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1 Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense; and 2 Department of Medical Physiology, University of Copenhagen, DK-2200 Copenhagen, Denmark
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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We have measured total renal blood flow (TRBF) as the difference between signals from ultrasound flow probes implanted around the aorta above and below the renal arteries. The repeatability of the method was investigated by repeated, continuous infusions of angiotensin II and endothelin-1 seven times over 8 wk in the same dog. Angiotensin II decreased TRBF (350 ± 16 to 299 ± 15 ml/min), an effect completely blocked by candesartan (TRBF 377 ± 17 ml/min). Subsequent endothelin-1 infusion reduced TRBF to 268 ± 20 ml/min. Bilateral carotid occlusion (8 sessions in 3 dogs) increased arterial blood pressure by 49% and decreased TRBF by 12%, providing an increase in renal vascular resistance of 69%. Dynamic analysis showed autoregulation of renal blood flow in the frequency range <0.06-0.07 Hz, with a peak in the transfer function at 0.03 Hz. It is concluded that continuous measurement of TRBF by aortic blood flow subtraction is a practical and reliable method that allows direct comparison of excretory function and renal blood flow from two kidneys. The method also allows direct comparison between TRBF and flow in the caudal aorta.
angiotensin II; candesartan; endothelin-1; dynamic autoregulation; transit time ultrasound flow probes
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE CONVENTIONAL APPROACH for measuring renal blood flow in conscious animals is to determine clearance of para-amino-hippuric acid (PAH). This method allows direct comparison between renal hemodynamics and excretory function. However, the fractional extraction of PAH is known to change, especially during maneuvers that increase renal blood flow (5, 6). Therefore, determination of both the arterial and renal venous concentrations of PAH is necessary to provide accurate values of renal blood flow. The PAH clearance method gives results on average renal blood flow during individual clearance periods. Consequently, determination of the detailed time course and dynamic analysis of renal blood flow in response to experimental procedures is not possible. Because of these inherent disadvantages of the clearance method, the gold standard for measuring renal blood flow in animal experiments has changed to continuous measurement by flow probes. The typical procedure includes implantation of a probe around one renal artery (usually the left). Two types of flow probes are available: the electromagnetic flow probe and the transit time ultrasound flow probe. The former has been used for decades but has technical disadvantages that include a variable zero offset, particularly cumbersome in long-term studies (1), and the need for intimate contact between probe and vessel wall, making it difficult to avoid stenosis and vessel wall necrosis over time (25). The transit time ultrasound flow probe has proved more useful, especially in long-term experiments, because the disadvantages of the electromagnetic flow probes have almost been eliminated (e.g., Ref. 11). A transit time ultrasound flow probe placed around one renal artery provides continuous measurement of unilateral renal blood flow. This method can be used to evaluate the effects of interventions on renal blood flow, to compare these effects with other hemodynamic effects, and to perform dynamic analysis. However, it cannot be used to directly compare renal blood flow with excretory function without a surgical intervention, such as uninephrectomy, split-bladder preparation, or implantation of a renal pelvis catheter (15); the two former techniques entail large deviations from normal physiology. Development of a new type of transit time ultrasound flow probe (A-series probes, Transonic Systems, Ithaca, NY) has increased the accuracy of continuous measurements of blood flow in large vessels (4). Because of the obvious need for a method to continuously measure renal blood flow from both kidneys in conscious animals, we have developed a method for measuring total renal blood flow (TRBF) as the real-time difference between the measurements of two transit time ultrasound flow probes implanted a few centimeters apart around the abdominal aorta, one above and one below the origin of the renal arteries.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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In Vitro Experiments
As recommended by the manufacturer, a gravity-driven, constant water flow setup was used to evaluate specific sets of A-series transit time ultrasound flow probes (10 mm, Transonic Systems) for measurement of a difference in flow similar to the renal blood flow in dogs. The two probes were placed in series on a piece of dialysis tubing in water. A T connection allowed fluid to flow both through the dialysis tubing and out between the probes, simulating the flow of the renal arteries. Water was led through the system and collected on two scales. Two-minute collections of the fluid simulating renal blood flow were compared with the difference in flow values measured by the two probes. The outflow between the probes was varied between 60 and 400 ml/min.In Vivo Experiments
Animals. The experiments were performed in six conscious female Beagle dogs weighing 10-13.5 kg. The dogs were kept on a fixed diet of commercial dog food (Special Diets Services, Witham, UK) and received one meal a day at ~1400. Mean daily sodium intake was 3.5 ± 0.3 mmol/kg body wt (mean ± SE). The dogs had free access to tap water. Before the study, the following surgical interventions were performed on separate days. The anesthetic procedure was identical during all surgical interventions. After premedication (propionyl promazine 0.15 mg/kg, methadone 0.25 mg/kg, atropine 0.02 mg/kg, and carprofen 40 mg/kg), general anesthesia was induced by 0.4 mg/kg propofol and maintained by inhalation of a mixture of N2O and O2 (2:1) and 1-1.5% halothane. With the use of standard aseptic procedures, both common carotid arteries were displaced into skin loops to minimize discomfort in connection with subsequent arterial puncture. In addition, a chronic episiotomy was performed to facilitate catheterization of the bladder. After at least 4 wk, bilateral ovariectomy and hysterectomy were performed to avoid cyclic alterations in sex hormones. After several months of training, two ultrasound flow probes (10A series, Transonic Systems) were implanted through a left flank incision by using blunt dissection to expose the aorta at the region of the renal arteries through a retroperitoneal approach. Flow probes were placed a few centimeters apart around the aorta, cranial and caudal to the origin of the renal arteries. The cables were fixed to the fascia of the psoas major muscle by silk sutures and tunneled subcutaneously to the interscapular area, at which the skin buttons were exteriorized. Sutures in three layers closed the flank incision. Appropriate postoperative treatment included antibiotics (amoxicillin 300 mg daily for 10 days) and analgesics (buprenorfin 0.3 mg for 1 day and carprofen 40 mg daily for 2 days). The dogs were allowed at least 14 days of recovery. The Danish Animal Experiments Inspectorate approved the experimental procedures, and this work fully conforms with the APS "Guiding Principles for Research Involving Animals and Human Beings."
Experimental protocol. In each dog, experiments were performed at intervals of >1 wk. At midnight before the experiment, an electric valve controlled by a timer interrupted the water supply. The following morning the dog was transferred to the laboratory and placed in a sling. A sterile catheter (Intracath, Becton Dickinson, Sandy, UT) was introduced into the right atrial area via the external jugular vein and used for infusions. Another catheter (Insyte-W, Becton Dickinson) was placed in the common carotid artery, allowing continuous measurement of arterial blood pressure interrupted by periodic sampling of arterial blood. A silicone Foley catheter (Argyle, Sherwood Medical, Tullamore, Ireland) was used for catheterization of the bladder. Three different experimental series were performed.
REPEATABILITY SERIES. Seven identical experiments were performed in one dog to test the repeatability of the renal blood flow measurement. Doses of substances with known effects on renal blood flow were used to induce up- and downregulation of renal blood flow. For clearance measurements, an intravenous bolus of creatinine (8.2 ml
14 mg/kg) was given
after instrumentation at 0900, immediately followed by a continuous
infusion of creatinine (7.2 ml/h 0.2 mg · kg
1 · min1) for the
remainder of the experiment. After a 60-min equilibration period, urine
was sampled every 30 min. To minimize the dead space effect, the
bladder was flushed with 3 × 10 ml of distilled water at the end
of each sampling period. After a control period (time t = 0-30 min), infusion of angiotensin II, at a rate of 5 ng · kg1 · min1, was
initiated and continued for the rest of the experiment. At
t = 60 min, a bolus injection of the
AT1-receptor antagonist candesartan (1 mg/kg) was
administered. A continuous infusion of endothelin-1 of 0.4 pmol · kg1 · min1 was
started at t = 90 min and, after one period
(t = 120 min), increased to 4 pmol · kg1 · min1 for the
rest of the experiment (to t = 180 min). A 5-ml sample of arterial blood was drawn at t = 
5, 25, 55, 85, 115, 145, and 175 min and used for determination of plasma creatinine.
Hemodynamic data were recorded continuously throughout the experiment
(see below).
BILATERAL CAROTID OCCLUSION SERIES.
In four experiments in three dogs, the preservation of sympathetic
nerve innervation after the surgical procedure was investigated. Bilateral carotid occlusion (BCO) is a well-known technique for stimulation of sympathetic outflow (e.g., Ref. 8). A 5-min control period (t = 0-5 min) was initiated at 1000 followed by 1-min BCO (t = 5-6 min) performed by
manual occlusion of the flow through both carotid loops. This maneuver
was repeated with a 5-min control period (t = 6-11
min) and a 1-min BCO period (t = 11-12 min). The
experiment was completed with a 5-min recovery period
(t = 12-17 min). Systemic hemodynamics and blood
flow data were continuously recorded throughout the experiment (see
below). On a separate day, the experiment was repeated in one dog after ganglion blockade performed by bolus injection of 5 mg/kg hexamethonium bromide at 0900, followed by a continuous infusion of 5 mg · kg1 · h1 hexamethonium bromide.
TIME CONTROL SERIES.
The stability of the blood flow measurements was investigated in all
six dogs. The experimental protocol was identical to that of the
repeatability series, apart from peptide and candesartan administration. Continuous hemodynamic measurements were
collected for 180 min.
Data acquisition and analyses. A blood pressure transducer (BLPR, World Precision Instruments, Stevenage, Hertfordshire, UK) measured arterial blood pressure continuously, and a blood pressure monitor (BP1-C, World Precision Instruments, Stevenage) amplified the pressure signal. The signals from the two flow probes were generated and displayed on a two-channel flowmeter (T206, Transonic Systems). A computer digitized and sampled the three analog signals at a sampling frequency of 100 Hz. TRBF was calculated on-line as the difference between the cranial aortic flow value and the caudal aortic flow value. The flow data were stored and, after the experiments, averaged over periods. Beat-to-beat determinations of systolic, diastolic, and mean arterial pressures and heart rate were obtained by computerized analysis (LabView, National Instruments, Hørsholm, Denmark) of the arterial pressure curve and subsequently averaged over appropriate periods. Total renal resistance and caudal resistance were calculated by dividing mean arterial blood pressure by TRBF or caudal aortic blood flow, respectively.
Arterial pressure and TRBF data from the time control series were analyzed by using the fast Fourier transformation procedure performed in segments of 32,768 points (corresponding to almost 5.5 min since data were collected at 100 Hz) and consecutive segments overlapped by 50%. Transfer functions (TFs) and admittance magnitudes were calculated with arterial pressure as input variable and renal blood flow as output variable, as described (10). Briefly, the magnitude of the TF is a measure of the dynamic autoregulatory efficiency. At any given frequency, TF is calculated as the ratio between fractional variation in arterial pressure and fractional variation in renal blood flow. In case TF < 1, fractional variation in flow is less than fractional variation in pressure, and autoregulation is present. If TF > 1, fractional variation in flow is greater than that of pressure, consistent with passive vasodilatation or autonomous oscillatory activity.Analyses
The concentrations of creatinine in plasma and urine were measured by a creatinine autoanalyzer (Beckman creatinine analyzer, Beckman Instruments, Fullerton, CA). The concentrations of sodium and potassium in urine were determined by flame photometry (IL423, Instrumentation Laboratory, Lexington, MA). Urine osmolality was determined by freezing-point depression (Advanced Osmometer, 3D3, Advanced Instruments, Needham Heights, MA).Statistics
Data obtained in the in vitro experiments were evaluated in accordance with the principles described by Bland and Altman (2). The results from the in vivo experiments were evaluated by one-way ANOVA for repeated measurements within groups. If the results of the ANOVA showed significance, all differences between means were investigated systematically by Newman-Keuls test. P values < 0.05 were considered to indicate significance.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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In Vitro Experiments
The results of the in vitro flow tests are shown in Fig. 1. Flow rates measured as the difference between the two flow probe measurements were grouped appropriately around the line of identity, compared with flow rates measured by weighing (Fig. 1A). The difference plot (Fig. 1B) was made from the calculated mean values (abscissa) and differences (ordinate) between flow probe and scale values. The lines of agreement (2 × SD) are at38.9 and 27.6 ml/min, which is within the
accuracy specified by the manufacturer for one probe only.
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In Vivo Experiments
Aortic blood flow subtraction.
The time course of arterial blood pressure and blood flows was
analyzed on the basis of data from one representative heartbeat from
each of the six control experiments (Fig.
2). The single cardiac cycle used for
analysis was selected on the basis of time only: the first complete
cycle occurring after 1000 sharp (i.e., 1000.00) was used. The signals
from the two aortic flow probes showed rather uniform flow profiles
(Fig. 2B), corresponding well to the arterial pressure
profile (Fig. 2A). Both aortic flows (cranial and caudal
blood flow curves) decreased to a nadir below zero, reflecting backward
flow in the aorta. The calculated volume flowing backward in that
period of 40 ms of negative flow was small, however, well below 1 ml of
blood. The TRBF produced by subtraction of the aortic flows showed an
early systolic peak, a midsystolic elevation, and constant diastolic
flow (Fig. 2C). Flow reversal was not observed. The caudal
aortic flow probe measured blood flow primarily to a large
musculocutaneous area. Consequently, changes in caudal aortic blood
flow may be used for calculation of representative changes in
extrarenal, peripheral resistance.
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Repeatability experiments.
During the 30-min control period, values of systemic and regional
hemodynamics were stable, and, in particular, a low standard error was
observed in the TRBF data (Tables 1 and
2). Angiotensin II infusion increased
mean arterial blood pressure by 12% (P < 0.001) and
decreased TRBF by 15% (P < 0.001). During angiotensin II infusion, total renal resistance was augmented by ~33% (Table 2),
concomitant with a 9% decrease in creatinine clearance (from 43 ± 2 to 39 ± 2 ml/min, P < 0.05). Renal sodium
excretion was decreased from 4.6 ± 0.8 to 2.5 ± 0.5 µmol/min, whereas urine flow was unchanged (0.15 ± 0.02 vs.
0.12 ± 0.01 ml/min). AT1-receptor blockade by
candesartan reversed the effects of angiotensin II infusion and further
decreased mean arterial blood pressure (5%, P < 0.05)
and increased TRBF (8%, P < 0.05) above control
levels, consistent with blockade of effects of both infused and
endogenous angiotensin II. Sodium excretion increased to 11.7 ± 3.2 µmol/min. The low dose of endothelin-1 infused from
t = 90-120 min decreased renal vascular resistance
and returned sodium excretion to control levels (6.9 ± 1.4 µmol/min), whereas urine flow increased to 0.48 ± 0.11 ml/min.
The high dose of endothelin-1 was infused for 1 h, elevated mean
arterial blood pressure by 12% (P < 0.003), and decreased TRBF by 22% (P < 0.001), compared with
control levels. Creatinine clearance and sodium excretion decreased
below control levels (31 ± 2 ml/min and 1.2 ± 0.1 µmol/min, respectively), concomitant with a decrease in urine flow to
control levels (0.19 ± 0.03 ml/min). Figure
3 shows absolute changes in mean arterial
blood pressure, TRBF, and total renal resistance from single
experiments. From this Fig. 3, it is obvious that there is a
satisfactory repeatability of the responses to these standardized
hormone manipulations. The relative scatter of the measurements of TRBF
is in the same order of magnitude as the relative scatter of the
intravascular measurements of arterial blood pressure.
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BCO experiments.
The results of the BCO experiments are presented in Table
3 and Fig.
4. After 20-30 s of the 1-min BCO
period, the effects on the hemodynamic parameters were stable, and,
therefore, the data of the last 30 s of the BCO period were used
for evaluation of the response. BCO increased mean arterial blood
pressure from 98 ± 4 to 145 ± 8 mmHg and heart rate from
65 ± 2 to 77 ± 4 beats/min, consistent with general
activation of the sympathetic nervous system. Despite the substantial
increase in mean arterial blood pressure, TRBF was significantly
reduced by ~12%, and the calculated total renal resistance was
elevated by ~70%. The caudal aortic blood flow tended to decrease in
response to BCO, but the decrease did not reach statistical
significance (P = 0.15). However, the calculated caudal
resistance increased by ~70%, quite similar to the increase in total
renal resistance. The results of the second BCO period are very similar
to those of the first and thus indicate a high degree of repeatability.
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Dynamic autoregulation analysis.
The TF calculated from data derived from the time control experiments
is shown in Fig. 5. The TF averaged
~1.7 at a frequency of 0.2 Hz and decreased <1 at ~0.07 Hz,
indicating the presence of autoregulation below this frequency. Around
a frequency of 0.03 Hz, the TF showed a peak that was consistent with
the tubuloglomerular feedback resonance. Below 0.03 Hz, it measured
0.5, indicating that autoregulatory activity resulted in flow
oscillations of less than one-half the size of those to be expected
from a passive vascular bed.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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The purpose of this study was to investigate an alternative method for measuring TRBF by aortic blood flow subtraction in chronically instrumented dogs. The in vitro experiments showed that the subtraction method could be used to measure mean flow with a scatter similar to that of a single probe. During the in vivo experiments, we observed physiologically relevant changes in renal blood flow in response to hormone infusions and sympathetic nerve activation. The dynamic analyses of arterial blood pressure and renal blood flow agree with previously reported data obtained by use of one probe only, which proves that this method can measure fluctuations in TRBF accurately. The method can be used to directly compare excretory function with TRBF in physiological experiments in awake animals without further surgical interventions. Furthermore, this method yields results on caudal aortic blood flow, which can be used to evaluate changes in extrarenal, peripheral resistance.
The waveforms of the flow curves measured in the abdominal part of the aorta show an early systolic increase, a midsystolic peak, and, thereafter, a deceleration to values below zero followed by a stable low-flow period throughout diastole (Fig. 2). Similar waveforms have been identified in the human abdominal aorta by magnetic resonance imaging (14). The waveforms of the TRBF curve measured by subtraction of aortic blood flows showed a pattern of an early systolic peak, a midsystolic elevation, and constant diastolic flow (Fig. 2). Only a few investigators have published pulsatile flow curves measured on one renal artery. However, Gross and Kirchheim (8) reported similar waveforms in the renal blood flow curves measured by electromagnetic flow probes. Furthermore, Schoenberg et al. (24) measured renal blood flow by both transit time ultrasound flow probes and a magnetic resonance cine phase-contrast method and found waveforms analogous to those obtained by the present method. Recently, Schoenberg et al. (23) showed that a diminished early systolic peak in the renal blood flow curve is a specific marker for renal artery stenosis. Under control conditions, Schoenberg et al. (23) demonstrated renal blood flow curve waveforms that were in good agreement with the present results. Altogether, the measured aortic blood flow curves and the calculated renal blood flow curve are essentially similar to the curves obtained by a variety of methods.
Frequency analysis of arterial blood pressure and renal blood flow is important in understanding the dynamics of renal autoregulation (e.g., Ref. 9). We used a method described by Holstein-Rathlou et al. (10) for analyzing arterial blood pressure and renal blood flow data based on the naturally occurring fluctuations in arterial blood pressure as the input variable and renal blood flow fluctuations as the output variable. The TFs of the present time control experiments show characteristics very similar to those of the results obtained by Just et al. (11) from one renal artery in conscious dogs. There was some degree of autoregulation below a frequency of 0.07 Hz, a resonance peak at ~0.03 Hz, probably originating from tubuloglomerular feedback-mediated oscillations (e.g., Ref. 11), and maximal autoregulation below the frequency of 0.01 Hz. The only difference is the bilateral measurement of renal blood flow in the present experiments. The similarity of the present TFs compared with literature data proves that the present method measures the fluctuations in TRBF with a high degree of accuracy.
By using aortic blood flow subtraction for measuring TRBF, one theoretical concern could be that the difference in aortic blood flows may change without a concomitant change in renal perfusion rate. Because the probes are placed a few centimeters apart and they measure flow with 100 Hz at exactly the same time, only a change in compliance of the artery between the probes can produce this phenomenon. A continuous change in compliance of the aorta is highly unlikely, at least in the present time frame of minutes. Furthermore, we have demonstrated that the method can produce 1) flow curves of a shape similar to that obtained by a variety of other methods and 2) a TF, which is very similar to the one published by Just et al. (11), based on data from one renal artery. These results would be impossible to achieve, if changes in measured difference between the probe signals differed from the changes in renal perfusion rate.
The constrictor effect of angiotensin II on the renal vasculature is mediated via AT1 receptors (18, 22, 23). Therefore, we used a moderate, physiologically relevant dose of angiotensin II to investigate whether the present method was able to detect a decrease in renal blood flow in response to angiotensin II. We observed a repeatable decrease in TRBF (range: 26-73 ml/min; Fig. 3B) comparable to published results from experiments on humans as well as conscious and anesthetized dogs (18, 22, 23). Angiotensin II tended to increase caudal blood flow, which might reflect a vasodilator effect of angiotensin II on muscle vessels, as indicated by recently published results obtained during clamped euglycemic hyperinsulinemic conditions in humans (7). Candesartan blocked these effects and further increased TRBF by ~8% and decreased mean arterial blood pressure. The results published on the effects of AT1-receptor blockade on renal blood flow have been variable, probably because of the confounding decrease in mean arterial blood pressure (16). However, when only a small decrease in mean arterial blood pressure is observed, the results in humans, dogs, and rats consistently show an increase in renal blood flow in response to AT1-receptor blockade (3, 17, 18, 22).
Endothelin-1 exerts a strong vasoconstrictor effect on renal
vasculature in dogs, at least in doses >1
pmol · kg1 · min1
(13, 21). Therefore, we used two doses, one below and one above 1 pmol · kg1 · min1
to induce renal vasoconstriction. The dose of 0.4 pmol · kg1 · min1 had no
effect on systemic hemodynamics, whereas a decrease in renal resistance
was observed. This might be a carry-over effect of candesartan.
However, earlier results in dogs have indicated that this low dose of
endothelin-1 increases glomerular filtration rate and, therefore, might
have a dilating effect on renal vasculature (21). During
administration of 4 pmol · kg1 · min1 to the
candesartan-treated animal, we measured a substantial decrease in TRBF
of 22% (range: 24-141 ml/min), which is comparable with previous
reports in conscious dogs instrumented with a transit time ultrasound
flow probe around one renal artery (13).
BCO has been used for years as a method to induce a moderate reflex stimulation of sympathetic nerve activity (8, 20). With regard to absolute changes in renal blood flow, the results have been variable, ranging from no change (8, 19, 20) to a 46% reduction when renal perfusion pressure was held constant (26). In the present experiment, we observed a repeatable decrease in TRBF of 12%, despite a substantial increase in renal perfusion pressure of ~45 mmHg. One explanation for these discrepancies might be a difference in experimental setup, for example, with regard to anesthesia. However, another possible explanation is that, by the present method, damage to the renal sympathetic nerves during surgery is minimized because the renal arteries are left untouched. Single-kidney use of electromagnetic flow probes has been associated with decreased levels of noradrenaline in the kidney, compatible with at least some damage to the renal nerves (12).
In summary, this study shows that adequate measurements of bilateral renal blood flow can be obtained by subtraction of flow values measured by transit time ultrasound flow probes placed around the abdominal aorta above and below the origin of the renal arteries. The obvious advantage is the possibility of comparing TRBF with the excretory parameters in time studies in conscious animals with two kidneys. Furthermore, this method yields results on hindlimb blood flow for concomitant evaluation of the peripheral circulation. Finally, it appears likely that, by use of the present technique, the sympathetic nerves to the kidneys are preserved to a higher extent than is the case when a flow probe is fitted directly around the renal artery.
Perspectives
The present method for measuring the collective blood flow in branches of vessels by subtracting blood flows measured in the mother vessel up- and downstream of the origin of the branches may prove valuable, especially as the integrity of the small vessel wall remains unthreatened during the procedure. These characteristics are important not only during flow measurements related to physiological functions in normal, conscious animals, but also during different kinds of vascular surgery, in which accurate transit time flow probes are presently used.| |
ACKNOWLEDGEMENTS |
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We thank Anne Mette Kragsig for expert technical assistance.
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FOOTNOTES |
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The A. P. Møller and Hustru Foundation, the Ruth I. E. Kønig Petersens Foundation, the Novo Nordisk Foundation, the Helen and Ejnar Bjørnows Foundation, the Eva and Robert Voss Hansens Foundation, and the Tømrermester Alfred Andersen and Hustrus Foundation supported the experiments.
Address for reprint requests and other correspondence: Niels C. F. Sandgaard, Dept. of Physiology and Pharmacology, Univ. of Southern Denmark, 21 Winsløwparken, DK-5000 Odense, Denmark (E-mail: ncfsand{at}dadlnet.dk).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpregu.00494.2001
Received 15 August 2001; accepted in final form 2 January 2002.
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TOP
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METHODS
RESULTS
DISCUSSION
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,
Aortic blood flow measured just cranial to the origin of the renal
arteries; 
, aortic blood flow measured just caudal to
the origin of the renal arteries. C: total renal blood flow
curve measured as the difference between the 2 aortic flow values
(ml/min). For all curves, values are means ± SE obtained during
the first heartbeat in 6 dogs just after the beginning of the time
control experiments at 1000.
