Prediction of post‐operative glomerular filtration rate after nephrectomy for renal malignancy

The importance of a correct estimation of contralateral renal function in cases of renal malignancy is obvious, necessitating a conservative approach to tumour resection when function of the contralateral kidney is markedly reduced. The aim of the present study was to determine the accuracy of preoperative gamma camera renography and ⁵¹Cr‐EDTA clearance to predict the glomerular filtration rate (GFR) early and up to 6 months after nephrectomy for renal malignancy. Patients (n=40) underwent both gamma camera renography (^99mTC‐DTPA) and ⁵¹Cr‐EDTA clearance preoperatively, whereas ⁵¹Cr‐EDTA clearance was measured within 1 week and up to 6 months after nephrectomy. The single kidney GFR values of the contralateral kidneys were estimated preoperatively and then compared with the post‐operative ⁵¹Cr‐EDTA clearance values. The predicted GFR values were lower compared with the measured post‐operative ⁵¹Cr‐EDTA clearance values (45 ± 2 vs. 54 ± 3 ml min^–1 1 week after nephrectomy and 53 ± 3 ml min^–1 6 months later, P<0·01, respectively). The difference between the measured and predicted GFR was larger in patients below the median age of 60 years (P<0·05) and confined to patients with a relative uptake of >30% by the tumour affected kidney. Prediction of post‐operative GFR by non‐invasive renal function tests performed prior to surgery for renal malignancy underestimate post‐operative GFR when the function of the tumour affected kidney is preserved, indicating an adaptive GFR increase in these cases.     

Estimating GFR in children with 99mTc‐DTPA renography: a comparison with single‐sample 51Cr‐EDTA clearance

Glomerular filtration rate (GFR) measurement by ⁵¹Cr‐ethylenediaminetetraacetic acid (EDTA) and blood sampling in children is usually cumbersome for the patient, parents and laboratory technicians. We have previously developed a method accurately estimating GFR in adults. The aim of the present study was to evaluate the accuracy of this non‐invasive method in children. We calculated GFR from ^99mTc‐diethylene triamine pentaacetic acid (DTPA) renography and compared with ⁵¹Cr‐EDTA plasma clearance of 29 children between the age of 1 month and 12 years (mean 4·7 years). The correlation between ^99mTc‐DTPA renography and ⁵¹Cr‐EDTA plasma clearance was for all children R = 0·96 (n = 29, P<0·0001), for children above 2 years of age R = 0·96 (n = 18, P<0·0001) and for children <2 years R = 0·84 (n = 11, P<0·001). We conclude that assessment of GFR from ^99mTc‐DTPA renography is reliable and comparable to GFR calculated from ⁵¹Cr‐EDTA plasma clearance. Because our method is non‐invasive and only takes 21 min, it may be preferable in many cases where an assessment of renal function is needed in children especially when renography is performed anyhow.     

Mannitol clearance for the determination of glomerular filtration rate–a validation against clearance of 51Cr‐EDTA

We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of ⁵¹Cr‐EDTA in outpatients with normal to moderately impaired renal function. Forty‐one patients with a serum creatinine <200 μmol l^?1 entered the study. ⁵¹Cr‐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 ⁵¹Cr‐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 ⁵¹Cr‐EDTA for the assessment of GFR.     

Gamma‐variate plasma clearance versus urinary plasma clearance of 51Cr‐EDTA in patients with cirrhosis with and without fluid retention

In patients with fluid retention, the plasma clearance of ⁵¹Cr‐EDTA (Cl_exp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma‐variate plasma clearance (Cl_gv) with the urinary plasma clearance of ⁵¹Cr‐EDTA (Cl_u) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of ⁵¹Cr‐EDTA followed by plasma and quantitative urinary samples for 5 h. Cl_gv was determined from the injected dose relative to the plasma concentration‐time area, obtained by a gamma‐variate iterative fit. Cl_exp and Cl_u were determined by standard technique. In patients without fluid retention, Cl_gv, Cl_exp and Cl_u were closely similar. The difference between Cl_gv and Cl_u (Cl_gv – Cl_u = ΔCl) was mean ?0·6 ml min^?1 1·73 m^?2. In patients with ascites, ΔCl was significantly higher (11·8 ml min^?1 1·73 m^?2, P<0·0001), but this value was lower than Cl_exp – Cl_u (17·5 mL min^?1 1·73 m^?2, P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Cl_gv and Cl_exp overestimates GFR substantially, but the overestimation is smaller with Cl_gv. Although Cl_u may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.     

Lopromide one-sample clearance as a measure of glomerular filtration rate

Objective: The pharmacokinetics of iopromide were analysed using a two‐compartment model. The optimal point of time for blood withdrawal for calculation of a one‐sample clearance was determined. Methods: Plasma concentration of iodine was measured up to 8 h postinjection (p.i.) in 62 adult patients who received 120 ml iopromide for computed tomography (CT). A two exponential function was fitted by a weighted least error square method. As reference method, clearance was calculated from this function and the injected amount of iodine. Empirical parameters for calculation of one‐sample clearance were determined. This one‐sample clearance was compared with one‐sample clearance calculated according to formulas developed for Tc99m‐DTPA by Jacobsson as well as a two sample method. Results: Total distribution volume of iopromide was calculated as 0·242 Lkg^?1± 5·9%. A high correlation of all one‐sample method and the two‐sample method with reference to clearance was found. Best estimation of iopromide plasma clearance was achieved by determining one‐sample clearance 270 or 285 min p. i. with SD_y.x of 5·8 ml min^–1. Conclusions: After administration of 120 ml iopromide, one‐sample plasma clearance can be calculated with low estimation error taking one blood sample at an appropriate time point. Late phase pharmacokinetics of iopromide found in the present study showed to be virtually identical to results published for iohexol and Tc99m‐DTPA.     

Pulmonary clearance of inhaled [99Tcm]DTPA: effects of ventilation pattern

Summary. While a rise in lung volume is known to increase the pulmonary clearance of technetium-99m-labelled dietylene triamine pentaacetate ([⁹⁹Tc^m]DTPA), little interest has been focused on the effects of changes in ventilation frequency, tidal volume and airway pressure. We studied adult, anaesthetized and intubated rabbits during three ventilation patterns (VP) using pressure controlled ventilation (Servo Ventilator 900C). VP was either deep slow (f=20 min^-1, tidal volume (V_T) = 30 ± 4 ml kg^-1 and positive end-expiratory pressure (PEEP) = 0·2 kPa [VP 20/ 0·2, n= 8]) or rapid shallow (f=80 min^-1, V_T= 11 ±2 ml kg^-1 and PEEP = 0·2 or 0·4 kPa [VP 80/0·2, n= 6 and VP 80/0·4, n= 6]). The mean airway pressure was similar at VP 20/0·2 and VP 80/0·4. During administration of [⁹⁹Tc^m]DTPA aerosol all animals were ventilated under the same conditions (f=40 min^-1 and PEEP = 0·2 kPa). The pulmonary clearance rate expressed as the half-life time (T^1/2) of [⁹⁹Tc^m]DTPA was at VP 80/0·2 = 113 ± 31 min, at VP 80/0·4 = 70 ± 24 min (P < 0·01 compared to VP 80/0·2) and at VP 20/0·2 = 36± 18 min (P <0·001 compared to VP 80/0·2 and P <0·01 compared to VP 80/0·4). We conclude that the pulmonary clearance of [⁹⁹Tc^m]DTPA increases

• 1 during rapid shallow ventilation when PEEP is increased from 0·2 to 0·4 kPa;
• 2 during deep slow ventilation relative to rapid shallow ventilation even when the mean airway pressure is similar.

     

Renal reserve filtration capacity in growth hormone deficient subjects

Abstract. In normal subjects, the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) acutely increase in response to infusion of amino acids and to low doses of dopamine. It is uncertain whether circulatory growth hormone (GH) is a permissive factor for these stimulatory effects. GFR and ERPF (constant infusion technique using ¹²⁵I-iothalamate and ¹³¹I-hippuran, respectively) were measured before and during the infusion of dopamine and amino acids in 8 GH deficient subjects. The clearance study was repeated during concomitant administration of octreotide to investigate whether this somatostatin analogue would modify the amino acid and dopamine-induced renal haemodynamic changes. Dopamine increased baseline GFR from 89± 3 (mean±SEM, n= 8) to 102 ± 4 ml min^-1 1.73 m^-2 and ERPF from 352± 19 to 476± 26 ml min^-1 1.73 m^-2, P<0.001 for both. During amino acid infusion GFR and ERPF increased to 108±3 and 415±23 ml min^-1 1.73 m^-2, respectively, P< 0.001 for both. Octreotide did not significantly decrease baseline and dopamine-stimu-lated renal haemodynamics but lowered the amino acid-stimulated GFR (98±4 ml min^-1 1.73 m^-2, P<0.05) and ERPF (381± 18 ml min^-1 1.73 m^-2, P<0.05). Basal plasma glucagon concentrations were not suppressed by octreotide, whereas the amino acid-induced increments in plasma glucagon were partially inhibited. It is concluded that GH is not a necessary factor for the stimulatory effects of amino acids and dopamine on renal haemodynamics. The renal reserve filtration capacity in GH deficiency was at least as large as previously documented in normal subjects. It is likely that there is a functional antagonism between the effects of amino acids and octreotide on renal haemodynamics in GH deficiency.     

Assessing Glomerular Filtration in Small Animals Using [<Superscript>68</Superscript>Ga]DTPA and [<Superscript>68</Superscript>Ga]EDTA with PET Imaging

Purpose

Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals.

Procedures

Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals.

Results

Both tracers did not bind to blood cells. [⁶⁸Ga]DPTA but not [⁶⁸Ga]EDTA showed strong binding to plasma proteins. For this reason, [⁶⁸Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [⁶⁸Ga]EDTA was 89 ± 1 %. The calculated GFR using [⁶⁸Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [⁶⁸Ga]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR.

Conclusions

[⁶⁸Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [⁶⁸Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.

     

Atrial natriuretic peptide and renal adaptation to contralateral nephrectomy in healthy man

Atrial natriuretic peptide (ANP), angiotensin II (AII), aldosterone (Aldo) and arginine vasopression (AVP) in plasma were determined in 12 healthy renal transplant donors before and 5, 12, 26, 54 days after uninephrectomy (N_x) in order to study the possible role of these hormones in functional adaptation to acute reduction in renal mass. Glomerular and tubular function was studied by measurements of the clearances of ⁵¹Cr-EDTA, lithium, sodium, postassium, and albumin. ANP was 7.4±3.1 pmol l^-1 (mean±SD) before N and 8.7±6.1 pmol l^-1 at 5 days after Nx and remained at this level through the observation period. Aldo showed a non-significant transient fall at 5 days after Nx. AII and AVP remained normal after Nx. At 5 days after Nx glomerular filtration rate (GFR) of the remaining kidney had risen from 45±7 ml min-1 before Nx to 57± ml min^-1 (p<0·01), lithium clearance had risen from 13±2 ml min^-1 before Nx to 20±7 ml min^-1 (p<0.01), and sodium and water balance was normal. To conclude, plasma ANP, AII, Aldo and AVP do not appear to be responsible for the hyperfiltration and depression of fractional proximal sodium and water reabsorption observed in recently uninephrectomized man with normal sodium and water balance.     

Patlak plot analysis CT‐GFR for the determination of renal function: comparison of normal dogs with autologous kidney transplant dogs

Glomerular filtration rate (GFR) can be determined using Patlak plot analysis with single‐slice dynamic computed tomography (CT). Acute autologous graft failure has several causes, all of which induce a measurable decrease in glomerular filtration rate. This study demonstrated in an experimental model of canine autologous renal transplant that CT‐derived renal plasma clearance was significantly lower (p = 0.002) in dogs having undergone transplant (0.077 ± 0.058 ml min^?1 ml renal tissue^?1) compared with control dogs (0.396 ± 0.139 ml min^?1 ml renal tissue^?1). A significant negative curvilinear relationship was seen between serum creatinine and total renal plasma clearance (R² = 0.84, p = 0.0001). Alterations in renal time attenuation curve shape in dogs having undergone transplant may have been related to increased renal vascular resistance related to tubular necrosis. CT‐GFR may be a useful experimental tool in the evaluation of renal dysfunction in transplant models. Copyright © 2010 John Wiley & Sons, Ltd.     

Clearance and renal extraction of technetium-99m- L, L-ethylenedicysteine,I-131-ortho-iodohippurate and I-125-iothalamate in pigs

99mTc- L , L -ethylenedicysteine (^99mTc-EC) has been proposed as a ^99mTc-labelled alternative to radio-iodinated ortho-iodohippurate (OIH) for renal imaging and evaluation of renal function. The kinetics of this new renal function agent were studied by a single-injection plasma clearance technique in pigs. ^99mTc-EC, ¹³¹I-OIH and ¹²⁵I-iothalamate were injected and the plasma concentration of the three tracers was followed for 240 min. Renal, hepatic and total plasma clearance were calculated. There was no difference between the renal plasma clearance of ^99mTc-EC and ¹³¹I-OIH (175 ± 9 versus 178 ± 8 ml min^?1, P=0·43), whereas the difference between the total plasma clearance of ^99mTc-EC and ¹³¹I-OIH was highly significant (268 ± 16 versus 185 ± 9 ml min^?1, P=0·0001). ^99mTc-EC had a significant hepatic clearance of 83 ± 10 ml min^?1 whereas the hepatic clearance of ¹³¹I-OIH was negligible. Renal plasma extraction of both ^99mTc-EC and ¹³¹I-OIH decreased significantly between 2 and 240 min post-injection from 0·85 to 0·45% for ^99mTc-EC and from 0·93 to 0·57% for ¹³¹I-OIH. Red blood cell binding of ^99mTc-EC and ¹³¹I-OIH was 6·1% and 20%, respectively. The protein binding of ^99mTc-EC and ¹³¹I-OIH was 32% for both tracers. We conclude that ^99mTc-EC is not a suitable tracer for measuring renal function by the single-injection plasma clearance technique in pigs. This is due to a decreasing renal extraction and a significant hepatic clearance.     

Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow

Summary. The present investigation was undertaken in order to study (1) the difference in arterial (C_a) and venous (C_v) concentration of [⁵¹Cr]EDTA (ethylenediaminetetra-acetate) after a single intravenous injection, (2) the impact of different physiological variables on this difference, and (3) the error introduced in the measurement of renal plasma clearance and total plasma clearance by using venous blood samples instead of arterial. In 13 patients with GFR ranging from 29 to 150 ml min^-1, C_a was higher than C_v immediately after the injection. After mean 38 min (range 12–82 min) the two curves crossed, and 180–300 min post-injection (p.i.) C_v was 5·9% higher than C_a (range 0·5–13·9%, P<0·001). The more reduced renal function, the smaller was the concentration difference. The areas under the arterial and the venous plasma concentration curves did not differ significantly at either 0–∞ or 0–300 min p.i., whereas the venous area 0–100 min p.i. underestimated the arterial area in the same period by 4·1% (P<0·05). In a computer simulation model, variation in the forearm capillary permeability–surface area product did not have any significant influence on the C_v–C_a difference, whereas the difference was very sensitive to even small changes in forearm blood flow within the physiological range. For measurement of renal plasma clearance it is recommended to use one long period: from the time of injection until 300 min p.i. or longer. If the clearance period is too short, the use of venous samples will overestimate the true renal clearance. Plasma clearance determined by venous and arterial blood samples does not differ significantly as long as the concentration is followed from the time of injection and a long period is applied. When simplified plasma clearance techniques are used, different results may be obtained from venous and arterial samples. The simplified techniques using venous blood samples—which usually include some empirical corrections—should be sufficiently reliable in daily clinical practice provided the forearm blood flow is reasonably high, e.g. exposure to cold should be avoided.     

Glomerular filtration rate in adults estimated from 123iodine-hippuran and 99mtechnetium-diethylenetriaminepenta-acetic acid gamma camera renography

Summary. In a retrospective study a close relationship was found between the rate constant for renal clearance of the radioactive indicator (λ_pk) and the glomerular filtration rate (GFR) measured by ⁵¹Cr-EDTA plasma clearance. The material comprised eighteen adult subjects submitted to ¹²³I-hippuran gamma camera renography (IHGR) and twenty-two adult subjects to ^99mTc-DTPA gamma camera renography (TDGR). The rate constant was calculated from a bi-exponential decomposition of the activity-time curve recorded within a small region of interest over the left ventricle. The total cleared renal fraction (TCRF) of the cardiac output with respect to the radioactive indicator has previously been shown to be closely related to GFR. A pooled estimate of GFR (GFR_p) was calculated from the stochastically independent estimates of GFR based on λ_pk and TCRF. The comparison of GFR_p with measured GFR was satisfactory and yielded substantially smaller standard deviations (SD) of GFR_p than estimates based on λ_pk and TCRF separately. The standard deviations of GFR_p were about 7 and 12 ml/min/1·73 m² in IHGR for GFR equal to 50 and 100 ml/min/1·73 m², respectively. The corresponding SD in TDGR were about 7 and 11 ml/min/1·73 m². These standard deviations are sufficiently small for many clinical purposes and the method requires no blood samples or urine collections.     

Renal fraction of cardiac output cleared of radioactive indicator in 123iodine-hippuran gamma camera renography

Summary. The renal images recorded during 1–2 min post-injection in ¹²¹I-hippuran gamma camera renography were used for determination of the total cleared renal fraction (TCRF) of cardiac output with respect to the radioactive indicator. In a study of sixty-seven normal children over two years old TCRF was 0·178 ± 0·026 (x?± 1 SEE). This was in agreement with the estimation of TCRF from values of renal fraction of cardiac output and renal extraction ratio of hippuran in the literature. The left and right cleared renal fractions of cardiac output were determined directly, i.e., assessment of single kidney uptake function within a few minutes post-injection was also possible. TCRF was closely related to the glomerular filtration rate (GFR) in a group of twenty-two subjects with GFR in the interval 20–130 ml/min/1·73 m². Intra-observer variability of TCRF was unbiased and equal to 4%. TCRF is proposed to represent an alternative to renal clearance for evaluation of renal uptake function.     

The clearance concept with special reference to determination of glomerular filtration rate in patients with fluid retention

In subjects without fluid retention, the total plasma clearance of a renal filtration indicator (inulin, ^99mTc‐DTPA, ⁵¹Cr‐EDTA) is close to the urinary plasma clearance. Conversely, in patients with fluid retention (oedema, pleural effusions, ascites), there is a substantial discrepancy between the total plasma clearance and the urinary plasma clearance. This is owing to delayed indicator distribution to smaller or larger parts of the interstitial space, which in patients with ascites may simulate a peritoneal dialysator. In patients with fluid retention, urinary plasma clearance should be assessed to obtain a correct measurement of the glomerular filtration rate (GFR). In theory, total plasma clearance with late samples (24‐h, 48‐h) may be applied in patients with fluid retention, but validation hereof has not been performed. Until such studies are completed, it is recommended that patients with fluid retention have their GFR measured by a urinary plasma clearance technique with controlled quantitative urinary sampling within a few hours after indicator injection.     

Determination of 99mTc-DTPA clearance by a single plasma sample method

Summary. To derive a formula for determination of ^99mTc-DTPA clearance (Cl) from the radioactivity in a single plasma sample, the relation Cl=ECV/ was used, where ECV is the extracellular volume and I is the mean transit time of the tracer in the organism. By studying ^99mTc-DTPA time activity curves of 45 consecutive patients we found that ECV could be estimated from the body surface area, and that I could be calculated from the radioactivity in a single plasma sample. Cl calculated by the single sample method was almost identical to Cl calculated by a standard multiple sample method (r=0·987). It is concluded that the single sample method is accurate and that it may prove useful as a routine method provided that (a) the method is not used in patients with ^99mTc-DTPA clearance less than 30 ml min^-1, since this investigation includes only patients with Cl>30 ml min^-1; (b) the method is not used for children, since the test material did not contain any children; (c) the method is only used for plasma samples drawn at 180≤t≤300 min.     

Effect of enteral versus parenteral feeding on hepatic blood flow and steady state propofol pharmacokinetics in ICU patients

Objective: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). Design and patients: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D –3, D –2, and D –1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day D0). All patients received a continuous intravenous infusion of propofol (4.5 mg · kg^–1· h^–1) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. Results: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 ± 8 ml · min^–1· kg^–1 (mean ± SD) and 33 ± 10 ml · min^–1· kg^–1 on D-3 and D –1, respectively, as compared to 37 ± 11 ml · min^–1· kg^–1 and 34 ± 8 ml · min^–1· kg^–1 on days D + l and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml · min^–1· kg^–1 and was not affected by switching from parenteral to enteral feeding. Conclusions: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol. Received: 18 July 1997 Accepted: 1 April 1998     

Subcutaneous blood flow over 24-hour periods in patients with severe leg ischaemia

Summary. This paper describes a method for studying the clearance of ¹³³Xenon from the subcutaneous tissue of the calf and foot over 24-h periods. The average blood flow over this period can be estimated from the clearance constant obtained. Two series of measurement of the radioactivity are made, the first 2 h after the injection of 1–2 mCi ¹³³Xenon in saline and the second 18–24 h later. The distance between the detector and the depot is reproduced using a cylinder 20 cm long. The median washout rate of the isotope (k) in 25 patients was 2–57 × 10^-3 min^-1 for the calf and 2·39 × 10^-3 min^-1 for the foot. The median difference between repeated measurements in the same patient was 0·24 × 10^-3 min^-1 in the calf and 0·43 × 10^-3 min^-1 in the foot. This method, which can be used to estimate the average blood flow over 24 h while the patient undertakes his normal activities, should be useful in assessing the effect of therapy on the blood flow to the limb.     

Reliability of routine clearance methods for assessment of glomerular filtration rate in advanced renal insufficiency

The reliability of different clearance methods to assess the glomerular filtration rate (GFR) was tested in fifteen patients with advanced chronic renal failure (range of GFR: 3-13 ml/min). The renal [51Cr]EDTA plasma clearance (Er) measured during optimal conditions with determination of residual bladder-urine was used as reference parameter of GFR and the reliability (+/-) of a thus corrected value to assess GFR of the individual patient are given in parenthesis. The arithmetic mean of the renal plasma clearance of endogenous creatinine (Clcreat) and urea (2.0 ml/min; +/- 1.5 ml/min); single determination of 25-h clcreat (3.4 ml/min; +/- 2.0 ml/min); Clcreat calculated from a measured plasma creatinine concentration, considering sex, age and body weight of the patient (2.9 ml/min; +/- 2.3 ml/min); total [51Cr]EDTA plasma clearance (Et) determined form three blood samples drawn 3-5 h after i.v. single injection 93.7 ml/min; +/- 2.2 ml/min); and Et determined form two blood samples drawn 4 and 24 h after i.v. injection (0.5 ml/min; +/- 0.5 ml/min). It is concluded that the most reliable assessment of GFR (=Er) is achieved either form a direct measurement or indirectly from Et determined from two blood samples drawn 5 and 24 h after i.v. single injection. use of the mean value of three 25-h Clcreat determinations is recommended if facilities for measurement of radioactivity are not available.     

Role of alpha-adrenoceptor subtypes mediating sympathetic vasoconstriction in human digits

Abstract. The effects of intra-arterial administration of alpha-1 and alpha-2 adrenoceptor agonists and antagonists on human digital blood flow were studied before and during reflex sympathetic vasoconstriction in normal subjects. Total finger flow was measured by venous occlusion air plethysmography and capillary flow by the disappearance rate of a radioisotope from a local injection in a fingerpad. Intra-arterial phenylephrine (0·2–1·3 μg min^-1) and clonidine (0·12–0·48 μg min^-1) produced dose-related decreases in finger blood flow and increases in vascular resistance. Clonidine was the more potent vasoconstrictor. Prazosin (0·48 μg min^-1) effectively blocked the vasoconstrictor effect of phenylephrine but not clonidine, while yohimbine (30–70 μg min^-1) blocked the effect of clonidine but not phenylephrine. In a 20°C room, prazosin (0·4–13·2 μg min^-1) caused no significant changes in finger blood flow (7·7 ± 2·1 to 11·7 ± 3·3 ml min^-1) 100 ml^-1) or vascular resistance (30·9 ± 8·8 to 28·1 ± 8·7 mmHg ml^-1 min^-1 100 ml^-1). In the 20°C room, yohimbine (30–70 μg min^-1) produced a significant increase in finger blood flow (7·8 ± 2·8 to 23·4 ± 6·8 ml, P>0·01) and decrease in vascular resistance (20·5 ± 5·7 to 6·0 ± 2·2 units, P>0·01). No significant changes occurred in finger capillary flow with prazosin or yohimbine infusions. It is concluded that alpha-1 and alpha-2 adrenoceptors are present in human digital vasculature and that alpha-2 adrenoceptors are more important than alpha-1 adrenoceptors in sympathetic neural vasoconstriction. Since capillary blood flow was unaffected by yohimbine infusions during reflex sympathetic vasoconstriction, the alpha-2 adrenoceptors predominantly influence arteriovenous shunts in the finger.