Renal Artery Flow Research Articles

Impact of different conditions of breath-holding on the results of renal artery Doppler sonography: A pilot study.

To investigate the impact of different breath-holding conditions on the results of renal artery Doppler ultrasonography (RADS). In 45 healthy volunteers, we performed RADS examination during breath-holding while breathing naturally and after a deep inspiration. We measured and compared peak systolic flow velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) of the right (RRA) and left (LRA) renal artery, and PSV, EDV, RI, acceleration time and acceleration index (AI) of the right and left interlobar arteries. The RRA and LRA PSV were, respectively, 76 ± 13 cm/s and 77 ± 15 cm/s under natural breathing and 93 ± 18 cm/s and 89 ± 24 cm/s after deep inspiration (P ≤ .001). The RRA and LRA EDV were also greater at deep inspiration (P < .001 and P = .019, respectively). There was no significant difference in RRA or LRA RI. The PSV, RI, and AI of the right and left interlobar arteries were greater after deep inspiration (P ≤ .001), without difference in AI. Breath-holding conditions may influence Doppler measurements of renal artery flow velocity and should be reported and taken into account.

Urine Recirculation Improves Hemodynamics and Enhances Function in Normothermic Kidney Perfusion.

Kidney pairs were recovered uninjured (as live-donor nephrectomy) and perfused consecutively. Pig kidneys (n = 10) were allocated to either NMP with URC (n = 5) or NMP with volume replacement (n = 5). Cold ischemia time was either 2 or 27 hours for the first or second perfusion (URC or UR) of a kidney pair. An autologous blood-based perfusate, leukocyte-filtered, was used and NMP performed up to 24 hours. Perfusion parameters, biochemistry/metabolic parameters were monitored and samples collected. Physiological mean arterial pressures and flows were achieved in both groups but were sustainable only with URC. Significantly higher arterial flow was observed with URC (326.7 ± 1.8 versus 242.5 ± 14.3 mL/min, P = 0.001). Perfusate sodium levels were lower with URC, 129.6 ± 0.7 versus 170.3±2.7 mmol/L, P < 0.001). Stable physiological pH levels were only observed with URC. Perfusate lactate levels were lower with URC (2.2 ± 0.1 versus 7.2 ± 0.5 mmol/L, P < 0.001). Furthermore, the hourly rate of urine output was lower with URC and closer to physiological levels (150 versus 548 mL/h, P = 0.008). Normothermic kidney perfusion with URC was associated with longer achievable durations of perfusion: the objective in all experiments was a 24-hour perfusion, but this was not achieved in every case. The mean perfusions were 17.3 ± 9.2 hours with URC versus 5.3 ± 1.3 hours NMP with UR; P = 0.02. There appeared to be no differences in baseline tubular condition with and without URC. URC facilitates long-term kidney NMP in a porcine model. Perfusate homeostasis and stability of renal arterial flow throughout the perfusion period was only achievable with URC, independent of cold ischemia time duration.

AIUM Practice Parameter for the Performance of Duplex Sonography of Native Renal Vessels

AIUM Practice Parameter for the Performance of Duplex Sonography of Native Renal Vessels

Renal Frame Count and High Blood Pressure.

The aim of the present study was to demonstrate the relationship between hypertension stages according to JNC-8 classification and mean renal frame count (RFC), which is an indicator of renal perfusion. In this retrospective study, 100 hypertensive patients without obstructive renal artery disease, who had been evaluated with renal artery angiography for hypertension, were allocated into 2 groups (Stage 1 and Stage 2 hypertension). During coronary angiography, the patients were evaluated by selective renal angiography using 6F Judkins catheter. Cineangiographic images were evaluated by the same clinician and mean RFC was estimated for both renal arteries. Injections during renal angiography were performed with power injector and same amount of radiopaque media with same speed was used for all patients. There was no significant difference between the groups in terms of age, sex, duration of hypertension, and laboratory markers. Stage 2 hypertensive patients (Group 2) had a significantly higher mean RFC than Stage 1 hypertensive patients (Group 1) (p<0.001). The mean RFC of both kidneys in Group 2 was significantly higher than that of Group 1 (p<0.001 and p=0.023, respectively). This study showed that the mean RFC increased with increases in hypertension levels and it could be used as an indicator of renal perfusion, which is an indirect marker of renal function. If renal artery flow gets slower, blood pressure levels increase and there is a proportional relationship between these two variables (mean RFC and blood pressure levels). This study also demonstrated that there was a statistically significant correlation between mean RFC and JNC-8 hypertension stages.

Critically Ill COVID-19 Patients with Acute Kidney Injury Have Reduced Renal Blood Flow and Perfusion Despite&amp;nbsp;Preserved Cardiac Function; A Case-Control Study Using Contrast Enhanced Ultrasound

Background: Acute Kidney Injury (AKI) is a common complication of COVID-19 critical illness but the pathophysiology is uncertain. Some evidence has indicated that a vascular aetiology may be implicated. We used contrast enhanced ultrasound (CEUS) and echocardiography to study renal perfusion and global blood flow and compared our findings with measurements taken in a group of septic shock patients and healthy volunteers. Method: Prospective case-control study. Renal perfusion variables were assessed with contrast enhanced ultrasound (CEUS); macrovascular blood flow was assessed using Doppler analysis of large renal vessels; echocardiography was used to assess right and left heart function and cardiac output. Findings: CEUS derived parameters were reduced in in COVID-19 associated AKI compared to healthy controls (perfusion index 3415 v 548 a.u., p=0·001; renal blood volume 7794 v 3338 a.u., p=0·04). Renal arterial flow quantified using time averaged peak velocity (TAPV) was also reduced compared to healthy controls (36·6 v 20·9 cm/s, p=0.004) despite cardiac index being similar between groups (2.8 v 3.7 L/min/m2, p=0.07). There were no differences in CEUS derived or cardiac parameters between COVID-19 and septic shock patients but patients with septic shock had more heterogeneous perfusion variables. Interpretation:Both large and small vessel blood flow is reduced in patients with COVID-19 associated AKI compared to healthy controls, which does not appear to be a consequence of right or left heart dysfunction. A reno-vascular pathogenesis of COVID-19 AKI seems likely. Funding: Royal Centre for Defence Medicine (UK Ministry of Defence), 2019; European Society of Intensive Care Medicine Point of Care Ultrasound award, 2019 Declaration of Interests: All authors declare that they have no conflicts of interest. Ethics Approval Statement: Yorkshire and Humber (Leeds East) Research Ethics committee (18/YH/0371).

Polyvinyl alcohol cryogel based vessel mimicking material for modelling the progression of atherosclerosis

PurposeThe stiffness of Polyvinyl-alcohol cryogel can be adjusted through application of consecutive freeze-thaw cycles. This material has potential applications in the production of tissue mimicking phantoms in diagnostic ultrasound. The aim of this study was to use PVA-c to produce a range of geometrically and acoustically identical vessel phantoms modelling stages of atherosclerosis which could be verified through mechanical testing, thus allowing for more precision in quantitative in-vitro flow analysis of atherosclerosis. MethodsA series of anatomically realistic walled renal artery flow phantoms were constructed using PVA-c. In order to ensure precise modelling of atherosclerosis, a modified procedure of ISO27:2017 was used to compare the mechanical properties of PVA-c. Results were compared for the standard “dumbbell” test object and a modified vessel test object. The geometric accuracy and reproducibility of the vessel models were tested before and after implantation in flow phantoms. ResultsNo significant difference was found between the mechanical properties of the dumbbell test samples and the vessels for any number of freeze thaw cycles, with a correlation coefficient of R2 = 0.9767 across the dataset, indicating that a direct comparison between the mechanical properties of the dumbbell test samples and the phantom vessels was established. The geometric reproducibility showed that before and after implantation there was no significant difference between individual vessel geometries (p = 0.337 & p = 0.176 respectively). ConclusionsPolyvinyl-alcohol cryogel is a useful material for the production of arterial flow phantoms. Care should be taken when using this material to ensure its mechanical properties have been correctly characterised. The guidelines of ISO37:2017 potentially provide the best procedure to ensure this.

Renal hemodynamics by return cannular position of extracorporeal membrane oxygenation in swine.

Whether arterial return cannula position affects the kidney during Veno-Arterial extracorporeal membrane oxygenation (ECMO) is unclear. Therefore, we compared hemodynamic parameters and acute kidney injury (AKI) biomarkers between ascending aorta return (aECMO) and femoral artery return ECMO (fECMO) in swine to evaluate the effect of cannula position on the kidney. A total of twelve swines were allocated randomly into two groups. ECMO was maintained for 6h. Hemodynamic parameters including mean arterial pressure (MAP), renal arterial flow rate (AF), energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) were measured at the left renal artery. For evaluation of kidney injury, samples were obtained for blood urea nitrogen, creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (before ECMO, and 1, 3, and 6 h after initiating ECMO). Before the start of ECMO, hemodynamic parameters were not different between the two groups. With regard to the rate of change before and after ECMO, the fECMO group showed a significantly higher increase in MAP, AF, and EEP and a greater decrease in SHE than the aECMO group (P<0.001). In inter-group analysis, no significant difference in time-dependent trends were observed for biochemical laboratory levels. fECMO support was associated with a higher energy profile at the renal artery than that with aECMO, whereas pulsatility was decreased.

Investigation of the assessment of low degree (

PurposeRenal arterial stenosis can lead to disrupted renal function due to reduced blood flow to the kidneys and is largely thought to be caused by atherosclerosis. Current diagnostic strategies for renal arterial stenosis rely on detecting large degree stenoses (>50%). This study aimed to test the viability of using Doppler ultrasound to assess velocity profiles to detect the presence of low degree (<50%) stenoses. MethodsA series of anatomically realistic renal artery flow phantoms were constructed exhibiting a range of low degree stenoses (symmetric and asymmetric). The behaviour of fluid flow in the phantoms was examined using Doppler ultrasound and analysed to calculate the clinical biomarker, wall shear stress. ResultsA number of fluid behaviours were observed in relation to stenosis degree: asymmetric stenoses tended to result in a skewing of peak velocities away from the centre of the vessel towards the outer wall, the magnitude of increase in velocity was observed to correlate with stenosis degree, and the wall shear stress curves observed large peaks in the presence of even the lowest degree stenosis (20%). ConclusionsDoppler ultrasound could potentially be utilised to diagnose low degree stenoses in a clinical setting. Doppler ultrasound in conjunction with wall shear stress analysis in particular has significant potential in the diagnosis of renal artery stenosis.

Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury

Norepinephrine exacerbates renal medullary hypoxia in experimental septic acute kidney injury. Here we examined whether dexmedetomidine, an α2-adrenergic agonist, can restore vasopressor responsiveness, decrease the requirement for norepinephrine and attenuate medullary hypoxia in ovine gram-negative sepsis. Sheep were instrumented with pulmonary and renal artery flow probes, and laser Doppler and oxygen-sensing probes in the renal cortex and medulla. Conscious sheep received an infusion of live Escherichia coli for 30 hours. Eight sheep in each group were randomized to receive norepinephrine, norepinephrine with dexmedetomidine, dexmedetomidine alone or saline vehicle, from 24-30 hours of sepsis. Sepsis significantly reduced the average mean arterial pressure (84 to 67 mmHg), average renal medullary perfusion (1250 to 730 perfusion units), average medullary tissue pO2 (40 to 21 mmHg) and creatinine clearance (2.50 to 0.78 mL/Kg/min). Norepinephrine restored baseline mean arterial pressure (to 83 mmHg) but worsened medullary hypoperfusion (to 330 perfusion units) and medullary hypoxia (to 9 mmHg). Dexmedetomidine (0.5 μg/kg/h) co-administration significantly reduced the norepinephrine dose (0.8 to 0.4 μg/kg/min) required to restore baseline mean arterial pressure, attenuated medullary hypoperfusion (to 606 perfusion units), decreased medullary tissue hypoxia (to 29 mmHg), and progressively increased creatinine clearance (to 1.8 mL/Kg/min). Compared with vehicle time-control, dexmedetomidine given alone significantly prevented the temporal reduction in mean arterial pressure, but had no significant effects on medullary perfusion and oxygenation or creatinine clearance. Thus, in experimental septic acute kidney injury, dexmedetomidine reduced norepinephrine requirements, attenuated its adverse effects on the renal medulla, and maintained renal function.

SAT-143 MILD HYPERCAPNIA DURING MAJOR SURGERY, A POSSIBLE STRATEGY TO PREVENT RENAL MEDULLARY HYPOXIA AND THE DEVELOPMENT ACUTE KIDNEY INJURY

Acute kidney injury (AKI) is a common complication of major surgery that increases short- and long-term morbidity and mortality. There is emerging evidence that decreased renal medullary perfusion, resulting in hypoxia, contributes to the development of AKI during prolonged surgery. Since hypercapnia can provide a degree of organ protection, possibly due to its vasodilator effects, we investigated whether increases in arterial carbon dioxide level (PaCO2) improve global and regional kidney oxygenation in anesthetised sheep. In addition, positive end expiratory pressure (PEEP) is used to increase oxygenation, but it also decreases cardiac output and may therefore reduce renal perfusion and oxygenation. Thus, we determined the effects of PEEP (0, 5, 10, 15 and 20 cmH2O for 15 min), and PEEP with mild hypercapnia (PaCO2 45-55mmHg), on renal perfusion and oxygenation. In Merino ewes, surgery was performed to implant pulmonary and renal artery flow probes and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex and to cannulate a renal vein. In anaesthetised sheep (isoflurane 2.5%), FiO2 was held at 0.4 and respiratory rate was changed to achieve target PaCO2 (normocapnia 35-45, mild hypercapnia 45-55 and severe hypercapnia 55-65 mmHg) for periods of 20 minutes, in random order. PEEP was held at (0, 5, 10, 15 and 20 cm H2O) for periods of 15 min during normocapnia and mild hypercapnia. Increases in PaCO2 from normocapnia, to mild and severe hypercapnia significantly increased medullary PO2 (39.1±5.5, 48.6±4.2 and 51.9±4.8 mmHg, respectively) and perfusion (336±66, 449±72 and 453±82 blood perfusion units, respectively). There were no changes in cortical perfusion or PO2, renal blood flow or renal oxygen delivery. During normocapnia, PEEP decreased cardiac output, renal blood flow, renal oxygen delivery, medullary perfusion (342±101 to 243±64 blood perfusion units (BPU)) and medullary PO2 (33.5±5.4 to 22.6±8.9 mmHg). Mild hypercapnia, for 30 min before and during PEEP, prevented the PEEP-induced decreases in medullary perfusion (586±165 to 491±93 BPU) and PO2 (54.6±7.8 to 57.4±7.6 mmHg), despite reductions in cardiac output and renal blood flow. Under volatile anaesthesia, increases in PaCO2 caused progressive increases in renal medullary perfusion and oxygenation. PEEP had detrimental effects on cardiac output, renal blood flow and medullary perfusion and PO2. Mild hypercapnia prevented the PEEP-induced decreases in medullary perfusion and PO2. During prolonged major surgery, increasing PaCO2 to prevent decreases in renal medullary PO2 may be a useful strategy to reduce the incidence of post-operative AKI.

Haemodynamics Imaging of Swine Segmental Kidney Artery Using Duplex Doppler Technique.

IntroductionThe aim of the study was to assess the usefulness of duplex Doppler to objectify swine renal arterial flow in physiological conditions. The pig kidney was selected for its morphological similarities to the human and for the results therefore offering data to wider research.Material and MethodsSix White Large x Landrace sows, of 48.5–53 kg b.w. were used. Vascular flow parameters were acquired with a convex probe USG device with a duplex Doppler function using pulsed waves (frequency range of 5–7.5 MHz). Segmental kidney arterial flow was measured.ResultsThe RI values were within the 0.57 (min) to 0.6 (max) range, x RI was 0.58 (±0.014), and the SD2value was 0.0002. The PI index values ranged from 1.21 (min) to 1.3 (max), and x PI was 1.24 (±0.035). The value of SD2was 0.00123. In the S/D index, the results fell between 2.2 (min) and 2.49 (max), with x S/D of 2.29 (±0.117). The value of variance SD2was 0.0139. A double analysis of correlation between indices showed this to be almost certain and highly positive as confirmed by high correlation coefficients: r RI & PI 0.857, rho RI & PI 0.739, r RI & S/D 0.930, rho RI & S/D 0.941, r PI & S/D 0.913, and rho PI & S/D 0.754. The segmental kidney arterial flow spectrum evinced falls in PSV and PSV/LDV ratio, also noticed in the filling of the spectral window, comparing the renal to an interlobar artery.ConclusionSwine were selected because of renal anatomical and haemodynamic similarity to humans. The most relevant values and indices approximated those in humans. The study anaesthetic protocol had a minor influence on the average RI, PI, and S/D indices.

Computational analysis of renal artery flow characteristics by modeling aortoplasty and aortic bypass interventions for abdominal aortic coarctation

ObjectiveSuprarenal abdominal aortic coarctation (SAAC) alters flow and pressure patterns to the kidneys and is often associated with severe angiotensin-mediated hypertension refractory to drug therapy. SAAC is most often treated by a thoracoabdominal bypass (TAB) or patch aortoplasty (PA). It is currently unclear what effect these interventions have on renal flow and pressure waveforms. This study, using retrospective data from a patient with SAAC subjected to a TAB, undertook computational modeling to analyze aortorenal blood flow preoperatively as well as postoperatively after a variety of TAB and PA interventions. MethodsPatient-specific anatomic models were constructed from preoperative computed tomography angiograms of a 9-year-old child with an isolated SAAC. Fluid-structure interaction (FSI) simulations of hemodynamics were performed to analyze preoperative renal flow and pressure waveforms. A parametric study was then performed to examine the hemodynamic impact of different bypass diameters and patch oversizing. ResultsPreoperative FSI results documented diastole-dominated renal perfusion with considerable high-frequency disturbances in blood flow and pressure. The postoperative TAB right and left kidney volumes increased by 58% and 79%, respectively, reflecting the increased renal artery blood flows calculated by the FSI analysis. Postoperative increases in systolic flow accompanied decreases in high-frequency disturbances, aortic pressure, and collateral flow after all surgical interventions. In general, lesser degrees of high-frequency disturbances followed PA interventions. High-frequency disturbances were eliminated with the 0% PA in contrast to the 30% and 50% PA oversizing and TAB interventions, in which these flow disturbances remained. ConclusionsBoth TAB and PA dramatically improved renal artery flow and pressure waveforms, although disturbed renal waveforms remained in many of the surgical scenarios. Importantly, only the 0% PA oversizing scenario eliminated all high-frequency disturbances, resulting in nearly normal aortorenal blood flow. The study also establishes the relevance of patient-specific computational modeling in planning interventions for the midaortic syndrome.

Human renal response to furosemide: Simultaneous oxygenation and perfusion measurements in cortex and medulla.

AimDisturbances of renal medullary perfusion and metabolism have been implicated in the pathogenesis of kidney disease and hypertension. Furosemide, a loop diuretic, is widely used to prevent renal medullary hypoxia in acute kidney disease by uncoupling sodium metabolism, but its effects on medullary perfusion in humans are unknown. We performed quantitative imaging of both renal perfusion and oxygenation using Magnetic Resonance Imaging (MRI) before and during furosemide. Based on the literature, we hypothesized that furosemide would increase medullary oxygenation, decrease medullary perfusion, but cause minor changes (<10%) in renal artery flow (RAF).MethodsInterleaved measurements of RAF, oxygenation (T 2*) and perfusion by arterial spin labelling in the renal cortex and medulla of 9 healthy subjects were acquired before and after an injection of 20 mg furosemide. They were preceded by measurements made during isometric exercise (5 minutes handgrip bouts), which are known to induce changes in renal hemodynamics, that served as a control for the sensitivity of the hemodynamic MRI measurements. Experiments were repeated on a second day to establish that the measurements and the induced changes were reproducible.ResultsAfter furosemide, T 2* values in the medulla increased by 53% (P < 0.01) while RAF and perfusion remained constant. After hand‐grip exercise, T 2* values in renal medulla increased by 22% ± 9% despite a drop in medullary perfusion of 7.2% ± 4.7% and a decrease in renal arterial flow of 17.5% ± 1.7% (P < 0.05). Mean coefficients of variation between repeated measurements for all parameters were 7%.ConclusionFurosemide induced the anticipated increase in renal medullary oxygenation, attributable exclusively to a decrease in renal oxygen consumption, since no change of RAF, cortical or medullary perfusion could be demonstrated. All measures and the induced changes were reproducible.

Polymorphism A1166C of AGTR1 Gene and the State of Intrarenal Blood Flow in Patients with Essential Arterial Hypertension 1-2 Degrees

to study relationship between genetic disorders and features of intrarenal blood flow in patients with essential arterial hypertension(AH) of 1-2 degree. We examined 100 patients (60 women, 40 men) aged 35 to 58 years with 1-2‑degree essentialarterial hypertension (AH) and chronic kidney disease (CKD) stages I-III. Examination included triplex scanning of renal arterieson the ultrasound scanner Vivid-7 Dimension, genotyping of single-nucleotide polymorphism А1166С of the AGTR1 gene by realtime polymerase chain reaction (PCR), estimation of glomerular filtration rate (GFR) using CKD-EPI formula. Patients were dividedinto 2 groups: group 1 included persons with I and II stage CKD (n=65, 25 men and 40 women), group 2 included patients with stagesIIIA and IIIB CKD (n=35, 15 men and 20 women). Among patients of group 1 prevailed genotype AA, while among group 2patients prevailed genotype AC. Speed of blood flow in interlobar renal arteries was higher in the group 1 compared with group 2, whilein the group 2 time of acceleration of blood flow was higher than in the group 1. The data obtained are indicative of the decreaseof systolic, diastolic, and averaged maximal blood flow velocity and the lengthening of acceleration time in patients with higherCKD stage. The presence in the genotype of patients with 1-2‑degree AH of AGTR1 1166С allele may be considered a riskfactor of early development of CKD. Lowering of speed characteristics of blood flow and lengthening of the acceleration time in patientswith AH can be a criterion of hypertensive nephropathy development.

Effects of Clonidine on the Cardiovascular, Renal, and Inflammatory Responses to Experimental Bacteremia.

Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses. In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 h, a high clinical dose of clonidine (HCDC) [1.0 μg/kg/h], a low clinical dose of clonidine (LCDC) [0.25 μg/kg/h] or vehicle, was infused for 8 h. Animals developed hyperdynamic, hypotensive sepsis with acute kidney injury. The HCDC decreased heart rate (153 ± 6 to 119 ± 7 bpm) and cardiac output (5.6 ± 0.4 to 5.0 ± 0.4 L/min), with no reduction in mean arterial pressure (MAP). In contrast, LCDC increased cardiac output with peripheral vasodilatation. Both doses induced a large transient increase in urine output, an increase in plasma osmolality and, with the high dose, an increase in plasma arginine vasopressin. Sepsis increased plasma interleukin-6 (IL-6) and IL-10 and clonidine further increased IL-10 (1.6 ± 0.1 to 3.3 ± 0.7 ng/mL), but not IL-6. Clonidine reduced rectal temperature. During recovery from sepsis, MAP returned to baseline values more rapidly in the HCDC group (P < 0.001). In hyperdynamic, hypotensive sepsis, the effects of clonidine at clinically relevant doses are complex and dose dependent. HCDC attenuated sepsis-related increases in heart rate and cardiac output, with little effect on arterial pressure. It also induced a water diuresis, increased AVP, reduced body temperature, and had an anti-inflammatory action. Low-dose clonidine had similar but less pronounced effects, except that it induced moderate vasodilatation and increased cardiac output.

Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats

Rho-kinase (ROCK) activation in hepatic stellate cells (HSC) is a key mechanism promoting liver fibrosis and portal hypertension (PTH). Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. In decompensated cirrhosis, presence of ascites is associated with reduced renal perfusion. Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFRβ) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFRβ-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. In vitro collagen contraction assays tested biological activity on LX2 cells. Hemodynamics were analyzed in BDL and CCl4 cirrhotic rats 3 h, 6 h and 24 h after i.v. administration of Y27pPBHSA (0.5/1 mg/kg b.w). Phosphorylation of moesin and myosin light chain (MLC) assessed ROCK activity in liver, femoral muscle, mesenteric artery, kidney and heart. Three Y27 molecules were coupled to pPBHSA as confirmed by HPLC/MS, which was sufficient to relax LX2 cells. In vivo, Y27pPBHSA-treated rats exhibited lower portal pressure, hepatic vascular resistance without effect on systemic vascular resistance, but a tendency towards lower cardiac output compared to non-treated cirrhotic rats. Y27pPBHSA reduced intrahepatic resistance by reduction of phosphorylation of moesin and MLC in Y27pPBHSA-treated cirrhotic rats. Y27pPBHSA was found in the liver of rats up to 6 hours after its injection, in the HSC demonstrated by double-immunostainings. Interestingly, Y27pPBHSA increased renal arterial flow over time combined with an antifibrotic effect as shown by decreased renal acta2 and col1a1 mRNA expression. Therefore, targeting the ROCK inhibitor Y27 to PDGFRβ decreases portal pressure with potential beneficial effects in the kidney. This unique approach should be tested in human cirrhosis.

Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep

BackgroundGlobal and intra-renal perfusion and oxygenation may be affected by the choice of anaesthetic. We compared the effects of isoflurane with those of propofol and fentanyl on renal blood flow (RBF) and intra-renal perfusion and oxygenation, and assessed how these were associated with renal sympathetic nerve activity (RSNA). MethodsA renal artery flow probe and laser Doppler and oxygen-sensing probes were surgically implanted in the renal medulla and cortex in 20 Merino ewes. RSNA was measured in 12 additional ewes. We compared the effects of volatile or i.v. anaesthesia on global RBF, renal oxygen delivery (RDO2), intra-renal perfusion, and RSNA with the non-anaesthetised state on postoperative day 3 as control reference. ResultsCompared with a non-anaesthetised state, volatile anaesthesia reduced global RBF [–76 (82–68)%], RDO2 [−76 (83–71)%], and cortical [–68 (74–54)%] and medullary [–76 (84–72)%] perfusion. I.V. anaesthesia reduced RBF [–55 (67–38)%], RDO2 [–55 (65–44)%], and cortical [–27 (45–6)%] and medullary [–35 (48–30)%] perfusion, but to a lesser extent than volatile anaesthesia. Renal PO2 was not influenced by anaesthesia, whilst RSNA was elevated during volatile, but not during i.v. anaesthesia. ConclusionsVolatile and i.v. general anaesthesia markedly reduced global RBF, RDO2, and regional kidney perfusion. These effects were greater with volatile anaesthesia, and were paralleled by an increase in RSNA. Our findings suggest a neurogenic modulatory effect of anaesthetics on renal perfusion and oxygenation.

Predictive value of fetal renal artery Doppler indices in idiopathic oligohydramnios and polyhydramnios

Objective The aim of this work was to study the relation of renal artery (RA) and umbilical artery (UA) flow velocity waveforms and amniotic fluid volume in normal pregnancies and those complicated by either polyhydramnios or oligohydramnios. Background There is a relation between RA and UA flow velocity waveforms and amniotic fluid volume in normal pregnancies and those complicated by either polyhydramnios or oligohydramnios. Patients and methods All patients were enrolled from patients attending the outpatient clinic of El-Galaa Maternity Teaching Hospital. All patients were matched for maternal age, gestational age, and parity at the time of sonography, comparing RA Doppler indices pulsatility index (PI) and resistance index at 22, 28, and 34 weeks in three groups. Group I consisted of 20 patients of normal amniotic fluid index, group II consisted of 20 patients with oligohydramnios, and group III consisted of 20 patients with polyhydramnios. Results RA PI values were higher in group II than group I at 22 weeks, 28 weeks, and 34 weeks. The PI value at 28 weeks of gestation was statistically significant (P = 0.016). At 28 weeks of gestation, group II also had higher UA PI and resistance index values than group I. Conclusion An increase in RA PI develops in early pregnancy before the development of oligohydramnios. In pregnancies developing polyhydramnios, RA PI was lower.

Assessment of Perfusion and Oxygenation of the Human Renal Cortex and Medulla by Quantitative MRI during Handgrip Exercise.

Renal flow abnormalities are believed to play a central role in the pathogenesis of nephropathy and in primary and secondary hypertension, but are difficult to measure in humans. Handgrip exercise is known to reduce renal arterial flow (RAF) by means of increased renal sympathetic nerve activity. To monitor medullary and cortical oxygenation under handgrip exercise-reduced perfusion, we used contrast- and radiation-free magnetic resonance imaging (MRI) to measure regional changes in renal perfusion and blood oxygenation in ten healthy normotensive individuals during handgrip exercise. We used phase-contrast MRI to measure RAF, arterial spin labeling to measure perfusion, and both changes in transverse relaxation time (T2*) and dynamic blood oxygenation level-dependent imaging to measure blood oxygenation. Handgrip exercise induced a significant decrease in RAF. In the renal medulla, this was accompanied by an increase of oxygenation (reflected by an increase in T2*) despite a significant drop in medullary perfusion; the renal cortex showed a significant decrease in both perfusion and oxygenation. We also found a significant correlation (R2=0.8) between resting systolic BP and the decrease in RAF during handgrip exercise. Renal MRI measurements in response to handgrip exercise were consistent with a sympathetically mediated decrease in RAF. In the renal medulla, oxygenation increased despite a reduction in perfusion, which we interpreted as the result of decreased GFR and a subsequently reduced reabsorptive workload. Our results further indicate that the renal flow response's sensitivity to sympathetic activation is correlated with resting BP, even within a normotensive range.

Experimental pericardial tamponade-translation of a clinical problem to its large animal model.

Pericardial tamponade is a life-threatening medical emergency, when the hemodynamic consequences of low cardiac output severely disturb the perfusion of the peripheral tissues. Our aim was to design a reliable large animal model to reproduce the clinical scenario with the relevant pathophysiological consequences of pericardial tamponade -induced cardiogenic shock. Anesthetized Vietnamese mini pigs were used (n=12). Following laparotomy, a cannula was fixed into the pericardium through the diaphragm without thoracotomy. A sham-operated group (n=6) served as control, while in the second group (n=6) pericardial tamponade was induced by intra-pericardial injection of heparinized own blood. Throughout the 60-min pericardial tamponade and the 180-min reperfusion, macro hemodynamics, renal circulation and the mesenteric macro- and micro-circulatory parameters were monitored. Myeloperoxidase activity was measured to detect neutrophil leukocyte accumulation and in vivo histology was performed by confocal laser scanning endomicroscopy to observe the structural changes of the intestinal mucosa. PT increased the central venous pressure, heart rate, and decreased mean arterial pressure. The mesenteric artery flow (from 355.5±112.4 vs 182.0±59.1 mL/min) and renal arterial flow (from 159.63±50.7 vs 35.902±27.9 mL//min) and the micro-circulation of the ileum was reduced. The myeloperoxidase activity was elevated (from 3.66±1.6 to 7.01±1.44 mU/mg protein) and manifest injury of the ileal mucosa was present. This experimental model suitably mimics the hemodynamics and the pathology of clinical pericardial tamponade situations, and on this basis, it provides an opportunity to study the adverse macro- and micro-circulatory effects and biochemical consequences of human cardiogenic shock.