Annexin-V imaging for noninvasive detection of cardiac allograft rejection.

Heart transplant rejection is characterized pathologically by myocyte necrosis and apoptosis associated with interstitial mononuclear cell infiltration. Any one of these components can be targeted for noninvasive detection of transplant rejection. During apoptotic cell death, phosphatidylserine, a phospholipid that is normally confined to the inner leaflet of cell membrane bilayer, gets exteriorized. Technetium-99m-labeled annexin-V, an endogenous protein that has high affinity for binding to phosphatidylserine, has been administered intravenously for noninvasive identification of apoptotic cell death. In the present study of 18 cardiac allograft recipients, 13 patients had negative and five had positive myocardial uptake of annexin. These latter five demonstrated at least moderate transplant rejection and caspase-3 staining, suggesting apoptosis in their biopsy specimens. This study reveals the clinical feasibility and safety of annexin-V imaging for noninvasive detection of transplant rejection by targeting cell membrane phospholipid alterations that are commonly associated with the process of apoptosis.

Myocardial kinetics of thallium-201 after dipyridamole infusion in normal canine myocardium and in myocardium distal to a stenosis.

The purpose of the present study was to define myocardial and blood thallium-201 (Tl-201) kinetics after infusion of dipyridamole in normal canine myocardium and in myocardium distal to a coronary artery stenosis. Miniature radiation detector probes were implanted in the left ventricle in 39 open-chest dogs. A balloon constrictor was placed around the proximal left circumflex coronary artery. Electromagnetic flow probes were positioned proximally around both the left circumflex and left anterior descending coronary arteries. In five control dogs (group 1) the balloon occluder was not inflated; in 12 dogs (group 2) a mild stenosis was created such that resting flow was not reduced, yet the hyperemic response after 10 s of total occlusion was partially attenuated; in nine dogs (group 3) a moderate stenosis was created such that resting flow was not reduced, yet the hyperemic response was completely eliminated; and in 13 dogs (group 4) a severe stenosis was created such that resting flow was reduced. After intravenous dipyridamole (0.08 mg/kg . min-1 x 4 min), 1.5 mCi Tl-201 was injected intravenously and probe counts were collected continuously for 4 h. The mean 4-h fractional myocardial Tl-201 clearance for nonstenotic zones was 0.35, 0.27 for group 2 stenotic zones, 0.19 for group 3 stenotic zones, and 0.05 for group 4 stenotic zones (P less than 0.0001). After reaching peak activity, myocardial Tl-201 activity cleared biexponentially with a final decay constant lambda 2 = 0.0017 +/- 0.0001 min-1 (SE) for nonstenotic zones, 0.0011 +/- 0.0001 min-1 for group 2 stenotic zones, and 0.0006 +/- 0.0001 min-1 for group 3 stenotic zones (P less than 0.01). Group 4 stenotic zone Tl-201 clearances were negligible (decay constant essentially zero). Blood Tl-201 activity decayed triexponentially with a final blood lambda 3 = 0.0018 +/- 0.0001 min-1, which was almost identical to the final myocardial lambda 2 decay constant. Thus, the rate of myocardial Tl-201 clearance can distinguish between coronary stenoses of graded hemodynamic severity. These results may be applicable to quantitative techniques for determining myocardial Tl-201 clearance rates on serial clinical images after dipyridamole administration.

Thallium reinjection versus standard stress/delay redistribution imaging for prediction of cardiac events.

OBJECTIVES: The purpose of this study was to compare thallium reinjection with standard stress/delay redistribution for the prediction of cardiac events. BACKGROUND: Although thallium reinjection enhances the detection of viable myocardium, its contribution to prognosis over stress/delay redistribution in a general referral population has not been clearly evaluated. METHODS: This retrospective analysis included 366 consecutive patients with coronary artery disease who underwent stress/delay redistribution imaging and thallium reinjection scintigraphy, with a mean follow-up of 33+/-12 months. RESULTS: Cardiac events occurred in 48 patients (40 deaths, 8 myocardial infarctions). Of the 366 original patients, 159 demonstrated ischemia by stress/delay redistribution, 107 showed ischemia by reinjection only, and 100 showed infarction only. Cardiac events occurred in 20 patients (12.6%) with stress/delay redistribution, 13 patients (12%) with ischemia detected by thallium reinjection only and 15 patients (15%) with infarction only. The size of the reversible thallium defect by either stress/delay redistribution imaging or reinjection scintigraphy did not predict cardiac events. Independent predictors of cardiac events included left ventricular cavity size, the size of the abnormal perfusion defect and patient age. CONCLUSIONS: Thallium reinjection does not contribute independent prognostic utility for cardiac events when compared with stress/delay redistribution. Left ventricular dilation and the size of the post-stress defect were predictors of cardiac events.

Prognostic value of dipyridamole thallium scintigraphy for evaluation of ischemic heart disease.

Exercise testing alone or in combination with thallium scintigraphy has significant prognostic value. In contrast, dipyridamole thallium imaging is not dependent on patients achieving adequate levels of exercise, but no long-term prognostic studies have been reported. Accordingly, imaging results of 516 consecutive patients referred for dipyridamole thallium studies were correlated with subsequent cardiac events, death (n = 23) and myocardial infarction (n = 43) over a mean follow-up period of 21 months. Patients with a history of congestive heart failure, prior myocardial infarction, diabetes mellitus or abnormal scans were significantly more likely to have a cardiac event (p less than 0.03). With use of logistic regression analysis, an abnormal scan was an independent and significant predictor of subsequent myocardial infarction or cardiac death and increased the relative risk of any event more than threefold. The presence of redistribution on thallium scanning further increased the risk of a cardiac event. Survival analysis demonstrated a significant difference between patients with an abnormal or normal thallium scan over a 30 month period. In conclusion, dipyridamole thallium scintigraphy demonstrates prognostic value in a large unselected population and may be an adequate clinical alternative to physiologic exercise testing in the evaluation of coronary heart disease.

Diagnostic value of a new myocardial perfusion agent, teboroxime (SO 30,217), utilizing a rapid planar imaging protocol: preliminary results.

Technetium-99m-labeled agents have advantages over thallium-201 in terms of photon statistics, cost and clinical availability. They have been suggested as an alternative to thallium for myocardial perfusion imaging. Teboroxime is a new boronic acid adduct of technetium dioxime (BATO) compound that demonstrates favorable characteristics in preliminary studies. With use of a novel (seated) patient positioning technique and a rapid dynamic acquisition protocol, 30 patients underwent planar imaging with teboroxoime while at rest and after maximal treadmill exercise. Postexercise scans were completed in an average time (mean +/- SD) of 4.4 +/- 1.6 min, with 4.8 +/- 1.5 min for the views at rest. These results were compared with coronary arteriography or thallium scintigraphy after treadmill exercise, or both. Diagnostic agreement (abnormal versus normal) was present in 28 of the 30 patients (p less than 0.001). Regarding physiologic assessment as compared with thallium scintigraphy, the finding of infarction and ischemia was concordant in 89% and 86% of patients, respectively. This report describes the initial use of teboroxime with a rapid dynamic planar imaging technique, resulting in a high correlation with exercise thallium scintigraphy. Delayed postexercise images obtained 5 to 10 min after exercise demonstrated rapid disappearance of exercise-induced defects noted on the initial (0 to 5 min) postexercise views. The rapid differential washout with teboroxime has not been previously described and the possible clinical significance is discussed.

Noninvasive evaluation of cardiac risk before elective vascular surgery.

The prognostic utility for predicting cardiac events was determined for dipyridamole-thallium scintigraphy, exercise stress testing (when possible; n = 69) and multiple clinical variables in 100 consecutive patients admitted for elective surgical repair of peripheral vascular disease. After initial noninvasive evaluation, 11 patients were referred for coronary angiography and the remaining 89 patients had surgery without further cardiac studies. Fifteen patients (17%) had a postoperative myocardial infarction, one of which was fatal. Of these 15 patients, 14 had thallium redistribution and 3 had positive ST segment depression during stress testing. Among the many variables tested, the presence of redistribution on serial dipyridamole-thallium images was the most significant predictor of serious cardiac events. All 11 patients who had coronary angiography had both redistribution and multivessel coronary artery disease. Four of these 11 patients died during follow-up and 6 had coronary artery bypass surgery. It is concluded that dipyridamole-thallium imaging has significant prognostic utility in predicting postoperative myocardial infarction and death in patients with severe peripheral vascular disease, and is superior to exercise testing or clinical variables in determining cardiac risk. The odds for a serious cardiac event were 23 times greater in a patient with thallium redistribution than in a patient without redistribution, strongly suggesting that myocardial imaging may be used as a primary screening test before elective vascular surgery.

Sequential teboroxime imaging during and after balloon occlusion of a coronary artery.

OBJECTIVES: We sought to assess whether sequential teboroxime imaging can rapidly evaluate vessel patency and identify the coronary artery occluded in patients undergoing balloon occlusion of a coronary artery. BACKGROUND: Intravenous thrombolytic therapy results in successful reperfusion of the infarct-related artery in only 50% to 80% of cases. A noninvasive technique to serially evaluate coronary perfusion would identify patients who might benefit from other interventions such as emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or increased intensity of thrombolytic therapy. METHODS: Teboroxime scans were performed during balloon occlusion in 15 nonconsecutive patients undergoing angioplasty of a major coronary artery. Equivalent views were repeated after successful angioplasty. RESULTS: The mean time between balloon occlusion and reperfusion imaging was 1.6 +/- 0.6 h. The mean number of defects decreased significantly from 4.13 +/- 1.01 during balloon occlusion to 0.27 +/- 0.44 after reperfusion (p = 0.0006). There was a 30% decrease in the defect/normal zone count/pixel ratios during balloon occlusion and normalization of these ratios after reperfusion (p = 0.0006). The scans correctly identified all nine left anterior descending coronary artery occlusions and both right coronary artery occlusions. One of the four left circumflex coronary artery occlusions was incorrectly identified as a right coronary artery occlusion by scan criteria. Overall, the scans correctly identified the occluded artery 93% of the time (kappa = 0.88). The scan was 100% accurate for distinguishing occlusion of the left anterior descending coronary artery (n = 9) from occlusions of the left circumflex or right coronary artery (n = 6). CONCLUSIONS: We believe that this is the first clinical study to demonstrate that sequential planar imaging with teboroxime can 1) rapidly detect acute coronary artery occlusion and reperfusion, and 2) identify the occluded coronary artery. A trial comparing rapid sequential teboroxime imaging with coronary angiography in patients receiving thrombolytic therapy for acute myocardial infarction is warranted.

Development and validation of a Bayesian model for perioperative cardiac risk assessment in a cohort of 1,081 vascular surgical candidates.

OBJECTIVES: This study sought to develop and validate a Bayesian risk prediction model for vascular surgery candidates. BACKGROUND: Patients who require surgical treatment of peripheral vascular disease are at increased risk of perioperative cardiac morbidity and mortality. Existing prediction models tend to underestimate risk in vascular surgery candidates. METHODS: The cohort comprised 1,081 consecutive vascular surgery candidates at five medical centers. Of these, 567 patients from two centers ("training" set) were used to develop the model, and 514 patients from three centers were used to validate it ("validation" set). Risk scores were developed using logistic regression for clinical variables: advanced age (>70 years), angina, history of myocardial infarction, diabetes mellitus, history of congestive heart failure and prior coronary revascularization. A second model was developed from dipyridamole-thallium predictors of myocardial infarction (i.e., fixed and reversible myocardial defects and ST changes). Model performance was assessed by comparing observed event rates with risk estimates and by performing receiver-operating characteristic curve (ROC) analysis. RESULTS: The postoperative cardiac event rate was 8% for both sets. Prognostic accuracy (i.e., ROC area) was 74 +/- 3% (mean +/- SD) for the clinical and 81 +/- 3% for the clinical and dipyridamole-thallium models. Among the validation sets, areas were 74 +/- 9%, 72 +/- 7% and 76 +/- 5% for each center. Observed and estimated rates were comparable for both sets. By the clinical model, the observed rates were 3%, 8% and 18% for patients classified as low, moderate and high risk by clinical factors (p<0.0001). The addition of dipyridamole-thallium data reclassified >80% of the moderate risk patients into low (3%) and high (19%) risk categories (p<0.0001) but provided no stratification for patients classified as low or high risk according to the clinical model. CONCLUSIONS: Simple clinical markers, weighted according to prognostic impact, will reliably stratify risk in vascular surgery candidates referred for dipyridamole-thallium testing, thus obviating the need for the more expensive testing. Our prediction model retains its prognostic accuracy when applied to the validation sets and can reliably estimate risk in this group.

Design and baseline characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. VANQWISH Trial Research Investigators.

OBJECTIVES: The Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial was designed to compare outcomes of patients with a non-Q wave myocardial infarction (NQMI) who were randomized prospectively to an early "invasive" strategy versus an early "conservative" strategy. The primary objective was to compare early and late outcomes between the two strategies using a combined trial end point (all-cause mortality or nonfatal infarction) during at least 1 year of follow-up. BACKGROUND: Because of the widely held view that survivors of NQMI are at high risk for subsequent cardiac events, management of these patients has become more aggressive during the last decade. There is a paucity of data from controlled trials to support such an approach, however. METHODS: Appropriate patients with a new NQMI were randomized to an early "invasive" strategy (routine coronary angiography followed by myocardial revascularization, if feasible) versus an early "conservative" strategy (noninvasive, predischarge stress testing with planar thallium scintigraphy and radionuclide ventriculography), where the use of coronary angiography and myocardial revascularization was guided by the development of ischemia (clinical course or results of noninvasive tests, or both). RESULTS: A total of 920 patients were randomized (mean follow-up 23 months, range 12 to 44). The mean patient age was 61 +/- 10 years; 97% were male; 38% had ST segment depression at study entry; 30% had an anterior NQMI; 54% were hypertensive; 26% had diabetes requiring insulin; 43% were current smokers; 43% had a previous acute myocardial infarction; and 45% had antecedent angina within 3 weeks of the index NQMI. CONCLUSIONS: Baseline characteristics were compatible with a moderate to high risk group of patients with an NQMI.

Effect of hyperaemia on thallium-201 redistribution in normal canine myocardium.

The specific effect of hyperaemia on thallium redistribution is not known. Therefore we evaluated the effect of initial (group A) and delayed (group B) hyperaemia on thallium kinetics in normal canine myocardium. In group A dogs (n = 14) adenosine was infused into the left circumflex artery (LCx) prior to thallium injection and was continued for either 5, 30 or 120 min after thallium administration. In group B dogs (n = 10) LCx adenosine was begun 10 min post thallium injection and continued for 2 h. Radioactive microspheres were injected simultaneously with thallium and just prior to death in all but the 5 min experiments. The region of the left anterior descending artery (LAD) served as a normal control for each heart. The mean LCx/LAD flow ratio in all group A hearts was 3.81 +/- 1.24 (SD) and the final thallium LCx/LAD ratios averaged 2.29 +/- 0.26, 1.52 +/- 0.27 and 0.93 +/- 0.16 at 5, 30 and 120 min respectively, which represents a significant redistribution of thallium (p less than 0.05). In group B hearts, the mean LCx/LAD flow ratio was 1.06 +/- 0.07 during thallium injection and after LCx adenosine infusion the flow ratio rose to 2.91 +/- 0.75 (p less than 0.001). This resulted in a final thallium LCx/LAD ratio of 0.96 +/- 0.07 which was significantly less than the initial microsphere determined flow ratio (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial uptake of thallium and rubidium during alterations in perfusion and oxygenation in isolated rabbit hearts.

The comparative effects of altered cellular function and coronary perfusion on myocardial 201Tl and 83Rb uptake were evaluated in three groups of isolated rabbit hearts having isovolumic contractions. Paired-indication dilution experiments were performed with 201Tl, 83Rb, and 111In-labeled albumin as an intravascular reference marker. In Group A hearts (n = 12), isotope transport was determined during control, hypoxia, and ischemia. In Group B hearts (n = 8), isotope transport was measured at control flow and again at a 50% and 80% reduction. In Group C hearts (n = 8) only 201Tl uptake was determined at control and following coronary reperfusion. Myocardial 201Tl and 83Rb transport were not significantly different and were proportional to flow. Although all interventions caused significant hemodynamic alterations, neither tracer was affected by hypoxia at constant flow. Thallium-201 permeation, however, was transiently decreased immediately after coronary reperfusion. We conclude that myocardial uptake of 201Tl and 83Rb are similar and directly related to flow, but do not reflect hypoxia induced cellular dysfunction.

Dipyridamole-thallium imaging: the lazy man's stress test.

Dipyridamole-thallium imaging is a relatively safe and accurate method to evaluate myocardial perfusion and "stress." It is independent of patient motivation, exercise capacity and antianginal medications. Overall it detects coronary artery disease as well as exercise thallium and has already shown utility in prognostic determinations. The continued use of this test on a wide scale appears warranted and additional large scale experience needs to be critically evaluated.

Dipyridamole myocardial perfusion imaging.

Dipyridamole is a pharmacologic stressor used in place of exercise for myocardial perfusion imaging in patients who cannot exercise due to various physical limitations. Perfusion studies with dipyridamole can identify coronary artery disease (CAD) as accurately as maximal exercise stress testing. In addition, dipyridamole myocardial perfusion studies are useful to stratify patients according to risk of subsequent cardiac events. As dipyridamole is infused, it blocks the reabsorption and metabolism of adenosine normally produced in the body, producing the desired effect on the heart, coronary hyperemia. Dipyridamole can be used with 201Tl and 99mTc myocardial perfusion tracers, for either planar or SPECT imaging, in patients who cannot exercise or who can only exercise at submaximal levels.

Comparison of hypoxia and ouabain effects on the myocardial uptake kinetics of technetium-99m hexakis 2-methoxyisobutyl isonitrile and thallium-201.

Effects of hypoxia and ouabain on transcapillary exchange of [99mTc]hexakis (2-methoxyisobutylisonitrile) [SESTAMIBI, also known as MIBI or HEXAMIBI] and 201TI were investigated with indicator-dilution studies using isolated rabbit hearts. Peak myocardial extraction (Emax), permeability-surface area products (PScap), and net myocardial extraction (Enet) were compared among serial injections during constant coronary flows. Overall, measures of transcapillary transport (Emax and PScap) for SESTAMIBI were significantly lower (p less than 0.001) than those simultaneously determined for thallium, but estimates of tissue retention (Enet) for SESTAMIBI and thallium were not statistically distinguishable. Hypoxia had no significant effect on mean (+/- s.d.) Emax for SESTAMIBI (0.31 +/- 0.13) or thallium (0.59 +/- 0.11), nor on mean PScap or Enet values. Ouabain (1.5 X 10(-7) M and 1.5 X 10(-6) M) had no effect on SESTAMIBI or thallium Emax (respectively, 0.29 +/- 0.08 and 0.60 +/- 0.05) or on PScap for SESTAMIBI. Thallium PScap was depressed with higher ouabain dose (control, 1.22 +/- 0.40; high ouabain, 1.06 +/- 0.41 ml/min/g; p less than 0.01). Ouabain also caused a significant and progressive increase in average SESTAMIBI Enet (control, 0.23 +/- 0.10 to high ouabain, 0.33 +/- 0.12; p less than 0.05), but depressed thallium Enet (control, 0.38 +/- 0.14 to high ouabain, 0.32 +/- 0.18; p less than 0.01). These results suggest myocardial metabolic and/or functional status have minor influence on transcapillary transport of SESTAMIBI and thallium, but significantly affects cellular retention.

Comparative myocardial extraction of two technetium-labeled BATO derivatives (SQ30217, SQ32014) and thallium.

The transcapillary exchange of a new class of 99mTc-labeled compounds (BATO) were compared to 201Tl in isolated, blood perfused rabbit hearts. During variable blood flow (0.15-2.44 ml/min/g), peak and net extraction (Emax and Enet, respectively), and capillary permeability-surface area product (PScap) were determined with paired indicator-dilution techniques. Serial bolus injections of 201Tl, [111In]albumin, and [99mTc]BATO; chloro[tris(cyclohexanedionedioxime)methyl boronic acid]Tc (SQ30217, n = 8) and a hydroxy-substituted derivative (SQ32014, n = 5) were given to a total of 13 hearts. Mean (+/- s.d.) SQ30217 Emax and Enet were 0.72 +/- 0.09 and 0.55 +/- 0.18, respectively, which were higher than thallium values of 0.57 +/- 0.10 and 0.46 +/- 0.17 (p less than 0.03). Mean SQ30217 PScap was 1.1 +/- 0.4 ml/min/g and was also higher than corresponding thallium determinations (0.7 +/- 0.3; p less than 0.001). SQ32014 Emax, Enet, and PScap were all significantly less than thallium values (p less than 0.001). Thallium and SQ30217 values for Emax and PScap were closely correlated with blood flow (r greater than or equal to 0.73), whereas those for SQ32014 were weakly correlated (r = 0.09). A small clinical pilot study (n = 3) was performed, which showed that SQ32014 was a poor myocardial perfusion agent in man. In summary, transcapillary exchange of SQ30217 is greater than thallium, which in turn, is greater than SQ32014. Therefore, SQ30217 appears to have good clinical potential, but SQ32014 does not.

Direct detection of regional myocardial ischemia with technetium-99m nitroimidazole in rabbits.

UNLABELLED: Conventional perfusion scintigraphy assesses disparities in regional myocardial blood flow but does not directly detect hypoxic tissue. Nitroimidazoles labeled with positron-emitting radionuclides have recently shown promise as direct markers of myocardial hypoxia. This study evaluates a new 99mTc-labeled nitroimidazole of potential benefit in standard myocardial scintigraphy. METHODS: Technetium-99m-labeled nitroimidazole was administered to rabbits during the early reperfusion phase after 10 min (Group 1) or 60 (Group 2) min of coronary occlusion or after 10 min of a fixed coronary occlusion (Group 3). Tracer retention at 1 hr was assessed in relation to microsphere-determined blood flow during coronary occlusion and at tracer injection. The pattern of nitroimidazole retention on autoradiographs was then compared with the pattern of myocardial hypoperfusion defined by fluorescein photography to precisely define tracer localization. RESULTS: The retention of nitroimidazole in Group 1 rabbits (brief occlusion) was independent of both occlusion and reperfusion blood flow and was uniformly distributed on the autoradiographs. In contrast, nitroimidazole retention in Groups 2 and 3 increased with the severity of hypoperfusion during the occlusion phase and precisely delineated the ischemic zone on all autoradiographs. CONCLUSION: This 99mTc-labeled hypoxia-avid tracer delineates severe ischemia even after blood flow to the compromised myocardium has been restored. This class of compounds can potentially enhance the physiological assessment of patients with ischemic heart disease.

Teboroxime, sestamibi and thallium-201 as markers of myocardial hypoperfusion: comparison by quantitative dual-isotope autoradiography in rabbits.

The scintigraphic assessment of myocardial hypoperfusion depends on the ability of imaging agents to delineate flow disparities. Accordingly, we compared the differential uptake of teboroxime, sestamibi and 201Tl in normal and hypoperfused myocardium using quantitative dual isotope autoradiography. Rabbits with acute coronary occlusions (n = 29) received dual isotope injections of teboroxime 201Tl or sestamibi 201Tl or single isotope tracer injections. A group of sham-operated controls (n = 15) received teboroxime and/or 201Tl. Multiple 30-mu short axis slices were collected from each heart and mounted on x-ray film along with tissue standards to independently generate separate 99mTc and 201Tl autoradiographs. Teboroxime and sestamibi produced greater normal-to-defect activity contrast than 201Tl in each dual isotope heart (range 8.4-48.9 [teboroxime] versus 2.6-12.3 [201Tl], p < 0.02 and 4.5-10.4 [sestamibi] versus 3.6-7.3 [201Tl], p < 0.03). Similar profiles were obtained in the single isotope hearts. Teboroxime produced larger autoradiographic defects than 201Tl in the dual-isotope hearts [16.0% +/- 5.6% (teboroxime) versus 12.9% +/- 5.3% (201Tl) of the LV, p < 0.02]. We conclude that the 99mTc-based perfusion agents teboroxime and, to a lesser extent, sestamibi, delineate hypoperfused myocardium more clearly than 201Tl. Teboroxime detects the largest area of hypoperfusion and may provide the most accurate assessment of myocardium at risk.

Myocardial uptake of indium-111-labeled antimyosin in acute subendocardial infarction: clinical, histochemical, and autoradiographic correlation of myocardial necrosis.

Indium-111-labeled antimyosin has been utilized in the diagnosis and localization of acute transmural myocardial infarction. The present report describes a patient who presented with a massive subendocardial infarction. Two days after the injection of antimyosin, the patient's clinical status markedly deteriorated and he expired. Postmortem examination demonstrated severe three-vessel coronary artery disease with extensive myocyte death in the endocardium. Autoradiography and histochemical staining of the prosected heart demonstrated high correlation for myocardial necrosis and corresponded to clinical evidence for diffuse subendocardial infarction.

Comparison of iodine-125-BMIPP and thallium-201 in myocardial hypoperfusion.

UNLABELLED: Radiolabeled fatty acids such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) have unique metabolic properties of potential use as myocardial perfusion tracers. Accordingly, we compared the in vivo pattern of uptake of BMIPP and 201Tl in hypoperfused rabbit myocardium. METHODS: Animals were intubated, ventilated and their arterial pressures monitored. A left thoracotomy was performed. After ligation of a major branch of the circumflex artery, an intravenous injection of BMIPP or BMIPP/201TI was given. Radiolabeled microspheres were used to document the area of risk. After the circulation period, the animals were killed. Tracer deposition within the hearts was determined by either dual-tracer autoradiography (Protocol I) or by segmental tissue analysis (Protocol II). RESULTS: Dual-tracer autoradiographic activity profiles for BMIPP were comparable to those of 201TI. Moreover, the two tracers yielded similar values for normal-to-defect contrast and defect size. The myocardial activity concentration of BMIPP for both protocols correlated strongly with coronary blood flow and compared favorably with 201TI. CONCLUSION: BMIPP and 201TI accurately delineate areas of hypoperfusion distal to a coronary occlusion. Therefore, differences in the myocardial distribution of BMIPP and 201TI in clinical studies may be related to cellular fatty acid metabolism.

Effect of triphenyl tetrazolium chloride staining on the distribution of radiolabeled pharmaceuticals.

Myocardial tissue is routinely exposed to the vital stain triphenyl tetrazolium chloride (TTC) to delineate infarction in conjunction with myocardial isotope research. However, it is unknown whether TTC has a direct effect on tracer deposition. We evaluated this possibility in rabbit hearts injected with either teboroxime, sestamibi or 201Tl. The hearts were excised and treated as follows: (1) TTC or normal saline was perfused through the heart and the residual activity monitored; (2) hearts were sliced into 0.5-cm thick sections, counted and incubated in either TTC or normal saline for 10 min then recounted; and (3) the circumflex artery was ligated postmortem and TTC perfused. Autoradiographic images were produced from 30-microns slices to depict any disparity in activity concentration from the selective perfusion of TTC. Both perfusion and incubation by TTC resulted in a significant activity loss of both 201Tl and sestamibi, but not teboroxime, compared to normal saline. An independent octanol extraction experiment measured the change in the partition coefficient of labeled teboroxime and sestamibi induced by the addition of TTC. TTC was shown to liberate the radiolabel from sestamibi, but not from teboroxime. We conclude that histochemical staining techniques involving TTC can alter the distribution of radiolabeled pharmaceuticals. As a result, experiments using TTC with 201Tl and sestamibi should be interpreted cautiously.