51Cr-EDTA plasma clearance in children: One, two, or multiple samples?

ABSTRACT: Plasma disappearance curves using multiple blood samples are a recognized reference method for measuring glomerular filtration rate (GFR). However, there is no consensus on the protocol for this type of measurement. A two-compartment model is generally considered acceptable for the mathematical description of the concentration-time decay curve. The impact of the fitting procedure on the reported GFR has not been questioned.We defined 8 different fitting procedures to calculate the area under the curve, and from this area under the curve, the GFR. We applied the 8 fitting methods (all considering a full concentration-time curve) on the multiple sample data (8 samples) of 20 children diagnosed with Duchenne muscular dystrophy. We evaluated the effect (variability) on the reported GFR from the different fitting methods and compared these results with GFR-values calculated from late samples only (samples after 120 minutes) and from one-sample methods.In 6 out of 20 cases, the fitting methods on the full concentration-time curve resulted in very different reported GFR-values, mainly because some methods were not able to fit the data, or methods resulted in GFR-values ranging from 0 to 120 mL/min. The reported GFR-result therefore strongly depends on the fitting method, making the full concentration-time method less robust than expected. Compared with a consensus reference GFR, the late sample models did not show fitting issues and may therefore be considered as more robust. Also the one-sample methods showed acceptable accuracy.The late sample methods (using 3 time-points) provide robust and reliable methods to determine GFR.

Comparison of simultaneous plasma clearance of 99mTc-DTPA and 51Cr-EDTA: can one tracer replace the other?

Both 99mTc-DTPA and 51Cr-EDTA are widely used to determine glomerular filtration rate (GFR), but few direct comparative studies exist. The shortage of 51Cr-EDTA makes a direct comparison highly relevant. The aim of the study was to investigate if there is any clinically relevant difference between plasma clearance of 99mTc-DTPA and 51Cr-EDTA. Patients ≥18 years of age referred for routine GFR measurement by 51Cr-EDTA were prospectively enrolled. The two tracers (10 MBq 99mTc-DTPA (CaNa3-DTPA) and 2.5 MBq 51Cr-EDTA) were intravenously injected at time zero. A standard 4-sample technique was applied with samples collected at 180, 200, 220 and 240 min, if the estimated GFR (eGFR) was ≥30 mL/min. A comparison of single-sample GFR based on the 200 min sample was also conducted. Fifty-six patients were enrolled in the study. All patients had an estimated GFR >30 mL/min/1.73 m2. No patients suffered from ascites or significant oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/min (range 16-226). The plasma clearances determined by the two methods were highly correlated (r = 0.993). The plasma clearance was significantly higher when measured by 99mTc-DTPA than by 51Cr-EDTA (p = 0.01), but the numerical difference was minimal (mean difference 1.4 mL/min; 95% limits of agreement (LOA) -6.6 to 9.4). The difference between the two methods was independent of the level of renal function. Similar results were found for one-sample GFR. No clinically relevant differences were found between the plasma clearance of 99mTc-DTPA and that of 51Cr-EDTA. Therefore, 99mTc-DTPA can replace 51Cr-EDTA when needed.

Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of 51 Cr-EDTA.

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of 51 Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine <200 µmol l-1 entered the study. 51 Cr-EDTA clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg-1 body weight (150 mg ml-1 ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for 51 Cr-EDTA was 59·7 ± 18·8 ml min-1 . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min-1 and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min-1 , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min-1 . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and 51 Cr-EDTA for the assessment of GFR.

Additive solution-7 reduces the red blood cell cold storage lesion.

BACKGROUND: Transfusion of long-stored red blood cells (RBCs) is associated with decreased in vivo RBC recovery, delivery of RBC breakdown products, and increased morbidity and mortality. Reducing the burden of this RBC "storage lesion" is a major challenge in transfusion medicine. Additive solution-7 (AS-7) is a new RBC storage solution designed to improve RBC metabolism by providing phosphate and increasing buffering capacity. STUDY DESIGN AND METHODS: Storage quality in AS-7 was measured in a prospective, randomized, three-center trial using units of whole blood from healthy human subjects whose RBCs were stored for up to 56 days in AS-7 (n = 120) or for 42 days in the control solution AS-1 (n = 60). RESULTS: Hemolysis and shedding of protein-containing microvesicles were significantly reduced in RBCs stored in AS-7 for 42 and 56 days compared with RBCs stored in AS-1. Autologous in vivo recoveries of RBCs stored in AS-7 was 88 ± 5% at 42 days (n = 27) and 82 ± 3% at 56 days (n = 27), exceeding recoveries of RBCs stored in currently used solutions. CONCLUSION: Increasing the phosphate, pH range, and buffer capacity of a RBC storage system allowed RBCs to be stored better and longer than currently approved storage systems. AS-7 ameliorates the long-term storage lesion resulting in significantly increased viability in vitro and in vivo.

Validation and impact of a new technique for assessment of glomerular filtration rate in patients with liver disease.

OBJECTIVES: Previously we have proposed a technique for the measurement of plasma clearance in patients with ascites. The impact of using the technique was assessed and the results compared with those from a reference technique in 111 patients having glomerular filtration rate measurements as part of their workup for liver transplantation. METHODS: Results of calculations using the new technique were compared with plasma clearance measurements obtained using a conventional slope-intercept technique and with clearance measurements based on urine collection. Discrepancies between the results of plasma clearance and urinary clearance assessments were investigated by using an uncollimated gamma camera to measure the total retention of the tracer. RESULTS: Conventional slope-intercept calculations overestimated clearance compared with the new technique by more than 20% in 21% of the patients. Significant differences between the results of the two methods were more likely in patients with more severe ascites. Results of urine collection-based measurements of Cr-51 EDTA clearance were frequently significantly lower than measurements using the new technique, whereas measurements of urinary clearance of creatinine were higher. Gamma camera measurements suggest that discrepancies between total and urinary clearance of Cr-51 EDTA are due to incomplete urine collection. CONCLUSION: The new technique is a practical method for assessment of kidney function and should be used in patients with liver disease who have or may have ascites.

Comparison of 51chromium-labeled ethylenediamine tetra-acetic acid and iohexol as blood markers for intestinal permeability testing in Beagle dogs.

(51)Chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) is the gold standard probe for assessing intestinal permeability (IP) in dogs, but exposure to radioactivity is a disadvantage. Iohexol is a safe contrast medium commonly used for medical imaging purposes and has been successfully applied more recently for the assessment of IP in animal models and humans. This study aimed at comparing (51)Cr-EDTA and iohexol as IP blood markers in dogs. A test solution containing (51)Cr-EDTA and iohexol was administered intragastrically to seven healthy laboratory Beagle dogs, and percentage recoveries in serum were calculated. The strong linear association (correlation, r=0.76 and linear regression, y=0.03+5.04x) between (51)Cr-EDTA and iohexol supports the potential usefulness of iohexol as an IP blood marker in dogs.

Reliability of 5¹Cr-EDTA plasma and urinary clearance as a measure of residual renal function in dialysis patients.

PURPOSE: In dialysis patients, longer survival is associated with a higher residual renal function. Randomized controlled trials are conducted to clarify how residual renal function can be preserved. However, existing methods for measuring residual renal function are uncertain and there is a need for establishing a standard for measurements of glomerular filtration rate (GFR) in dialysis patients. METHODS: 5¹Cr-EDTA clearances in plasma, urine, and dialysate were evaluated in a sample of 12 hemodialysis and 12 peritoneal dialysis patients. The patients' condition was generally stable, and all patients were investigated twice within 4-10 days. RESULTS: Plasma clearances of 5¹Cr-EDTA for all patients ranged between 2.1 and 30.8 mL/min/1.73 m², whereas urinary 5¹Cr-EDTA clearances ranged from 0.7-20.0 mL/min/1.73 m². This difference was statistically significant (p < 0.001). Week-to-week reproducibility expressed as coefficients of variation were below or equal to 10% for plasma clearances and 13% for urinary clearances in hemodialysis patients and 14% in peritoneal dialysis patients. CONCLUSIONS: This study demonstrated a difference between 5¹Cr-EDTA plasma and urinary clearances in dialysis patients. Plasma clearance of 5¹Cr-EDTA had the best reproducibility. For repeated measurements as in clinical prospective trials, we recommend 5¹Cr-EDTA plasma clearance based on blood sampling at 5 + 24 hours with subtraction of 5¹Cr-EDTA dialysate clearance in peritoneal dialysis patients. Further studies are needed to corroborate our findings.

Correlation of various published radionuclide glomerular filtration rate estimation techniques and proposed paediatric normative data.

OBJECTIVE: The aim of this study is to assess the comparability and interchangeability of the radionuclide glomerular filtration rate (GFR) using different published techniques, and propose normative data for paediatrics. METHODS: A total of 476 paediatric oncology patients aged 2-17 years, referred between January 2001 and December 2008 for GFR estimation, were reviewed for any potential cause of renal impairment. Sixty-nine patients met the stringent inclusion criteria, and were included in the study. GFR estimation was carried out using either technetium-99m diethylene triamine penta-acetic acid (99mTc-DTPA) or chromium-51 EDTA (5¹Cr-EDTA). Multiple GFR results were calculated from the same blood sample data (counts/min/ml), according to previously published GFR estimation techniques using one to three blood samples. These techniques were slope-intercept, slope-only and half life. For slope-intercept techniques, GFR was normalized to body surface area or extracellular fluid volume. RESULTS: The GFR values obtained using different techniques were highly variant. The intraclass correlation (ICC) for different methods was moderate (ICC=0.56-0.66). A reliable empiric formula to allow conversion of GFR values from one technique to another could not be derived because of this variability, with some exceptions. 5¹Cr-EDTA yielded the same or lower variability than 99mTc-DTPA. The British Nuclear Medicine Society-recommended method had the lowest coefficient of variation, with a mean value of 116 (SD 22) normalized to 1.73 m² for 5¹Cr-EDTA using two samples. CONCLUSION: The GFR values obtained from different calculation techniques are not readily interchangeable or comparable, with some exceptions. For both 99mTc-DTPA and 5¹Cr-EDTA, the British Nuclear Medicine Society-recommended technique appears to be the most robust, with the least coefficient of variation.

Red blood cell survival in long-term dialysis patients.

BACKGROUND: Shortening of red blood cell (RBC) survival contributes to the anemia of chronic kidney disease. The toxic uremic environment accounts for the decreased RBC life span. The contribution of mechanical damage caused by hemodialysis to the shortened life span is unclear. Reductions up to 70% in RBC survival have been reported in uremic patients. To date, no accurate well-controlled RBC survival data exist in dialysis patients treated using different dialysis modalities and receiving erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to determine RBC survival in hemodialysis (HD) and peritoneal dialysis (PD) patients compared with healthy persons. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 14 HD patients and 5 PD patients were recruited from the dialysis unit. Healthy volunteers (n = 14) age- and sex-matched to HD participants were included. All dialysis patients received either ESA therapy or regular iron supplementation. PREDICTOR: Dialysis patients versus age- and sex-matched healthy controls. OUTCOMES: RBC survival. MEASUREMENTS: RBC survival was determined using radioactive chromium labeling. RESULTS: More than 85% of dialysis patients were anemic (hemoglobin, 12.0 ± 1.1 g/dL); hemoglobin concentrations were not significantly different between HD and PD patients. Median RBC survival was significantly decreased by 20% in HD patients compared with healthy controls: 58.1 (25th-75th percentile, 54.6-71.2) versus 72.9 (25th-75th percentile, 63.4-87.8) days (P = 0.02). No difference was shown between the PD and HD groups: 55.3 (25th-75th percentile, 49.0-60.2) versus 58.1 (25th-75th percentile, 54.6-71.2) days (P = 0.2). LIMITATIONS: Label loss from RBCs associated with the chromium 51 labeling technique needs to be accounted for in the interpretation of RBC survival data. CONCLUSIONS: Despite current ESA therapy, decreased RBC survival contributes to chronic kidney disease-related anemia, although the reduction is less than previously reported. There does not appear to be net mechanical damage associated with HD therapy resulting in decreased RBC life span.

Measurement of glomerular filtration rate with chromium-51 ethylene diamino tetraacetic acid in the presence of gallium-67 citrate: a novel method for the solution of the problem.

Chromium-51 (5¹Cr)-ethylene diamino tetraacetic acid plasma clearance is commonly used in glomerular filtration rate measurements. In the presence of additional radionuclides in plasma samples, glomerular filtration rate may be seriously underestimated and a correction of the crosstalk interference may be necessary. This type of correction is problematic in the case of gallium-67 (67Ga) mainly because of the close vicinity of its 300 keV photopeak with that of the 320 keV photopeak of 5¹Cr. A novel method of calculating and removing the interfering 67Ga counts within the 5¹Cr counting window, based on the different decay rates of the two radionuclides, is presented, requiring two series of sample counting in the 5¹Cr counting window only, separated by a 3-day interval. This method was developed to solve a clinical problem and then it was validated by a controlled 67Ga contamination of plasma samples with known counts from 5¹Cr-ethylene diamino tetraacetic acid.

Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies.

Accurate measurement of extracellular fluid volume from the slope/intercept technique after bolus injection of a filtration marker.

Extracellular fluid volume (ECV) is studied infrequently. The zero-time distribution volume (Vd) generated in the slope-intercept technique for measuring the glomerular filtration rate (GFR) substantially overestimates ECV. The aim was to validate a new technique for measuring ECV from the slope-intercept approach. GFR and ECV were measured using Cr-51-EDTA and iohexol injected into opposite arms in 51 patients undergoing routine measurement of GFR and on 48 occasions in 20 healthy volunteers. Blood samples were obtained bilaterally 20, 40, 60, 120, 180 and 240 min post-injection and assayed for indicator injected contralaterally. Reference ECV (ECV6) was calculated from all six samples as the product of indicator transit time and multi-sample GFR. GFR/ECV was calculated as the rate constant of the exponential fitted to the last three samples (GFR/ECV3). Slope-intercept GFR was calculated from the last three samples using the slope-intercept technique (GFR3). ECV (ECV3) was calculated by dividing GFR3 by GFR/ECV3, having corrected both for their one-compartment assumptions. ECV6(EDTA) correlated closely with ECV3(EDTA) (ECV3(EDTA) = 1.01.ECV6(EDTA)-0.5 L; r = 0.97; n = 99), but less closely with Vd (Vd = 1.17.ECV6(EDTA) + 0.7 L; r = 0.86). ECV6(iohexol) correlated slightly better with ECV6 (EDTA) (ECV6(EDTA) = 0.81.ECV6(iohexol) + 3.3 L; r = 0.86) than with ECV3(EDTA) (ECV3(EDTA) = 0.83.ECV6(iohexol) + 2.9 L; r = 0.84) and had slightly narrower 95% limits of agreement (-3.82 and 2.82 L versus -3.90 to 3.43 L). In conclusion, ECV can be measured from three samples almost as accurately as ECV from multiple samples.

The measurement and importance of red cell survival.

The measurement of red blood cell survival in the circulation has progressed from the original differential agglutination technique of Ashby to current isotopic and flow cytometric methods. While occasionally useful in the clinic, these methods find widespread use in a number of important research areas, including the evaluation of new red cell storage media in transfusion medicine and studies of the pathophysiology of sickle cell disease and diabetes. In this review, measurement techniques are placed in historical perspective and examined for relative merits and suitable application.

Red cell volume can be accurately determined in sheep using a nonradioactive biotin label.

The sheep has served as an informative animal model for investigation of human fetal and newborn erythropoiesis and red blood cell (RBC) kinetics. We previously validated the permanent label (14C)cyanate for measuring red cell volume (RCV) in sheep. Here, we validate biotin labeling of RBCs as a nonradioactive method for measuring RCV in sheep with the anticipation that it can be applied in studies of human infants. The RCV was determined simultaneously using two techniques for quantitation of the biotin label. The first one quantified total blood concentration of biotin label on biotin-labeled RBCs using (125I)streptavidin. The second one enumerated biotin-labeled RBCs by flow cytometry after incubation with fluorescein-conjugated avidin. RCV measurements made using the two biotin quantitation techniques were validated against both (14C)cyanate and 51Cr as reference methods. Both biotin techniques produced RCV values that agreed well with the reference methods and with each other, producing correlation coefficients averaging >or =0.93. Sequential repetitive measurements in the same animal also agreed with the (14C)cyanate method and each other (average difference <10%). These results establish biotin-labeled RBCs as an accurate method for performing RCV measurements in sheep. This biotin method can be applied in studies that model neonatal erythropoiesis.

Estimation of renal function in children and adolescents with spinal dysraphism.

PURPOSE: In children with spinal dysraphism such as myelomeningocele the relation between muscle mass and body composition varies considerably. Therefore, it is difficult to evaluate the relevance of renal function assessments done with serum creatinine. Since serum cystatin C has been suggested to be independent of body size and composition, this evaluation was compared to chromium(51) edetic acid clearance. MATERIALS AND METHODS: Simultaneous measurements of cystatin C and chromium(51) edetic acid clearance were performed prospectively in 65 patients 2 to 19 years old with spinal dysraphism. RESULTS: Cystatin C values were within the normal range in all patients, while chromium(51) edetic acid clearance was reduced in 10. A significant relation was seen. CONCLUSIONS: Using chromium(51) edetic acid clearance as a gold standard, children with spinal dysraphism and slightly to moderately reduced renal function may remain undiagnosed if cystatin C is used for evaluation.

The clearance kinetics of autologous RhD-positive erythrocytes coated ex vivo with novel recombinant and monoclonal anti-D antibodies.

Anti-D is given routinely to pregnant RhD-negative women to prevent haemolytic disease of the fetus and newborn. To overcome the potential drawbacks associated with plasma-derived products, monoclonal and recombinant forms of anti-D have been developed. The ability of two such antibodies, BRAD-3/5 monoclonal anti-D IgG (MAD) and rBRAD-3/5 recombinant anti-D IgG (RAD), to clear RhD-positive erythrocytes from the circulation was compared using a dual radiolabelling technique. Six RhD-positive males received autologous erythrocytes radiolabelled with (99m)Tc and (51)Cr and coated ex vivo with MAD and RAD. Blood samples were collected up to 1 h following intravenous injection, and percentage dose of radioactivity in the samples determined. Three different levels of coating were used on three separate occasions. No significant differences between MAD and RAD were observed in the initial clearance rate constant at any dose level. The log[activity]-time clearance plots were curved, showing a reduction in the clearance rate constant with time. This reduction was more marked for RAD than for MAD. The results support a dynamic model for the clearance of antibody-coated erythrocytes that may have wider relevance for the therapeutic use of antibodies.

Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study.

OBJECTIVE: To assess the clinical outcome and imaging features of neonatal primary vesicoureteral reflux (VUR). STUDY DESIGN: We prospectively followed 43 infants with primary VUR identified from among a cohort of 497 infants with fetal renal pelvis dilatation. Postnatal renal ultrasound (US) examinations were performed at 5 days and 1, 3, 6, 12, and 24 months of life. Voiding cystourethrography was performed in the neonatal period and repeated at 12 and 24 months when VUR was persistent. Two radioisotopic examinations, including a 99mTc-MAG3 renogram and a plasma clearance of Cr-51 EDTA, were performed in all children with high-grade reflux. RESULTS: The incidence of primary VUR in our study group was 9%. Among the 43 patients followed, 11 (26%) had high-grade (IV-V) VUR and 32 (74%) had low-grade VUR. Resolution of reflux occurred in 2 of 11 (18%) patients with high-grade VUR and in 29 of 32 (90.6%) patients with low-grade VUR at age 2 years (P < .001). At age 2 years, 91% of the low-grade refluxing kidneys were normal on US, compared with only 35% of the high-grade refluxing kidneys. Split renal function was within normal range and single-kidney GFR was significantly increased in 13 of the 17 high-grade refluxing kidneys during follow-up. Furthermore, a strong association between dysplasia on US and poor renal function outcome was found. CONCLUSIONS: In most infants with VUR, the reflux is of low grade and resolves rapidly. In those children with high-grade VUR, spontaneous resolution is rare at age 2 years, but persistent reflux rarely impairs the maturation of renal function.

Short-term distribution of Cs in relation to Cr-EDTA after intravenous dose in goats.

AIM: The aim of this study was to gather information about the short-term rate of caesium uptake (incorporation) in different animal tissues and explain them with known physiological mechanisms affecting ion distribution. METHODS: Six goats were given an intravenous bolus containing (134)Cs as a tracer and (51)Cr-EDTA as an extracellular marker. After 30 min, the animals were killed and the activity concentration of radioactive isotopes in different tissues and fluid compartments were measured. RESULTS: The highest relative activity concentration of (134)Cs was found in kidney cortex, with a tissue/plasma-ratio around 50. In urine, the ratio varied between 5 and 28. In the salivary gland, cardiac muscle and small intestine the ratio was around 11, 7 and 6, respectively. The contents of small intestine had an average activity concentration five times that of plasma. In skeletal muscle the terminal activity concentration was surprisingly low, with a tissue/plasma ratio mostly far less than unity. Even in connective tissue and cartilage the terminal activity concentration was generally higher than in skeletal muscle. CONCLUSION: The rate of uptake of caesium varies widely from tissue to tissue. Many of these differences can be explained with differences in Na,K-ATPase activity. Also, perfusion and accessibility play a role in some tissues, like brain and possibly part of the skeletal muscles. The short-term distribution of caesium differs distinctly from the long-term distribution reported in literature.

Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model.

Carbon monoxide is produced in the endothelial cells and has possible vasodilator activity through three different pathways. The aim of this study was to demonstrate circulatory effects after administration of saturated carbon monoxide blood and to describe the pharmacokinetics of carbon monoxide. Six pigs were anesthetized and 150 ml blood was removed. This blood was bubbled with carbon monoxide until the carboxyhemoglobin (COHb) levels were 90-99%. A specific amount of this blood was then injected back to the animal. At predetermined times; arterial and mixed venous blood was drawn and analyzed for carbon monoxide. Systemic and pulmonary vascular resistance index (SVRi and PVRi) were measured and exhaled air was sampled and measured for carbon monoxide. Blood samples were gathered over 300 minutes along with measurements of invasive pressures, heart rate, cardiac output, oxygen saturation (SpO2), Hb, temperature and blood gases. We conclude that this type of exposure to carbon monoxide appears to have little or no effect on general vasomotor tone and, after correcting for basal levels of carbon monoxide, elimination occurs through the lungs as predicted by a single compartment model. The half-life of carbon monoxide was determined to be 60.5 minutes (SEM 4.7).

51Cr-EDTA absorption blood test: an easy method for assessing small intestinal permeability in dogs.

The 51Cr-EDTA test is a valuable clinical tool for screening intestinal diseases in dogs. The test is performed by calculating the percentage of recovery from urine of a PO-ingested dose of 51Cr-EDTA after 6 or 24 hours. Careful urine collection is a practical limitation of this test in dogs, and our goal was to develop a simpler test that measures 51Cr-EDTA in blood. A 51Cr-EDTA absorption test was simultaneously performed on urine and serum 43 times in healthy Beagle Dogs. Timed blood samples were withdrawn, and urine was collected during a 6-hour period. Percentages of the ingested dose were then calculated in urine and serum. The mean +/- standard deviation (range) percentage in urine after 6 hours was 14.07 +/- 8.72% (3.81-34.18%), whereas results in serum from samples taken at 2, 3, 4, 5, and 6 hours were 0.49 +/- 0.45% (0.02-2.13%), 0.75 +/- 0.52% (0.03-1.89%), 0.82 +/- 0.57% (0.13-2.21%), 0.70 +/- 0.53% (0.12-1.99%), and 0.47 +/- 0.44% (0.11-1.79%), respectively. The results for blood specimens showed good concordance with those for urine, especially for the samples taken at 4 hours (r = 0.89). Moreover, the correlation between urine and blood was better when the sum of the percentages of the recovered analyte from various blood samples was compared with urine. The correlation coefficient when summing 4 blood samples was excellent (r = 0.97) and remained excellent when summing only 2 blood samples taken at 3 and 5 hours (r = 0.95) or at 3 and 4 hours (r = 0.94). We conclude that a serum 51Cr-EDTA test determined by summing successive blood samples provides an easier means of estimating small intestinal permeability in dogs and gives results comparable to those of the 6-hour urine test.