely related agents currently being developed.

Animals

Superiority of quantitative exercise thallium-201 variables in determining long-term prognosis in ambulatory patients with chest pain: a comparison with cardiac catheterization.

The purpose of this study was to determine the prognostic utility of quantitative exercise thallium-201 imaging and compare it with that of cardiac catheterization in ambulatory patients. Accordingly, long-term (4 to 9 years) follow-up was obtained in 293 patients who underwent both tests for the evaluation of chest pain: 89 had undergone coronary artery bypass graft surgery within 3 months of testing and were excluded from analysis, 119 experienced no cardiac events and 91 had an event (death in 20, nonfatal myocardial infarction in 21 and coronary artery bypass operations performed greater than 3 months after cardiac catheterization in 50). When all variables were analyzed using Cox regression analysis, the quantitatively assessed lung/heart ratio of thallium-201 activity was the most important predictor of a future cardiac event (chi 2 = 40.21). Other significant predictors were the number of diseased vessels (chi 2 = 17.11), patient gender (chi 2 = 9.43) and change in heart rate from rest to exercise (chi 2 = 4.19). Whereas the number of diseased vessels was an important independent predictor of cardiac events, it did not add significantly to the overall ability of the exercise thallium-201 test to predict events. Furthermore, information obtained from thallium-201 imaging alone was marginally superior to that obtained from cardiac catheterization alone (p = 0.04) and significantly superior to that obtained from exercise testing alone (p = 0.02) in determining the occurrence of events. In addition, unlike the exercise thallium-201 test, which could predict the occurrence of all categories of events, catheterization data were not able to predict the occurrence of nonfatal myocardial infarction. The exclusion of bypass surgery and previous myocardial infarction did not alter the results. In conclusion, data from this study demonstrate that exercise thallium-201 imaging may be superior to data from both exercise testing alone and cardiac catheterization data alone for predicting future events in ambulatory patients who have undergone both exercise thallium-201 imaging and catheterization for the evaluation of chest pain.

Adult

Myocardial kinetics of technetium-99m-hexakis-2-methoxy-2-methylpropyl-isonitrile.

To study the potential usefulness of technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) as a cardiac perfusion imaging agent, the left circumflex coronary arteries of 12 dogs were partially occluded. Eight additional control dogs had no coronary artery stenosis. Myocardial Tc-MIBI activities in the left circumflex and left anterior descending zones were continuously monitored by miniature implantable radiation detectors for 4 hr after administration of the isotope. The dogs were then killed. Serial gamma camera images were also acquired during the study. Heart rate, arterial blood pressure, pressure distal to the stenosis, and cardiac output did not change significantly during the experiment. Microsphere-determined regional myocardial blood flow was significantly reduced in the left circumflex distribution in the 12 dogs with coronary artery stenoses. In the 12 dogs with left circumflex coronary artery stenoses, the 4 hr fractional Tc-MIBI clearances from the normal and ischemic zones were minimal and equivalent (0.15 +/- 0.05 vs 0.15 +/- 0.07). In the eight control dogs, 4 hr fractional Tc-MIBI clearances from the left anterior descending and left circumflex artery zones were minimal and equivalent (0.11 +/- 0.06 vs 0.10 +/- 0.07). Four hour fractional Tc-MIBI clearance from the blood was 0.98 +/- 0.03 for the dogs with stenosis and 0.97 +/- 0.02 for the dogs without stenosis. One additional dog had complete occlusion of the left circumflex coronary artery followed by administration of Tc-MIBI and scandium-46-labeled microspheres. This heart was immediately sectioned and counted to determine the relationship of regional blood flow to Tc-MIBI distribution (r = .92).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Increased exercise thallium-201 lung uptake: a noninvasive prognostic index in two-vessel coronary artery disease.

To determine the physiologic impact of two-vessel coronary artery disease and its effect on prognosis, a series of clinical, angiographic, exercise and quantitative thallium-201 (Tl-201) imaging parameters were analyzed in 85 consecutive two-vessel coronary artery disease patients followed for 52 +/- 27 months after coronary angiography and Tl-201 scintigraphy. End points were cardiac death (n = 3), myocardial infarction (n = 6) and coronary bypass graft surgery more than three months after testing (n = 16). Using Cox Hazards survival analysis, early cardiac events were not predicted by: myocardial infarction or anginal history; resting left ventricular function; exercise blood pressure response; angina or severity of ECG ST segment depression (mm); Tl-201 defect size; redistribution or clearance; angiographic patterns; or the presence of proximal left anterior descending disease. Significant predictors of adverse cardiac events were: increased exercise lung to heart Tl-201 ratio (0.59 +/- 0.12 versus 0.46 +/- 0.1; P less than 0.0001); ECG lead extent of ST segment depression (P less than 0.03); and exercise heart rate response (P less than 0.047). Event-free survival for patients with normal and abnormally increased lung to heart Tl-201 ratios at 48 months was 76% versus 63% (P less than 0.003). It was concluded that two-vessel coronary artery disease survival correlates with exercise Tl-201 uptake which reflects exercise induced left ventricular dysfunction.

Actuarial Analysis

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension.

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Measurement of both left ventricular function and regional myocardial perfusion with 133Xe in dogs.

A technique to measure left ventricular (LV) function and myocardial perfusion was validated in 12 dogs. 133Xe in saline was injected into the left atrium (LA) or LV and two data sets were obtained using gamma camera imaging: 1) A first pass gated scan for LV function; followed by 2) Sequential images for regional myocardial perfusion. LV ejection fraction and wall motion measurements from the 133Xe blood pool images were compared to ejection fraction (r = 0.88, P less than 0.01) and wall motion (r = 0.83, P less than 0.01) data from 99mTc labeled blood pool scans. The perfusion measurements obtained with the 133Xe method were compared to microsphere data (r = 0.79, P less than 0.01). Measurements after LV 133Xe injection were similar to data following LA injection. Thus, quantitative assessment of global LV function, regional wall motion and myocardial perfusion is possible with LA or LV 133Xe injection and gamma camera imaging.

Animals

Computer versus visual analysis of exercise thallium-201 images: a critical appraisal in 325 patients with chest pain.

Although computer-aided analysis of planar thallium images has been previously reported to be superior to visual analysis, a segment-by-segment comparison of all thallium variables (presence of initial defect, presence of redistribution, and presence of abnormal lung:heart thallium ratio) has not been performed with the use of both methods. In the present study, such a comparison was performed to determine which thallium variable(s) are superior, when the computer method is used. In addition, both methods were compared to determine their correlations with the angiographic extent of coronary artery disease (no disease, or one-vessel disease vs multivessel, or left main disease) and the occurrence of future events (cardiac-related death or nonfatal myocardial infarction). Computer-aided analysis was superior to visual analysis (an average of three independent blinded observers) for detection of coronary disease because: (1) it was more specific for detecting initial defects despite having the same sensitivity (89.6% vs 91.0%, p = NS) and (2) it was more sensitive for detecting redistribution in the territory of a stenosed vessel (68% vs 46%, p less than 0.001). However, absolute myocardial clearance of thallium had very poor specificity compared to visually assessed redistribution. Only when segmental clearance was considered abnormal on a relative basis (if it was slower by 98% or more than the fastest clearing segment in the heart) did abnormal clearance achieve the same specificity (99%) and a better sensitivity (60% vs 48%, p less than 0.01) than visual analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases

Differentiation of viable and nonviable myocardium after acute reperfusion using serial thallium-201 imaging.

This study was performed to determine if differences in regional myocardial thallium clearance rates could differentiate salvaged from nonsalvaged myocardium after reperfusion. Twenty-one dogs underwent 2 hours of left anterior descending coronary artery ligation followed by reperfusion. Thallium was administered 5 minutes later and serial images were acquired over 3 hours. Of the 21 dogs, 15 had infarctions of which nine had initially reduced anterior wall thallium activity (group 1) and six had normal or increased activity (group 2). Six dogs did not have an infarction (group 3). All group 1 dogs demonstrated reduced clearance rates in the anterior wall (T1/2 = 15.0 +/- 4.7 hours, SD) compared to the posterior wall (T1/2 = 9.0 +/- 4.4 hours; p less than 0.001). Group 2 dogs demonstrated increased clearance rates in the anterior wall (T1/2 = 5.7 +/- 2.0 hours) compared to the posterior wall (T1/2 = 10.5 +/- 4.6 hours; p less than 0.001). Group 3 dogs demonstrated no difference in clearance rates. In conclusion, although thallium uptake is frequently reduced in nonsalvaged myocardium, tracer uptake can be normal or increased if perfusion has been completely restored. However, an increased clearance rate from the reperfused zone compared to the normal zone is a reliable indicator of nonsalvaged myocardium, despite normal initial thallium uptake.

Animals

Comparison of intravenous dipyridamole thallium cardiac imaging with exercise radionuclide angiography.

Sixty-eight patients underwent dipyridamole thallium imaging and exercise blood pool imaging in order to determine the functional significance of various dipyridamole thallium imaging redistribution patterns. Serial thallium images and blood pool regional wall motion were interpreted by three independent observers. Rest and exercise left ventricular ejection fractions were calculated by two observers and were averaged. Transient thallium defects were associated with normal rest and exercise left ventricular ejection fraction and regional wall motion. Mild persistent thallium defects were associated with normal ejection fraction and regional wall motion at rest, with a deterioration in both with exercise. Severe persistent thallium defects were associated with reduced ejection fraction and regional wall motion at rest, but no further deterioration with exercise. These data support the following postulates: Transient dipyridamole thallium defects are due to mild coronary artery stenoses that cause no detectable functional consequence during levels of exercise achieved in this study. Mild persistent defects are due to more severe stenoses that do cause a functional reduction in wall motion during exercise. Although appearing qualitatively persistent, these defects probably represent very slow thallium redistribution and ischemia rather than scar. Finally, severe persistent defects probably represent myocardial scar.

Adult