The kinetics of β-methyl-substituted labelled fatty acids in ischaemic myocardium: an analysis in man and with a blood-perfused isolated heart model

β-Methyl-substituted free fatty acids (FFAs) have been developed for myocardial single-photon emission tomography (SPET) imaging, but little is known about their kinetics in ischaemic conditions. The aim of this study was to determine the changes in the myocardial kinetics of a β-methyl-branched FFA, [¹²³I]16-iodo-3-methyl-hexadecanoic acid (MIHA), under ischaemic conditions. The kinetics of MIHA were analysed: (a) using a blood-perfused isolated heart model subjected to moderate ischaemia (50% flow reduction) and (b) in patients who had an exercise thallium-201 SPET defect corresponding to either necrotic (n = 13) or chronically ischaemic and viable (n = 15) myocardium, and who underwent two consecutive SPET studies after MIHA injection. In animals, the myocardial early retention fraction of MIHA, but not its clearance rate, was dependent on coronary flow, the early retention fraction being higher in ischaemic than in normoxic conditions (0.24±0.10 vs 0.14±0.04, P = 0.004). In the patient SPET studies, the uptake of MIHA calculated in ischaemic and viable areas (G1: 74%±9% of maximal left ventricular value) was different from that calculated in necrotic (G2: 59%±7%, P<0.001) or normal (G3: 88±6%, P<0.001) areas. By contrast, MIHA-clearance calculated between the two consecutive SPET studies was not different in G1, G2 and G3. Unlike in the case of other FFAs, the myocardial clearance of MIHA is not decreased by ischaemia. However, the early retention of MIHA is increased in the case of a moderate reduction in coronary flow, a property which might help in the detection of viability in chronically ischaemic myocardium. Received 3 November 1998 and in revised form 15 January 1999     

Myocardial viability: What do we need?

Coronary revascularization in patients with chronic coronary heart disease (CHD) or acute myocardial infarction (AMI) is mainly based on factors such as coronary anatomy, ventricular function, accompanying diseases and the patient's biological age. Rest- or exercise-induced ischaemia should be proven before a bypass operation or percutaneous transluminal coronary angioplasty. Although a significant amount of ischaemic but still viable myocardium is a necessary condition for successful revascularization, the detection of viable myocardium is of major importance in a rather small subset of patients. These are patients with hibernating (or a combination of hibernating and stunned) myocardium in whom the aforementioned parameters do not yield an unequivocal result. Thallium-201 myocardial scintigraphy with re-injection or rest-redistricution is an established, proven and cost-effective way of detecting viable myocardium. Other methods such as positron emission tomography with different tracers or technetium-99m sestamibi SPET are discussed and compared to thallium-201 SPET. In conclusion, the detection of ischaemic but still viable myocardium is of importance in only a rather small subset of patients with CHD. In this context thallium-201 myocardial SPET is and still remains the method of choice. Correspondence to: H. Schoeder     

Dipyridamole and exercise SPET provide different estimates of myocardial ischaemic areas: role of the severity of coronary stenoses and of the increase in heart rate during exercise

In patients unable to perform a maximal exercise test, dipyridamole single-photon emission tomography (SPET) has a higher capacity than exercise SPET to detect coronary artery disease (CAD). However, in patients with myocardial ischaemia who are able to perform a maximal exercise test, it is not known whether these two tests may be equally used to assess the areas of myocardial ischaemia. This study was aimed at comparing the results provided by dipyridamole and exercise SPET in CAD patients with documented exercise myocardial ischaemia. Forty CAD patients who had undergone exercise thallium-201 SPET and who had myocardial ischaemia documented by an unequivocally positive exercise test underwent an additional 201Tl SPET study after dipyridamole infusion and low-level (40 W) exercise. The extent of defects was compared between the two tests and predictors of discrepant results were sought among data from exercise testing and coronary angiography. The extent of SPET defects was equivalent between the two tests in only 11 patients (28%), larger defects being observed with exercise in 18 [average difference: 12%+/-5% of left ventricle (LV)] and with dipyridamole in 11 (average difference: 15%+/-11% of LV). The best independent predictors of discrepancies between the two tests were: (1) increase in heart rate at exercise SPET, with defects being smaller at exercise than after dipyridamole in none of the patients with an increase >60 bpm (0/14), but in 42% of the others (11/26; P=0.004); and (2) an ischaemic territory related to a <70% coronary stenosis, for which SPET defects were always induced at exercise (10/10) but in only 30% (3/10) with dipyridamole (P=0.0004). Exercise and dipyridamole SPET provide different estimates of myocardial ischaemic areas. Dipyridamole allows the unmasking of perfusion abnormalities in patients who have low increases in heart rate at exercise SPET. However, dipyridamole is also much less efficient at inducing perfusion abnormalities in the ischaemic areas supplied by coronary stenoses of intermediate severity at rest angiography.     

A comparison of the overall first-pass kinetics of thallium-201 and technetium-99m MIBI in normoxic and low-flow ischaemic myocardium

The specific impact of ischaemia on the myocardial kinetics of thallium-201 and technetium-99m 2-methoxy-2-isobutylisonitrile (MIBI) remains a matter of debate. Using an isolated heart model perfused with red blood cell-enhanced perfusate, we compared the overall first-pass kinetics of 201Tl and MIBI under haemodynamically stable conditions of low-flow ischaemia (> 50% reduction in normal coronary flow and a > or = 20 mmHg fall in systolic contraction pressure, n = 10) and normoxia (n = 11). For both 201Tl and MIBI, we found that under ischaemic conditions (as compared with normoxia) there was a higher initial net extraction fraction (201Tl: 0.78 +/- 0.03 vs 0.72 +/- 0.06, P = 0.006; MIBI: 0.49 +/- 0.10 vs 0.39 +/- 0.11, P = 0.03), a lower clearance rate in the 30 min following extraction (% decrease in cardiac uptake: 201Tl: 30 +/- 12 vs 47 +/- 14, P = 0.02; MIBI: 5 +/- 5 vs 13 +/- 11, P = 0.02) and a higher retention fraction at 30 min (20lTl: 0.54 +/- 0.10 vs 0.39 +/- 0.12, P = 0.004; MIBI: 0.46 +/- 0.08 vs 0.33 +/- 0.12, P = 0.01). Multivariate analyses, however, revealed that all myocardial kinetic parameters of both tracers were dependent only on coronary flow rates, without any additional significant impact of the presence of ischaemia or states of contractility or oxidative metabolism. We conclude that the myocardial fractional retention of both 201Tl and MIBI is strongly correlated with the decrease in coronary flow during ischaemia. This inverse relationship with coronary flow derives from both the flow-dependent increase in the initial myocardial extraction and the decrease in the subsequent myocardial washout of the tracers.     

Low-dose dobutamine stress gated SPET for identification of viable myocardium: comparison with stress-rest perfusion SPET and PET

The detection of viable myocardium is important for the prediction of functional recovery after revascularisation. However, a fixed perfusion defect often includes viable myocardium, and perfusion imaging then underestimates myocardial viability. We previously reported that low-dose dobutamine stress gated single-photon emission tomography (SPET) provides similar findings to dobutamine stress echocardiography in the assessment of myocardial viability. The present study investigated whether low-dose dobutamine stress gated SPET is of additional value as compared with stress-rest technetium-99m tetrofosmin SPET for the detection of myocardial viability. Standard stress-rest perfusion SPET, low-dose dobutamine stress gated SPET and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) were studied in 23 patients (mean age 67+/-7.6 years) with previous myocardial infarction. Twenty-one of them were successfully studied with each technique. FDG PET viability (FDG uptake >/=50%) was employed as the gold standard. One-day stress-rest (99m)Tc-tetrofosmin myocardial SPET was performed. After the resting study, gated SPET was acquired following infusion of 7.5 microg kg(-1) min(-1) of dobutamine. Left ventricular wall motion in 16 segments was assessed by cine mode display using a four-point scale. Myocardial viability was considered present when there was improvement by one point. Of a total of 336 segments analysed, 53 had persistent defects on stress-rest perfusion SPET. FDG viability was seen in 16 of 17 dobutamine-responsive segments, but in only 11 of 36 dobutamine non-responsive segments ( P<0.01). Thus, in the segments with persistent defects, viability findings on low-dose dobutamine stress gated SPET were concordant with those on FDG PET in 77% of segments (kappa value =0.55). For the detection of FDG-viable myocardium, the combination of stress-rest perfusion SPET and low-dose dobutamine stress gated SPET achieved a better sensitivity than stress-rest perfusion SPET alone (35/46, 76% vs 19/46, 41.3%, P<0.001), with a similar specificity (25/29, 86% vs 26/29, 90%, P=NS). We conclude that in the identification of viable myocardium, low-dose dobutamine stress gated SPET may provide additional information missed on a routine stress-rest perfusion scan. Dobutamine stress gated SPET may provide new insights into myocardial viability on the basis of ischaemia and contractile reserve.     

Hypoxia imaging of patients with acute myocardial infarction by using dual isotopes of 201Tl and 99mTc-HL91

OBJECTIVE: To evaluate the myocardial ischaemia/viability in patients with acute myocardial infarction (AMI) using the ischaemia-avid agent (99m)Tc-HL91. METHODS: Thirty-three AMI patients received 740 MBq (20 mCi) (99m)Tc-HL91, i.v., first and then 148-185 MBq (4-5 mCi) (201)Tl around 3 h later. The patient underwent initial imaging and 24 h late imaging, 10-15 min and 24 h later, respectively, after intravenous injection of (201)Tl. Myocardial segmental radioactive counts of (99m)Tc-HL91 were quantified by the region of interest technique. The segmental radioactive counts/pixel divided by those of the corresponding left ventricular cavities were ratios, which were compared among normal, ischemic/viable and fixed defect myocardium. The correlation analysis between the segmental scores from (201)Tl imaging and the ratios was performed. RESULTS: The cross-talk of (99m)Tc into (201)Tl could be neglected in the present study. Out of the 33 AMI patients, the (99m)Tc-HL91 image quality analysis classified seven cases into excellent, accounting for 21%, eight cases into good, for 24%, eight cases into fair, for 24%, and 10 cases into poor, for 31%. The ratios were 1.16 (1.01, 1.35) ((median (25th to 75th percentile)), 1.15, 0.20 and 1.01 (0.86, 1.30), respectively, in normal, ischaemic/viable and fixed defect myocardium. Significant differences (chi2=17.2069, P=0.0002) were found in the ratios. The ratios of the ischaemic/viable myocardial segments were significantly higher than those of the fixed defect segments. Unexpectedly, the normal myocardial segments took up (99m)Tc-HL91, too, even slightly higher than the ischaemic/viable myocardial segments. CONCLUSIONS: Myocardial uptake of (99m)Tc-HL91 is perfusion-dependent as well as ischaemia dependent. (99m)Tc-HL91 hypoxia imaging alone is not sufficient to identify ischaemic/viable myocardium. Dual-isotope imaging with (201)Tl and (99m)Tc-HL91 can characterize the myocardium into normal, ischaemic/viable and necrotic (scarred) myocardium.     

Concordance between rest MIBG and exercise tetrofosmin defects: possible use of rest MIBG imaging as a marker of reversible ischaemia

Perfusion imaging combined with pharmacological stress is the study of choice in patients with ischaemic heart disease who are incapable of exercising. Some medical conditions, however, can preclude the use of pharmacological stress. In these particular situations, availability of a diagnostic test which allows for the assessment of ischaemic territory at rest would be desirable. With the purpose of providing a marker of reversible ischaemia, we evaluated myocardial iodine-123 metaiodobenzylguanidine (MIBG) uptake in regions with fixed and reversible defects defined by exercise/rest perfusion study. Fifty-four male patients with ischaemic heart disease and previous myocardial infarction were studied by means of exercise/rest tetrofosmin and MIBG single-photon emission tomography (SPET). Regional tracer uptake was quantified and expressed as a percentage of maximum peak activity. Areas with denervated but perfused myocardium and areas with ischaemic myocardium were calculated. Regions with<75% of peak activity in the exercise perfusion study were divided into two groups according to whether the increase in peak activity in the respective rest study was >10% (reversible regional defect) or <10% (fixed regional defect). These percentages were compared with the percentages of the innervation study. The area of the innervation defect was significantly larger when the perfusion defect was reversible than when it was fixed. In regions with reversible perfusion defects, the size of the area of denervated but perfused myocardium was similar to the size of the area of ischaemic myocardium. In regions with reversible defects, the percentage of myocardial MIBG uptake was not significantly different from the percentage of tetrofosmin uptake at exercise, while it was significantly lower than the percentage of tetrofosmin uptake at rest. In regions with fixed defects, the percentage of myocardial MIBG uptake was significantly lower than the percentage of tetrofosmin uptake at exercise and at rest. In patients who developed angina during exercise test, the area of denervated but perfused myocardium was significantly larger than in patients without angina (4.1+/-2.4 vs 3.4+/-2.5, P=0.02). The same trend was observed with regard to the size of the innervation defect (8.6+/-2.4 vs 5.7+/-2.2, P=0.02). It is concluded that when the use of pharmacological stress is not possible in patients incapable of exercising, rest studies with MIBG combined with rest myocardial perfusion studies may be useful as a marker of reversible ischaemia.     

Myocardial distribution of (18)F-FDG and (99m)Tc-sestamibi on dual-isotope simultaneous acquisition SPET compared with PET

A dual-isotope simultaneous acquisition (DISA) single-photon emission tomography (SPET) protocol with fluorine-18 fluorodeoxyglucose ((18)F-FDG) and a technetium-99m labelled flow tracer is attractive because it permits assessment of both myocardial glucose utilisation and flow within a single study. Differences in physical and physiological characteristics between (18)F-FDG and the (99m)Tc-labelled flow tracer, however, may cause differences in myocardial activity distribution between the agents. The aim of this study was to investigate the relation between the myocardial distribution of (18)F-FDG and a (99m)Tc-labelled flow tracer on DISA SPET in comparison with nitrogen-13 ammonia/(18)F-FDG positron emission tomography (PET). Nine normal volunteers without cardiac disease and ten patients with known coronary artery disease (CAD) underwent (13)N-ammonia/(18)F-FDG PET and (99m)Tc-sestamibi/(18)F-FDG DISA SPET. Using a semiquantitative polar map approach, the left ventricular myocardium was divided into nine segments, and relative regional activity was calculated for each segment. A segment was considered to have concordant uptake between (18)F-FDG and flow tracer if the difference in measured regional activity between the tracers was < or =10% of peak activity, and the percentage of concordant segments was calculated for each subject. There was a good overall concordance of myocardial activity between the agents on DISA SPET (84.0%+/-14.8%) in normals, which was comparable to that seen on PET (86.4%+/-14.5%, NS vs DISA SPET). However, the myocardial activity distributions of (18)F-FDG and flow tracer were not identical in that reduced flow tracer activity was seen in the basal segments on DISA SPET in both normals and CAD patients. It is concluded that there is good overall concordance of activity between (18)F-FDG and flow tracer in normal myocardium on DISA SPET, which is comparable to that on PET, supporting the use of combined (99m)Tc-flow tracer/(18)F-FDG imaging for the detection of viable myocardium. However, there is a difference in the myocardial activity distribution between the agents in both normals and CAD patients, the difference being particularly evident in the basal segments. Therefore, careful image interpretation that takes into consideration the different normal activity distribution between the tracers and/or a tracer-specific normal database is necessary for comparison with patient studies.     

Regional 11C-hydroxyephedrine retention in hibernating myocardium: chronic inhomogeneity of sympathetic innervation in the absence of infarction.

We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium. METHODS: Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately. RESULTS: After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The regional reduction in sympathetic nerve function was persistent and unaltered for at least 2 mo after the development of hibernating myocardium. CONCLUSION: Hibernating myocardium is associated with persistent reductions in regional uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic innervation in viable dysfunctional myocardium is similar to that occurring after myocardial infarction and may contribute to arrhythmic death in patients with ischemic cardiomyopathy.     

Myocardial metabolism of 123I-BMIPP during low-flow ischaemia in an experimental model: comparison with myocardial blood flow and 18F-FDG.

Risk stratification of coronary artery disease may provide a basis for selection of treatment to prevent myocardial events and to assist functional recovery. Iodine-123 (rho-iodophenyl)-3-R,S-methylpentadecanoic acid (123I-BMIPP) is a radioiodinated fatty acid analogue for single-photon emission tomographic (SPET) imaging, and several reports have demonstrated that the abnormal uptake of 123I-BMIPP is associated with wall motion abnormality and severe coronary artery stenosis. Clarification of the contribution of fatty acids to myocardial metabolism would be highly valuable in recognising this critical condition. In this study, we investigated the myocardial uptake of 123I-BMIPP under low-flow ischaemia, and compared it with the uptake of fluorine-18 fluorodeoxyglucose (18F-FDG). Using open chest dogs, the flow of the left anterior descending coronary artery was controlled using a pneumatic occluder in order to maintain a 30%-40% reduction of Doppler flow. 123I-BMIPP and 18F-FDG were injected into the left atrium after 90 min of ischaemia (protocols 1 and 3). Canine hearts were excised after 120 min of ischaemia for the measurement of radioactivity. In protocol 2, 123I-BMIPP alone was injected and hearts were excised 8 min after the injection. A time-course biopsy study was also performed at the same time (protocol 3). Wall thickening was evaluated using a wall tracker module. The uptake of 18F-FDG increased significantly in the ischaemic region (232%+/-135% vs non-ischaemic, P<0.05 in protocol 1) even on mild reduction of myocardial blood flow (MBF). The increased uptake of 18F-FDG did not correlate well with the severity of MBF. On the other hand, 123I-BMIPP uptake decreased gradually (78.9%+/-23.6%, P<0.05 in protocol 1, and 85.9%+/-24.3% in protocol 2) in the ischaemic region, specifically in the endocardium (64.0%+/-28.9%, P<0.05 in protocol 1, and 75.1%+/-28.8%, P<0.05 in protocol 2), and correlated strongly with MBF (r=0.93 in protocol 1 and r=0.97 in protocol 2) as a logarithmic function. This indicated that the abnormal uptake of 123I-BMIPP was associated not only with wall motion abnormality but also with the severity of MBF. In the biopsy study (protocol 3), the radioactivity of either 123I-BMIPP or 18F-FDG correlated well with the MBF at the time of tracer injection and was similar to post-mortem analysis. It is concluded that 18F-FDG is a valid tool for identifying ischaemic myocardium even in its earliest stages. On the other hand, 123I-BMIPP might be used to detect moderately to severely ischaemic myocardium such as hibernation, suggesting the potential value of 123I-BMIPP in the risk stratification of patients with severe coronary artery disease who require revascularisation without delay.     

Low-flow ischaemia has no deleterious effect on the steady-state kinetics of 201Tl and 99mTc sestamibi within myocardial tissue

OBJECTIVES: This study aimed to specifically analyse the impact of low-flow ischaemia on the ability of myocytes to trap and accumulate Tl and sestamibi (MIBI) within myocardial tissue. METHODS: In order to reach steady-state conditions for the interstitial/cellular concentration ratios (Ci/Cc) of the tracers and thereby simulate the conditions of cell cultures studies, Tl and MIBI were injected continuously during an 80 min period within the coronary circulation of isolated hearts submitted to normoxia (n=7) or low-flow ischaemia (n=7; >50% reduction in coronary flow). Ci was determined by using interstitial microdialysis and Cc was determined from Ci and myocardial retention values of the tracers. RESULTS: At the end of the experiments, under steady-state conditions, Ci/Cc was equivalent between low-flow ischaemia and normoxia for both Tl (ischaemia, 0.60 +/- 0.25% vs normoxia, 0.63 +/-0.34%; NS) and MIBI (ischaemia, 1.00 +/- 0.68% vs normoxia, 0.76 +/- 0.32%, NS), whereas tissue concentrations of ATP were more than 4-fold lower in ischaemia than in normoxia (5.1 +/- 3.5 nmol.g vs 22.5 +/- 4.8 nmol.g; P< 0.001). CONCLUSIONS: In contrast to the published results concerning the effects of anoxia on cell cultures, low-flow ischaemia within myocardial tissue has no deleterious effects on the ability of the cells to accumulate Tl and MIBI under steady-state conditions. This gives definitive evidence of the negligible impact of cellular metabolic disorders in the decrease in Tl or MIBI uptake, which is documented by stress-SPECT within low-flow ischaemic myocardium.     

99mTc-HL91 is inferior to 201Tl in scintigraphic detection of chronic myocardial ischaemia

AIM: 99mTc-HL91 is a new hypoxia agent and can identify acutely ischaemic viable myocardium in a canine model using a standard gamma camera. The purpose of the study was to determine whether this tracer could be used to detect regional ischaemia in chronic ischaemic myocardium in a swine model. METHOD: Using a porcine model of chronic myocardial ischaemia, five mini-pigs with proximal left anterior descending artery (LAD) stenoses were studied. Injection of 462.5 MBq (12.5 mCi) 99mTc-HL91 was followed by imaging over 2 h. Coronary angiography and dipyridamole stress-re-injection 201Tl single photon emission computed tomography (SPECT) were performed within 1 day of each other. RESULTS: None of the five pigs demonstrated positive hot 99mTc-HL91 uptake throughout the 2 h imaging, whereas four of the five animals showed significant myocardial ischaemia on 201Tl SPECT. The region of interest analysis of LAD/left circumflex artery count ratios at 1 and 2 h demonstrated similar 99mTc-HL91 uptake and retention in chronic ischaemic as well as non-ischaemic myocardium. CONCLUSION: 99mTc-HL91 is inferior to 201Tl in scintigraphic detection of chronic myocardial ischaemia.     

Kinetic analysis of 99mTc-sestamibi evaluates the protective effects by ischaemic preconditioning on ischaemic myocardium in an isolated rabbit heart

OBJECTIVE: To analyse the kinetic changes of uptake, washout and retention of Tc-sestamibi in order to evaluate the protective effects and possible mechanism of ischaemic preconditioning and adenosine preconditioning on myocardium injured by ischaemia/reperfusion. METHODS: Isolated ischaemia/reperfusion rabbit heart models, as established by Langendorff, were used. Eighteen rabbit hearts perfused in Krebs-Henseleit (KH) buffer were randomly assigned to three groups: ischaemia/reperfusion (I/R, n=6), adenosine preconditioning (AD, n=6), and ischaemic preconditioning (IPC, n=6). Tc-sestamibi (55.5 MBq) in KH was perfused for 40 min and washed out for 40 min. The kinetic changes of Tc-sestamibi within myocardial tissue was monitored during the uptake and washout phases. Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage in coronary effluent, and myocardial infarct size were measured to assess myocardial injuries in rabbit hearts. RESULTS: In the early phases of uptake, there were no significantly different uptake rates of Tc-sestamibi between AD (before 20 min), IPC (before 15 min) and I/R myocardium (all P>0.05). Uptake rates of Tc-sestamibi in myocardium of the three groups all tended to increase, with the uptake time increasing. In the late phases of uptake, AD and IPC were significantly higher than I/R (all P<0.05). In the washout phases, the retention fractions of Tc-sestamibi in myocardium of the three groups all showed a descending tendency with washout time increasing. The retention fractions in AD and IPC were all higher than I/R (all P<0.05). There were no statistical differences in uptake rates and retention fractions of Tc-sestamibi between AD and IPC (all P>0.05). Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage, and myocardial infarct size demonstrated there is lighter injury in AD and IPC myocardium than in I/R (all P<0.05). The retention of Tc-sestamibi and myocardial infarction weight were significantly negatively correlated (r=-0.8384, P<0.001). CONCLUSION: Adenosine preconditioning has similar myocardial protective effects on ischaemia/reperfusion myocardium as does ischaemic preconditioning. Tc-sestamibi may be a sensitive and reliable measure for evaluating the importance and mechanism of ischaemic preconditioning and adenosine preconditioning.     

Influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation in ischaemic heart disease

Exercise rehabilitation improves the clinical status in ischaemic heart disease. The purpose of this study was to assess the influence of exercise rehabilitation on myocardial perfusion and sympathetic heart innervation. Sixteen patients with ischaemic heart disease and previous myocardial infarction were investigated by means of exercise/rest tetrofosmin and metaiodobenzylguanidine (MIBG) exercise/rest single-photon emission tomography (SPET) studies, before and 6 months after starting an exercise rehabilitation programme. Tomograms were divided into 15 segments, and these were grouped into five myocardial anatomical regions. Regional uptake of both tracers was quantified and expressed as a percentage of maximum peak activity. The percentage < or =55% was chosen to evaluate defect size, and the results were expressed as a percentage of left ventricular mass. Areas with perfused and denervated myocardium and areas with ischaemic myocardium were calculated. In addition, regions with <75% of peak activity in the exercise perfusion study at baseline were divided into two groups according to whether there was an increase in peak activity of >10% (representing reversible regional defects) or an increase of <10% (representing fixed regional defects) in the rest study. These percentages were compared with the percentages obtained in the innervation study, and with the percentages obtained in exercise/rest perfusion and innervation studies performed 6 months after starting rehabilitation. Myocardial perfusion defects were significantly smaller than myocardial innervation defects before and 6 months after starting exercise rehabilitation. The area of ischaemia 6 months after starting exercise rehabilitation was significantly smaller than that before rehabilitation (0.31%+/-1.4% vs 1.4%+/-1.6%, P<0.01). The size of innervation defects and the area of perfused and denervated myocardium did not show significant differences between the two studies performed before and 6 months after starting exercise rehabilitation. In reversible regional defects the percentage of peak activity was significantly increased 6 months after starting exercise rehabilitation in exercise and rest studies (P<0.001), while in fixed regional defects it was significantly increased only in exercise studies (P<0.001). There was no significant change in the regional MIBG percentages. We conclude that in ischaemic heart disease, exercise rehabilitation over a period of 6 months improves myocardial perfusion, but does not cause changes in sympathetic myocardial innervation.     

Scintigraphic evaluation of myocardial ischaemia using a new fatty acid analogue: iodine-123-labelled 15-(p-iodophenyl)-9-(R, S)-methylpentadecanoic acid (9MPA).

Iodine-123-labelled 15-(p-iodophenyl)-9-(R,S)-methylpentadecanoic acid (9MPA) is a branched fatty acid analogue for myocardial imaging, which has been recently designed for medium washout rates from the myocardium. The purpose of this study was to assess the clinical feasibility of use of 9MPA for the evaluation of myocardial ischaemia. Twenty-one patients were injected with 9MPA at rest, and sequential single-photon emission tomography (SPET) acquisitions were performed 5, 45 and 240 min after administration to calculate washout rates from the myocardium. The findings of 9MPA images were analysed in comparison with those of perfusion images with thallium-201 or sestamibi, coronary angiography and left venticulography. In general, reduction of 9MPA uptake was more remarkable than that of perfusion tracers. The findings of 9MPA early images correlated better with those of exercise perfusion images than with the rest images. Measured washout rates of 9MPA from ischaemic myocardium were significantly slower than those from normal myocardium. The majority of areas with abnormal 9MPA distribution manifested wall motion abnormality, while all areas with normal tracer distribution presented normal wall motion. The detectability of myocardial ischaemia was improved by adding mid and delayed images in six cases. However, both washout and fill-in patterns were encountered in ischaemic lesions, rendering the interpretation of images difficult. In conclusion, the results of this study indicated that 9MPA has acceptable myocardial uptake, that its use is feasible for the detection of ischaemia and that the abnormal distribution of the tracer correlates well with wall motion abnormality reflecting metabolic disorders.     

Nitrate administration increases blood flow in dysfunctional but viable myocardium, leading to improved assessment of myocardial viability: A PET study.

SPECT with 99mTc-labeled agents is better able to detect viability after nitrate administration. Nitrates induce vasodilation and may increase blood flow to severely hypoperfused but viable myocardium, thereby enhancing tracer delivery and improving the detection of viability. Quantitative data on the changes in blood flow are lacking in SPECT but can be provided by PET. The aim of the present study was to use PET to evaluate whether nitrate administration increases blood flow to chronically dysfunctional but viable myocardium. METHODS: 13N-Ammonia PET was used to quantitatively assess blood flow, and 18F-FDG PET was used as the gold standard to detect viable myocardium. Twenty-five patients with chronic ischemic left ventricular dysfunction underwent 13N-ammonia PET at rest and after nitrate administration. RESULTS: A significant increase in nitrate-enhanced blood flow was observed in viable segments (from 0.55 +/- 0.15 to 0.68 +/- 0.24 mL/min/g, P < 0.05). No statistically significant change in blood flow was observed in nonviable segments (0.60 +/- 0.20 vs. 0.55 +/- 0.18 mL/min/g). A ratio of at least 1.1 for nitrate-enhanced flow to resting flow allowed optimal detection of viable myocardium, yielding a sensitivity of 82% with a specificity of 100%. CONCLUSION: 13N-Ammonia PET showed a significant increase in nitrate-enhanced blood flow in viable myocardium, whereas blood flow remained unchanged after nitrate administration in nonviable myocardium. Nitrate use during myocardial perfusion imaging will lead to improved assessment of myocardial viability.     

Gated single-photon emission tomography imaging protocol to evaluate myocardial stunning after exercise

This study was designed to apply ECG-gating to stress myocardial perfusion single-photon emission tomography (SPET) for the evaluation of myocardial stunning after exercise. Technetium-99m sestamibi was selected as the perfusion agent and a rest/exercise 1-day protocol was employed. Fourteen patients without coronary stenosis and 33 patients with coronary stenosis were enrolled in the study. We carried out three data acquisitions with ECG-gating: a 15-min data acquisition starting 30 min after the rest injection (AC1), a 5-min acquisition starting 5 min after the stress injection (AC2) and a 15-min acquisition starting 20 min after the stress injection (AC3). Calculation of left ventricular ejection fraction (LVEF) values was performed by means of automatic determination of the endocardial surface for all gating intervals in the cardiac cycle. Measured global EF values in 14 patients without coronary stenosis were 52.3% +/- 7.6% (AC1), 60.6% +/- 8.9% (AC2) and 55.6% +/- 5.6% (AC3), and those in 11 patients with severe ischaemia were 53.6% +/- 8.0% (AC1), 45.6% +/- 12.1% (AC2) and 49.7% +/- 10.7%. The magnitude of the depression of post-stress LVEF relative to the rest LVEF correlated with the severity of ischaemia (r = 0.594, P = 0.002), and segments manifesting post-stress functional depression were associated with ischaemic segments showing reversible perfusion defects. Stress myocardial perfusion SPET with ECG-gating is a feasible method for the evaluation of myocardial stunning as well as exercise-induced ischaemia.     

Assessment of the effect of revascularization early after CABG using ECG-gated perfusion single-photon emission tomography

When an arterial graft is used, reversible perfusion defects on single-photon emission tomography (SPET) perfusion images are occasionally observed early after coronary artery bypass graft surgery (CABG), owing to the restricted flow capacity. The purpose of this study was to determine whether the functional information obtained with electrocardiography (ECG)-gated perfusion SPET could be helpful in evaluating the effect of revascularization early after CABG. Twenty-three patients (18 men and 5 women, mean age 65+/-9 years) underwent stress/re-injection thallium-201 ECG-gated SPET before and 4 weeks after CABG (13 with exercise and 10 with dipyridamole). Patency of all grafts was confirmed by coronary angiography 1 month after CABG. Cardiac functional data including the left ventricular ejection fraction (LVEF) and the transient ischaemic dilatation (TID) ratio were analysed using a commercially available automated program. The conventional stress and re-injection tomograms were interpreted by means of a five-point scoring system in a nine-segment model. Stress-induced reversible 201Tl perfusion defects were present in 64% of the myocardial segments bypassed by patent arterial grafts, in contrast to 42% of the myocardial segments bypassed by patent venous grafts (chi2=7.8, P=0.005). Of the 23 patients, 12 showed improvement in summed ischaemic scores (group 1), while 11 had no change or deterioration (group 2), although all grafts were patent on postoperative catheterization. The TID ratio improved in both group 1 and group 2 before and after CABG (1.14+/-0.13 vs 0.99+/-0.07, P=0.001 and 1.09+/-0.07 vs 0.94+/-0.05, P=0.002, respectively). However, LVEF did not significantly improve in group 1 or group 2 after CABG (42.5%+/-9.9% vs 47.5%+/-11.8%, and 52.1%+/-7.5% vs 53.1%+/-5.9%, respectively). Perfusion imaging or LVEF assessment is of limited value early after CABG. The TID ratio obtained with ECG-gated perfusion SPET may be a useful marker to evaluate the effect of revascularization early after surgery.     

Prediction of improvement in global left ventricular function in patients with chronic coronary artery disease and impaired left ventricular function: rest thallium-201 SPET versus low-dose dobutamine echocardiography

Accurate assessment of myocardial viability permits selection of patients who would benefit from myocardial revascularization. Currently, rest-redistribution thallium-201 scintigraphy and low-dose dobutamine echocardiography are among the most used techniques for the identification of viable myocardium. Thirty-one consecutive patients (all men, mean age 60 +/- 8 years) with chronic coronary artery disease and reduced left ventricular ejection fraction (31% +/- 7%) were studied. Rest 201Tl single-photon emission tomography (SPET), low-dose dobutamine echocardiography and radionuclide angiography were performed before revascularization. Radionuclide angiography and echocardiography were repeated after revascularization. An a/dyskinetic segment was considered viable on 201Tl SPET when tracer uptake was >65%, while improvement on low-dose dobutamine echocardiography was considered a marker of viability. Increase in global ejection fraction was considered significant at > or = 5%. In identifying viable segments, rest 201Tl SPET showed higher sensitivity than low-dose dobutamine echocardiography (72% vs 53%, P<0.05), while specificity was not significantly different (86% vs 88%). In 17 patients, global ejection fraction increased > or = 5% (group 1) while in 14 it did not (group 2). A higher number of a/dyskinetic segments were viable on 201Tl SPET in group 1 than in group 2 (2.6 +/- 1.9 vs 0.6 +/- 1.2, P < 0.005), while no significant differences were observed on low-dose dobutamine echocardiography (1.7 +/- 1.6 vs 1.1 +/- 1.6). A significant correlation was found between the number of a/dyskinetic segments viable on 201Tl SPET and post-revascularization changes in ejection fraction (r = 0.52, P < 0.05), but such a correlation was not observed for low-dose dobutamine echocardiography. Using as the cut-off the presence of at least one viable a/dyskinetic segment, rest 201Tl SPET had a higher sensitivity (82% vs 53%, P = 0.07) and showed a trend towards higher accuracy and specificity (77% vs 58%, and 71% vs 64%, respectively) as compared with low-dose dobutamine echocardiography. In conclusion, these findings suggest that when severely reduced global function is present, rest 201Tl SPET evaluation of viability is more accurate than low-dose dobutamine echocardiography for the identification of patients who will benefit most from revascularization.     

Effects of low-dose dobutamine on left ventricular function in normal subjects as assessed by gated single-photon emission tomography myocardial perfusion studies.

Electrocardiography gated single-photon emission tomography (gated SPET) allows the assessment of regional perfusion and function simultaneously and in full spatial congruency. In this study changes in global and regional left ventricular function in response to dobutamine infusion were assessed in ten healthy volunteers using sequential gated SPET myocardial perfusion acquisitions. Four consecutive gated SPET images were recorded 60 min after injection of 925 MBq technetium-99m tetrofosmin on a three-head camera equipped with focussing collimators. Two acquisitions were made at rest (baseline 1 and 2), and the third and fourth acquisitions were started 5 min after the beginning of the infusion of 5 and 10 microg kg(-1) min(-1) dobutamine, respectively. Systolic wall thickening (WT) was quantified using a method based on circumferential profile analysis. Left ventricular ejection fraction (LVEF) and volumes were calculated automatically using the Cedars-Sinai program. Nine of the ten subjects presented a definite increase in WT during dobutamine infusion. WT increased on average from 46%+/-14% at baseline to 71%+/-23% (range: 37%-106%; P<0.05) during 5 microg kg(-1) min(-1) dobutamine infusion and to 85%+/-25% (range: 62%-123%; P<0.05 with respect to WT at 5 microg kg(-1) min(-1)) during 10 microg kg(-1) min(-1) dobutamine infusion. Apical segments showed the largest WT at baseline. The average WT response to dobutamine was similar for all parts of the myocardium. It is concluded that changes in WT induced by infusion of low-dose dobutamine can be assessed by sequential gated SPET myocardial perfusion studies. The "stress gated SPET" protocol proposed in this study might be helpful to distinguish viable from scar tissue in patients with coronary artery disease, by demonstrating a preserved inotropic response in hypoperfused myocardium.