Comparison of adenosine and exercise stress test for quantitative perfusion imaging in patients on beta-blocker therapy.

UNLABELLED: Beta-blocker therapy is used to decrease myocardial ischemia during exercise but may cause suboptimal diagnostic performance in exercise stress testing. The aim of the present study was to compare results of quantitative technetium-99-sestamibi single photon emission tomography (SPECT), following exercise stress test or pharmacological stress test with adenosine. We chose adenosine as comparison, since betablockers may not interfere with adenosine induced vasodilatation and therefore possibly may not interfere with its diagnostic performance. Sixteen patients with angiographically documented coronary disease (5 single-vessel, 6 two-vessel and 5 three-vessel disease), who were chronically treated with beta-blockers, performed SPECT imaging at rest, following bicycle exercise and following adenosine infusion in random order. The SPECT data were analyzed visually and quantitatively, using dedicated computer software (CEqual). According to both visual and quantitative SPECT analysis, adenosine was superior to show reversibility. Higher reversibility extent (50 +/- 15 vs. 26 +/- 12 pixels, p < 0.01) and more intense reversibility severity (110 +/- 29 vs. 49 +/- 23 sum of SDs, p < 0.05) were observed during adenosine than exercise. CONCLUSIONS: Less myocardial perfusion abnormalities during exercise than during adenosine stress in patients treated with beta-blockers may indicate less ischemia but also an impaired diagnostic performance. Thus adenosine stress test should be preferred to optimize the diagnostic sensitivity in patients during beta-blocker treatment.

Captopril-induced changes in MAG3 clearance in patients with renal arterial stenosis and the effect of renal angioplasty.

UNLABELLED: Angiotensin-converting enzyme inhibition by captopril decreases renal (131)I-o-iodohippurate sodium or iothalamate extraction in patients with renal artery stenosis (RAS). This study investigated the effect of captopril on another renal radiopharmaceutical, (99m)Tc-mercaptoacetyltriglycine (MAG3), in particular its plasma clearance. METHODS: Three groups of patients were studied. Group I contained 22 patients with hypertension but a low likelihood of RAS according to negative captopril renography results, confirmed by angiography in 5. Group II contained 22 hypertensive patients with RAS documented by angiography and positive captopril and plasma renin response. Group III contained 10 patients after successful percutaneous transluminal renal angioplasty (PTRA) with negative captopril renography results. The 60-min, single-sample technique was used for measurement of the plasma clearance of MAG3 during baseline and captopril renography. RESULTS: In 18 of 22 group I patients, clearance increased (P < 0.01) during captopril renography compared with baseline conditions, whereas in 18 of 22 group II patients, clearance decreased (P< 0.01). In group III patients, clearance was not significantly altered. The clearance decrease in group II did not correlate with the blood pressure decrease or plasma renin activity increase during captopril renography. CONCLUSION: Renal function assessed by MAG3 plasma clearance decreases in hypertensive patients with RAS but increases in patients without RAS. MAG3 clearance measurements during baseline and captopril renography can thus serve as additional diagnostic information when investigating patients with hypertension for the possibility of an RAS.

Primary lymphoma of the heart.

Primary tumors of the heart are rare. Most patients have very few clinical manifestations and present with uncharacteristic symptoms, often misdiagnosed as heart failure. As investigation techniques such as echocardiography, computed tomography and magnetic resonance imaging become more widespread, the clinician will be confronted with the diagnosing of cardiac masses. Early identification is essential for optimum treatment. We present a case of malignant lymphoma of the heart, where treatment led to remission from cardiac growth of the tumor.

Tubular reabsorption of technetium-99m-DMSA.

UNLABELLED: Intrarenal handling of 99mTc-DMSA is still controversial, particularly in the existence of tubular reabsorption from the tubular fluid. Experiments were performed with micropuncture technique on the rat kidney in an attempt to elucidate this question. METHODS: The concentration profile of 99mTc-DMSA along the nephron was measured in fluid from Bowman's space of surface glomeruli and from the proximal and distal tubules collected by micropuncture. Superficial loops of proximal tubules were micropunctured and microperfused with 99mTc-DMSA or [99mTc] pertechnetate for 10 or 20 min at physiological flow rates; the recovery of activity was measured in the final urine. RESULTS: Bowman's space urine contained only 14% of the 99mTc activity of arterial plasma, indicating low filtration of 99mTc-DMSA, likely due to high plasma protein binding. Tubular fluid-to-plasma activity ratios of 0.31 in the proximal tubules and 1.31 in the distal tubules suggest that 99mTc-DMSA is neither secreted nor reabsorbed along the nephron. Ninety-eight percent of the 99mTc-DMSA activity was recovered in the final ipsilateral urine, while only 0.5% was found in the urine of the contralateral kidney. CONCLUSION: A low fraction of 99mTc-DMSA enters the tubule by glomerular filtration and is not reabsorbed from the tubular fluid. Thus, only peritubular extraction by the tubular cell is responsible for renal uptake of 99mTc-DMSA.

Renal effects of aspirin and low dose methotrexate in rheumatoid arthritis.

OBJECTIVES: The aim of this investigation was to study the glomerular and tubular effects of low doses (15 mg) of methotrexate in patients with rheumatoid arthritis with and without combined treatment with aspirin (2 g single dose). METHODS: Renal function was measured by the plasma clearance of EDTA labelled with chromium-51 (51Cr-EDTA) and mercaptoacetyltriglycine labelled with technetium-99m (99mTc-MAG-3). RESULTS: Clearance of 51Cr-EDTA was reduced from 98 (6) to 87 (5) ml/min (mean (SEM)) for patients receiving methotrexate only and further reduced to 76 (5) ml/min for patients receiving methotrexate and aspirin. This effect was reversible as 51Cr-EDTA increased to 85 (6) ml/min during continued treatment with methotrexate alone. Clearance of 99mTc-MAG-3 also decreased from 366 (18) to 315 (17) ml/min in patients receiving methotrexate alone and further to 295 (17) ml/min during treatment with aspirin and methotrexate. Continued treatment with methotrexate alone resulted in a further decrease in the 99mTc-MAG-3 clearance to 253 (17) ml/min. CONCLUSIONS: The study shows that treatment with low doses of methotrexate particularly when combined with aspirin affects glomerular and tubular function. These effects may be of clinical importance and renal function should therefore be monitored with more sensitive methods than serum creatinine as this may not reflect these changes.

Renal effects of low dose methotrexate in rheumatoid arthritis.

OBJECTIVE: Methotrexate (MTX) treatment at high doses may cause renal failure. The effects of treatment with low MTX doses on kidney function are, however, unknown. The objective of our study was to investigate the effect of low MTX doses on kidney function. METHODS: The glomerular filtration rate was measured as the plasma clearance of 51Cr-EDTA and the clearance of 99mTc-dimercaptoacetyl-triglycine (correction of triglycerine) (99mTc-MAG3), a new renal tubular function agent, was used to measure tubular effects of MTX. RESULTS: Significant decrease of both 51Cr-EDTA clearance from 92 +/- 7 to 83 +/- 5 ml/min x 1.73 m2 (mean +/- SEM) and of the 99mTc-MAG3 clearance from 360 +/- 18 to 309 +/- 15 ml/min x 1.73 m2 (p < 0.05) was observed. CONCLUSION: Our results indicate that low dose MTX treatment (15 mg weekly) may significantly impair kidney function which has to be considered particularly in situations with combined treatment with other potentially nephrotoxic substances.

Coronary angiographic changes during 2 years after myocardial infarction largely undetected by repeated tomographic thallium-201 scintigraphy and not reflected by clinical symptoms.

Repeated coronary angiographies and single photon emission computed tomographies (SPECT) were performed at 9 and 33 months after myocardial infarction (MI) in 47 young men. Coronary lesions were classified in eight grades with respect to the reduction of the luminal diameter. The progression and regression of two steps or more in lesions of grade 2 or more, the recanalization of coronary thrombosis and an increase in collaterals were recorded. Patients were divided into three groups with regard to (A) deterioration, (B) improvement and (C) no changes in the three major coronary regions, respectively. Overall, 23 patients (49%) showed changes between the first and the second investigation. A simplified method using summarized short-axis slices for evaluation of the thallium-201 SPECT showed a significant difference in change of regional myocardial uptake of thallium-201 between groups A and B (P = 0.047) but not between the groups A and C, in lateral myocardial regions. No significant differences were found between any of the groups in respect of the anterior or inferior myocardial regions. These findings were not explained by changes in clinical status, maximum heart rate or workload, or by changes in medication. Our results suggest that substantial changes in coronary morphology can take place during the 2 years following MI without consistent changes in clinical symptoms or regional myocardial perfusion.

Influence of excessive weight loss on respiratory function. A study of obese patients following gastroplasty.

The influence of excessive weight loss, with decreased muscle mass, on pulmonary function was evaluated in 16 obese patients without clinical evidence of respiratory disease. Weight loss was induced with vertical banded gastroplasty. Six nonobese age-matched patients undergoing elective cholecystectomy acted as controls. Preoperative values for static and dynamic lung function variables and for pulmonary gas distribution and respiratory muscle strength were compared with postoperative values after approximately 10% and 18% weight reduction. Before gastroplasty the dominant abnormality of respiratory function was slight restrictiveness, with reduced lung volumes. Body weight and lean body mass decreased significantly during the study period, and respiratory muscle strength was significantly reduced after 10% weight loss. Lung function tests nevertheless showed significant increase of vital capacity, functional residual capacity, total lung capacity and maximal voluntary ventilation. No correlation was found between the reduction of respiratory muscle strength and that of lean body mass. The controls did not diminish the body weight after surgery and the lung volumes and respiratory muscle strength was not changed.

Estimation of technetium 99m mercaptoacetyltriglycine plasma clearance by use of one single plasma sample.

Recent studies have shown that technetium 99m mercaptoacetyltriglycine (MAG-3) is a suitable replacement for iodine 131 or 123 hippurate in gamma-camera renography. Also, the determination of its clearance is of value, since it correlates well with that of hippurate and thus may be an indirect measure of renal plasma flow. In order to simplify the clearance method we developed formulas for the estimation of plasma clearance of MAG-3 based on a single plasma sample and compared them with the multiple sample method based on 7 plasma samples. The correlation to effective renal plasma flow (ERPF) (according to Tauxe's method, using iodine 123 hippurate), which ranged from 75 to 654 ml/min per 1.73 m2, was determined in these patients. Using the developed regression equations the error of estimate for the simplified clearance method was acceptably low (18-14 ml/min), when the single plasma sample was taken 44-64 min post-injection. Formulas for different sampling times at 44, 48, 52, 56, 60 and 64 min are given, and we recommend 60 min as optimal, with an error of estimate of 15.5 ml/min. The correlation between the MAG-3 clearances and ERPF was high (r = 0.90). Since normal values for MAG-3 clearance are not yet available, transformation to estimated ERPF values by the regression equation (ERPF = 1.86 x CMAG-3 + 4.6) could be of clinical value in order to compare it with the normal values for ERPF given in the literature.

A comparative study of renal scintigraphy and clearance with technetium-99m-MAG3 and iodine-123-hippurate in patients with renal disorders.

The aim of this study was to compare kit prepared technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) with our routine radiopharmaceutical, iodine-123-hippurate our routine radiopharmaceutical, iodine-123-hippurate ([123I]OIH) for renal dynamic scintigraphy. Seventeen patients with different nephrologic disorders or hypertension were first studied with OIH and then reinvestigated with MAG3 2-8 days later. Renal MAG3 gamma camera images were almost identical with those of OIH except for higher (p less than 0.01) liver-to-background ratios at 20 min postinjection, irrespective of kidney function. Urinary peristalsis was visible longer and more clearly in the MAG3 studies. MAG3 and OIH renograms showed identical relative kidney uptake (r = 0.99), but elimination of MAG3 from the kidneys was slower (p less than 0.01). The plasma clearance of MAG3 was lower than that of OIH, but correlated (r = 0.92) significantly. The plasma distribution volume and content in blood cells was lower (p less than 0.01), but the binding of MAG3 to plasma proteins was higher, 90%, as compared with 74% for OIH, p less than 0.01. Urinary excretion expressed as a percent of the given dose 60 min after injection was the same for the two substances. Thus, there are some significant differences in the renal handling, plasma distribution, and cell penetration between MAG3 and [123I]OIH. MAG3, however, seems to have particular qualifications as a radionuclide for dynamic renal scintigraphy, especially in patients who require acute investigations or in those with low renal function.

Glomerular filtration and tubular secretion of MAG-3 in the rat kidney.

Technetium-99m mercaptoacetyltriglycine (MAG-3) has recently been introduced as a new radiopharmaceutical for dynamic renal scintigraphy. To elucidate the mechanism of renal excretion, micropuncture experiments were performed in rat kidneys for direct measurements of glomerular filtration and tubular secretory capacity. Fluid of Bowman space was collected from superficial glomeruli and analyzed for its contents of [99mTc]MAG-3, [125I]hippurate and [3H]inulin during constant infusion of these compounds. The ratio of activity of ultrafiltrate to that of arterial plasma was 0.23 for MAG-3, 0.68 for hippurate and 1.04 for inulin which demonstrates that the filtrated amount of MAG-3 is only 23% of that of inulin, presumably because of higher plasma protein binding which was also measured in vitro and found to be 80 +/- 1.5% for MAG-3 and 32 +/- 2% for [125I]hippurate. Proximal and distal tubules were also micropunctured and their tubular fluid as well as the final urine analyzed for the activity of hippurate and MAG-3. The tubular fluid to plasma ratio values along the nephron and in the final urine were all lower for MAG-3 than for hippurate, indicating a lower secretory capacity. From measurements of whole renal clearance, GFR and plasma protein binding the filtered amount of MAG-3 was 0.26 and of hippurate 0.87 ml/min.g kidney weight (p less than 0.001) and the secreted amount 2.01 and 2.38 ml/min.g kidney weight (p less than 0.05), respectively. We conclude that MAG-3 is predominantly excreted by tubular secretion and that the lower renal clearance of MAG-3 as compared with that of hippurate is a result both of a substantially decreased glomerular filtration and of a lower tubular secretion.