Force-generating preparation from human atria as a model for studying myocardial uptake of radiopharmaceuticals.

UNLABELLED: The aim of this study was to assess whether an in vitro preparation of force-generating human atrial trabeculae driven by external electrical stimulation is a suitable model for determining myocardial uptake of cardiotropic radiopharmaceuticals. METHODS: Human atrial trabeculae were excised from specimens removed during cardiac surgery for insertion of heart-lung apparatus. Preparations were kept under physiologic conditions in a chamber continuously perfused by Tyrode's solution at 37 degrees C under permanent oxygenation. Electrical stimulation was performed at a frequency of 1 Hz. Contractile response was continuously measured by a force transducer and registered by a lineacorder. The optimum length of the trabeculae was achieved by stepwise increases of 0.1 mm muscle length. A premixed solution containing 1.92-4.06 MBq 201TI-TICI was added to the perfusate of the chamber. After 10, 30, and 60 min, respectively, of incubation with 201TI-TICI, the atrial trabeculae were removed from the chamber and their activity was measured by a gamma counter. These experiments were repeated with nonviable trabeculae pretreated by potassium cyanide (KCN). Myocardial uptake values were measured as cts/min, normalized to cts/min/mg, and expressed as percentages of cts/mL/min in the perfusate (RUP). RESULTS: Thallium uptake was found to be dependent on the functional integrity of the tissue preparations and increased over time in intact atrial trabeculae. RUP was 325% +/- 108% after 10 min of incubation and rose to 838% +/- 160% and 1196% +/- 493%, respectively, at 30 and 60 min of incubation (P < 0.01). After 30 min of incubation, RUP was significantly higher in viable than in nonviable trabeculae (838% +/- 160% versus 90% +/- 65%; P < 0.01). CONCLUSION: These preliminary results indicate that the model proposed is suitable for studying the mechanisms of uptake of cardiotropic radiopharmaceuticals by human myocardial tissue.

Diagnostic accuracy and predictive value of the tumor-associated antigen S100 in malignant melanomas: validation by whole body FDG-PET and conventional diagnostics.

UNLABELLED: We investigated the predictive value of the protein S100 as a tumor-marker in the post-surgical follow-up staging of patients with High Risk melanomas (Clark Levels IV/V, Thickness > 0.75 mm). METHODS: In 51 follow-up studies, performed in 50 patients, serum concentrations of the protein S100 were measured and evaluated with respect to their diagnostic value based on the findings of whole body F-18-FDG-PET studies. The findings of FDG-PET were correlated with the findings of CT, MRI, lymph node sonography, bone scintigraphy, and with histological findings, or a follow-up staging after at least 6 months, respectively. Thus, FDG-PET exhibited a sensitivity of 100% and a specificity of 95%. S100 concentrations were measured by an established RIA (Ria-mat Sangtec 100) and by a novel LIA (Lia-mat Sangtec 100 beta). Subsequently, S100 was compared with thymidine kinase for the predictive values of both tumor-markers in the follow-up of malignant melanoma. RESULTS: Intraindividual comparison of S100 concentrations measured by LIA with those obtained by RIA showed a calculated correlation coefficient of 0.97 (Cutoff-levels were 0.1 microgram/l [RIA] and 0.2 microgram/l [LIA]). The arrangement of these cutoff-levels leads to a sensitivity of 85% at a specificity of 55% for Protein S100 when measured by RIA, and to a sensitivity of 77% at a specificity of 61% when measured by LIA. The negative predictive values are 91% (RIA) and 88% (LIA), in association with positive predictive values of 39% (RIA) and 40% (LIA). At a cutoff-level of 4.0 micrograms/l, thymidine kinase showed a sensitivity of 70% and a specificity of 41%. CONCLUSIONS: a) The results obtained by LIA are in a very good correlation with the results measured by the well-established RIA. Thus, the LIA is a suitable method for the clinical routine. b) The protein S100 as a tumor-marker of malignant High Risk melanomas has no clinically important sensitivity and specificity as could be proved by a comparison with the predictive value of FDG-PET. c) Whether or not during therapy information concerning progression/remission of the disease can be received out of repetitive measurements of the S100, has to be shown by the results of validated long term follow-up studies.

[Myocardial scintigraphy]. / Myokardszintigraphie.

Myocardial scintigraphy allows the assessment of myocardial perfusion and viability and has been validated in tens of thousands of patients. This article reflects current developments of radiopharmaceuticals as well as of acquisition systems; additionally, comparisons are drawn with stress echocardiography and myocardial positron emission tomography. Furthermore, the prognostic value and the cost-efficiency of this technique are demonstrated.

Economy of contraction of cardiomyocytes as influenced by different positive inotropic interventions.

In the present study the effects of the novel cardiotonic agent EMD-57033 on contraction and energetic demand of isolated, electrically stimulated cardiomyocytes were investigated and compared with the effects of enhancement of extracellular calcium and of the beta-mimetic isoproterenol. In a specially designed setup [H. Rose, K.H. Strotmann, S. Pöpping, Y. Fischer, D. Kulsch, and H. Kammermeier. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): H1329-H1334, 1991] parameters of contractile behavior and metabolic demand (O2 consumption) of isolated cardiac myocytes were measured. For a given enhancement of contractile performance (cell shortening) the increase in energetic demand (VO2) after application of EMD-57033 were markedly lower than on treatment with elevated extracellular Ca2+ concentration or with isoproterenol. This economization of positive inotropic effects was proposed to be due to two factors. First, stimulation-related ion cycling was only slightly enhanced with marked increase in contraction amplitude after application of EMD-57033. Second, calcium sensitization reflected in a leftward shift of the calcium concentration needed for half-maximum force development could be interpreted to be mediated by modulation of the cross-bridge dynamics of the myofilaments, where reduction of the switch-off rate of the cross bridges and prolongation of their force-generating states were presumed to be involved. Lowered pH (7.0) decreased economy of contraction. EMD-57033 restored contraction amplitude and economy of contraction at lowered pH.