Left Renal Blood Flow Research Articles

Assessment of Hepatic Function, Perfusion and Parenchyma Attenuation with Indocyanine Green, Ultrasound and Computed Tomography in a Rat Model: Preliminary Standardization of Baseline Parameters in a Healthy Liver

Introduction: The standardization in experimental animal models plays a crucial role in pre-clinical studies. However, it is necessary to combine these determinations with dynamic functional test and imaging techniques to implement a non-invasive protocol for liver evaluation. Methods: Six healthy SD rats were followed for 4 weeks. The aim of the study was to determine hepatic function, perfusion and parenchyma attenuation with analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography. Results: Indocyanine green clearance 5 and 10 minutes after its injection was 80.12% and 96.59%, respectively. Approximate rate of decay during the first 5 minutes after injection was 38% per minute. Hepatic perfusion evaluation with the high-frequency ultrasound was related to cardiovascular hemodynamic and renal perfusion. Portal area, hepatic artery resistance index, hepatic artery and portal peak systolic velocity and average between hepatic artery and porta was 3.41 ± 0.62 mm2, 0.57 ± 0.04 mm2/s, 693.24±102.53 mm2/s, 150.72 ± 17.80 mm2/s and 4.82 ± 0.96 mm2/s, respectively. Heart rate, cardiac output, left renal artery diammetre and renal blood flow were 331.01 ± 22.22 bpm, 75.58 ± 8.72 mL/min, 0.88 ± 0.04 mm2 and 13.65 ± 1.95 mm2/s. CT-scan hepatic average volume for each rat were 21.08±3.32, 17.57±2.76, 14.87±2.83 and 13.67±2.45 cm3 with an average attenuation coefficient of 113.51±18.08, 129,19±7.18, 141,47±1.95 y 151,67±1.2 HU (Figure). Conclusion: Indocyanine green and high-frequency ultrasound could be used in rats as a suitable marker of liver function. Computed tomography, through the study of raw data could help to characterize liver parenchyma.

Assessment of hepatic function, perfusion and parenchyma attenuation with indocyanine green, ultrasound and computed tomography in a healthy rat model: Preliminary determination of baseline parameters in a healthy liver.

Defining reference intervals in experimental animal models plays a crucial role in pre-clinical studies. The hepatic parameters in healthy animals provide useful information about type and extension of hepatic damage. However, in the majority of the cases, to obtain them require an invasive techniques. Our study combines these determinations with dynamic functional test and imaging techniques to implement a non-invasive protocol for liver evaluation. The aim of the study was to determine reference intervals for hepatic function, perfusion and parenchyma attenuation with analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography in six healthy SD rats. Six males healthy SD rats were followed for 4 weeks. To determine hepatic function, perfusion and parenchyma attenuation analytical and biochemical blood parameters, indocyanine green, ultrasound and computed tomography were studied. Results were expressed as Means ± standard error of mean (SEM). The significance of differences was calculated by using student t-test, p < 0.05 was considered statistically significant. Indocyanine green clearance 5 and 10 minutes after its injection was 80.12% and 96.59%, respectively. Approximate rate of decay during the first 5 minutes after injection was 38% per minute. Hepatic perfusion evaluation with the high-frequency ultrasound was related to cardiovascular hemodynamic and renal perfusion. Portal area, hepatic artery resistance index, hepatic artery and portal peak systolic velocity and average between hepatic artery and porta was 3.41 ± 0.62 mm2, 0.57 ± 0.04 mm2/s, 693.24±102.53 mm2/s, 150.72 ± 17.80 mm2/s and 4.82 ± 0.96 mm2/s, respectively. Heart rate, cardiac output, left renal artery diammetre and renal blood flow were 331.01 ± 22.22 bpm, 75.58 ± 8.72 mL/min, 0.88 ± 0.04 mm2 and 13.65 ± 1.95 mm2/s. CT-scan hepatic average volume for each rat were 21.08±3.32, 17.57±2.76, 14.87±2.83 and 13.67±2.45 cm3 with an average attenuation coefficient of 113.51±18.08, 129,19±7.18, 141,47±1.95 y 151,67±1.2 HU. Indocyanine green and high-frequency ultrasound could be used in rats as a suitable marker of liver function. Computed tomography, through the study of raw data, help to characterize liver parenchyma, and could be a potential tool for early detection of liver parenchymal alterations and linear follow-up of patients. Further studies in rats with liver disease are necessary to verify the usefulness of these parameters.

Abstract 12867: Neuromodulation Of The Renal Nerves In Spontaneously Hypertensive Rats

Introduction: Hypertension is a global burden. Renal denervation has been touted as a possible therapeutic strategy for the treatment of hypertension. However, neuromodulation of the renal nerves’ traffic in hypertension has yet to receive a similar attention. Aim: This study investigated cardio-respiratory responses to renal nerve stimulation in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Methods: In pentobarbital-anesthetized male SHRs (n = 9), the left renal nerve was stimulated 5 times (5-6 minutes apart) at 5 Hz, 0.5 ms, 0.5 mA for 30s. Mean arterial pressure (MAP), heart rate (HR), left renal cortical blood flow (CBF) and cortical vascular resistance (CVR), hindquarter aortic blood flow (ABF) and vascular resistance (AVR), upper (UAP) and lower (LAP) airway pressure, airway flow (AF), airway resistance (AR), respiration rate (RR) and diaphragmatic EMG (dEMG) were measured and averaged. Results: Cardiovascular responses to renal nerve stimulation were characterized by reductions in MAP, HR, CBF and AVR, which were associated with increases in ABF and CVR. Respiratory responses to renal nerve stimulation, on the other hand, demonstrated increases in AF, RR and dEMG, decreases in AR and no change in UAP and LAP. Conclusions: Under hypertensive conditions, the renal nerves not only modulate cardiovascular function but also improve respiratory function. These studies suggest that neuromodulation of the renal nerves may offer a therapeutic alternative for hypertensive patients.

Assessment of Hepatic Function and Parenchyma Attenuation with Indocyanine Green, Ultrasound and CT in a Rat Model: Preliminary Standardization of Baseline Parameters

Purpose: Standardization in experimental animal models plays a crucial role in preclinical studies by providing useful information on the type and extent of liver disease. However, it is necessary to combine these determinations with functional dynamics imaging and testing techniques to implement a non-invasive protocol for liver evaluation. Method: Six healthy SD rats were followed for 4 weeks. The aim was to determine hepatic function, perfusion and parenchyma attenuation with biochemical blood parameters, indocyanine green, ultrasound and computed tomography. Results: Indocyanine green clearance 5 and 10 minutes after its injection was 80.12% and 96.59%, respectively. Hepatic perfusion evaluation with the high-frequency ultrasound was related to cardiovascular hemodynamic and renal perfusion. Portal area, hepatic artery resistance index and average between hepatic artery and porta was 3.41 ± 0.62 mm 2 , 0.57 ± 0.04 mm 2 /s and 4.82 ± 0.96 mm 2 /s, respectively. Heart rate, cardiac output, left renal artery diammetre and renal blood flow were 331.01 ± 22.22 bpm, 75.58 ± 8.72 mL/min, 0.88 ± 0.04 mm 2 and 13.65 ± 1.95 mm 2 /s. CT-scan hepatic average volume for each rat were 21.08±3.32, 17.57±2.76, 14.87±2.83 and 13.67±2.45 cm 3 with an average attenuation coefficient of 113.51±18.08, 129,19±7.18, 141,47±1.95 y 151,67±1.2 HU. Conclusion: Indocyanine green and high-frequency ultrasound could be used in rats as a suitable marker of liver function. Computed tomography help to characterize liver parenchyma, and could be a potential tool for early detection and linear follow-up of patients. Further studies in rats with liver disease are necessary to verify the usefulness of these parameters.Table 1Indocyanine Green plasma clearance (ICG) rateICG plasma concentration (μg/mL)Min 1Min 5Min 10Rat 1128.1±55.61819.45±2.285.41±3.32Rat 2161.47±65.8228.58±9.235.75±3.60Rat 3160.63±27.6833.14±6.957.44±0.52Rat 4189.16±51.0538.13±2.863.47±0.05Rat 5165.91±23.9147.51±8.822.90±0.76Rat 6130.65±10.2119.24±3.546.91±0.99Average ICG Concentration (μg/mL)155.99±23.1131.01±11.015.31±1.82Average Clearance %0.0080.1296.59 Open table in a new tab μg/mL: microgram/mililitre

Pathophysiology of unilateral ischemia-reperfusion injury: importance of renal counterbalance and implications for the AKI-CKD transition.

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX. Male Sprague-Dawley rats underwent left UIR or sham UIR and 2 wk later CNX or sham CNX. Blood pressure, left renal blood flow (RBF), and total glomerular filtration rate were assessed in conscious rats for 3 days before and over 2 wk after CNX or sham CNX. In the presence of a contralateral uninjured kidney, left RBF was lower (P < 0.05) from 2 to 4 wk following UIR (3.6 ± 0.3 mL/min) versus sham UIR (9.6 ± 0.3 mL/min). Without CNX, extensive renal atrophy, TIF, and tubule dedifferentiation, but minimal pimonidazole and hypoxia-inducible factor-1α positivity in tubules, were present at 4 wk post-UIR injury. Conversely, CNX led (P < 0.05) to sustained increases in left RBF (6.2 ± 0.6 mL/min) that preceded the increases in glomerular filtration rate. The CNX-induced improvement in renal function was associated with renal hypertrophy, more redifferentiated tubules, less TIF, and robust pimonidazole and hypoxia-inducible factor-1α staining in UIR injured kidneys. Thus, contrary to expectations, indexes of hypoxia are not observed with the extensive TIF at 4 wk post-UIR injury in the absence of CNX but are rather associated with the improved recovery of renal function and structure following CNX.

Reduction of circulating renin‐angiotensin following unilateral nephrectomy signals kidney hypertrophy via increase in renal blood flow

RationaleThe compensatory hypertrophy of a remaining kidney after nephrectomy has long been recognized and the molecular and functional responses to these events have been well characterized. However, the signal that triggers these events is unknown. Recent studies have found that nephrectomy of the right kidney in rats results in a rapid increase of renal blood flow of the remaining kidney within the first 30 minutes and activation of the mTOR pathway with consequent hypertrophy. In the present study, we hypothesized that a reduction of circulating renin would immediately occur with removal of the right kidney which could produce an immediate peripheral vasodilation and increase of renal blood flow within the remaining left kidney.MethodsSprague Dawley rats (male; 7 wk age) were anesthetized, the left kidney was denervated and then the right kidney was removed while monitoring immediate changes of systemic mean arterial blood pressure (MAP), left renal arterial blood flow (RBF), and left urine volume (V). Three groups were studied: 1) No drug treatment (n=5); 2) Pretreated with the AT1 receptor blocker Losartan (n=4); 3) Pretreated with Losartan and Angiotensin II administered to return aortic pressure and RBF to normal before removing the right kidney (n=2).ResultsLeft RBF gradually increased from 3.8 to 4.7 ml/min and became stable 30 minutes following removal of the right kidney. A slight decrease of MAP occurred during that time (~4 mmHg) and urine volume nearly doubled from 2.7 to 5.3 μl/min. Rats treated with Losartan exhibited a reduced baseline level of MAP and increased level of RBF but the changes in MAP and RBF following right nephrectomy were abolished. Rats treated with Losartan with Angiotensin II infused to normalize baseline levels of RBF and MAP, also exhibited no increases of RBF following removal of the right kidney.ConclusionWe conclude that rapid reductions of circulating renin‐angiotensin following right kidney nephrectomy produce increased RBF in the remaining kidney which in turn may trigger the compensatory hypertrophy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Esmolol Administration to Control Tachycardia in an Ovine Model of Peritonitis.

Excessive adrenergic signaling may be harmful in sepsis. Using β-blockers to reduce sympathetic overactivity may modulate sepsis-induced cardiovascular, metabolic, immunologic, and coagulation alterations. Using a randomized ovine fecal peritonitis model, we investigated whether administration of a short-acting β-blocker, esmolol, could control tachycardia without deleterious effects on hemodynamics, renal perfusion, cerebral perfusion, cerebral metabolism, or outcome. After induction of fecal peritonitis, 14 anesthetized, mechanically ventilated, and hemodynamically monitored adult female sheep were randomly assigned to receive a continuous intravenous infusion of esmolol to control heart rate between 80 and 100 bpm (n = 7) or a saline infusion (control group, n = 7). Esmolol was discontinued when the mean arterial pressure decreased below 60 mm Hg. Fluid resuscitation was titrated to maintain pulmonary artery occlusion pressure at baseline values. Left renal blood flow and cerebral cortex perfusion and metabolism were monitored in addition to standard hemodynamic variables. Esmolol was infused for 11 (9-14) hours; the target heart rate (80-100 bpm) was achieved between 3 and 8 hours after feces injection. In the first 5 hours after the start of the infusion, the decrease in heart rate was compensated by an increase in stroke volume index; later, stroke volume index was not statistically significantly different in the 2 groups, so that the cardiac work index was lower in the esmolol than in the control group. Hypotension (mean arterial pressure <60 mm Hg) occurred earlier (10 [8-12] vs 14 [11-20] hours; P= .01) in the esmolol group than in the control animals. Renal blood flow decreased earlier in the esmolol group, but there were no differences in urine output, cerebral cortex perfusion, metabolism, or survival between the groups. In this ovine model of abdominal sepsis, early control of tachycardia by esmolol was associated with a transient increase in stroke volume, followed by earlier hypotension. There were no significant effects of esmolol on cerebral perfusion, metabolism, urine output, or survival.

MP67-19 ALISKIREN PROVIDES INCOMPLETE PROTECTION OF THE KIDNEY IN UNILATERAL URETERIC OBSTRUCTION IN THE RAT

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology II1 Apr 2016MP67-19 ALISKIREN PROVIDES INCOMPLETE PROTECTION OF THE KIDNEY IN UNILATERAL URETERIC OBSTRUCTION IN THE RAT Fayez Hammad and Loay Lubbad Fayez HammadFayez Hammad More articles by this author and Loay LubbadLoay Lubbad More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1335AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ureteric obstruction (UO) is a common urological condition caused by several conditions such as urolithiasis and might lead to renal impairment. UO induces alterations in renin angiotensin system (RAS) which plays an important role in obstruction-induced renal dysfunction. Renin catalyzes the first and rate limiting step of RAS. However, until recently, direct renin inhibitors were not used effectively in clinical practice due to toxicity, poor bioavailability and limited efficacy. Aliskiren is the first commercially available FDA-approved oral direct renin inhibitor. Very few studies showed that aliskiren ameliorates some of the UO-induced markers of acute renal injury. However, these protective effects do not necessarily imply an improvement in the UO-induced alterations in some of the clinically more relevant parameters such as the glomerular filtration rate (GFR), renal blood flow (RBF) and tubular functions. Indeed, the effect of aliskiren on these parameters in the post-obstruction period has not been studied yet. Thus, the aim of this study was to investigate the effect of aliskiren on the alterations in renal dysfunction following reversible unilateral UO in the rat. METHODS Male Wistar rats underwent reversible left UO for 72 hours. Group-1 (n=10) received aliskiren (60 mg/kg/day) dissolved in water by oral gavage starting one day before and continued throughout the period of UO until the terminal experiment 5 days post reversal when the renal functions were measured using clearance techniques. Group-2 (n=10) underwent similar protocol but had drinking water only. In addition, gene expression of some markers of kidney injury was measured in the kidney tissue using PCR technique. RESULTS The mean arterial blood pressure and heart rate in both groups were similar. UO affected all hemodynamic and tubular parameters in the affected kidney. So in Group-2, left RBF, was 57% of the right RBF (1.82±0.12 vs. 3.19±0.40, P<0.01). Similarly, left GFR was 55% that of the right GFR (0.81±0.08 vs. 1.44±0.09, P<0.01). On the other hand, the left fractional excretion of sodium (FENa) was higher than the right FENa (0.76±0.17 vs. 0.56±0.09, P<0.05). Aliskiren attenuated the UO-related alterations in hemodynamic parameters; so when the left obstructed kidney in Group-2 and Group-1 were compared, RBF was significantly higher in Group-1 (2.44±0.30 vs. 1.82±0.12, P=0.049). GFR was also higher in Group-1 (1.02±0.10 vs. 0.81±0.08, P=0.07) but did not reach statistical significance. On the other hand, the left renal FENa was similar in both groups (0.53±0.08 vs. 0.76±0.17, P=0.12). Aliskiren also decreased the gene expressions of some of the markers of kidney injury such as Lipocalin-2 (2.7±0.2 vs. 5.5±1.2, P=0.03). CONCLUSIONS Aliskiren attenuated the UO-induced alterations in the hemodynamic renal parameters and some of the markers of kidney injury but not the tubular alterations indicating an incomplete protective effect of this renin inhibitor © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e888 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Fayez Hammad More articles by this author Loay Lubbad More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Changes of renal hemodynamics in dogs with endotoxemic shock

To explore the changes of renal hemodynamic in dogs with endotoxemic shock (ES) and their potential roles in acute kidney injury (AKI). Canine endotoxic shock model was induced by an infusion of lipopolysaccharide of Escherichia coli through pulmonary artery catheter (PAC). Systemic hemodynamics and left renal blood flow (RBF) was monitored by PAC, pulse index continuous cardiac output (PiCCO) and ultrasonic blood flow meter. Blood and urine specimens were harvested timely for blood gas analysis, renal function tests and biochemical detection. Hemodynamics: CO and RBF fluctuated widely but without any significance (P > 0.05). The values of mean arterial pressure (MAP), systemic vascular resistance (SVR), renal vascular resistance (RVR) and 2-hour urine volume significantly decreased (all P < 0.05) while extravascular lung water (EVLW) increased markedly (P < 0.05). Renal function: There was a drop in CCr, urine osmotic pressure and an elevation in SCr and NAG. RBF was correlated positively with CO (R(2) = 0.630, P = 0.001) .However, it had no correlation with MAP (R(2) = 0.009, P = 0.758) . CCr was correlated positively with MAP (R(2) = 0.415, P = 0.003) . However, it had no correlation with RBF or CO (P > 0.05 ). The auto-regulation curve of GFR had a shift to the right. RBF is positively correlated with cardiac output in endotoxin shock. Renal pressure perfusion may decrease obviously without any noticeable change of renal flow perfusion. The shift of renal auto-regulation under pressure perfusion occurs at the early stage of septic shock.

Does Aliskiren Protect the Kidney Following Ischemia Reperfusion Injury?

The effect of blocking the first and rate-limiting step in renin-angiotensin cascade on the renal function in ischemia reperfusion injury has not been previously investigated. We investigated the effect of aliskiren, the first approved direct oral renin inhibitor, on the alterations in renal functional parameters in this condition. Wistar rats underwent left renal ischemia for 40 min. Group-1 received normal saline whereas Group-2 received aliskiren (30 mg/kg/day) by gavage for 6 days commencing one day before IRI. The hemodynamic and tubular functions and gene expression of neutrophil gelatinase-associated lipocalin (NGAL) and plasminogen activating inhibitor (PAI-1) in the right and left kidneys were measured five days following the IRI. Comparing Group-1 and Group-2, the left renal blood flow was significantly higher in Group-2 (1.28+/-0.36 vs. 0.39+/-0.05, P=0.007). Left kidney glomerular filtration rate was also higher in Group-2 but did not reach statistical significance (0.18+/-0.05 vs. 0.10+/-0.02, P=0.07). The left renal FE(Na) was significantly lower in Group-2 (29.9+/-6.4 vs. 49.7+/-7.8, P=0.03). Aliskiren also caused a significant decrease in the gene expression of both NGAL and PAI-1 in the left ischemic kidney. In conclusions, the administration of aliskiren before and after IRI appears to have ameliorated the IRI effect on the total renal artery blood flow, fractional excretion of sodium and gene expression of both NGAL and PAI-1 indicating a renoprotective effects in IRI.

An incidental detection of aortic aneurysm on Tc-99m MAG3 renal scintigraphy

A 71-year-old man with newly diagnosed hypertension was referred for Technetium-99m mercaptoacetyltriglycine (Tc-99m MAG3) renal scintigraphy to evaluate the recent onset of impairment in renal functions. Dynamic imaging revealed activity flow which was suspicious for aortic aneurysm (AA) with a concurrent decrease in left renal blood flow. CT angiography of the thoracoabdominal aorta confirmed that this area corresponded to AA. The purpose of this report was to present the first case of incidental detection of AA on Tc-99m MAG3 scintigraphy and highlight the importance of correlative imaging for the diagnosis of abnormal radioactivity accumulation in the region of vascular structures.

Curcumin Provides Incomplete Protection of the Kidney in Ischemia Reperfusion Injury

Curcumin, a component of the spice turmeric, was shown to have a protective effect on acute kidney injury markers following ischemia-reperfusion injury (IRI). However, its effect on glomerular and tubular renal functions following IRI is not known and this data is probably of more clinical relevance. In this study, curcumin was tested for its effect on renal functional parameters following two different periods of warm IRI in the rat. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 received oral curcumin (200 mg/kg/day) whereas V-30 and V-45 received a vehicle. The left renal artery blood flow was measured by a flowmeter before and 15 minutes after reperfusion. Serum TNF-alpha was measured before and 2 days after ischemia. The function of both kidneys was measured 2 days following ischemia using clearance technique. IRI caused significant increase in TNF-alpha in all groups. Curcumin significantly ameliorated the ischemia-induced alterations in serum TNF-alpha and associated histological changes but did not affect the alterations in renal artery blood flow, glomerular (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions following 30 or 45 min of IRI.

2264 DOES CURCUMIN PROTECT THE KIDNEY FOLLOWING ISCHEMIA REPERFUSION INJURY?

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery II1 Apr 20122264 DOES CURCUMIN PROTECT THE KIDNEY FOLLOWING ISCHEMIA REPERFUSION INJURY? Fayez Hammad, Suhail Al-Salam, and Loay Lubbad Fayez HammadFayez Hammad Al Ain, United Arab Emirates More articles by this author , Suhail Al-SalamSuhail Al-Salam Al Ain, United Arab Emirates More articles by this author , and Loay LubbadLoay Lubbad Al Ain, United Arab Emirates More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2442AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES There is limited number of studies which demonstrated a protective effect of curcumin on the markers of acute renal injury following ischemia-reperfusion injury. However, none of these studies have investigated the effect of curcumin on the glomerular and tubular renal functions which are probably more clinically relevant compared to the markers of acute renal injury. Thus, the aim of this study was to investigate the effect of curcumin on the alterations in renal functional parameters following different periods of warm ischemia-reperfusion injury in the rat. METHODS Male Wistar rats underwent left renal ischemia. Groups V-30 (n=10) and C-30 (n=10) underwent ischemia for 30 minutes whereas groups V-45 (n=8) and C-45 (n=8) underwent ischemia for 45 minutes. C-30 and C-45 groups received oral curcumin (200mg/kg/day) whereas V-30 and V-45 groups received a vehicle. The left renal artery blood flow was measured by a flowmeter before the induction of the renal ischemia and 15 minutes after kidney reperfusion. Serum tumor necrosis factor-alpha (TNF-á) was measured before and 2 days after ischemia. The functions of the ischemic left kidney and the contra-lateral non-ischemic right kidney were measured 2 days following the ischemia-reperfusion injury. RESULTS Ischemia-reperfusion caused significant increase in the serum level of TNF-á in all groups. However, post-ischemia levels in C-30 and C-45 groups were significantly lower than the V-30 and V-45 groups, respectively. Curcumin did not affect the alterations in renal artery blood flow, hemodynamic (glomerular filtration rate, renal blood flow) or tubular (urinary volume, urinary sodium and fractional excretion of sodium) functions in the C-30 or C-45 group. Curcumin improved the ischemia-induced histological alterations in the C-30 vs. V-30 groups. CONCLUSIONS Curcumin ameliorated the ischemia-induced alterations in serum TNF-á and associated histological changes but did not have any significant effect on glomerular and tubular functions following renal ischemia-reperfusion injury. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e913-e914 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fayez Hammad Al Ain, United Arab Emirates More articles by this author Suhail Al-Salam Al Ain, United Arab Emirates More articles by this author Loay Lubbad Al Ain, United Arab Emirates More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The Feasibility of Measuring Renal Blood Flow Using Transesophageal Echocardiography in Patients Undergoing Cardiac Surgery

There is no reliable method to monitor renal blood flow intraoperatively. In this study, we evaluated the feasibility and reproducibility of left renal blood flow measurements using transesophageal echocardiography during cardiac surgery. In this prospective noninterventional study, left renal blood flow was measured with transesophageal echocardiography during three time points (pre-, intra-, and postcardiopulmonary bypass) in 60 patients undergoing cardiac surgery. Sonograms from 6 subjects were interpreted by 2 blinded independent assessors at the time of acquisition and 6 mo later. Interobserver and intraobserver reproducibility were quantified by calculating variability and intraclass correlation coefficients. Patients with Doppler angles of >30 degrees (20 of 60 subjects) were eliminated from renal blood flow measurements. Left renal blood flow was successfully measured and analyzed in 36 of 60 (60%) subjects. Both interobserver and intraobserver variability were <10%. Interobserver and intraobserver reproducibility in left renal blood flow measurements were good to excellent (intraclass correlation coefficients 0.604-0.999). Left renal arterial luminal diameter for the pre, intra, and postcardiopulmonary bypass phases, ranged from 3.8 to 4.1 mm, renal arterial velocity from 25 to 35 cm/s, and left renal blood flow from 192 to 299 mL/min. In patients undergoing cardiac surgery, it was feasible in 60% of the subjects to measure left renal blood flow using intraoperative transesophageal echocardiography. The interobserver and intraobserver reproducibility of renal blood flow measurements was good to excellent.

Abstract 1495: Existence of Hyperfiltration in an Early Diabetic Rat was Visualised by Multiphoton Microscopy

To visualise glomerular filtration under physiological conditions in an early diabetic rat and to evaluate filtration molecularly and quantitatively. We used 4 week STZ (50 mg/kg) model as early diabetic rats. We measured diameters of afferent (aff) and efferent (eff) arterioles, glomerular red blood cell velocities and left renal blood flow with our intravital videomicro-scope. Glomerular filtration was visualised by multiphoton microscopy. Various sizes of dextran (3k, 10k, 40k and 70k dalton (Dal)) conjugated with Texas Red in 0.5 ml were administered intravenously by bolus shot and for the next 60 seconds glomerular filtration was observed. FITC conjugated 500k Dal dextran was administered to dye intravascular area. The time course of Texas Red intensity in Bowman’s space was measured from the recorded images. Intensity peak values were normalized by the peak value of 3k Dal as sieving coefficients since the intensity reached its peak within 10 seconds after administration of Texas Red conjugated dextrans. Afferent arteriolar diameters were larger than efferent arteriolar diameters in both control (n=6) and diabetic (n=7) rats. Increases of both afferent and efferent diameters were remarkable in diabetic rats (p&lt;0.05) (aff/eff diameter, DM rats: 14.0 ± 1.9, 9.4 ± 0.7, Control rats: 11.9 ± 0.8, 8.8 ± 0.7 μm). Glomerular red blood cell velocity in diabetic rats was larger than that in control rats (p&lt;0.05) (DM/Control rats: 0.236 ± 0.030, 0.196 ± 0.076 mm/s). Left renal blood flow in diabetic rats was larger than that in control rats (p&lt;0.05) (DM/Control rats: 1.84 ± 0.16, 1.60 ± 0.17 ml/100 gBW). All of these findings suggest the existence of hyperfiltration in early diabetic rats. In fact, filtration of the larger dextrans (40k and 70k Dal) were clearly visualized by multiphoton microscopy in early diabetic rats indicating greater leakage even from the early stage of diabetes with a significant difference by about 20% for the 40k and 70k Dal sieving coefficients comparing with the control group (p&lt;0.05). Both afferent and efferent arteriolar diameters were increased in early diabetic rats suggesting the existence of hyperfiltration and the hyperfiltration was clearly visualised by multiphoton microscopy.

The role of nitric oxide in the peripheral vasoconstriction caused by human placental lactogen in anaesthetized pigs

Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of beta2-adrenergic receptors. Since nitric oxide is known to modulate or mediate beta2-adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of beta2-adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release.

Renal sympathetic and circulatory responses to activation of the exercise pressor reflex in rats

We investigated the role played by the exercise pressor reflex in sympathetic regulation of the renal circulation in rats. In mid-collicular decerebrate rats, mean arterial pressure (MAP), heart rate (HR), left renal cortical blood flow (RCBF) and left renal sympathetic nerve activity (RSNA) were recorded before and during 30 s of static contraction of the left triceps surae muscles evoked by electrical stimulation of the tibial nerve, which activates both metabo- and mechanosensitive muscle afferents, and during 30 s of passive stretch of the left Achilles tendon, which selectively activates mechanosensitive muscle afferents. Static contraction (n = 17, +344 +/- 34 g developed tension) significantly (P < 0.05) increased MAP (+14 +/- 3 mmHg), HR (+6 +/- 1 beats min(-1)) and RSNA (n = 11, +19 +/- 5%) and significantly decreased renal cortical vascular conductance (RCVC, n = 11, -11 +/- 2%). Passive stretch (n = 20, +378 +/- 11 g) also significantly increased MAP (+11 +/- 2 mmHg), HR (+7 +/- 2 beats min(-1)) and RSNA (n = 15, +14 +/- 4%) and significantly decreased RCVC (n = 11, -12 +/- 3%). RCBF showed no significant changes during static contraction or passive stretch. Renal denervation abolished the decrease in RCVC during contraction (n = 12) or stretch (n = 13). These data indicate that both the exercise pressor reflex and its mechanically sensitive component, the muscle mechanoreflex, induced renal cortical vasoconstriction through sympathetic activation in rats.

The effect of dehydroepiandrosterone on regional blood flow in prepubertal anaesthetized pigs.

Dehydroepiandrosterone has been implicated in vascular disease and its associated insulin resistance and hypertension, though little is known about its vascular effects. We have recently shown in prepubertal anaesthetized pigs that intravenous infusion of dehydroepiandrosterone caused coronary vasoconstriction through the inhibition of a vasodilatory beta-adrenergic receptor-mediated effect related to the release of nitric oxide. The present study was designed to investigate the effect of dehydroepiandrosterone on mesenteric, renal and iliac vascular beds. In prepubertal pigs of both sexes anaesthetized with sodium pentobarbitone, changes in superior mesenteric, left renal and left external iliac blood flow caused by intravenous infusion of dehydroepiandrosterone were assessed using electromagnetic flowmeters. Changes in heart rate and arterial blood pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 22 pigs, infusion of 1 mg h(-1) of dehydroepiandrosterone decreased mesenteric, renal and iliac blood flow. In a further 10 pigs, dose-response curves were obtained by graded increases in the infused dose of hormone between 0.03 and 4 mg h(-1). The mechanisms of the above response were studied in the 22 pigs by repeating the experiment after haemodynamic variables had returned to the control values observed before infusion. Blockade of alpha-adrenoceptors with intravenous phentolamine (five pigs) did not affect the dehydroepiandrosterone-induced mesenteric, renal and iliac vasoconstriction. This response was abolished by blockade of beta(2)-adrenoceptors with intravenous butoxamine (five pigs) and by blockade of mesenteric, renal and iliac nitric oxide synthase with intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (seven pigs), even after reversing the increase in local vascular resistance caused by the two blocking agents with intravenous infusion of papaverine. In five pigs, the increase in measured blood flow caused by intravenous infusion of isoproterenol (isoprenaline) was significantly reduced by infusion of dehydroepiandrosterone. The present study showed that intravenous infusion of dehydroepiandrosterone primarily caused mesenteric, renal and iliac vasoconstriction. The mechanisms of this response were shown to be due to the inhibition of a vasodilatory beta(2)-adrenergic receptor-mediated effect, which possibly involved the release of nitric oxide.

The effect of testosterone on regional blood flow in prepubertal anaesthetized pigs.

This work was undertaken to study the effects of testosterone on the coronary, mesenteric, renal and iliac circulations and to determine the mechanisms of action involved. In prepubertal pigs of both sexes anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary, superior mesenteric, left renal and left external iliac blood flow caused by intra-arterial infusion of testosterone were assessed using electromagnetic flowmeters. Changes in heart rate and arterial blood pressure were prevented by atrial pacing and by connecting the arterial system to a pressurized reservoir containing Ringer solution. In 12 pigs, intra-arterial infusion of testosterone for 5 min to achieve a stable intra-arterial concentration of 1 microg l(-1) increased coronary, mesenteric, renal and iliac blood flow without affecting the maximum rate of change of left ventricular systolic pressure (left ventricular dP/dt(max)) and filling pressures of the heart. In a further five pigs, a concentration-response curve was obtained by graded increases in the intra-arterial concentration of the hormone between 0.125 and 8 microg l(-1). The mechanisms of these responses were studied in the 12 pigs by repeating the experiment after haemodynamic variables had returned to the control values before infusions. In six pigs, blockade of muscarinic cholinoceptors and adrenoceptors with atropine, propranolol and phentolamine did not affect the responses caused by intra-arterial infusion of testosterone performed to achieve a stable intra-arterial concentration of 1 microg l(-1). In the same pigs and in the remaining six pigs, the increases in coronary, mesenteric, renal and iliac blood flow caused by intra-arterial infusion of testosterone performed to achieve a stable intra-arterial concentration of 1 microg l(-1) were prevented by intra-arterial injection of N(omega)-nitro-L-arginine methyl ester. The present study shows that intra-arterial infusion of testosterone dilated coronary, mesenteric, renal and iliac circulations. The mechanism of this response involved the release of nitric oxide.

The effect of aprotinin on ischemia–reperfusion injury in the rabbit kidney

Tissue subjected to a period of ischemia undergoes functional and morphological damage that increases during the reperfusion phase. In this study, the protective effect of aprotinin, which is a protease inhibitor, was assessed in a rabbit unilateral renal ischemia–reperfusion (I/R) model. New Zealand rabbits, weighing 1.5–2 kg, were randomized to receive either aprotinin 30.000 KIU kg−1and 10.000 KIU kg−1h−1i.v. infusion (group I, n= 7) or equivalent volumes of 0.09% sodium chloride (SF) (group II, control, n= 7) i.v. 15 minutes before a 45 minutes interruption of left renal artery blood flow and then 45 minutes of reperfusion. Blood samples were obtained before and after the ischemia–reperfusion period for measurement of nitric oxide serum (NO) levels with the nitrite/nitrate colorimetric method. Histological changes were evaluated by quantitative measurements using a numerical score (0–4) and immunohistochemical analysis of inducible nitric oxide synthase (iNOS) expression was determined. A Wilcoxon W -test was used for statistical analysis of biochemical measurements and mean values were expressed as ±sd. Histological examination revealed the distinctive pattern of ischemic renal tissue injury with obvious signs of epithelial necrosis. The intensity of epithelial necrosis was more extensive in the SF group. Immunohistochemical analysis showed that there was severe immunostaining in the tubular epithelium in both cortical and medullary regions and iNOS expression was more intense in SF-only cases. The staining results for aprotinin cases did not differ much from the non-ischemic kidney. Biochemical analysis revealed an increase in serum NO levels in both groups (P< 0.05), but this was more evident in the SF group (mean NO levels were 38.63 ± 19.03μ mol L−1in group I, 50.63 ± 24.28 μ mol L−1in group II). No statistically important difference was observed between the two groups. These resultssuggest that aprotinin may be beneficial in the prevention of systemic inflammation after transient renal ischemia.