Predicting digoxin dosage from creatinine clearance.
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Aged↗
Biomedical subjects
R D Okada
Publications and source records attributed to R D Okada.
Advances in cardiovascular nuclear medicine.
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Cardiovascular Diseases↗
Technetium-99m stannous pyrophosphate myocardial scintiphotos in patients admitted to rule out acute myocardial infarction.
Technetium-99m stannous pyrophosphate (Tc-PYP) cardiac scintiphotos were performed on 101 of 221 patients admitted to the Coronary Care Unit to rule out acute myocardial infarction (AMI). Criteria were defined for the diagnosis of AMI, variant angina and unstable angina. 42 patients were diagnosed as having had an AMI. 22 patients had transmural and 20 patients had nontransmural AMI. 40 of the 42 patients with AMI (95%) had positive scintophotos; 2 (5%) had negative scintiphotos. 59 patients did not have an AMI; (97%) had negative scintiphotos. Four of these 59 patients had variant angina; all had negative scintiphotos. Seven of these 59 patients had unstable angina; 2 had positive scintiphotos. Tc-PYP scintiphotos have high sensitivity and specificity and are accurate in correctly classifying patients as having or not having AMI.
Acute Disease↗
Excitation, contraction, and excitation-contraction coupling of frog muscles in hypotonic solutions.
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Action Potentials↗
Myocardial technetium 99m-labeled teboroxime clearance derived from canine scans differentiates severity of stenosis after dipyridamole.
BACKGROUND: The purposes of this study were to determine (1) whether perfusion defects and differential teboroxime clearance observed on serial postdipyridamole planar gamma camera images have utility in differentiating severity of coronary stenosis in canine myocardium and (2) whether single-zone (99mTc activity in one zone over time) or dual-zone (99mTc activity ratio in two zones over time) quantitative analysis provides the most useful characterization of teboroxime clearance kinetics. METHODS AND RESULTS: Accordingly, eight dogs received a mild coronary stenosis (microsphere-determined, post-dipyridamole flow > or = 0.4 ml/min/gm) and 10 dogs received a severe coronary stenosis (flow < or = 0.3 ml/min/gm). In three control dogs there was no coronary stenosis. Teboroxime (5 mCi) was injected after dipyridamole (0.8 mg/kg/min), and gamma camera imaging was begun immediately and continued for 60 minutes. Quantitative analysis of single-zone clearance curves indicated that teboroxime retention for both zones of stenosis (mild = 66.3% +/- 2.8%, SEM; severe = 69.5% +/- 3.7%) was significantly greater than control zone retention (54.5% +/- 3.0%; p < 0.05) at 10 minutes. Retention in mild (37.2% +/- 1.9%, SEM) and severe (42.3% +/- 1.5%) zones of stenosis was significantly different from each other at 60 minutes (p < 0.05). There was a significant direct, linear correlation of flow with teboroxime clearance at 20 minutes (r = +0.74, normal and ischemic zones). Quantitative analysis with dual-zone count ratios (stenosed/normal) demonstrated significant differences among control (0.93 +/- 0.04, SEM), mild stenoses (0.54 +/- 0.04), and severe stenoses (0.39 +/- 0.03) as early as 2 minutes after administration of 99mTc-labeled teboroxime. The correlation coefficient for flow ratio versus dual-zone counts/pixel ratio at 20 minutes was r = +0.74. CONCLUSION: Thus in this canine stenosis model with dipyridamole, gamma camera imaging could distinguish mild from severe coronary stenoses by either single- or dual-zone analysis.
Animals↗
Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction.
To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.
Animals↗
The alterations of magnetic resonance relaxation parameters in excised myocardial tissue during NMR spectroscopy: the effects of time, environmental exposure and TTC staining.
To investigate the potential impact of air exposure, time delay and vital tissue staining on the MR relaxation parameters in normal and pathological heart tissues, myocardial samples from a canine model of myocardial infarction were subject to (a) air exposure for up to 20 hours or (b) wrapping in Parafilm for up to 20 hours; immersion in (c) full strength pathological stain consisting of triphenyl tetrazolium chloride (TTC), or (d) half strength TTC, or (e) normal saline for 30 minutes. We found that (a) exposure to air produced rapid change in both T1 and T2 such that there is a reduction of T1 by 12.2% and T2 by 14.4% (p less than 0.001) in one hour; (b) airtight wrapping attenuated dramatically these changes, but T1 still was reduced by 2.9% and T2 by 4.8% in one hour (p less than 0.01). These changes followed similar but non-linear changes of tissue water content. T1 did not change significantly after exposure to full strength TTC, but did increase significantly after exposure to half strength TTC, and increased even further after exposure to saline. T2 on the other hand increased significantly with all of these test solutions. We conclude that the in vitro processing of excised myocardial tissues should be done by wrapping in an airtight container with T1 and T2 parameters measured within one hour, if possible. All tissue processing, including stains and saline exposure, should be done after spectrometer measurements.
Air↗
Clearance of technetium 99m N-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium.
BACKGROUND: Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (99mTcN-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro. The purpose of this study was to determine the clearance kinetics of 99mTcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium. METHODS AND RESULTS: After a 100 microCi (3.7 x 10(6) Bq) bolus of 99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3). Six hearts were perfused with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The 99mTcN-NOET myocardial clearance was near linear in the control (0.6 +/- 0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2% +/- 4.0%; p < 0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9% +/- 1.4% for all groups combined. CONCLUSION: Thus 99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that 99mTc-NOET is localized predominantly in or on cell membranes. 99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.
Animals↗
Planar imaging of 99mTc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium[V]) can detect resting ischemia.
BACKGROUND: (99m)Tc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(V)) ([99m]TcN-NOET) is a new lipophilic, neutral-charge cardiac perfusion imaging agent that demonstrates apparent redistribution in animal models and humans. The purpose of this study was to determine whether the kinetics of (99m)TcN-NOET are suitable for the detection of resting ischemia. METHODS AND RESULTS: Microspheres were injected at baseline and simultaneously with (99m)TcN-NOET after a 90% reduction in resting flow in the left circumflex coronary artery in six open-chest canine experiments. The relationship of flow and activity early after injection was determined in one experiment by termination at 10 minutes. The flow ratio (left circumflex/left anterior descending coronary artery) after stenosis fell significantly (0.87 +/- 0.04 vs 0.46 +/- 0.04; p < 0.05). The end-tissue (99m)Tc ratio (0.78 +/- 0.05) was significantly higher than the flow ratio at injection (0.46 +/- 0.04; p < 0.05), indicating substantial redistribution. In vivo imaging was conducted during 2 hours in five experiments, followed by ex vivo imaging. Myocardial clearance from 10 minutes onward was biphasic in left anterior descending and monophasic in left circumflex coronary arteries. Myocardial clearance from 10 to 60 minutes was delayed in left circumflex (35.5% +/- 8.1%) versus left anterior descending coronary arteries (49.2% +/- 8.6%; p < 0.05). No significant difference was observed from 60- to 120-minute clearance. Five of five experiments demonstrated initial defects and complete fill-in at 90 to 120 minutes by qualitative assessment. Quantitation of ex vivo images confirmed significant redistribution. CONCLUSIONS: Resting ischemia caused by moderate to severe stenosis can be detected on scans with (99m)TcN-NOET. Redistribution was near complete in this model by 90 to 120 minutes. (99m)TcN-NOET is a promising new agent for the detection of coronary artery disease in viable myocardium and warrants further investigation.
Animals↗
Technetium 99m-HL-91: a potential new marker of myocardial viability assessed by nuclear imaging early after reperfusion.
OBJECTIVE: 99mTc-HL-91 (Prognox) is a potential new hypoxia-avid myocardial imaging agent. The purpose of this study was to determine whether this tracer would demonstrate increased activity in nonviable myocardium in vivo. METHODS AND RESULTS: A 3-hour left circumflex artery (LCx) occlusion was followed by 1 hour of reperfusion, injection of 99mTc-HL-91 (185 MBq), and 2 hours of gamma camera imaging in 6 open-chest canine experiments. Microspheres were injected during baseline, at occlusion, at the time of tracer injection, and at the end of the experiment. After the animals were killed, heart slices were imaged. Blood flow and tracer activity were determined by well counting. Mean infarct size was 19.2% +/- 2.2% (SEM). All six dogs demonstrated no increased 99mTc-HL-91 myocardial activity other than small foci on in vivo and ex vivo gamma camera images. The mean large region of interest (ROI)-determined LCx/LAD (left anterior descending) ratio was 1.10 +/- 0.03 in vivo, and 1.0 +/- 0.02 ex vivo. Mean clearance curves from LCx and LAD ROI were not significantly different, and 2-hour retention was 15.2% +/- 2.1% for the LCx and 18.6% +/- 2.7% for the LAD (p = NS). ROI clearance curves demonstrated biexponential clearance over the first hour and linear clearance over the second hour. Myocardial blood flow (microspheres) versus well-counted tracer uptake curves were linear with near-zero slopes for viable tissue, nonviable tissue, and mosaic tissue. Blood clearance was triexponential with a 2-hour retention of 7.8% +/- 1.1%. CONCLUSIONS: In contrast to viable ischemic tissue, normal and nonviable myocardium demonstrate similar 99mTc-HL-91 uptake and retention kinetics. This agent warrants further clinical studies in situations where there is a need to differentiate ischemic viable from nonviable myocardium.
Animals↗
HL-91-technetium-99m: a new marker of viability in ischemic myocardium.
BACKGROUND: Technetium 99m-HL91 is a new hypoxia imaging agent that demonstrates increased uptake in ischemic, viable myocardium. This study was performed to determine whether HL91 is taken up by nonviable myocardium. METHODS: Twenty-three Krebs-Henseleit buffer-perfused, isolated rat hearts were studied. Tc-99m-HL91 300 microCi was infused over 10 minutes, followed by a 60-minute clearance. Myocardial activity was monitored by use of an NaI crystal. Four groups were studied: control (flow = 12 mL/min, n = 7), low flow (flow = 1 mL/min, n = 6), no flow/reflow (60 minutes no flow/60 minutes reflow before Tc-99m-HL91 infusion, flow = 12 mL/min, n = 5), and cyanide-treated (before Tc-99m-HL91 infusion, flow = 12 mL/min, n = 5). Injury was assessed by creatine kinase, transmission electron microscopy, and triphenyltetrazolium chloride. RESULTS: Control (no injury) and cyanide-treated (severe injury) hearts demonstrated low uptake (6.3+/-0.5 mean+/-SEM and 5.7+/-1.2 microCi, respectively) and low 60-minute retention (13.8%+/-2.2% and 13.7%+/-3.9%, respectively). Low-flow hearts (minimal injury) demonstrated markedly increased uptake (43.5+/-2.8 microCi, P < .01) and increased 60-minute retention (33.2%+/-2.9%, P < .01) compared with control. No-flow/reflow hearts (moderate injury) demonstrated intermediate uptake (8.7+/-0.5 microCi, P < .05 to control), although retention was not significantly different (18.9%+/-3.5%, P = ns). Severely and rapidly injured myocardium demonstrated Tc-99m-HL91 peak uptake and retention indistinguishable from normal. Moderately injured myocardium demonstrated uptake intermediate between severely injured and low-flow-induced ischemic, viable myocardium. CONCLUSION: Thus Tc-99m-HL91 is not taken up or retained in nonviable and irreversibly injured myocardium.
Animals↗
Detection of myocardial viability in ischemic-reperfused rat hearts by Tc-99m sestamibi kinetics.
BACKGROUND: The purpose of this study was to evaluate technetium 99m sestamibi (MIBI) kinetics in assessing myocardial viability in hearts subjected to different ischemia-reperfusion treatments, resulting in graded severity of injury. METHODS AND RESULTS: Sixteen isolated Krebs-Henseleit-perfused rat hearts were divided into 3 groups: control (flow, 12 mL/min; n = 5), ischemic-reperfused with glucose (IR+G, n = 6), and ischemic-reperfused without glucose (IR-G, n = 5). MIBI (11.1 mBq [300 microCi]) was infused for 60 minutes (uptake), followed by a 60-minute clearance. MIBI uptake (percent injected dose per gram) was significantly decreased in the IR+G (2.07 +/- 0.31) and IR-G groups (2.03 +/- 0.23; P = not significant with IR+G) compared with the control group (3.06 +/- 0.25, P <.05). Fractional washout of MIBI was more rapid in the IR-G group (72.7% +/- 3.9%, P <.05) than in the control (21.9% +/- 1.9%) and IR+G groups (20.3% +/- 1.7%). End retention (percent injected dose per gram) of MIBI in the IR-G (0.60 +/- 0.12) and IR+G groups (1.60 +/- 0.18) was significantly less than in the control group (2.30 +/- 0.11, P <.05), respectively. The retention in the IR-G group was less than in the IR+G group (P <.05). Creatine kinase assay, triphenyltetrazolium chloride staining, and transmission electron microscopy analysis demonstrated more serious myocardial damage in the IR-G group than in the IR+G group. End MIBI activity was highly correlated with myocardial viability determined by triphenyltetrazolium chloride staining (r = 0.94; P <.05) and creatine kinase assay (r = -0.86; P <.05). CONCLUSIONS: Clearance of Tc-99m sestamibi is sensitive to metabolic states and may be used for assessment of ongoing myocardial damage.
Animals↗
Myocardial kinetics of Tc-99m glucarate in low flow, hypoxia, and aglycemia.
BACKGROUND: Technetium-99m glucarate is a myocardial infarct-avid imaging agent. Recent conflicting and inconclusive reports have suggested that the agent may be taken up by ischemic but viable myocardium. The purposes of this study were (1) to determine conclusively whether there is Tc-99m glucarate uptake in ischemic viable myocardium and (2) to investigate the potential mechanisms for such uptake by studying components of ischemia, namely, low flow, hypoxia, and aglycemia. METHODS AND RESULTS: Rat hearts were isolated and perfused in a modified Langendorff preparation with a crytalloid perfusate. Tc-99m glucarate was studied in control (n = 6), low-flow (n = 5), hypoxic (n = 5), and aglycemic (n = 5) conditions. The experimental protocol consisted of 20-minute baseline (12 mL/min flow) and 20-minute treatment (low flow at 1 mL/min, hypoxia, or aglycemia), followed by tracer uptake (20 minute) and washout (20 minutes). Activity was monitored with a sodium iodide detector. The tracer was delivered continuously over a 20-minute uptake period. The injected dose was 150 micro Ci (5.6 MBq). Hemodynamics were monitored throughout. Triphenyltetrazolium chloride staining was used to assess myocardial viability. There was no evidence of myocardial necrosis. Low flow tended to delay tracer uptake compared with control for the first 10 minutes, but this did not reach statistical significance. Low flow increased end fractional retention significantly compared with control (mean +/- SEM, 59.0% +/- 0.9% peak vs 41.2% +/- 1.4%, respectively; P <.05). Hypoxia resulted in a trend toward increased uptake; however, this was significant only at one early time point during the uptake phase. Retention in the hypoxia group was similar to control. Tc-99m glucarate uptake was significantly increased in aglycemia from 16 minutes to peak compared with control (1.36% +/- 0.71% injected dose per gram vs 0.91% +/- 0.37% injected dose per gram, respectively; P <.05). Aglycemia produced significantly higher end fractional retention compared with control (51.6% +/- 1.8% peak vs 41.2% +/- 1.4%, respectively; P <.05). CONCLUSIONS: Tc-99m glucarate myocardial retention is increased in the setting of ischemia, even in the absence of necrosis. This increased retention is not due to hypoxia. Furthermore, the retention is only partially explained by tissue hypoglycemia. Thus low flow per se appears to have a role in this increased retention, probably as a result of delayed flow-dependent washout.
Animals↗
Value of computer analysis of exercise thallium images in the noninvasive detection of coronary artery disease.
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Adult↗