Regional Renal Perfusion Research Articles

Near-Infrared Spectroscopy Monitoring to Detect Changes in Cerebral and Renal Perfusion During Hypovolemic Shock, Volume Resuscitation, and Vasoconstriction.

Rapidly changing hemodynamic conditions, such as uncontrolled hemorrhage and the resulting hypovolemic shock, are a common contributor to active duty military deaths. These conditions can cause cerebral desaturation, and outcomes may improve when regional cerebral oxygen saturation (CrSO2) is monitored using near-infrared spectroscopy (NIRS) and desaturation episodes are recognized and reversed. The purpose of this porcine study was to investigate the ability of NIRS monitoring to detect changes in regional cerebral and regional renal perfusion during hypovolemia, resuscitation by volume infusion, and vasoconstriction. Hemorrhagic shock was induced by removing blood through a central venous catheter until mean arterial pressure (MAP) was <40 mmHg. Each blood removal step was followed by a 10-minute stabilization period, during which cardiac output, blood pressure, central venous pressure, blood oxygen saturation, and CrSO2 and regional renal oxygen saturation (RrSO2) were measured. Shock was reversed using blood infusion and vasoconstriction separately until MAP returned to normal. Statistical comparisons between groups were performed using the paired t-test or the Wilcoxon signed-rank test. Using volume resuscitation, both CrSO2 and RrSO2 returned to normal levels after hypovolemia. Blood pressure management with phenylephrine returned CrSO2 levels to normal, but RrSO2 levels remained significantly lower compared to the pre-hemorrhage values (P < .0001). Comparison of the percent CrSO2 as a function of MAP showed that CrSO2 levels approach baseline when a normal MAP is reached during volume resuscitation. In contrast, a significantly higher MAP was required to return to baseline CrSO2 during blood pressure management with phenylephrine (P < .0001). Evaluation of carotid blood flow and CrSO2 indicated that during induction of hypovolemia, the two measures are strongly correlated. In contrast, there was limited correlation between carotid blood flow and CrSO2 during blood infusion. This study demonstrated that it is possible to restore CrSO2 by manipulating MAP with vasoconstriction, even in profound hypotension. However, MAP manipulation may result in unintended consequences for other organs, such as the kidney, if the tissue is not reoxygenated sufficiently. The clinical implications of these results and how best to respond to hypovolemia in the pre-hospital and hospital settings should be elucidated by additional studies.

Decreased renal apparent diffusion coefficient after COVID-19 associated acute kidney injury

Study objective: To investigate if there are any differences in total renal blood flow, regional renal perfusion, renal oxygenation or renal tissue properties, studied by non-invasive MRI, in patients having recovered from severe COVID-19 with different grades of acute kidney injury (AKI). Hypothesis: We hypothesize that the decrease in renal blood flow and perfusion that our research group have previously found in severe COVID-19 patients with AKI 1 may persist together with possible renal edema and development of fibrosis. Material and methods: We identified patients with AKI grade 3 from a cohort of patients previously treated in the intensive care unit for severe COVID-19 with respiratory failure. These patients were matched to possible extent regarding age, sex, height, weight, body mass index (BMI) and body surface area (BSA) with patients from the same cohort that had AKI grade 1 and patients that did not have AKI. A total of 22 patients were included. Because of common occurrence of oliguria without a reduction of glomerular filtration, AKI grade was determined using the Kidney Disease Improving Global Outcome (KDIGO) creatinine criteria only. All patients had a record of a plasma creatinine inside normal range within two years prior to ICU care, and had no history of renal disease. Comorbidities were common in the study population. Follow up examination was performed approximately five months after the patients were admitted the ICU. Results: Significant differences in cortical and medullary ADC were demonstrated between the study groups. Both cortical and medullary ADC was significantly reduced in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and the ‘AKI grade 1’ group. Total renal blood flow was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ group and global renal perfusion was significantly lower in the ‘AKI grade 3’ group compared to the ‘no AKI’ and ‘AKI grade 1’ groups. No significant differences in either cortical or medullary perfusion were seen between the groups. Cortical and medullary oxygenation and renal vein oxygen saturation did not differ significantly between the groups. Conclusion: In this study we demonstrates that, approximately five months after intensive care for severe COVID-19, patients that had high grades of AKI during hospitalization have reduced cortical and medullary ADC together with reduced total renal blood flow and global renal perfusion compared to similar patients that did not have AKI. These findings might indicate development of renal fibrosis. No differences regarding renal oxygenation were observed between the studied groups. 1. Luther T, Eckerbom P, Cox E, Lipcsey M, Bulow S, Hultstrom M, et al. Decreased renal perfusion during acute kidney injury in critical COVID-19 assessed by magnetic resonance imaging: a prospective case control study. Crit Care. 2022;26(1):262. Public and private funding sources. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Microcirculatory Response to Endotoxemia and Resuscitation Is a Marker of Regional Renal Perfusion, Renal Metabolic Stress, and Tubular Injury.

Aims: We sought to investigate the relationship between macrohemodynamic resuscitation and microcirculatory parameters with the response of microcirculatory flow, tissue-specific parameters of metabolic stress and injury. We hypothesized that early resuscitation based on macrohemodynamic parameters does not prevent the development of organ dysfunction in a porcine model of endotoxemic shock, and that sublingual microcirculatory parameters are associated with markers of tissue metabolic stress and injury. Results: Both resuscitation groups had significant increases in creatinine and neutrophil gelatinase-associated lipocalin as compared with baseline. Neither the macrovascular response to endotoxemia or resuscitation, nor group allocation predicted the development of acute kidney injury (AKI). Only a microvascular flow index (MFI) <2.5 was associated with the development of renal tubular injury and AKI, and with increased renal, liver, peritoneal, and sublingual lactate/pyruvate (L/P) ratio and lactate. Among systemic parameters, only partial pressure of carbon dioxide (PCO2) gap >6 and P(a-v)CO2/C(v-a)O2 >1.8 were associated with increased organ L/P ratio and AKI. Innovation and Conclusion: Our findings demonstrate that targeting macrohemodynamics to guide resuscitation during endotoxemic shock failed to predict tissue metabolic stress and the response of the microvasculature to resuscitation, and was unsuccessful in preventing tubular injury and AKI. Mechanistically, our data suggest that loss of hemodynamic coherence and decoupling of microvascular flow from tissue metabolic demand during endotoxemia may explain the lack of association between macrohemodynamics and perfusion goals. Finally, we demonstrate that MFI, PCO2 gap, and P(v-a)CO2/C(a-v)O2 ratio outperformed macrohemodynamic parameters at predicting the development of renal metabolic stress and tubular injury, and therefore, that these indices merit further validation as promising resuscitation targets. Antioxid. Redox Signal. 35, 1407-1425.

Noninvasive Renal Perfusion Measurement Using Arterial Spin Labeling (ASL) MRI: Basic Concept.

The kidney is a complex organ involved in the excretion of metabolic products as well as the regulation of body fluids, osmolarity, and homeostatic status. These functions are influenced in large part by alterations in the regional distribution of blood flow between the renal cortex and medulla. Renal perfusion is therefore a key determinant of glomerular filtration. Therefore the quantification of regional renal perfusion could provide important insights into renal function and renal (patho)physiology. Arterial spin labeling (ASL) based perfusion MRI techniques, can offer a noninvasive and reproducible way of measuring renal perfusion in animal models. This chapter addresses the basic concept of ASL-MRI.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This introduction chapter is complemented by two separate chapters describing the experimental procedure and data analysis.

Arginine and tetrahydrobiopterin supplementation in rats with salt-induced blood pressure increase: minor hypotensive effect but improvement of renal haemodynamics.

High salt (HS) intake can lead to hypertension, probably the result of the predominance of vasoconstrictor reactive oxygen species over vasodilator nitric oxide (NO). We aimed to examine if the supposed NO deficiency and the resultant blood pressure increase could be corrected by supplementation of L-arginine, the substrate, and tetrahydrobiopterin (BH4), a co-factor of NO synthases. Wistar rats without known genetic background of salt sensitivity were exposed to HS diet (4%Na) for 10 or 26 days, without or with supplementation with oral L-arginine, 1.4 mg/kg b.w. daily, alone or together with intraperitoneal BH4, 10 mg/kg daily. Systolic blood pressure (SBP, tail-cuff method) was measured repeatedly and found to increase ~40 mmHg after 26 days; L-arginine and BH4 did not significantly attenuate this increase. At the end of chronic studies, in anaesthetized rats the diet- and treatment-induced changes in renal haemodynamics were assessed. HS diet selectively decreased (-30%, P < 0.03) the inner medullary blood flow (IMBF, laser-Doppler flux) without changing total or cortical renal perfusion. Arginine supplementation tended to raise all renal circulatory parameters, and distinctly increased IMBF, to 61% above the HS diet level (P < 0.05). In conclusion, unlike in confirmed genetically determined salt-dependent hypertension, L-arginine and BH4 supplementation failed to attenuate the SBP increase observed after exposure to HS diet. On the other hand, arginine increased total and regional renal perfusion, especially IMBF. This suggests that the delivery of arginine increased intrarenal NO synthesis, an action of renoprotective potential which presumably countered the harmful influence of the local tissue oxidative stress.

Multiparametric assessment of renal physiology in healthy volunteers using noninvasive magnetic resonance imaging.

Noninvasive methods of magnetic resonance imaging (MRI) can quantify parameters of kidney function. The main purpose of this study was to determine baseline values of such parameters in healthy volunteers. In 28 healthy volunteers (15 women and 13 men), arterial spin labeling to estimate regional renal perfusion, blood oxygen level-dependent transverse relaxation rate (R2*) to estimate oxygenation, and apparent diffusion coefficient (ADC), true diffusion (D), and longitudinal relaxation time (T1) to estimate tissue properties were determined bilaterally in the cortex and outer and inner medulla. Additionally, phase-contrast MRI was applied in the renal arteries to quantify total renal blood flow. The results demonstrated profound gradients of perfusion, ADC, and D with highest values in the kidney cortex and a decrease towards the inner medulla. R2* and T1 were lowest in kidney cortex and increased towards the inner medulla. Total renal blood flow correlated with body surface area, body mass index, and renal volume. Similar patterns in all investigated parameters were observed in women and men. In conclusion, noninvasive MRI provides useful tools to evaluate intrarenal differences in blood flow, perfusion, diffusion, oxygenation, and structural properties of the kidney tissue. As such, this experimental approach has the potential to advance our present understanding regarding normal physiology and the pathological processes associated with acute and chronic kidney disease.

Non-Invasive Renal Perfusion Imaging Using Arterial Spin Labeling MRI: Challenges and Opportunities.

Tissue perfusion allows for delivery of oxygen and nutrients to tissues, and in the kidneys is also a key determinant of glomerular filtration. Quantification of regional renal perfusion provides a potential window into renal (patho) physiology. However, non-invasive, practical, and robust methods to measure renal perfusion remain elusive, particularly in the clinic. Arterial spin labeling (ASL), a magnetic resonance imaging (MRI) technique, is arguably the only available method with potential to meet all these needs. Recent developments suggest its viability for clinical application. This review addresses several of these developments and discusses remaining challenges with the emphasis on renal imaging in human subjects.

Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep.

Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the absence of anesthesia remain largely unknown. Therefore, we assessed the effects of multiple vasoactive agents on regional kidney oxygenation in awake sheep. Sheep were surgically instrumented with pulmonary and renal artery flow probes, and combination fiber-optic probes, in the renal cortex and medulla, comprising a fluorescence optode to measure tissue Po2 and a laser-Doppler probe to assess tissue perfusion. Carotid arterial and renal venous cannulas enabled measurement of arterial pressure and total renal oxygen delivery and consumption. Norepinephrine (0.1 or 0.8 μg·kg(-1)·min(-1)) dose-dependently reduced cortical and medullary laser Doppler flux (LDF) and Po2 without significantly altering renal blood flow (RBF), or renal oxygen delivery or consumption. Angiotensin II (9.8 ± 2.1 μg/h) reduced RBF by 21%, renal oxygen delivery by 28%, oxygen consumption by 18%, and medullary Po2 by 38%, but did not significantly alter cortical Po2 or cortical or medullary LDF. Arginine vasopressin (3.3 ± 0.5 μg/h) caused similar decreases in RBF and renal oxygen delivery, but did not significantly alter renal oxygen consumption or cortical or medullary LDF or Po2. Captopril had no observable effects on cortical or medullary LDF or Po2, at a dose that increased renal oxygen delivery by 24%, but did not significantly alter renal oxygen consumption. We conclude that vasoactive agents have diverse effects on regional kidney oxygenation in awake sheep that are not predictable from their effects on LDF, RBF, or total renal oxygen delivery and consumption.

Contrast-Enhanced Ultrasound Identifies Reduced Overall and Regional Renal Perfusion During Global Hypoxia in Piglets

It is well known from both clinical experience and animal research that renal hypoxia may lead to temporary or permanent renal failure, the severity being dependent largely on the duration and grade of the hypoxia. The medulla is more susceptible to hypoxic injury than the cortex because approximately 90% of the renal blood flow supplies the cortex. Various methods have been applied to evaluate renal perfusion in both experimental and clinical settings, including magnetic resonance imaging, computed tomography, laser Doppler, and contrast-enhanced ultrasound (CEUS). The aim of this study was to evaluate changes in overall and regional renal perfusion with CEUS in response to global hypoxia. Twelve newborn anesthetized piglets were exposed to general hypoxia with a fraction of inspired oxygen of 8% of 30 minutes duration. Resuscitation was performed with either 100% oxygen (n = 6) or air (21% oxygen) (n = 6) for 30 minutes followed by 7 hours of reoxygenation with air. Before, during, and after hypoxia, the left kidney was examined with CEUS using 0.2 mL IV of SonoVue followed by 2 mL saline flush. Five additional piglets served as controls. The kidney was examined using a 9-MHz linear transducer with low mechanical index (0.21) and pulse inversion contrast program. One region of interest was drawn in the renal cortex and 1 in the medulla to obtain the corresponding time intensity curves (TICs). From these curves, the peak intensity (PI), time to peak (TTP), upslope of the curve, area under the curve, and mean transit time (MTT) were recorded. Also, the renal arteriovenous transit time (AVTT) was registered. The resistance index (RI) was repeatedly measured in the renal artery. Contrast-enhanced ultrasound was repeated at regular intervals until the animals were sacrificed 8 hours after the hypoxic period. In the group of 12 piglets subjected to hypoxia, RI increased from 0.69 ± 0.08 at baseline to 0.99 ± 0.09 during hypoxia (P < 0.01), indicating severe general renal vasoconstriction. The AVTT increased from 2.6 ± 0.5 seconds at baseline to 6.7 ± 2.8 seconds during hypoxia (P < 0.001). The PI in the cortex decreased from a mean value of 38.6 ± 6.1 dB at baseline to 30.3 ± 9.7 dB during hypoxia (P < 0.05). In the medulla, only a minor, nonsignificant reduction in PI was observed during hypoxia. In the medulla, TTP and MTT increased from 6.4 ± 1.5 and 9.2 ± 1.7 seconds at baseline to 14.6 ± 8.4 seconds (P < 0.01) and 15.2 ± 5.6 seconds (P < 0.01), respectively, during hypoxia. In the cortex, no statistically significant changes in TTP or MTT were observed during hypoxia. A return to near-baseline values was observed for TTP, PI in both the medulla and cortex, as well as for RI and AVTT within 1 to 3 hours after hypoxia, and they remained relatively constant for the duration of the experiment.Less than 1 hour after the hypoxia, PI both in the cortex and the medulla was significantly higher in the group resuscitated with air than in the group resuscitated with 100% oxygen, 36.0 ± 4.3 versus 27.2 ± 2.2 dB (P < 0.05) and 33.3 ± 8.2 versus 21.1 ± 2.0 dB (P < 0.01), respectively. Global hypoxia induced changes in overall and regional renal perfusion detectable with CEUS. Cortical and medullary flows were affected differently by hypoxia; a strong increase in medullary TTP and MTT was observed, indicating a reduction in medullary blood flow velocity. In the cortex, a significant reduction in PI was found, probably because of a reduction in cortical blood volume. A faster recovery of both medullary and cortical PI in the group resuscitated with air could indicate that air might be more beneficial for renal perfusion than hyperoxia during resuscitation after renal hypoxia.

Apport de la tomodensitométrie par rayons X dans l’évaluation de la performance rénale

X-ray computer assisted tomography scanner is an imaging method based on the use of X-ray attenuation in tissue. This attenuation is proportional to the density of the tissue (without or after contrast media injection) in each pixel image of the image. Spiral scanner, the electron beam computed tomography (EBCT) scanner and multidetector computed tomography scanner allow renal anatomical measurements, such as cortical and medullary volume, but also the measurement of renal functional parameters, such as regional renal perfusion, renal blood flow and glomerular filtration rate. These functional parameters are extracted from the modeling of the kinetics of the contrast media concentration in the vascular space and the renal tissue, using two main mathematical models (the gamma variate model and the Patlak model). Renal functional imaging allows measuring quantitative parameters on each kidney separately, in a non-invasive manner, providing significant opportunities in nephrology, both for experimental and clinical studies. However, this method uses contrast media that may alter renal function, thus limiting its use in patients with chronic renal failure. Moreover, the increase irradiation delivered to the patient with multi detector computed tomography (MDCT) should be considered.

Role of l‐arginine uptake mechanisms in renal blood flow responses to angiotensin II in rats

To examine whether reduced renal arginine transport increases the responsiveness of the renal circulation to angiotensin II in salt sensitivity, renal perfusion responses to angiotensin II were examined in the presence of L-arginine transport inhibitor, L-lysine and subsequent L-arginine in Sprague Dawley (SD) and Dahl salt-sensitive (Dahl S) rats. Laser Doppler probes and a transonic flow probe were used to measure regional renal perfusion and total renal perfusion respectively. Renal perfusion responses to intravenous (i.v.) angiotensin II were sequentially examined under control conditions and during i.v. infusion of L-lysine, L-arginine or nitric oxide synthase inhibitor, N(G)-nitro-L-arginine. Angiotensin II (10 and 100 ng kg(-1) min(-1) , i.v.) reduced total renal (-10 ± 3 and -36 ± 5%) and cortical (-10 ± 2 and -28 ± 4%) but not medullary perfusion in SD rats. In these rats L-lysine enhanced the renal perfusion response (P = 0.003), whereas subsequent L-arginine reversed this effect (P = 0.04). Angiotensin II reduced total renal, cortical and medullary perfusion in Dahl S rats. In Dahl S rats fed high salt, L-lysine did not affect renal perfusion responses to angiotensin II, but subsequent L-arginine blunted the renal blood flow response (P = 0.01) and increased the medullary perfusion during angiotensin II infusion (P = 0.006). Intact renal L-arginine transport attenuates the vasoconstrictor effects of circulating angiotensin II in the renal cortex in SD rats. L-arginine also plays an important role in protecting the renal medullary circulation from the ischemic effects of angiotensin II in Dahl S rats.

Renal Perfusion: Noninvasive Measurement with Multidetector CT versus Fluorescent Microspheres in a Pig Model

To validate the measurement of renal perfusion with multidetector computed tomography (CT) with a low-rate injection of contrast medium (ie, 3 mL/sec) through a catheter placed peripherally with gamma variate extended modeling in a pig model, compared with a reference method of fluorescent microspheres. This study was approved by the Institutional Animal Care and Use Committee. Renal perfusion was measured in 10 anesthetized pigs simultaneously with multidetector CT and with fluorescent microspheres, which are the reference standard for measuring regional renal perfusion. In each pig, measurements were obtained under three conditions. These were dopamine infusion, dopamine infusion with vascular expansion, and angiotensin II infusion. Aortic and cortical time-attenuation curves were modeled to measure renal perfusion with the gamma variate model. The renal perfusion measurements with the multidetector CT and that with microspheres were compared with least squares regression analysis and Bland-Altman plots. Perfusion as measured with multidetector CT and that as measured with microspheres were strongly correlated (ρ = 0.93, P < .0001). Multidetector CT renal perfusion with dopamine infusion (3.13 mL/min/g ± 0.53) was not changed after volume expansion (3.37 mL/min/g ± 0.75, P = .35) but was significantly decreased after angiotensin II injection (2.01 mL/min/g ± 0.57, P = .0001). Multidetector CT provides reliable measurements of single-kidney perfusion with peripheral low-rate contrast medium injection.

Assessment of Cu-ETS as a PET radiopharmaceutical for evaluation of regional renal perfusion

The copper(II) complex of ethylglyoxal bis(thiosemicarbazone) (Cu-ETS) was evaluated as a positron emission tomography (PET) radiopharmaceutical for assessment of regional renal perfusion. The concordance of renal flow estimates obtained with 11- and 15-microm microspheres was confirmed in four immature farm pigs using co-injected (46)Sc- and (57)Co-microspheres administered into the left ventricle. With the use of both immature farm pigs (n=3) and mature Göttingen minipigs (n=6), regional renal radiocopper uptake following intravenous [(64)Cu]Cu-ETS administration was compared to microsphere measurements of renal perfusion. The distribution and kinetics of [(64)Cu]Cu-ETS were further studied by PET imaging of the kidneys. The rate of [(64)Cu]Cu-ETS decomposition by blood was evaluated in vitro, employing octanol extraction to recover intact [(64)Cu]Cu-ETS. The co-injected 11- and 15-microm microspheres provided similar estimates of renal flow. A linear relationship was observed between the renal uptake of intravenous [(64)Cu]Cu-ETS and regional renal perfusion measured using microspheres. [(64)Cu]Cu-ETS provided high-quality PET kidney images demonstrating the expected count gradient from high-flow outer cortex to low-flow medulla. When incubated with pig blood in vitro at 37 degrees C, the [(64)Cu]Cu-ETS radiopharmaceutical was observed to decompose with a half-time of 2.8 min. Cu-ETS appears suitable for use as a PET radiopharmaceutical for evaluation of regional renal perfusion, affording renal uptake of radiocopper that varies linearly with microsphere perfusion measurements. Quantification of renal perfusion (in ml min(-1) g(-1)) with [(60,61,62,64)Cu]Cu-ETS will require correcting the arterial input function for the fraction of blood radiocopper remaining present as the intact Cu-ETS radiopharmaceutical, since the Cu-ETS chelate has limited chemical stability in blood. Rapid octanol extraction of blood samples appears suitable as an approach to capturing the actual blood concentration of [(60/61/62/64)Cu]Cu-ETS.

1721: The Effect of Shockwave Lithotripsy on Regional Renal Perfusion

You have accessJournal of UrologyPodium, Wednesday, May 24, 2006, 3:30 - 5:30 pm1 Apr 20061721: The Effect of Shockwave Lithotripsy on Regional Renal Perfusion Brian R. Matlaga, Mark A. Green, Rajash K. Handa, Bret A. Connors, Andrew P. Evan, James E. Lingeman, and Lynn R. Willis Brian R. MatlagaBrian R. Matlaga More articles by this author , Mark A. GreenMark A. Green More articles by this author , Rajash K. HandaRajash K. Handa More articles by this author , Bret A. ConnorsBret A. Connors More articles by this author , Andrew P. EvanAndrew P. Evan More articles by this author , James E. LingemanJames E. Lingeman More articles by this author , and Lynn R. WillisLynn R. Willis More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)33900-4AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "1721: The Effect of Shockwave Lithotripsy on Regional Renal Perfusion." The Journal of Urology, 175(4S), p. 553 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4SApril 2006Page: 553 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Brian R. Matlaga More articles by this author Mark A. Green More articles by this author Rajash K. Handa More articles by this author Bret A. Connors More articles by this author Andrew P. Evan More articles by this author James E. Lingeman More articles by this author Lynn R. Willis More articles by this author Expand All Advertisement PDF DownloadLoading ...

Lack of contribution of P2X receptors to neurally mediated vasoconstriction in the rabbit kidney in vivo

The contribution of adenosine triphosphate (ATP) to the neural control of regional renal perfusion in vivo remains unknown. We therefore examined whether P2X receptors mediate renal vascular responses to electrical stimulation of the renal nerves (RNS) in pentobarbitone anaesthetized rabbits. Responses to RNS were tested before and during renal arterial infusion of alpha,beta-methylene ATP (alpha,beta-mATP, 7-56 microg kg(-1) min(-1)) to desensitize P2X1 receptors. RNS consisted of 3 min trains at graded frequencies and short trains of RNS (4-32 pulses). Three-minute trains of RNS reduced renal blood flow (RBF), cortical laser Doppler flux (CLDF), and medullary LDF (MLDF) by -90 +/- 3%, -89 +/- 3% and -31 +/- 11%, respectively, at 4 Hz. MLDF was reduced less than CLDF or RBF. During short train RNS, RBF, CLDF and MLDF were reduced by -22 +/- 2%, -15 +/- 2% and -12 +/- 2%, respectively, for 32 s at 1 Hz. CLDF and MLDF were reduced to a similar extent. Infusion of alpha,beta-mATP induced transient reductions in RBF, CLDF and MLDF, but within 5 min these variables had recovered to control levels. Vascular responses to RNS were not significantly altered by alpha,beta-mATP treatment. In the rabbit kidney in vivo, alpha,beta-mATP-sensitive receptors mediate vasoconstriction and reduce perfusion in both cortical and medullary vascular beds. However, these receptors do not mediate neurally induced reductions in renal perfusion.

Type 1 neuropeptide Y receptors and α1-adrenoceptors in the neural control of regional renal perfusion

The aim of this study was to determine the contribution of neuropeptide Y (NPY) Y1 receptors in neurally mediated reductions in renal medullary perfusion. In pentobarbital sodium-anesthetized rabbits, electrical stimulation of the renal nerves (RNS, 0.5-16 Hz) decreased renal perfusion in a frequency-dependent manner. Under control conditions, 4 Hz reduced cortical and medullary perfusion by -85 +/- 3% and -43 +/- 7%, whereas 8 Hz reduced them by -93 +/- 2% and -73 +/- 4%, respectively. After Y1 receptor antagonism with BIBO3304TF (0.1 mg/kg plus 0.2 mg x kg x (-1) x h(-1)), RNS reduced perfusion less (by -65 +/- 9% and -12 +/- 8% at 4 Hz) x alpha1-Adrenoceptor antagonism with prazosin (0.2 mg/kg plus 0.2 mg kg(-1)h(-1)) also inhibited RNS-induced reductions in renal perfusion (-80 +/- 4% and -37 +/- 10% reductions in the cortex and medulla, respectively, at 8 Hz). When given after BIBO3304TF treatment, prazosin inhibited RNS-induced reductions in cortical and medullary perfusion more profoundly (-57 +/- 12% and -25 +/- 9% reductions, respectively, at 8 Hz) x Y1 receptor- and alpha1-adrenoceptor-blockade were confirmed by testing vascular responses to renal arterial NPY and phenylephrine boluses. NPY-positive immunolabeling was observed around interlobular arteries, afferent and efferent arterioles, and in the outer medulla. In conclusion, Y1 receptors and alpha1-adrenoceptors contribute to RNS-induced vasoconstriction in the vessels that control both cortical and medullary perfusion. Consistent with this, NPY immunostaining was associated with blood vessels that control perfusion in both regions. There also seems to be an interaction between Y1 receptors and alpha1-adrenoceptor-mediated neurotransmission in the control of renal perfusion.

An autoradiographic study of regional blood flow distribution in the rat kidney during ureteric obstruction--the role of vasoactive compounds.

To determine the changes in regional renal blood flow during ureteric obstruction and to examine the role of vasoactive mediators in effecting these changes. Renal blood flow in Sprague-Dawley rats was assessed after periods of ureteric obstruction using a quantitative autoradiographic technique based on Kety's theory of diffusion of an inert tracer (14C-iodoantipyrine). Prostaglandins, thromboxanes and renin-angiotensin were inhibited pharmacologically using diclofenac sodium and enalapril. Baseline blood flow to the outer cortex, inner cortex and medulla was 807, 258 and 105 mL/100 g/min, respectively. There was an increase in outer cortical blood flow after 10 min of ureteric obstruction which became significant at 30 min (P < 0.05). There was a significant decrease in inner cortical and medullary blood flow at 30 min, to 210 and 68 mL/100 g/min, respectively (P < 0.05). Diclofenac sodium abolished the increase in outer cortical blood flow. After 24 h of unilateral ureteric obstruction, outer cortical blood flow decreased to 492 mL/100 g/min; inner cortical blood flow also decreased but to a lesser extent, to 190 mL/100 g/min. Inhibition of prostaglandins, thromboxanes and the renin-angiotensin system reduced the degree of renal vasoconstriction but there was still a significant decrease in outer cortical perfusion despite the presence of these blocking agents. The control of the renal vasculature involves a complex interplay between a variety of vasoactive mediators. Quantitative autoradiography offers the opportunity to evaluate changes in regional renal perfusion with high resolution and will allow a greater understanding of the pathophysiology of renal diseases.

Quantification of renal blood flow with contrast-enhanced ultrasound

OBJECTIVESThe goal of this study was to determine the ability of contrast-enhanced ultrasound (CEU) to quantify renal tissue perfusion.BACKGROUNDThe kinetics of tracers used to assess renal perfusion are often complicated by countercurrent exchange, tubular transport or glomerular filtration. We hypothesized that, because gas-filled microbubbles are pure intravascular tracers with a rheology similar to that of red blood cells, CEU could be used to quantify renal tissue perfusion.METHODSDuring a continuous venous infusion of microbubbles (SonoVue), regional renal perfusion was quantified in nine dogs using CEU by destroying microbubbles and measuring their tissue replenishment with intermittent harmonic imaging. Both renal blood volume fraction and microbubble velocity were derived from pulsing-interval versus video-intensity plots. The product of the two was used to calculate renal nutrient blood flow. Renal arterial blood flow was independently measured with ultrasonic flow probes placed directly on the renal artery and was increased using dopamine and decreased by placement of a renal artery stenosis.RESULTSAn excellent correlation was found between cortical nutrient blood flow using microbubbles and ultrasonic flow probe-derived renal blood flow (r = 0.82, p < 0.001) over a wide range (2.5 fold) of flows.CONCLUSIONSUltrasound examination during microbubble infusion can be used to quantify total organ as well as regional nutrient blood flow to the kidney.

A Combination of Hypercholesterolemia and Hypertension Augments an Impairment in Intra-Renal Perfusion Responses

P105 The kidney is a target organ for cardiovascular risk factors, such as atherosclerosis and hypertension (HT), and is particularly susceptible to their combination. Even at an early stage, hypercholesterolemia (HC) and HT are individually associated with impaired renal perfusion responses to challenge with vasodilators. However, the effect of combined HC and HT on renal perfusion remains uncertain. To examine this, regional renal perfusion response to the renal vasodilator acetylcholine (Ach) was quantified in 4 groups of pigs, using electron beam CT, after 12 weeks of either normal (n=6), HC diet (n=6), HT (unilateral renal artery stenosis, n=5), or combined HC and HT (HC+HT, n=6). The HC and HC+HT groups had increased cholesterol levels vs. normal and HT (430±82 and 351±52 vs. 71±6 and 83±4 mg/dl, ANOVA p&lt;0.05, respectively). Mean arterial pressure was significantly elevated in HT and HC+HT vs. normal and HC (132±6 and 127±13 vs. 88±5 and 92±6 mmHg, p&lt;0.05, respectively). The combination of HC and HT was associated with a greater impairment in cortical and papillary perfusion responses than HC or HT alone (Table). Medullary perfusion response was not significantly different among the four groups (Table). These results demonstrate that concurrent HC and HT have a greater detrimental effect on renal perfusion responses than HC or HT alone, and that this effect is regionally heterogeneous. These effects may potentially lead to enhanced renal functional impairment and may play a role in the progression of renal damage in HT and atherosclerosis.

A Combination of Hypercholesterolemia and Hypertension Augments an Impairment in Intra-Renal Perfusion Responses

P105 The kidney is a target organ for cardiovascular risk factors, such as atherosclerosis and hypertension (HT), and is particularly susceptible to their combination. Even at an early stage, hypercholesterolemia (HC) and HT are individually associated with impaired renal perfusion responses to challenge with vasodilators. However, the effect of combined HC and HT on renal perfusion remains uncertain. To examine this, regional renal perfusion response to the renal vasodilator acetylcholine (Ach) was quantified in 4 groups of pigs, using electron beam CT, after 12 weeks of either normal (n=6), HC diet (n=6), HT (unilateral renal artery stenosis, n=5), or combined HC and HT (HC+HT, n=6). The HC and HC+HT groups had increased cholesterol levels vs. normal and HT (430±82 and 351±52 vs. 71±6 and 83±4 mg/dl, ANOVA p