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PubMed1976

Cardioversion and "false positive" technetium-99m stannous pyrophosphate myocardial scintigrams.

The present studies performed in experimental animals demonstrate that electrical direct current cardioversion can produce skeletal muscle damage and increased technetium-99m stannous pyrophosphate (99mTc-PYP) uptake; in experimental animals the electrically damaged skeletal muscle shows necrosis with extensive calcium deposition. In addition, the frequent administration of high energy cardioversion produces myocardial necrosis with calcium deposition, increased 99mTc-PYP myocardial uptake and a positive 99mTc-PYP myocardial scintigram. The data indicate that, if diagnostic 99mTc-PYP myocardial scintigraphy is contemplated after cardioversion, paddle placement should be slightly removed from the anteroposterior projection of the heart on the external chest wall to avoid possible subsequent confusion between increased myocardial and skeletal muscle uptake of 99mTc-PYP. If multiple high energy cardioversion episodes are necessary, myocardial necrosis resulting from electrical injury may occur and be responisble for increased myocardial uptake of 99mTc-PYP with a resultant positive 99mTc-PYP myocardial scintigram.

Animals↗
PubMed1976

Relationships between myocardial perfusion, myocardial necrosis, and technetium--99m pyrophosphate uptake in dogs subjected to sudden coronary occlusion.

The quantitative relationship between abnormalities seen on technetium-99m pyrophosphate (99mTc-PYP) infarct scintigrams and the size of the myocardial infarction is unclear. We evaluated two possible determinants of 99mTc-PYP accumulation: myocardial perfusion measured with 7-10 mu microspheres and the extent of necrosis determined histologically. Hemodynamics and myocardial perfusion to small segments of the left ventricle were measured prior to, 5-10 min, and 44-48 hours following sudden occlusion of the left anterior descending coronary artery in ten awake dogs. 99mTc-PYP was injected i.v. following the third injection of microspheres and the animals were killed 2 hours later. The important findings were as follows: 1) there is a close relationship between the extent of myocardial necrosis observed and the perfusion of segments 5-10 min following coronary occlusion; and 2) that segmental myocardial perfusion is an important determinant of 99mTc-PYP accumulation by myocardial segments which contain areas of necrosis. Although the present data preclude statistical analysis of the relationship between the level of necrosis in a segment and the accumulation of 99mTc-PYP by that segment, the two do not appear to be related, a finding which would discourage use of intensity of 99mTc-PYP images for infarct size. The distribution of an abnormality on the scintigram may provide an estimate of infarct size. However, the geometry of the infarct and the resolving power of the scanning equipment will significantly limit this in many clinical situations.

Animals↗
PubMed1976

Myocsrdial uptake of technetium-99m stannous pyrophosphate following direct current transthoracic countershock.

The effect of direct current (DC) countershock upon myocardial technetium-99m stannous pyrophosphate (PYP) uptake was studied in 22 dogs. All eight dogs imaged had positive abnormal PYP scintigrams that were usually indistinguishable from experimental infarction. In three animals, additional areas of radionuclide uptake were seen in overlying noncardiac tissue. Left and right ventricular myocardial PYP uptake averaged (+/- SEM) 23 +/- 5 times control and 24 +/- 6 times control, respectively. These activity ratios occurred without reduction in regional myocardial blood flow (RMBF), and were associated with histologic evidence of necrosis. The necrosis was usually epicardial, corresponding to the transmural site of greatest PYP uptake. The magnitude of PYP accumulation and the weight of damaged tissue increased with increasing applied energy. Thus, PYP uptake following DC countershock could result in false-positive interpretation of acute ischemic myocardial infarction. Since RMBF is normal in regions of PYP uptake, the major determinant of radionuclide accumulation is the extent of cellular damage.

Animals↗
PubMed1977

The specificity of the diffuse pattern of cardiac uptake in myocardial infarction imaging with technetium-99m stannous pyrophosphate.

To analyze the specificity of the diffuse pattern of cardiac uptake with technetium-99m stannous pyrophosphate (TcPYP), we evaluated the bone scans of 1,383 noncardiac patients and the myocardial scintigrams of 120 cardiac patients. Seventy (14.4%) of 483 bone scans performed on a scintillation camera revealed diffuse TcPYP cardiac uptake. Among the total 603 camera bone scans and myocardial scintigrams, the incidence of diffuse cardiac uptake was 16% among patients with clinical coronary disease but 13% among those patients without clinical symptoms. Discrete myocardial uptake was seen in 25 of 26 patients with transmural infarction. Femoral vasculature was more frequently visualized (84% vs 3%, P less than 0.001) and left mastectomy occurred more often (30% vs 1%, P less than 0.001) among patients with diffuse cardiac uptake than among patients with negative images, indicating possible blood pool imaging. The diffuse pattern of cardiac uptake appeared nonspecific and may be due to unintentional cardiac blood pool imaging.

Bone and Bones↗
PubMed1977

Localization of radiolabeled cardiac myosin-specific antibody in myocardial infarcts. Comparison with technetium-99m stannous pyrophosphate.

The myocardial uptake of radioiodinated (Fab')2 fragments of antimyosin antibody [125I-(Fab')2] was compared with simultaneously administered 99mTc-pyrophosphate (Tc-PYP) in dogs undergoing coronary occlusion for 24 (N=6) or 72 hours (N=5). Relative concentrations of both agents in normal and infarcted myocardium were related to regional blood flow as determined by distribution of 55Sr-labeled microspheres in the same animals. There was an inverse exponential relationship between 125I-(Fab')2 localization and regional blood flow in 24 hr (r=-0.64) and 72 hr (r=-0.80) occluded animals. The greatest uptake of 125I-(Fab')2 was observed in subendocardial layers of the center of the infarct where regional flow was most severely impaired (1-10% of normal flow). Maximal localization of Tc-PYP was observed in subepicardial layers in samples from the periphery of the infarct where flow was only moderately reduced (31-50% of normal). Differences in distribution of these two agents in ischemic myocardium are probably related to differences in kinetics of exit from the blood pool.

Animals↗
PubMed1977

Follow-up technetium-99m stannous pyrophosphate myocardial scintigrams after acute myocardial infarction.

Technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigrams were obtained in 68 patients during acute myocardial infarction (AMI) and at follow-up 15.9 +/- 8.8 weeks later. All patients with AMI had a positive scintigram (2+ or greater); only one of 46 control patients (2%) had a positive (2+) scintigram. At follow-up scintigraphy 6 to 37 weeks following AMI, 57% of patients had a persistently positive scintigram even though recurrent AMI was suspected in only one of these patients. Patients with persistently positive scintigrams tended to have more severe disease as evidenced by compensated congested heart failure (41%) persistent angina (77%), and ECG evidence of ventricular dyssynergy (51%), We conclude that 1) in patients with prior AMI, a 2+ abnormality on 99mTc-PYP scintigram may not represent new AMI; 2) a persistently positive 99mTc- PYP scintigram may have prognostic implications since it occurs predominantly in patients with severe symptomatic coronary disease.

Acute Disease↗
PubMed1977

Technetium-99m stannous pyrophosphate myocardial scintigraphy. Reliability and limitations in assessment of acute myocardial infarction.

Two hundred-three patients had -echnetium 99m (stannous) pyrophosphate myocardial scintigrams for the evaluation of chest pain and suspected acute myocardial infarction. In addition to routine imaging at 60--90 minutes after injection of the radio-pharmaceutical, the blood pool was imaged immediately in each patient for comparison with routine anterior, left anterior oblique, and left lateral views. Further delayed studies were obtained when residual blood pool activity was identified. Seventy patients had acute myocardial infarction by clinical, electrocardiographic, and enzymatic (CK-MB) criteria. Sixty-five of these 70 patients with acute infarction had positive myocardial scintigrams, with one technically unsatisfactory study. Only four of the 70 patients had negative scintigrams when imaged 18--72 hours after infarction in this study. Technically satisfactory scintigrams were recorded in 125 patients without evidence of infarction. Ninety-six had negative scintigrams at 60--90 minutes, while 19 patients (15%) had precordial activity at 60--90 minutes which was identical in distribution to early blood pool images and cleared with further delay. With these included, the true negative incidence was 92%. Ten of 125 patients had false positive scintigrams; two had recent cardioversion with resultant chest wall damage. The other eight patients had previous infarction 1 1/2 to 72 months earlier and had akinetic segments shown angiographically in the areas of the persistently positive scintigrams. Myocardial scintigraphy correlates well with the presence of other evidence of acute infarction, as well as with the absence of acute infarction when residual blood pool activity is identified. False positive scintigrams can occur following cardioversion and in patients with previous myocardial infarction and resultant ventricular wall motion abnormalities.

Acute Disease↗
PubMed1977

Effect of methylprednisolone upon technetium-99m pyrophosphate assessment myocardial necrosis in the canine countershock model.

Repeat DC countershock reproducibly results in myocardial necrosis in dogs. In this model, myocardial technetium-99m pyrophosphate (PYP) uptake correlates linearly with tissue creatine kinase depletion (r = -0.83). The effect of pretreatment with methylprednisolone (MP) was studied with PYP in 25 dogs. In myocardium damaged by countershock, 12 MP dogs had higher tissue radioactivity sample:normal (S:N) ratios than control (P less than 0.05), suggesting increased tissue injury. However, by several other measures of tissue damage, the two groups did not differ. MP-elevated PYP S:N ratios were explained by reduced PYP activity in normal myocardium of MP dogs. Further experiments in 21 dogs revealed that renal PYP clearance, which correlated with glomerular filtration rate (GFR) as measured by creatinine clearance, was increased in Mp dogs, resulting in accelerated urinary excretion of PYP (46.9+/-3.6 vs 35.8+/-2.4 percent injected dose in one hour, P less than 0.01), and reduced blood PYP. Thus MP does not modify countershock-induced myocardial injury. However, by increasing GFR, MP increased PYP excretion, resulting in lowered blood and normal zone myocardial PYP, thereby spuriously affecting myocardial PYP tissue uptake data.

Animals↗
PubMed1978

The clinical estimation of acute myocardial infarct size with 99mTechnetium pyrophosphate scintigraphy.

We evaluated scintigraphic techniques in estimating infarct size. In 26 patients with acute transmural myocardial infarction, 99mTechnetium pyrophosphate (TcPYP) infarct scintigraphy, gated cardiac blood pool scintigraphy and 201-Thallium (201-Tl) perfusion scintigraphy were performed. Invasive hemodynamic measurements were obtained and serial venous blood specimens taken for measurement of total and MB creatine phosphokinase (CPK). In farct size was estimated from the area of abnormal TcPYP uptake, the extent of reduced 201-Tl uptake, the percentage of abnormally contracting segments, and serial enzyme measurements. Left ventricular ejection fraction (LVEF) and stroke work index (LVSWI) were calculated. TcPYP infarct area was associated with the extent of reduced 201-Tl uptake (r = 0.66), the percentage of abnormally contracting segments (r = 0.64), and with both LVSWI (r = 0.73) and LVEF (r = 0.58). TcPYP infarct area did not correlate with cumulative total or MB-CPK release or the integrated total CPK-time curve, nor did the enzyme estimates of infarct size correlate with LVSWI or LVEF. Variable perfusion of infarcts of different sizes may explain the lack of correlation between TcPYP infarct area and enzyme estimates of infarct size. A combination of anatomic and functional indices derived from scintigraphic and hemodynamic measurements may provide the best assessment of infarct size.

Acute Disease↗
PubMed1978

Technetium-99m stannous pyrophosphate imaging of experimental infective endocarditis.

Technetium-99m stannous pyrophosphate (99mTc-PYP) cardiac scintigraphy was performed in 15 rabbits with experimental Streptococcus sanguis aortic valve infective endocarditis. The animals were imaged five to seven days after the administration of bacteria, and in each case abnormal accumulation of the tracer was visualized in the region of the aortic valve. Three types of cardiac scintigraphic patterns were demonstrated: focal, multifocal and extensive, each correlating well with the anatomical extent of the lesion as defined by gross pathology. Tissue distribution studies demonstrated a 30 +/- 5.3 (mean +/- SEM) fold excess of radionuclide uptake in the infective endocarditis lesion compared with that of normal myocardium. Imaging of excised hearts from four animals showed an excellent correlation with in vivo imaging as well as gross pathology. Five animals with nonbacterial thrombotic aortic valve endocarditis demonstrated similar scintigraphic and tissue distribution results. In contrast, four normal animals failed to demonstrate abnormal 99mTc-PYP cardiac scintigrams or tissue uptake. This study demonstrates that 99mTc-PYP cardiac scintigraphy is a sensitive technique to detect experimental aortic valve endocarditis.

Animals↗
PubMed1979

Clinicopathologic findings in 52 patients studied by technetium-99m stannous pyrophosphate myocardial scintigraphy.

Scintigraphic, clinical and pathological findings were correlated in 52 patients studied by technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigraphy before death or surgical resection of myocardium. Fifty-nine clinical events were studied with scintigraphy in the 52 patients; 41 of the 59 were associated with one or more abnormal 99mTc-PYP studies and 18 with normal 99mTc-PYP scintigrams. Myocardial scintigrams were positive in 29 of 31 cases with clinicopathological evidence of a corresponding discrete, grossly obvious acute myocardial infarct, including 16 of 16 transmural myocardial infarcts and 13 of 15 subendocardial infarcts. In 16 of 18 cases, negative myocardial scintigrams correlated with the absence of acute myocardial infarction determined by clinicopathological evidence. In two cases small subendocardial infarcts (less than 3 g) were not detected by 99mTc-PYP myocardial scintigraphy. Of the 12 additional instances of positive 99mTc-PYP myocardial scintigrams, five were associated with clinical unstable angina pectoris and seven were in the category of persistently positive scintigrams, since the scans were obtained 2.5 months or longer after proven or suspected acute myocardial infarcts. In all 12 instances, the positive 99mTc-PYP scintigrams were associated with evidence of multifocal irreversible myocardial damage consisting of myocytolysis, coagulation necrosis and/or fibrosis, and the histological age of the lesions was compatible with acute injury corresponding to the time of scintigraphy. The findings indicate that a positive 99mTc-PYP myocardial scintigram is a sensitive indicator of significant myocardial injury which may occur as confluent coagulation necrosis corresponding to clinical acute myocardial infarction, or as multifocal coagulation necrosis or myocytolysis associated with unstable angina pectoris or recurrent ischemic heart disease, especially after previous infarctions.

Acute Disease↗
PubMed1979

Technetium-99m stannous pyrophosphate myocardial scintigraphy after cardiopulmonary resuscitation with cardioversion.

Thirty consecutive patients underwent technetium-99m stannous pyrophosphate myocardial scintigraphy 48--72 hours after successful cardiopulmonary resuscitation and direct current cardioversion. Five patients with transmural myocardial infarctions by ECG and enzyme determinations were correctly identified by scintigraphy. Myocardial scans were positive in five of nine patients with nontransmural infarction. Of 16 patients without evidence of myocardial infarction, only two (13%) had false-positive myocardial scans. The overall accuracy of imaging in this series was 80%. We conclude that false-positive scans after cardiopulmonary resuscitation with electrical cardioversion are infrequent, and do not significantly detract from the value of myocardial scintigraphy in the diagnosis of myocardial infarction.

Aged↗
PubMed1980

Technetium-99m pyrophosphate uptake in experimental viral perimyocarditis. Sequential study of myocardial uptake and pathologic correlates.

The myocardial uptake of technetium-99m pyrophosphate (99mTc-PYP) in perimyocarditis induced by coxsackievirus B3 in BALB/c mice was studied. 99mTc-PYP uptake ratio, measured by the ratio of counts/min per gram for the heart to counts/min per gram for the skull, began to increase 5 days after virus inoculation when myocardial necrosis was evident. On the seventh day after the inoculation, 99mTc-PYP ratio reached a maximum. Histologically, fine, dystrophic calcification appeared in the necrotic fibers. 99mTc-PYP uptake was in proportion to the extent of the myocardial lesions. Thereafter, cellular infiltrations increased with time and were most severe on the fourteenth day, but 99mTc-PYP ratio had begun to fade. On the twenty-eighth day, perimyocardial fibrosis increased and calcification was still present, but 99mTc-PYP ratio had decreased. Myocardial uptake with severe pathologic lesions was visualized on a whole-body image on the seventh day after inoculation with the virus. The findings may provide a basis upon which 99mTc-pyp imaging may be applied to viral perimyocarditis in humans.

Animals↗
PubMed1973

Identification of inorganic pyrophosphate in human platelets and its release on stimulation with thrombin.

Serum inorganic pyrophosphate (PPi) levels were consistently two- to threefold higher than plasma PPi prepared from the same blood. PPi was found in platelets in amounts ranging from 1.4 to 3 nmol/10(8) cells, using three different techniques for quantification. These levels are approximately 800 times higher than the mean PPi concentration in normal plasma and approximate the levels of ADP found in platelets by other workers. About 50% of platelet PPi was specifically released extracellularly after stimulation with thrombin. Timed release experiments showed a pattern of release that resembled that described for ADP and ATP. This pattern was clearly different from that shown by platelet calcium, serotonin, or beta-glucuronidase. Platelet inorganic pyrophosphatase was not released into the supernate in detectable amounts. Platelets from patients with nucleotide storage pool deficiency showed greatly reduced levels of PPi as compared with control. There was no detectable release of PPi into extracellular medium after thrombin addition to a suspension of these platelets.

Blood Platelets↗
PubMed1973

Measurement of inorganic pyrophosphate in biological fluids. Elevated levels in some patients with osteoarthritis, pseudogout, acromegaly, and uremia.

A rapid and relatively simple method for measurement of inorganic pyrophosphate (PPi) in biological samples has been described. The mean +/-SEM of plasma samples from 94 normal subjects was 1.8+/-0.06 muM, giving a normal range (99% confidence limits) of 0.16 - 3.40 mumol/liter. Analysis of 17 plasma samples in duplicate showed a standard deviation of 0.18, giving a 99% probability that a single determination of plasma PPi would be +/-0.68 muM of the true value. The mean PPi levels in plasma from subjects with osteoarthritis, pseudogout, acromegaly, and uremia were significantly greater than the normal mean (P < 0.01). Samples from rheumatoid arthritis showed PPi levels distributed about a mean identical to the normal mean. Plasma inorganic orthophosphate levels correlated positively with PPi levels in samples from normal subjects and in samples from patients with osteoarthritis, pseudogout, and uremia, but not with acromegaly. This correlation was statistically significant only in the normal samples and in those from patients with osteoarthritis.

Acromegaly↗
PubMed1976

Pathophysiology of technetium-99m stannous pyrophosphate and thallium-201 scintigraphy of acute anterior myocardial infarcts in dogs.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.

Acute Disease↗
PubMed1995

Alkaline phosphatase: placental and tissue-nonspecific isoenzymes hydrolyze phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5'-phosphate. Substrate accumulation in carriers of hypophosphatasia corrects during pregnancy.

Hypophosphatasia features selective deficiency of activity of the tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (ALP) isoenzyme (TNSALP); placental and intestinal ALP isoenzyme (PALP and IALP, respectively) activity is not reduced. Three phosphocompounds (phosphoethanolamine [PEA], inorganic pyrophosphate [PPi], and pyridoxal 5'-phosphate [PLP]) accumulate endogenously and appear, therefore, to be natural substrates for TNSALP. Carriers for hypophosphatasia may have decreased serum ALP activity and elevated substrate levels. To test whether human PALP and TNSALP are physiologically active toward the same substrates, we studied PEA, PPi, and PLP levels during and after pregnancy in three women who are carriers for hypophosphatasia. Hypophosphatasemia corrected during the third trimester because of PALP in maternal blood. Blood or urine concentrations of PEA, PPi, and PLP diminished substantially during that time. After childbirth, maternal circulating levels of PALP decreased, and PEA, PPi, and PLP levels abruptly increased. In serum, unremarkable concentrations of IALP and low levels of TNSALP did not change during the study period. We conclude that PALP, like TNSALP, is physiologically active toward PEA, PPi, and PLP in humans. We speculate from molecular/crystallographic information, indicating significant similarity of structure of the substrate-binding site of ALPs throughout nature, that all ALP isoenzymes recognize these same three phosphocompound substrates.

Alkaline Phosphatase↗
PubMed1998

Calcium pyrophosphate deposition disease of the temporal bone.

Massive calcium pyrophosphate crystal deposition is a rare disorder that may affect the temporomandibular joint and temporal bone. The diagnosis is difficult, and misdiagnosis as malignancy, particularly chondrosarcoma, is frequent. This can lead to unnecessarily aggressive management. The clinical, radiographic, and pathologic features of this entity are reviewed, and treatment options are discussed.

Aged↗