Technetium-99m Pyrophosphate Research Articles

Rate of reperfusion blood flow modulates reperfusion injury in skeletal muscle

The mechanisms of ischemia-reperfusion (I-R) injury in skeletal muscle remain controversial. We investigated the effect of the rate of reperfusion blood flow on I-R injury in an isolated in vivo canine gracilis muscle model in six anesthetized dogs. In all animals, both gracilis muscles were subjected to 6 hr of ischemia followed by 1 hr of reperfusion. During reperfusion, one gracilis artery was partially occluded to limit the rate of reperfusion blood flow to its preischemic rate (limited reperfusion, LR), while the contralateral artery was allowed to perfuse freely at a normal rate (normal reperfusion, NR). Muscle injury was quantified by histochemical staining (triphenyltetrazolium chloride, TTC) with computerized planimetry of the infarct size, and by spectrophotometric determination of technetium-99m pyrophosphate uptake. Endothelial permeability was quantified by measurement of gracilis muscle weight gain and 125I-albumin radioactivity after intravenous injection. Results are presented as the means ±SEM, and differences are considered to be statistically significant if P < 0.05 by Student's t test for paired data. LR resulted in significantly less blood flow (9.7 ± 1.7 cc/min/100 g) when compared to NR (55.7 ± 11.6 cc/min/100 g). I-R injury was significantly reduced by LR as evidenced by a decrease in TTC infarct size from 41 ± 7% to 11 ± 5%, and a decrease in technetium-99m pyrophosphate uptake from 512 ± 20 to 163 ± 44 × 10 3 counts/min/g. LR also significantly decreased the postreperfusion edema formation as evidenced by a reduction in the muscle weight gain from 27 ± 6 to 9 ± 1 g, and a reduction in the 125I-albumin radioactivity from 45 ± 14 to 32 ± 8 counts/min/g. These data suggest that the hyperemic rate of reperfusion blood flow is a significant factor in the pathophysiology of postreperfusion edema and that clinical control of reperfusion injury in skeletal muscle may be achieved by limiting the rate of reperfusion blood flow.

Muscle necrosis in the extremities: evaluation with Tc-99m pyrophosphate scanning--a retrospective review.

A retrospective review was done of 34 extremities studied between 1981 and 1985 with technetium-99m pyrophosphate scanning; 22 were subsequently amputated. Results of detailed pathologic examination or immediate postoperative examination of the resected extremity were available in 16 cases. In these cases, scanning had allowed correct prediction of the level of amputation and of the specific areas of muscle infarction in 13 cases. In the one case in which amputation was performed for infection rather than muscle necrosis, the lack of necrosis was correctly predicted with the scan. The limited results of this study indicate that the Tc-99m pyrophosphate scan allows the location of necrotic muscle to be predicted accurately and may therefore be a useful adjunct in determining the best level for ultimate amputation. Special caution is required in those cases in which muscle necrosis is due to acute causes (e.g., traumatic thrombosis) rather than chronic vascular disease.

Experimental hemarthrosis in dogs: progressive synovitis monitored with technetium-99m pyrophosphate joint imaging.

We examined the time course of the development of hemorrhagic synovitis in response to repeated autologous blood injections into knee joints in mature dogs and the possible usefulness of joint imaging with technetium-99m pyrophosphate (Tc99m-PYP) in monitoring the early response of synovium to blood. Experimental hemarthrosis was induced in dogs by twice weekly injection of autologous blood into the knee joints. Sequential examination of the synovium at monthly intervals over a period of 12 weeks revealed early inflammatory cell infiltration and capillary neovascularization with eventual replacement of the normal fatty synovium by dense fibrous tissue. Serial Tc99m-PYP joint images demonstrated a progressive increase in isotope accumulation in the knees during the course of the study. Further isotope accumulation was observed after CO2 laser synovectomy. During the 24-week course of the entire study, no changes in joint cartilage or bone were observed by gross inspection or radiologic and light-microscopic examination. The findings indicate that the progressive proliferative, inflammatory, fibrotic changes in joint synovium associated with experimental hemarthrosis in dogs may be noninvasively and semiquantitatively assessed with the use of Tc99m-PYP scintigraphy. Evidence is also presented that the intensity of Tc99m-PYP joint accumulation (immediate static images) may not readily reflect synovial vascularity or synovial tissue mass.

Usefulness of early positive technetium-99m stannous pyrophosphate scan in predicting reperfusion after thrombolytic therapy for acute myocardial infarction

To test the hypothesis that scans with technetium-99m pyrophosphate (Tc-99m-PPi) are positive when performed early after successful thrombolytic therapy for acute myocardial infarction (AMI), 16 consecutive patients with AMI who received thrombolytic therapy within 5 hours after the onset of chest pain were studied. Patients were included if chest pain lasted for >30 minutes, was unresponsive to sublingual nitroglycerin and was associated with at least 0.2 mV ST-segment elevation in at least 2 contiguous electrocardiographic leads. All patients received 1.5 million IU of streptokinase intravenously, a mean of 195 ± 99 minutes after onset of chest pain. Tc-99m-PPi scans and coronary cineanglograms were recorded 491 ± 156 minutes and 518 ± 202 minutes, respectively, after the onset of symptoms. Effective reperfusion was present in 10 patients, 6 of whom had positive Tc-99m-PPi scans (sensitivity of 60% to detect reperfusion). Of the 6 patients without effective reperfusion, 3 had positive Tc-99m-PPi scans (specificity of 50%, p >0.05). Analysis of the data using various definitions of effective reperfusion or artery patency yielded similar results. Thus, our findings indicate that early AMI scanning with Tc-99m-PPi does not accurately detect the presence or absence of reperfusion in patients with AMI after treatment with intravenous streptokinase. At this time, coronary cineangiography is the only reliable method to detect reperfusion promptly after thrombolytic therapy.

Experimental animal models of viral myocarditis

Animal models of congestive heart failure and dilated cardiomyopathy following encephalomyocarditis (EMC) virus infection have been developed. Differences were found between different strains of mice in the frequency of occurrence and severity of myocarditis, and even in the character of the pathological lesions. Genetic factors may play an important role in pathogenesis. Right ventricular aneurysm and arrhythmias were seen in these models. Viral myocarditis may play a pathogenetic role in right ventricular dysplasia. Auto-antibodies against heart developed and the distribution of cardiac myosin isoenzymes was altered during the course of myocarditis. Myocardial uptake of technetium-99m pyrophosphate and changes in NMR relaxation parameters have been studied in these models. Virus vaccine, passive immunization, recombinant interferon α A/D and ribavirin protected mice from developing myocarditis. Immunosuppressive agents such as prednisolone and cyclosporinwere studied, but had no beneficial effect on these models. An animal model of perimyocarditis induced by coxsackie virus B3 is also described. Because the myocardial lesions are severe and occur frequently, our animal models are considered suitable for studying pathogenetic mechanisms and for the evaluation of diagnostic methods and prevention and therapeutic interventions of viral myocarditis.

Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate

Early appearance of positive findings on a technetium-99m pyrophosphate scan has been shown to be associated with the presence of a reperfused acute myocardial infarction (AMI). Early technetium-99m pyrophosphate imaging was performed by emission computed tomography to evaluate reperfusion and to test the feasibility of estimating infarct size soon after coronary reperfusion based on acute positive tomographic findings. Twenty-seven patients with transmural AMI who were treated with intracoronary urokinase infusion followed by percutaneous transluminal coronary angloplasty underwent pyrophosphate imaging 8.7 ± 2.1 hours after the onset of AMI. None of the 8 patients in whom reperfusion was unsuccessful had acute positive findings. Of 19 patients in whom reperfusion was successful, 17 had acute positive findings (p < 0.001). In these 17, tomographic infarct volumes were determined from reconstructed transaxial images. The threshold for areas of increased pyrophosphate uptake within the infarct was set at 60% of peak activity by the computerized edge-detection algorithm. The total number of pixels in all transaxial sections showing increased tracer uptake were added and multiplied by a size factor and 1.05 g/cm 3 muscle to determine infarct volume. The correlations of tomographic infarct volumes with peak serum creatine kinase (CK) levels (r = 0.82) and with cumulative release of CK-MB isoenzyme (r = 0.89) were good. Moreover, the time to positive imaging was significantly shorter than that to peak CK level (8.5 ± 2.3 vs 10.4 ± 2.2 hours, p < 0.005). In conclusion, early positive acute technetium-99m pyrophosphate imaging with emission computed tomography is a reliable and safe means of documenting early reperfusion and an effective method of sizing and localizing infarct soon after coronary reperfusion as early as 8 hours after the onset of AMI.

Comparison of early myocardial technetium-99m pyrophosphate uptake to early peaking of creatine kinase and creatine kinase-MB as indicators of early reperfusion in acute myocardial infarction

The value of technetium-99m pyrophosphate (Tc99m-PYP) scintigraphy as an indicator of reperlusion 2.8 to 8 hours after the onset of symptoms of acute myocardial infarction was compared with the value of early peak creatine kinase (CK) and CK-MB release within 16 hours after the onset of symptoms. In 29 patients who received thrombolytic therapy, recanalization was seen (group 1) and in 7 it was not (group 2). In 23 patients (79%) in group 1 scintigraphic findings were positive and in all 7 in group 2 they were negative. In 15 patients (52%) in group 1 and 1 patient (14%) in group 2, CK reached its peak level within 16 hours. In 20 patients (69%) in group 1 and 3 (43%) in group 2 the CK-MB level reached a peak within 16 hours. The sensitivity, specificity and predictive accuracy of positive results of early Tc-99m-PYP scintigraphy in predicting the reperfusion were 79%, 100% and 83%. These values are significantly higher than or similar to those of early peaking of CK and CK-MB release. In contrast to measurements of enzyme release, reperfusion data for Tc-99m-PYP scintigraphy are available immediately after thrombolytic therapy. Therefore, early Tc-99m-PYP scintigraphy (3 to 8 hours after onset of symptoms) is valuable as a noninvasive technique for early diagnosis of reperfusion.

Early identification of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy: A study with familial amyloid polyneuropathy

To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of famillial amylold polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic lmages ( p < 0.01), and values for diastolic function were reduced in four of the five and normal in the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of famllial amyloid polyneuropathy than two-dimensional echocardiography.

Technetium-99m pyrophosphate single-photon emission computed tomography of the heart in familial amyloid polyneuropathy

A patient with familial amyloid polyneuropathy and congestive heart failure underwent myocardial imaging using technetium-99m pyrophosphate. Planar scintigraphy showed an intense, diffuse biventricular uptake of the radiotracer. Single-photon emission computed tomography demonstrated an unevenly distributed uptake of the isotope. The greatest activity corresponded to regions with marked echocardiographic changes. Emission tomography may aid in assessing the degree and distribution of the infiltrative lesions in cardiac amyloidosis.

Technetium pyrophosphate muscle scans in inflammatory muscle disease.

Technetium-99M pyrophosphate (TcPYP) nuclear scans of extremities were performed on 15 patients at 10 minutes and 2 hours after isotope injection. Scans were carried out both to confirm the diagnosis of myositis and to direct subsequent muscle biopsy. Five of six patients with clinical features strongly suggestive of inflammatory muscle disease had positive scans. All muscle biopsies performed at areas of increased isotope uptake showed inflammatory muscle disease. All nine patients not suspected of active inflammatory muscle disease had negative scans. Two of these underwent muscle biopsy with negative results. Our observations suggest that TcPYP muscle scans may be useful both to confirm the clinical suspicion of inflammatory muscle disease and in directing the choice of site for muscle biopsy.

Technetium-99m pyrophosphate imaging in acute renal failure associated with nontraumatic rhabdomyolysis.

Technetium-99m pyrophosphate (Tc-PYP) imaging was performed in five patients with acute renal failure associated with nontraumatic rhabdomyolysis. Four patients had phencyclidine intoxication and one had viral pneumonia. During the acute phase, marked uptake of pyrophosphate was seen in all patients in several muscle groups, but always in the thigh adductors. The results show that phencyclidine intoxication can result in diffuse muscle uptake of Tc-PYP without overt evidence of muscle injury. Tc-PYP imaging may provide a clue to the cause of acute renal failure in patients with suspected rhabdomyolysis in whom elevations of serum creatine phosphokinase concentrations are equivocal.

Hyperbaric oxygen reduces edema and necrosis of skeletal muscle in compartment syndromes associated with hemorrhagic hypotension.

This study examined the effect of exposures to hyperbaric oxygen on the development of the edema and necrosis of muscle that are associated with compartment syndromes that are complicated by hemorrhagic hypotension. A compartment syndrome (twenty millimeters of mercury for six hours) was induced by infusion of autologous plasma in the anterolateral compartment of the left hind limb of seven anesthetized dogs while the mean arterial blood pressure was maintained at sixty-five millimeters of mercury after 30 per cent loss of blood volume. These dogs were treated with hyperbaric oxygen (two atmospheres of pure oxygen) and were compared with six dogs that had an identical compartment syndrome and hypotensive condition but were not exposed to hyperbaric oxygen. Forty-eight hours later, edema was quantified by measuring the weights of the muscles (the pressurized muscle compared with the contralateral muscle), and necrosis of muscle was evaluated by measuring the uptake of technetium-99m stannous pyrophosphate. The ratio for edema was significantly (p = 0.01) greater in dogs that had not been exposed to hyperbaric oxygen (1.15 +/- 0.01) than in the dogs that had been treated with hyperbaric oxygen (1.01 +/- 0.03), and the ratio for necrosis of muscle was also significantly (p = 0.04) greater in dogs that had not had hyperbaric oxygen (1.96 +/- 0.41) than in those that had been treated with hyperbaric oxygen (1.05 +/- 0.11). Comparisons were also made with the muscles of four normal control dogs and separately with the muscles of six normotensive dogs that had an identical compartment syndrome and normal blood pressure and were not treated with hyperbaric oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Thallium-201/technetium-99m pyrophosphate overlap in patients with acute myocardial infarction after thrombolysis: Prediction of depressed wall motion despite thallium uptake

Intracoronary thallium-201/technetium-99m pyrophosphate planar scintigraphy was performed in 60 patients with acute myocardial infarction undergoing intracoronary thrombolysis to predict salvage of myocardium immediately after thrombolysis. In eight patients a significant overlap of new thallium uptake and technetium pyrophosphate accumulation was found after thrombolysis. Intravenous planar thallium scintigraphy revealed thallium uptake in the region of overlap in all patients; circumferential profile analysis showed no difference in the thallium scintigrams before and after technetium injections. Both findings indicate that overlap is not the result of scattering of technetium into the thallium window. Emission computed tomography revealed thallium/technetium pyrophosphate uptake in identifical slices and regions. Regional wall motion in the area of overlap remained depressed in all patients, in contrast to patients with similar thallium uptake without overlap. These data suggest that thallium/technetium pyrophosphate overlap reflects the close proximity of viable and necrotic myocardial cells and predicts depressed wall motion after thrombolysis.

Skeletal muscle damage: a study of isotope uptake, enzyme efflux and pain after stepping.

We have studied the occurrence of skeletal muscle uptake of 99mtechnetium pyrophosphate (Tc-PYP), creatine kinase (CK) release and muscle pain in normal subjects after exercise. Five subjects stepped on and off a high bench in such a way that one leg stepped up and the other down. Pain only developed in the muscles used for descending: quadriceps, adductors and gluteal muscles of one leg and the calf muscle of the other. A large rise in plasma CK occurred in four subjects but no increased Tc-PYP muscle uptake was seen in the quadriceps. In the four subjects with high CK effluxes, increased isotope uptake was seen in the thigh adductors used when stepping down; in the two subjects with the largest CK effluxes there was extensive uptake into the gluteal muscles. Muscle pain preceded and was not well correlated with either the magnitude of the enzyme release or the amount and distribution of increased muscle isotope uptake. We conclude that delayed onset muscle pain, the cause of which remains unknown, is a poor indicator of muscle damage as indicated by circulating muscle enzymes and muscle isotope uptake. Tc-PYP uptake by skeletal muscle can provide useful information about the localisation and time course of muscle damage.

Cardiac Amyloidosis

Two male patients with primary cardiac amyloidosis are described. Patient 1 presented with typical effort angina pectoris with no ischemic electrocardiographic changes and a normal coronary angiogram. At necropsy, a severe diffuse, intravascular amyloid deposition was observed in the intramural coronary arteries. In patient 2 the presenting symptom was congestive heart failure with echocardiographic evidence of asymmetric septal hypertrophy and pericardial effusion. Technetium-99m pyrophosphate scintigraphy showed diffuse myocardial uptake, and the diagnosis of cardiac amyloidosis was confirmed in the postmortem examination. The diagnostic and therapeutic problems associated with cardiac amyloidosis are discussed in the light of these case reports.

Delayed use of hyperbaric oxygen for treatment of a model anterior compartment syndrome

This study examines the effect of delayed exposure to hyperbaric oxygen on muscle necrosis and edema development following compartment syndromes in the canine hindlimb. Compartment syndromes (100 mm Hg for 8 h) were generated in one anterolateral compartment of six anesthetized dogs. After a 2-h delay, three 1-h hyperbaric oxygen treatments (2 atm absolute pure oxygen) were given during the next 12 h. Two days later, technetium-99m stannous pyrophosphate (99mTc Sn-PYP) was injected intravenously; 3 h later, samples were obtained from the pressurized and contralateral control muscles, weighed for edema development, counted for 99mTC Sn-PYP uptake, and evaluated histologically. Hyperbaric oxygen treatments, even when delayed 2 h, reduced muscle necrosis and intramuscular edema to negligible levels (p less than 0.05) compared with untreated animals. In addition, muscle morphology remained essentially normal in all hyperbaric oxygen-treated animals. We conclude that even if hyperbaric oxygen treatments are delayed 2 h, edema and muscle necrosis are reduced significantly in a model compartment syndrome.

Sequential uptake patterns of technetium-99m pyrophosphate in hepatoma.

Sequential liver scintiphotography with Tc-99m pyrophosphate (PYP) was used to prospectively evaluate its uptake patterns in hepatoma. The scintiphotos and time-activity curves of 40 cases were analyzed. Two distinct patterns of tumor activity were noted: gradual but complete extraction and trapping of Tc-99m PYP in hepatoma in 38% of the patients (group 1), and absence of subsequent Tc-99m PYP uptake in hepatoma after initial blood pool activity in 62% of the patients (group 2). Since extraction and trapping of Tc-99m PYP occur approximately in two fifths of the patients with hepatoma, we conclude that Tc-99m PYP liver scintigraphy is not worthwhile supplementing the conventional radionuclide studies for diagnosing hepatoma, even in the selected patients in the countries where the prevalence of hepatoma is high.

Technetium-99m-pyrophosphate scintigraphy in patients with suspected acute myocardial infarction: Impact of interobserver variability

Technetium-99m-pyrophosphate (TcPYP) scintigraphy may have great value in patients with suspected acute myocardial infarction (AMI), but interobserver variability undoubtedly has adverse impact on predictive value. TcPYP scintigrams for 133 (80%) of 166 consecutive patients admitted for suspected AMI were interpreted independently by three experienced readers. Although there was complete agreement for 87 interpretations (65%), major discrepancies (i.e., at least one positive and one negative reading on the same scan) occurred for 28 scans (21%). To assess predictive accuracy, patients were categorized as follows: 36 had definite AMI manifest by new ECG Q waves and/or CK-MB evidence of AMI (group I), 56 were classified as possible AMI (group II), and 41 had AMI excluded (group III). Using only the definitive diagnostic categories (groups I and III), accuracy for each reader approximated 0.68, with no single reader being correct more often than any other.

Measurement of myocardial infarction fraction using single photon emission computed tomography

Although infarct size correlates generally with prognosis after acute myocardial infarction, an absolute measure of infarct size may have differing prognostic significance depending on absolute left ventricular mass. To test the hypothesis that single photon emission computed tomography can accurately measure myocardial infarct size as a percent of total left ventricular mass ("infarction fraction"), thallium-201 and technetium-99m pyrophosphate tomograms were acquired in 21 dogs 24 to 48 hours after fixed occlusion of the left anterior descending or circumflex coronary artery. Pathologic infarct weight was measured as the myocardial mass that showed no staining with triphenyltetrazolium chloride. Scintigraphic infarct mass by technetium-99m pyrophosphate was calculated from the total number of left ventricular volume elements (voxels) demonstrating technetium-99m pyrophosphate uptake X voxel dimension [( 0.476 cm]3) X specific gravity of myocardium (1.05 g/cm3). Scintigraphic left ventricular mass was calculated in a similar fashion using an overlay of the thallium-201 and technetium-99m pyrophosphate scans. The "infarction fraction" was calculated as: infarction fraction = infarct mass/left ventricular mass. There was good correlation between single photon emission computed tomography and pathologic measurements of infarct mass (technetium-99m pyrophosphate mass = 1.01 X pathologic infarct mass + 0.96; r = 0.98), left ventricular mass (single photon emission computed tomographic left ventricular mass = 0.60 X pathologic left ventricular mass + 37.4; r = 0.86) and "infarction fraction" (single photon emission computed tomographic infarction fraction = 1.09 X pathologic infarction fraction - 1.7; r = 0.94).(ABSTRACT TRUNCATED AT 250 WORDS)

C-reactive protein in femoral head necrosis.

Serum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin, orosomucoid, and haptoglobin were determined in 28 patients with a medial fracture of the femoral neck. The serum concentrations were compared with the result of hip scintigraphy with technetium-99m pyrophosphate, a method which can detect femoral head necrosis and predict the development of late segmental collapse. Serum concentrations of the four acute-phase proteins were measured immediately before osteosynthesis and at the time of hip scintigraphy 1 to 4, 8 to 13, and 37 to 47 days postoperatively. During the same period 15 patients had constantly normal, five varying abnormal/normal, and eight constantly abnormal scintigrams, the latter indicating femoral head necrosis. All four acute-phase proteins had a typical course of concentration changes, which were most pronounced for CRP. However, none of them were useful for the detection of femoral head necrosis or the prediction of late segmental collapse, since the observed serum concentrations could not be used to distinguish between the three scintigraphic groups.