Over-expression of apoptosis-related proteins contributes to muscular damage in the obstructed ureter of the rat

OBJECTIVE: To determine the role of apoptosis-related proteins (Myc, Bax, Bcl-2, and Bcl-X(L)) in muscular damage in obstructed rat ureters. MATERIALS AND METHODS: The in situ end-labelling of DNA fragments and the expression of apoptosis-related proteins were assessed, using immunohistochemistry, in 54 female Sprague-Dawley rats in which unilateral ureteric obstruction was caused by ureteric ligation. RESULTS: The severity of ureteric damage increased during the period of obstruction. Apoptotic cells and the expression of Bax were detected in the smooth muscle layer from 14 days after ligation. The percentage of apoptotic cells and the expression of Bax in the smooth muscle layer increased and reached a peak 21 days after ligation, and then declined. The expression of Myc was also detected in the smooth muscle layer 14 days after ligation but reached a peak at 28 days. The expressions of Bcl-2 and Bcl-X(L) in the smooth muscle layer were only detected 21 and 28 days after ligation. The numbers of apoptotic cells in the smooth muscle layer correlated significantly with the expressions of Myc and Bax (r = 0.7360 and 0.7432, respectively; both P < 0.005), and with the expression index of Bax/Bcl-2 and Bax/Bcl-X(L) (r = 0.8909 and 0.8592, respectively; both P < 0.001). CONCLUSIONS: Apoptosis-related proteins might be important in regulating cell apoptosis in ureteric damage during the development of obstructive uropathy.     

Pressure and flow measurements in the partially obstructed ureter of the rat

Hydronephrosis in man or experimental animals can be caused by an increased ureteral flow resistance. This condition can in the long run prove harmful to renal function. We compared two ways of measuring ureteral flow resistance in animals with and without a ureteral hindrance, the hindrance being induced by embedding the ureter in the psoas muscle. One needle connected via catheters to a pressure recording system and another connected to a pump system were introduced through the parenchyma into the renal pelvis. Experiments were carried out with two procedures: 1) infusion of 0.5 ml x min-1 of saline into the renal pelvis was performed while recording the pressure response; 2) a servocontrolled pump system was used which regulated the flow introduced into the renal pelvis to keep a preset pressure at a constant level. In the first group of experiments we did not establish a steady-state pressure despite 20-30 min of infusion. The result from the second series of experiments indicated that steady-state flow measurements could be achieved at the different pressure levels between zero and 30 mmHg. A good linear relationship between pressure and flow was found, even though a considerable hysteresis was observed. Furthermore, a reduced flow resistance down to a certain level at increased pressure was also recorded. As expected, the resistance to flow was significantly lower in the control than in the hydronephrotic animals. In order to investigate the diagnostic ability of the linear relationship between pressure and flow, prediction regions for one future animal were calculated. It seemed possible that determination of the whole pressure-flow relationship in the pressure range between zero and 30 mmHg will prove useful to determine the flow hindrance in hydronephrotic animals.     

Serial microscopic changes in cell proliferation and apoptosis in obstructed ureter of rat

PURPOSE: We investigated the histologic findings and serial changes in cell proliferation and apoptosis in obstructed rat ureters. MATERIALS AND METHODS: After unilateral ligation of the ureter, animals from each of five groups of Sprague- Dawley rats were sacrificed for examination at 1, 5, 10, 15, 20, 25, 30, or 35 days. Cell division was detected with proliferating cell nuclear antigen (PCNA) immunohistochemistry, and apoptosis was detected with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) in-situ nick-end labeling (TUNEL) study. RESULTS: The epithelial layer was thickened in 5-day-obstructed ureters (5 DOUs). The severity of thickening of the fibrous and smooth-muscle layers progressed consistently to 15 DOUs and were maintained in 35 DOUs. Expression of PCNA in the epithelial layer was present in every ureter, and a significant increase in the number of labeled cells was present in 1 and 5 DOUs. Expression of PCNA in the fibrous and smoothmuscle layers was detectable in 10 DOUs and was maintained in 20 DOUs, after which, it declined significantly in the 25 DOUs. TUNEL-positive cells in the epithelial layer were shown in 10, 15, 20, 25, 30, and 35 DOUs, with the peak being reached at 25 days. TUNEL-positive cells in the fibrous and smooth-muscle layers were found in 25, 30, and 35 DOUs. CONCLUSIONS: Cell proliferation and apoptosis may play an important role in the pathogenesis of damage in obstructed ureters. Peak times of proliferation and apoptosis were different in the epithelial and fibrous and smooth-muscle layers.     

Tubular dimensions and Juxtaglomerular Granulation Index in rat kidneys after unilateral obstruction of the ureter

The effect of ligation of a ureter on the tissues in the kidneys in male Wistar rats was studied by morphometry. Dilation of the lumen in the obstructed kidney persisted after ligation only in distal convolutions and collecting ducts. Swelling of epithelial cells in the obstructed kidney was noted only in the distal convolutions and collecting ducts. The Juxtaglomerular Granulation Index (JGI) in the obstructed kidney increased to a maximum 7 days after ligation of the ureter. In the control kidney the lumen of Bowman's space was expanded, epithelial cells in both proximal and distal parts of the nephron were swollen, and the JGI was increased after ligation of the contralateral ureter. The morphological findings support the assumption that reduced cortical blood flow and decreased intratubular flow are the cause of proximal tubular atrophy rather than a persisting increase of proximal intratubular pressure.     

Norepinephrine inhibits the pelvic pressure increase in response to flow perfusion

PURPOSE: We evaluated the effects of norepinephrine on transport pressures in the normal upper urinary tract of the pig during increasing perfusion rates. MATERIALS AND METHODS: Anesthetized Danish landrace Yorkshire pigs weighing 38 to 40 kg were studied. Transparenchymally 2, 6Fr catheters were introduced into the left renal pelvis for pressure measurements and perfusion, respectively. An ultrasonic flow probe was inserted around the left renal artery to record blood flow. A 10Fr catheter was placed transurethrally for bladder drainage and the bladder was maintained empty during the entire study. In the 5 group 1 pigs the pelvic pressure increase was examined at increasing perfusion rates of the renal pelvis (2, 4, 6, 8, 10 and 15 ml per minute) in response to endoluminal administration of increasing concentrations of norepinephrine (0, 5, 50 and 100 microg/ml) in saline. In the 5 group 2 pigs the pressure flow study was also done 4 times per animal using isotonic saline. RESULTS: Endoluminal norepinephrine had a dose dependent effect on the pressure flow relationship. Perfusion with 5 and 50 microg/ml norepinephrine caused a delayed increase and a decrease in pelvic pressure in response to increasing flow rates, whereas perfusion with 100 microg/ml norepinephrine significantly inhibited and almost eliminated the pressure increase at all perfusion rates compared with saline perfusion. Importantly there were no changes in blood pressure, the heart rate or renal arterial blood flow. In group 2 perfusion with isotonic saline resulted in the same pressure response to increasing flow rates each time. CONCLUSIONS: Endoluminal administration of norepinephrine caused a dose dependent inhibition on the pressure phases of the pressure flow relationship of the upper urinary tract in pigs. No systemic changes were observed. These observations may provide a useful adjuvant treatment strategy for upper urinary tract stone treatment and endoscopy.     

Recanalization of pelvic ureter in prostatic neoplastic obstruction: endoscopic and radiologic approach]

Obstruction of the lower ureter by pelvic cancer requires a palliative treatment. Percutaneous derivation is often performed as an emergency. If obstruction is limited to the peri-meatic area (a few mm or a cm) resection of the ureteral orifice can be enough to catheterize the obstructed ureter. Stenting of the ureter can be done even if the obstruction is longer, using the extra vesical repermeabilization. METHODS: A guide wire is passed via the nephrostomy, and ureteral stent is passed over the guide wire. Dye additionned with methylene blue is injected tovisualize the lower extremity of the ureter. A regular resectoscope is placed transuretraly, and resection is conducted using X ray localisation with a C arm and several incidences. The tissue resected first is usually extravesical, in the adipous perivesical tissue. Dissection of this area can be performed bluntly with the tip of the resectoscope until the ureter is reached. At this time, the resectoscope is used to open the lower extremity of the ureter, localized with the C arm. It is important to open widely the ureter, so as to be sure to catheterize easily this opening with a ureteral catheter. A double J can then be passed easily. Tunnel of several cm can be performed using this technique. RESULTS: Seven patients with pelvic cancer with obstruction of the last cm of the pelvic ureter were included in this series. They were recurrent prostate cancer already treated with hormone therapy, stage T3, T4. All procedures were performed under rachianesthesia or general anesthesia according to general status. After this procedure normal miction were obtain in all patients and nephrostomies were removed. This technique is possible for extended pelvic obstruction. Blunt dissection with the endoscope is usualy blood less. This palliative procedure can be done in patients with poor general condition and allows for a better quality of life than nephrostomy or urinary diversions.     

Polyuria due to vasopressin V2 receptor antagonism is not associated with increased ureter diameter in ADPKD patients

Background

Tolvaptan, a vasopressin V2 receptor antagonist, has been shown to reduce the rates of growth in total kidney volume (TKV) and renal function loss in ADPKD patients, but also leads to polyuria because of its aquaretic effect. Prolonged polyuria can result in ureter dilatation with consequently renal function loss. Therefore, we aimed to investigate the effect of tolvaptan-induced polyuria on ureter diameter in ADPKD patients.

Methods

70 ADPKD patients were included (51 were randomized to tolvaptan and 19 to placebo). At baseline and after 3 years of treatment renal function was measured (mGFR) and MRI was performed to measure TKV and ureter diameter at the levels of renal pelvis and fifth lumbar vertebral body (L5).

Results

In these patients [65.7 % male, age 41 ± 9 years, mGFR 74 ± 27 mL/min/1.73 m² and TKV 1.92 (1.27–2.67) L], no differences were found between tolvaptan and placebo-treated patients in 24-h urine volume at baseline (2.5 vs. 2.5 L, p = 0.8), nor in ureter diameter at renal pelvis and L5 (4.0 vs. 4.2 mm, p = 0.4 and 3.0 vs. 3.1 mm, p = 0.3). After 3 years of treatment 24-h urine volume was higher in tolvaptan-treated patients when compared to placebo (4.7 vs. 2.3 L, p < 0.001), but no differences were found in ureter diameter between both groups (renal pelvis: 4.2 vs. 4.4 mm, p = 0.4 and L5: 3.1 vs. 3.3 mm, p = 0.4).

Conclusions

Tolvaptan-induced polyuria did not lead to an increase in ureter diameter, suggesting that tolvaptan is a safe therapy from a urological point of view.

     

Endothelin contributes to basal vascular tone and endothelial dysfunction in human obesity and type 2 diabetes

Endothelium-dependent vasodilation is impaired in clinical states of insulin resistance such as obesity and type 2 diabetes. Individuals who have hyperinsulinemic insulin resistance have relatively elevated circulating levels of endothelin (ET)-1, suggesting that ET-1 may be important in the endothelial dysfunction and alterations of vascular tone in these conditions. In 8 lean subjects, 12 nondiabetic obese subjects, and 8 subjects with type 2 diabetes, we measured basal and methacholine-stimulated rates of leg blood flow (LBF) and total serum nitrates (NOx) before and after the intrafemoral arterial administration of BQ123, a specific blocker of ET(A) receptors. BQ123 produced significant vasodilation in the obese and type 2 diabetic subjects (leg vascular resistance = mean arterial pressure/LBF fell by 34 and 36%; P < 0.005) but not in the lean subjects (13%; P = NS, P = 0.018 comparing all groups). ET(A) blockade did not change basal NOx flux (NOx*LBF). This suggests increased basal ET-1 constrictor tone among obese and type 2 diabetic subjects. BQ123 corrected the baseline defect in endothelium-dependent vasodilation seen in obese and type 2 diabetic subjects, suggesting an important contribution of ET-1 to endothelial dysfunction in these subjects. In contrast to basal conditions, stimulated NOx flux was augmented by BQ123 in obese and type 2 diabetic subjects but not in L subjects (P = 0.04), suggesting a combined effect of ET(A) blockade to reduce constrictor tone and augment dilator tone. Endothelin seems to contribute to endothelial dysfunction and the regulation of vascular tone in human obesity and type 2 diabetes.     

Angiotensin type 2 receptor is important in the normal development of the ureter

 In humans, the actions of angiotensin II are transduced through the AT1 and AT2 receptors which have recently been implicated in renal organogenesis. Polymorphisms in the human angiotensin II receptor genes have been linked to cardiovascular and nephrological disorders. In this study we evaluated 35 patients with either primary obstructive megaureter or posterior urethral valves. Each was genotyped for the A1166 AT1 polymorphism and the recently described A-1332G AT2 transition. The incidence of these genetic variants was also evaluated in normal controls without any ultrasonographic urological abnormalities. Similar to our previous findings in congenital urological abnormalities, the AT1 receptor genotype distribution did not differ between patients with either primary obstructive megaureter or posterior urethral valves versus controls. In contrast, compared with normal controls, there was a dramatic increase in the occurrence of the AT2 A-1332G transition in patients with primary obstructive megaureter (75.0% vs. 41.9% in controls, P<0.025). In patients with posterior urethral valves, there was no difference in the occurrence of the transition versus controls (36.9%, P=NS). Thus, there is no correlation between the AT1 receptor gene polymorphism and urological abnormalities. However there is an increased incidence in the AT2 genetic variant in patients with primary obstructive megaureter. Received: 2 March 1998 / Received: 1 July 1998 / Accepted: 6 July 1998     

Renal blood flow and pelvic pressure after 4 weeks of total upper urinary tract obstruction in the pig

Summary In 8 female pigs complete unilateral ureteral obstruction was investigated over a 4 weeks period. The pigs were monitored with intrapelvic pressure measurements and by 131-I-hippuran scintigraphy twice a week; one group without and one with TxA₂ blocking, UK-38,485 [3-(1H-imidazol-1-yl-methyl)-2methyl-1H-indol-1-propanoic acid], which is a well-known selective thromboxane synthetase inhibitor. During the course of obstruction there was an ipsilateral linear reduction of split function to background level and a net reduction in total hippuran clearance in both groups. On the obstructed side there was a linear reduction of hippuran clearance from 116±26 ml/min to 11±3 ml/min during the first 2 weeks of obstruction. The TxA₂ synthetase inhibitor, 5 mg/kg reduced se-TxB₂ to almost zero for at least one hour after i.v. administration. One week after obstruction the pelvic pressure was 45±5 cm H₂O administration of the TxA₂ synthetase inhibitor. The pelvic pressure remained elevated throughout the period of observation. The study confirmed earlier work which showed that total ureteral obstruction caused complete cessation of kidney function within a few weeks, but contradicts previous studies because there was no increase in renal blood flow after thromboxane blockade. These differences may be explained by several mechanisms. The continuing increase in pelvic pressure suggested that it was not only a preglomerular vasoconstriction which was responsible for the renal flow reduction, but that there was also a postglomerular vasoconstriction.     

Heme oxygenase-2 deficiency contributes to diabetes-mediated increase in superoxide anion and renal dysfunction

Heme oxygenase-1 (HO-1) and -2 play an important role in cytoprotection and are physiologic regulators of heme-dependent protein synthesis in renal tissues. The impact of HO-2 deletion comparing hyperglycemic HO-2 (+/+) mice and HO-2 knockout (-/-) mice was examined. Hyperglycemia was induced by streptozotocin (STZ) injection, and its effect on renal HO-1/HO-2 protein, HO activity, and creatinine levels were assessed. The effect of HO induction using systemic administration of the HO inducers heme or cobalt protoporphyrin and the effect of HO inhibition using systemic administration of the HO inhibitor tin mesoporphyrin also were assessed in STZ-treated mice. In STZ-treated HO-2 (-/-) mice, there was marked renal functional impairment as reflected by an increase in plasma creatinine, associated with acute tubular damage and microvascular pathology as compared with HO-2 (+/+). In these animals, HO activity was decreased with a concomitant increase in superoxide anion. Upregulation of HO-1 in HO-2 (-/-) mice by weekly administration of cobalt protoporphyrin prevented the increase in plasma creatinine levels and tubulointerstitial and microvascular pathology. Inhibition of HO activity by administration of tin mesoporphyrin accentuated superoxide production and increased creatinine levels in hyperglycemic HO-2 (-/-) mice. In conclusion, HO-2 deficiency enhanced STZ-induced renal dysfunction and morphologic injury and HO-1 upregulation in HO-2 (-/-) mouse rescue and prevented the morphologic damage. These observations indicate that HO activity is essential in preserving renal function and morphology in STZ-induced diabetic mice probably via mitigation of concomitant oxidative stress.     

Acute increase in blood flow to the rat bladder subsequent to partial bladder outlet obstruction

Partial obstruction of the rat bladder outlet initiates a multi-step process during which the bladder progressively loses its functional ability. The first step in this progression is bladder hypertrophy; the organ dramatically increases in size and weight to compensate for the effects of obstruction. Unoperated female rats, age-matched, sham-obstructed rats, and rats that received a partial bladder outlet obstruction were studied. During the first 24 hours after partial bladder outlet obstruction, relative bladder blood flow was measured using a fluorescent microsphere infusion technique and laser Doppler imaging. Nitric oxide synthase (NOS) activities of control and obstructed rat bladder tissues were determined using an enzymatic assay that measures the conversion of (3)H-L-arginine to (3)H-L-citrulline. Using the microsphere infusion technique, a significant increase in blood flow to the obstructed rat bladder was observed during the first 24 hours after partial bladder outlet obstruction. Relative bladder blood flow increased approximately sixfold at 4 and 6 hours post-obstruction and remained elevated through 24 hours of obstruction. Sham operations (evaluated after 6 hours after surgery) resulted in a minor increase in blood flow that did not reach statistical significance. Relative blood flow to the spleen, measured in the same rats, was not significantly changed. Laser Doppler measurements also identified a significant increase in rat bladder blood flow after outlet obstruction and showed that increased blood flow could be detected as early as 1 hour post-obstruction. Interestingly, despite the significant differences in bladder blood flow between control and early post-obstructed rat bladders, NOS activities of control and obstructed rat bladders were comparable. The increase in bladder blood flow precedes the urothelial, fibroblast and smooth muscle cell hyperplasia, and the smooth muscle hypertrophy that occurs after obstruction. We propose that, in response to surgical induction of partial outlet obstruction, acute up-regulation of bladder blood flow may be an initiating factor for subsequent bladder cell proliferation and smooth muscle hypertrophy. Neurourol. Urodynam. 19:195-208, 2000.     

Glucose-6-phosphatase flux in vitro is increased in type 2 diabetes

Despite the effects of hyperinsulinemia and hyperglycemia, 2 factors known to inhibit endogenous glucose production (EGP) in nondiabetic subjects, increased EGP is a consistent feature of type 2 diabetes. Recent studies have suggested that increased glucose-6-phosphatase (G6Pase) and/or decreased glucokinase (GK) may explain the increase in EGP. However, no studies to date have clearly established this relationship in type 2 diabetes. The present studies were designed to determine rates of EGP and the activities of G6Pase and GK in obese patients scheduled for gastric bypass surgery. The study group consisted of 14 obese nondiabetic subjects and 13 patients with type 2 diabetes (BMI 53.7 +/- 2.4 vs. 50.1 +/- 1.6 kg/m2). Rates of EGP were determined after an overnight fast with a 4-h infusion of [6,6]-D-glucose, and they were significantly higher in the type 2 diabetic patients (85.9 +/- 10.0 vs. 137.8 +/- 14.4 mg x m(-2) x min(-1), P < 0.001) despite greater plasma glucose (5.1 +/- 0.1 vs. 12.0 +/- 1.1 mmol/l) and similar insulin concentrations (130.8 +/- 19.8 vs. 112.8 +/- 16.2 pmol/l, NS). Moreover, resistance to insulin-induced suppression of EGP was observed in the patients with type 2 diabetes when insulin concentrations were increased from approximately 120 to 180 pmol/l. Hepatic G6Pase activity determined from freshly isolated microsomes was significantly increased in the type 2 diabetic patients compared with the obese control subjects (0.16 +/- 0.02 vs. 0.09 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.02), whereas levels of GK were decreased (1.20 +/- 0.16 vs. 2.01 +/- 0.01 micromol x min(-1) x mg(-1) protein, P < 0.01). Net flux through G6Pase was significantly increased in type 2 diabetic patients (P < 0.01). We conclude that increased EGP is mediated in part by increased G6Pase flux in type 2 diabetes.     

Changes to the contractile function of ureter smooth muscle after partial infravesical obstruction in fetal sheep

OBJECTIVE

To measure spontaneous contractile activity, and the responses to agonists using in vitro preparations of sheep ureter after a period of bladder outlet obstruction (BOO) initiated at mid‐gestation.

MATERIAL AND METHODS

Date‐mated Romney Marsh ewes, bearing fetuses of 70–75 days of gestation (term in this breed is 145 days) were used. Five fetuses underwent urachal obstruction and partial urethral constriction for 30 days. Six fetuses at the same gestational time underwent a sham operation (control group). Small strips of mid‐ureter were cut in the longitudinal axis, and in the cross‐sectional (transverse) plane of the ureter. Spontaneous contractile activity and the response to carbachol, high‐K⁺ (120 mm ) solution and α,β‐methylene ATP (ABMA) were characterized by measuring the magnitude of evoked responses and the magnitude and frequency of spontaneous activity.

RESULTS

The ureters from fetuses with BOO were significantly larger in diameter and had expanded lumens. The proportion of smooth muscle was not significantly different between the BOO and control groups. Spontaneous contractile activity in all preparations was resistant to atropine and the neurotoxin, tetrodotoxin. With transverse sections, the magnitude of spontaneous contractions was smaller in the BOO group, but the frequency was greater. The response to carbachol was also smaller in the BOO group, but the response to high‐K⁺ solution was similar to that of the control group. ABMA did not generate a response in any preparation. With longitudinal ureteric preparations, spontaneous or agonist‐induced activity was negligible in the control group, while preparations from the BOO sheep had spontaneous activity and responded to carbachol and high‐K⁺ solutions.

CONCLUSION

These results show that in fetuses with BOO and dilated ureters absolute ureteric contractile activity is diminished. However, there is functional reorganization of the muscle layers that generates more force in the longitudinal rather than the transverse axis. This would contribute to a reduced ability of the ureter to propel urine and contribute to the development of raised upper tract pressures.     

Lipopolysaccharide-induced bone resorption is increased in TNF type 2 receptor-deficient mice in vivo

The release of tumor necrosis factor (TNF)-alpha from macrophages upon stimulation of lipopolysaccharide (LPS) is a major etiological factor of inflammatory bone disease and elicits the effects through TNF receptors type 1 and 2. Given the importance of TNF-alpha action on osteoclastic bone resorption, the role of TNF type 2 receptor (TNFR2) on bone resorption has not been elucidated well so far. The purpose of this study is to investigate the role of TNFR2 on LPS-induced inflammatory bone resorption in vivo. LPS at 10 mg/kg (Re 595) was injected subcutaneously on calvariae of wild-type (WT), TNF type 1 receptor (TNFR1)-deficient (KO), and TNFR2 KO mice, killed on day 5 after the LPS injection. The calvarial bone mineral density (BMD) was significantly decreased by LPS compared to the vehicle-injected control in WT mice, but not in TNFR1 KO mice. Interestingly, the decrease of calvarial BMD and the increase of the osteoclast number by LPS in TNFR2 KO mice seemed to be more than those in WT mice. Furthermore, the significant decrease by LPS on the BMD of tibiae, femurs, and lumber vertebrae were observed only in TNFR2 KO mice. Histomorphometric analysis of tibiae showed the significant increases of osteoclast number and surface in the LPS-injected TNFR2 KO mice, and the levels of urinary deoxypyridinoline reflected these increases of bone resorption parameters. The present data indicate that TNFR1 is critical for bone resorption at the site of LPS injection and that TNFR2 might have a protective role on the LPS-induced inflammatory bone resorption process.     

Obstruction and normal recanalization of the ureter in the human embryo. Its relation to congenital ureteric obstruction.

In this work, after the study of 45 normal human embryos of 5-55 mm from vertex to coccyx, it is shown that the ureteric ducts, which in the first phases of development are permeable (embryos of 5-13 mm), constantly undergo a process of obstruction and posterior recanalization of their lumen, which takes place when they are from 14 to 22 mm. These processes begin in the middle zone of the ureters and progress proximally and distally until they cover its entire length, for which these ducts, which in embryos of approximately 17 mm in length form solid cords, but in the embryos of 23 mm are totally permeable. This obstructive process is found in relation to atrophy and loss of activity of the mesonephros, while that of recanalization follows the intense longitudinal growth of the ureters in this phase of development. These modifications, which the ureteric lumen normally undergoes during its embryonic development, are of great importance for correct interpretation of the pathogenic mechanism of congenital ureteric strictures and valves.     

Increased pulmonary venous resistance contributes to increased pulmonary artery diastolic-pulmonary wedge pressure gradient in acute respiratory distress syndrome

BACKGROUND: Pulmonary artery diastolic (PAD)-pulmonary wedge pressure (PWP) gradient has been shown to be increased in sepsis and acute respiratory distress syndrome (ARDS). Because pulmonary venous vasoconstriction induced by endotoxemia in sepsis or postcapillary leukocyte aggregation in ARDS or both can increase pulmonary venous resistance (Rpv), it is possible that the elevated Rpv increases PAD-PWP. The authors examined this possibility by assessing the correlation between Rpv and PAD-PWP gradient in patients with ARDS. METHODS: Included were 20 patients with ARDS who required surgical procedures during general anesthesia. Rpv was calculated as the difference between mean pulmonary artery (PA) output pressure and PWP divided by cardiac index. Mean PA output pressure was computed from harmonic form of the recorded PA pressure by applying an attenuating factor to its phasic components, for which Fourier analysis was used. Total pulmonary vascular resistance (TPVR) was calculated as the difference between mean PA input pressure and PWP divided by cardiac index. To avoid the effect of PA resistance on TPVR and Rpv, the relative pulmonary venous resistance (Rpv/TPVR) was used. RESULTS: There was a good correlation between Rpv/TPVR and PAD-PWP gradient (R = 0.698, P < 0.0001). When patients were classified into two groups based on PAD-PWP gradient, the Rpv/TPVR was 0.66 +/- 0.06 in the group with a PAD-PWP gradient of 6 mmHg or greater and 0.46 +/- 0.08 in the other group (P < 0.0001). CONCLUSION: A strong correlation between Rpv/TPVR and PAD-PWP gradient suggests that the increased Rpv contributes to increased PAD-PWP gradient in patients with ARDS.     

Endoluminal pelvic perfusion with norepinephrine causes only minor systemic effects and diminishes the increase in pelvic pressure caused by perfusion

OBJECTIVE: To evaluate the effect of endoluminal norepinephrine (NE) on transport pressures of the normal upper urinary tract of the pig and on plasma levels of NE in relation to possible systemic effects. MATERIAL AND METHODS: Six anaesthetized pigs weighing approximately 39 kg were studied. Transparenchymally, two 6-F catheters were introduced into the renal pelvis bilaterally to measure pressure and perfusion. Ultrasonic flow probes recorded renal arterial blood flow, and a transurethral 10-F catheter drained the bladder and monitored diuresis. In all six animals, the bilateral pelvic pressure response was examined at increasing perfusion rates (2, 4, 6, 8, 10 and 15 ml/min) and with increasing doses of NE (0, 5, 50 and 100 microg/ml). Arterial blood samples were analysed for NE, epinephrine and blood glucose. The systemic blood pressure, heart rate and electrocardiogram were registered. RESULTS: At all the investigated concentrations, endoluminal NE significantly diminished the increase in pelvic pressure caused by pelvic perfusion at all flow rates. At the lowest concentration of NE, no significant increase in the plasma level of NE was observed and the blood pressure did not increase. During perfusion with 50 and 100 microg/ml NE, plasma levels of NE increased significantly from 487+/-398 to 1798+/-910 and 2961+/-2093 pg/ml, respectively. This was accompanied by significant rises in mean systolic blood pressure from a baseline value of 95+/-10 mmHg to 111+/-20 and 118+/-23 mmHg, respectively. Heart rate, renal arterial blood flow and plasma levels of epinephrine and glucose did not change. CONCLUSIONS: Endoluminal NE diminished the increase in pelvic pressure caused by pelvic perfusion even at concentrations too low to cause significant changes in NE plasma levels or systemic effects. Very high NE concentrations in the perfusion fluid caused increased plasma levels and a modest but significant increase in blood pressure. Administration of endoluminal NE may be useful in upper urinary tract stone treatment and endoscopy.