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99mTc-labelled pyrophosphate myocardial scanning in experiment and in clinical practice.

A survey is presented of research results of pyrophosphate myocardial scanning in 130 dogs and 150 patients with various myocardial lesions. The results of experiments in animals were immediately applied in clinical practice. The results showed that acute transmural myocardial lesions yielded practically in all instances positive scintigraphic findings. The findings in nontransmural infarctions were less convincing--they were positive in 60% of cases. Positive scintigraphic findings were also obtained in 80% of dogs with experimentally induced temporary ischaemia, and in 80% of dogs with experimentally induced dystrophy of the myocardium. In patients with angina pectoris positive findings were obtained in 1/3 of the cases, and in patients with cardiomyopathies, in 1/3 to 1/4 of the cases (in dependence on the etiology of the cardiomyopathy). It appears that 99mTc-PYP is a highly sensitive, but nonspecific, detector of myocardial lesions.

Angina Pectoris↗

Massive articular chondrocalcinosis. Its occurrence with calcium pyrophosphate crystal deposits in nucleus pulposus.

We studied a case of long-standing chondrocalcinosis that after 40 years affected almost all fibrocartilages, hyaline cartilages, and articular cavities within the subject. Massive deposits of dihydrocalcium pyrophosphate (CPP) were also found in nonfissured nucleus pulposus of the vertebral disks. To our knowledge, this is the first report of CPP deposits in these disks.

Aged↗

The distal femoral defect: technetium-99m pyrophosphate bone scan results.

To determine the scintigraphic findings in children with distal femoral defects (or subperiosteal desmoids) the authors retrospectively examined 94 sets of radiographs and technetium-99m pyrophosphate bone scans of 54 children. Twenty-four examples of distal femoral defects were identified in 19 children. Only two children demonstrate focally increased uptake of radionuclide in the distal femur. The positive bone scan was caused by osteomyelitis in one of these patients and by metastatic lymphoma in the other. None of the 17 other children with distal femoral defects on radiography had a corresponding focal increase in uptake of radionuclide. The bone scan appears to be a useful method for confirming that a distal femoral defect is benign and, when positive, indicates the presence of other disease.

Adolescent↗

[Metastatic calcifications as demonstrated by technetium-99m-pyrophosphate bone scanning. Case reports].

Two cases of chronic renal failure showing very interesting technetium-99m-pyrophosphate bone scans are presented. In both cases striking uptake of activity was shown in the left ventricle of the heart, the mucosa of the stomach and in both lungs. This picture was attributed to metastatic calcification in these organs. Cases of metastatic calcification demonstrated with bone-seeking agents have been presented previously, but have mainly shown intense uptake of activity in the lungs and in a few cases, and to a lesser degree, in the stomach. However, we believe that our cases are unique in showing especially the left ventricle of the heart as well as the mucosa of th stomach with exceptional clarity.

Adult↗

Arthropathy in calcium pyrophosphate dihydrate crystal deposition disease. Pathologic study of 12 cases.

The pathologic features of calcium pyrophosphate crystal deposition disease (CPDD), particularly the synovial abnormalities, have not been adequately described or depicted in textbooks or journals; this report details the findings in 12 cases. Attention is drawn to the practical reasons for distinguishing CPDD arthropathy from other arthropathies, particularly osteoarthritis; clinical and gross pathologic features that should suggest CPDD arthropathy in cases that are not suspected preoperatively; and characteristics of the tophaceous deposits in CPDD.

Aged↗

A comparison of infarct identification with technetium-99m pyrophosphate and staining with triphenyl tetrazolium chloride.

The topographic relationship between the uptake of technetium-99m pyrophosphate (PPi) and myocardial infarction delineated by 2,3,5-triphenyl tetrazolium chloride (TTC) was studied in a canine model of permanent coronary occlusion (24-48 hr). Photographs of TTC staining and scintigraphic images of PPi uptake were planimetered for infarct area. In addition, narrow tissue samples (3 X 10 mm) were taken on both sides of the TTC border and counted for PPi uptake. A significant correlation (p less than 0.001) was found between area of PPi uptake and area of myocardium unstained by TTC (r = 0.84 in epicardium and r = 0.91 in endocardium). The slope relating PPi to TTC for all infarcts was 1.01 +/- 0.11, indicating that variations in infarct size were followed equally by the two techniques. Tissue counting showed the ratio of PPi activity just inside the infarct to activity just outside the infarct to be 9.2 +/- 0.6 (mean +/- s.e.m.). Thus, PPi is distributed topographically in a manner identical to the distribution of irreversibly injured myocardium as delineated by TTC.

Animals↗

Analytical scanning and transmission electron microscopy and x-ray microdiffractometry of calcium pyrophosphate dihydrate crystal deposits in tissues.

This paper reviews current methods and applications for the detection and identification of calcium pyrophosphate dihydrate (CPPD) crystals. Methods reviewed include compensated polarized light microscopy, scanning electron microscopy, transmission electron microscopy, x-ray energy-dispersive elemental analysis, x-ray powder microdiffractometry, and selected area electron diffractometry. Although compensated polarized light microscopy is the best technique for crystal detection in pathologic fluids and tissues, because of crystal size this technique cannot discriminate easily between CPPD(M) and CPPD(T) polymorphs. To determine the presence and relative concentration of CPPD(M) and CPPD(T), x-ray or electron microdiffractometry is required. Analytical scanning and transmission electron microscopy are needed to localize crystals ultrastructurally and to determine the relationship of the crystal deposits to tissue components. The correlative application of multiple techniques on the same sample or adjacent samples provides more precise localization and identification than any single technique.

Calcium Pyrophosphate↗

[Myocardial tomoscintigraphy with technetium pyrophosphate in the diagnosis of recent infarction].

Technetium pyrophosphate myocardial scintigraphy has become, together with Thallium scintigraphy, a common diagnostic aid in recent myocardial infarction. However, some cases with moderate diffuse fixation (2+ diffuse in Parkey's classification) are considered equivocal results by many workers. We tried to assess the value of emission tomoscintigraphy in classifying these border-line cases. This non-invasive investigation requires sophisticated equipment, including a rotating gamma camera coupled to a computer. The computer reconstructs tomographic images in the three planes (frontal, sagittal, transverse) at 6 mm intervals. After analysis of 34 coronary patients using classical clinical criteria, standard and tomographic scintigraphy were performed and the results interpreted by a double blind procedure. The following conclusions were drawn: Interpretation of the results of tomography was more reproducible than that of standard scintigraphy (91 p. 100 compared with 79 p. 100). The sensitivity of detection of myocardial infarction was higher (96 p. 100 compared to 80 p. 100) without any loss of specificity (preliminary study in 15 non-coronary patients); this improvement is due to the elimination of the "equivocal" cases observed on standard scintigraphy. The infarcted area was easier to determine as the interpretation was more reproducible. The estimation of the size of the infarcted area and the detection of rudimentary infarcts did not seem to be improved by emission tomography. Our criteria of positivity for the tomographic images were : at least 2+ fixation (significant but less intense than that of the sternum); fixation visible in at least 2 different tomographic planes (e.g. sagittal and frontal); fixation visible on at least 2 consecutive images in each plane.

Adult↗

[Results of computerized processing of myocardial 99mTc-pyrophosphate scans in ischemic heart disease].

Myocardial scintigraphy was carried out in 105 coronary heart disease patients using 99mTc -pyrophosphate. Twenty-nine of these patients suffered from acute myocardial infarction. The scintigrams were analyzed with the aid of original " MAREA " programmes devised for the diagnosis of acute myocardial infarction. The results obtained suggest the possibility of using this method of the scintigram processing for assessing the severity and predicting the course of coronary heart disease.

Acute Disease↗

[Value of 99m-pyrophosphate myocardial scanning and scintigraphy in the diagnosis of acute myocardial infarction].

Visualization of the myocardial necrotic focus with the aid of 99mTc -pyrophosphate is an informative method of determining the infarction degree and localization in the cardiac muscle. Scanning enables evaluation of the area of the necrotic focus in patients with acute myocardial infarction within two weeks of the disease onset. Scintigraphy with both the diffuse and the focal variants of isotope accumulation is shown to be of high diagnostic value in acute myocardial infarction. The specificity and sensitivity of scintigraphy are 87% and 96%, respectively.

Aged↗

Escherichia coli pyruvate dehydrogenase complex. Thiamin pyrophosphate-dependent inactivation by 3-bromopyruvate.

Inactivation of the pyruvate dehydrogenase complex by 3-bromopyruvate is thiamin pyrophosphate (TPP)-dependent. Inactivation with 2-14C- or 3-14C-labeled 3-bromopyruvate results in TPP-dependent covalent labeling of more than 60 sites in the complex, all of which are associated with the dihydrolipoyl transacetylase component. Inactivation by 3-bromo[1-14C]pyruvate labels up to 20 sites associated with dihydrolipoyl transacetylase, also with TPP dependence. Systemic chemical degradation of the complex inactivated by 3-bromo[2-14C]pyruvate under conditions that would convert lipoyl groups to S,S,-biscarboxymethyl dihydrolipoic acid produces S,S,-bis[14C]carboxymethyl dihydrolipoic acid. It is concluded that 3-bromopyruvate inactivates this complex by initially undergoing the first two steps of the usual catalytic pathway, TPP-dependent decarboxylation followed by reductive bromoacetylation of lipoyl moieties. The sulfhydryl groups of S-bromoacetyl dihydrolipoyl moieties generated by reductive bromoacetylation are then alkylated by 3-bromopyruvate as well as by bromoacetyl thioester groups associated with the complex.

Affinity Labels↗

Direct physical evidence for stabilization of branched-chain alpha-ketoacid dehydrogenase by thiamin pyrophosphate.

Branched-chain alpha-ketoacid dehydrogenase is a multienzyme complex composed of four subunits. The 46,500-dalton protein is a subunit of the decarboxylase component, which is selectively digested by chymotrypsin. Two peptides of apparent mol. wts. of 36,000 and 15,000 result with loss of enzyme activity. When the complex is saturated with thiamin pyrophosphate and ketoacid substrate, digestion by chymotrypsin does not occur. These data provide direct physical evidence for the stabilization of the complex by the presence of the vitamin B1-derived cofactor.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Pyrophosphate scanning in early frostbite injury.

Early identification of soft tissue injury is a major problem in the patient with frostbite injury. A patient is presented with a method for early (less than 2 days) identification of nonviable tissue. This is a noninvasive method employing technetium 99m stannous pyrophosphate which was used to accurately predict the level of ultimate amputation.

Adult↗

[Enzyme activity of thiamine pyrophosphate in the rat after oxythiamine administration].

Intraperitoneal injection of hydroxythiamine to rats (1 mmol per kg bw) resulted after 2-4 h in a more than 4-fold decrease in the activity of the oxoglutarate dehydrogenase complex, pyruvate dehydrogenase complex and NADP-dependent isocitrate dehydrogenase in adrenal mitochondria. Inhibition of hyaloplasmic transketolase, 6-phosphogluconate dehydrogenase and NADP-dependent malate dehydrogenase occurred later. Based on the correlation of the time course of enzymatic activity in the adrenals and the decreased concentration of 11-hydroxycorticosteroids in the blood the paramount role in the maintenance of the steroidogenesis among thiamine pyrophosphate-containing enzymes is assigned to the oxoglutarate dehydrogenase and pyruvate dehydrogenase complexes.

11-Hydroxycorticosteroids↗

Effect of oxythiamine on adrenal thiamine pyrophosphate-dependent enzyme activities.

The effect of parenterally administered low doses of oxythiamine (0.5 mumol/100 g body weight every 12 h) on rat adrenal transketolase, pyruvate dehydrogenase ( PDC ) and 2-oxoglutarate dehydrogenase complex ( OGDC ) activities was studied. It was found that the transketolase and the PDC activities decreased after 12, 16, and 20 injections. When the activities were measured in the absence of exogenous thiamine pyrophosphate (TPP), the PDC inhibition was significant after 20 oxythiamine injections. The OGDC activity was resistant to oxythiamine administration. The oxythiamine effects seem to be due to its being phosphorylated to yield diphosphate ester which, as kinetic studies on highly purified PDC from bovine adrenals have shown, is a strong competitive inhibitor (Ki = 0.07 microM) with respect to TPP (Km = 0.11 microM). The data obtained provide evidence for the possibility of a partial selective in vivo inhibition of the adrenal TPP-dependent enzymes.

Adrenal Glands↗

[Different efficiency of Mn2+, Ca2+ and Mg2+ ions, in the reaction of the pyruvate dehydrogenase complex of adrenal glands with thiamine pyrophosphate].

In systems with pyruvate dehydrogenase complex from bovine adrenal glands and endogenous residual thiamine pyrophosphate (TPP), Mn2+, Ca2+ and Mg2+ decreased the lag period and increased the rate of steady-state reaction. Relative efficiency of the cations was the following: Mn2+ greater than Ca2+ greater than Mg2+. The activating effect of these cations was also exhibited in presence of low content of exogenous TPP but it was not found under conditions of saturation of pyruvate dehydrogenase complex with the coenzyme. In the systems with the cations concentrations approaching the optimal ones, the apparent Km value for TPP in the presence of calcium was about 4-fold and in presence of manganese about 7-fold lower as compared with the systems containing magnesium.

Adrenal Glands↗

Technetium-99m(Sn2+)pyrophosphate in ischemic and infarcted dog myocardium in early stages of acute coronary occlusion: histochemical and tissue-counting comparisons.

We have investigated the pattern of accumulation of Tc-99m(Sn2+)pyrophosphate (Tc-99m PPi) in myocardial tissue of dogs during the early stages of acute occlusion of the left anterior descending coronary artery. Three groups were studied after: (a) 40 min occlusion followed by 6 hr reperfusion (n = 6); (b) 6 hr occlusion followed by one hour reperfusion (n = 5); and (c) 7 hr occlusion with no reperfusion (n = 4). Areas of myocardial infarction were defined with triphenyl-tetrazolium chloride (TTC) staining, and blood flow was determined with 9-mu radioactive microspheres. In Group C uptake in infarcted and peri-infarct areas was not enhanced, most likely owing to low flow. In Group B, with late reperfusion, Tc-99m PPi sequestration was increased in both infarcted and peri-infarcted tissues. In Group A, areas ischemic during occlusion but with normal flow and viability by TTC after 6 hr of reperfusion showed significant uptake of Tc-99m PPi (twice the uptake of nonischemic regions).

Animals↗