Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice

AIM:To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics(ketamine,propofol,thiopental,and fentanyl)in rats with obstructive jaundice.METHODS:There is an increased incidence of postoperative acute renal failure in patients with obstructive jaundice.Thirty-two Wistar-albino rats were randomly divided into four equal groups.Laparatomy was performed on each animal in the four groups and common bile ducts were ligated and severed on day 0.After 7 d,laparotomy was again performed using ketamine,propofol,thiopental,or fentanyl anesthesia whose antioxidative properties are well known in oxidative stress in a rat liver model of obstructive jaundice.After 2 h,the rats were sacrificed.Renal tissue specimens were analyzed for catalase,superoxide dismutase and malondialdehyde enzymes activities.All values are expressed as the mean±SD.P values less than 0.05 were considered statistically significant.RESULTS:All animals survived without complications until the end of the study.Enlargement in the bile duct and obstructive jaundice were observed in all rats.Catalase was found to be significantly lower in the fentanyl group than in the ketamine(P=0.039),propofol(P=0.012),and thiopental(P=0.001)groups.Superoxide dismutase activities were similar in all groups(P>0.05).Malondialdehyde was found to be significantly lower in the ketamine group than in the propofol(P=0.028),thiopental(P=0.002)and fentanyl(P=0.005)groups.Malondialdehyde was also lower in the fentanyl group than in the thiopental group(P=0.001).The results showed that obstructive jaundice sensitizes renal tissue to damage under the different anesthetics.CONCLUSION:Among the agents tested,ketamine and propofol generated the least amount of oxidative stres on renal tissues in this rat model of obstructive jaundice created by common bile duct ligation.The importance of free radical injury in renal tissue in obstructive jaundice under different intravenous anesthetics during hepatobiliary and liver transplant surgery should be considered for prevention of postoperative acute renal failure.     

Tissue ACE inhibition improves microcirculation in remote myocardium after coronary stenosis: MR imaging study in rats

ACE inhibition has been shown to improve left ventricular (LV) and myocardial blood flow. Previous data regarding changes in capillary density and angiogenesis during ACE inhibition are controversial. The aim of the following study was to determine myocardial microcirculation and heart function in the rat after coronary stenosis using non invasive MR imaging techniques.MR spin labeling and cine techniques have been performed in female Wistar rats 2 weeks after coronary artery stenosis. In one group, animals were treated with quinapril in a dose of 6 mg/kg/day. Perfusion, relative blood volume (RBV), LV mass and function were determined non-invasively 2 weeks after treatment. Finally, fibrosis and capillary density were analyzed histologically. Additionally, hemodynamic measurements were realized in a further group in order to calculate systemic vascular resistance (SVR).Quinapril resulted in a significant increase in perfusion at rest in the remote and the poststenotic myocardium with improved systolic function and a decrease in SVR compared to the non treated control group. Additionally, maximum perfusion and RBV were slightly elevated whereas capillary density was unchanged among the groups.MRI allows for non-invasive quantification of functional microcirculation and heart function. In addition to the well known effect of ACE inhibition on systolic function, treatment with the tissue specific ACE inhibitor quinapril revealed an important microvascular improvement, especially at arteriolar level. These findings may support the use of tissue ACE inhibitors to improve cardiac microcirculation after ischemia.     

Tissue ACE inhibition improves microcirculation in remote myocardium after coronary stenosis: MR imaging study in rats

ACE inhibition has been shown to improve left ventricular (LV) and myocardial blood flow. Previous data regarding changes in capillary density and angiogenesis during ACE inhibition are controversial. The aim of the following study was to determine myocardial microcirculation and heart function in the rat after coronary stenosis using non invasive MR imaging techniques.MR spin labeling and cine techniques have been performed in female Wistar rats 2 weeks after coronary artery stenosis. In one group, animals were treated with quinapril in a dose of 6 mg/kg/day. Perfusion, relative blood volume (RBV), LV mass and function were determined non-invasively 2 weeks after treatment. Finally, fibrosis and capillary density were analyzed histologically. Additionally, hemodynamic measurements were realized in a further group in order to calculate systemic vascular resistance (SVR).Quinapril resulted in a significant increase in perfusion at rest in the remote and the poststenotic myocardium with improved systolic function and a decrease in SVR compared to the non treated control group. Additionally, maximum perfusion and RBV were slightly elevated whereas capillary density was unchanged among the groups.MRI allows for non-invasive quantification of functional microcirculation and heart function. In addition to the well known effect of ACE inhibition on systolic function, treatment with the tissue specific ACE inhibitor quinapril revealed an important microvascular improvement, especially at arteriolar level. These findings may support the use of tissue ACE inhibitors to improve cardiac microcirculation after ischemia.     

In vitro effects of intravenous anesthetics on the sphincter of Oddi strips of sheep.

BACKGROUND: Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the direct effects of some intravenous anesthetics on SO in sheep. METHODS: In sheep SO rings, changes in isometric tension in response to cumulative concentrations of intravenous anesthetics were determined, and values for Emax (mean maximal inhibition) and pD2 (i.e. the negative logarithm of the concentration for the half-maximal response, EC50) were compared. RESULTS: Meperidine (10(-7) to 3 x 10(-5) M), fentanyl (10(-7) to 3 x 10(-5) M), midazolam (10(-7) to 3 x 10(-5) M) and propofol (10(-7) to 3 x 10(-4) M) induced concentration-dependent relaxations on SO precontracted with carbachol (10(-6) M). Emax and pD2 values following meperidine, fentanyl and midazolam administration were significantly greater than after propofol (p < 0.05). There were no significant differences in Emax and pD2 values for meperidine, fentanyl and midazolam. CONCLUSION: These results suggest that meperidine, fentanyl and midazolam are equipotent relaxants in the sheep SO in vitro. The relaxatory effect of propofol was 10 times less potent compared to the above agents, and it can be beneficial during SO manometry in controlled clinical human studies.     

Differential effects of dopamine on glucoregulatory hormones in rats

The effect of dopamine at different doses on serum concentrations of insulin, glucose and corticosterone and on plasma glucagon concentration was investigated in rats. Dopamine was given intravenously over 6 h with infusion rates of 2.5, 7.5, 15, and 60 micrograms/kg.min and in combination with phentolamine. Serum insulin concentration was unchanged at low doses of dopamine. It was significantly increased from 6.0 +/- 0.7 ng/ml to 13.7 +/- 2.3 ng/ml (P less than 0.01) when 7.5 micrograms/kg.min of dopamine were used, whereas it was significantly depressed to 3.96 +/- 0.89 and to 4.0 +/- 0.34 ng/ml (P less than 0.01), respectively, at the high doses of dopamine. This latter effect could be reversed to 6.7 +/- 1.19 ng/ml and inverted to 9.2 +/- 1.7 ng/ml (P less than 0.01) by simultaneously applied phentolamine at appropriate dosages. Serum glucose levels were markedly elevated from 154 +/- 7 to 234 +/- 42 mg/dl (P less than 0.01) by the higher doses of dopamine. A significant alteration of glucagon plasma concentrations from 18.9 +/- 2.8 to 42.3 +/- 14 pg/ml (P less than 0.01) was elicited only by 7.5 micrograms/kg.min of dopamine. The data clearly demonstrate that exogenous dopamine acts differently on glucose homeostasis according to the dosage. The study provides strong evidence that dopamine decreases insulin levels via alpha-adrenergic receptor stimulation. This effect may contribute to the deterioration of glucose homeostasis with high doses of dopamine.     

Differential effects of intravenous magnesium on atrioventricular node conduction in supraventricular tachycardia

Evidence from noninvasive studies suggests magnesium has a differential effect on atrioventricular nodal (AVN) pathways. To further explore the electrophysiologic effects of intravenous magnesium sulfate (MgSO(4)) on supraventricular tachycardia, with particular reference to AVN conduction pathways, we studied 23 patients with supraventricular tachycardia at the time of electrophysiologic study. Tachycardia cycle length; AH, HV, and VA intervals; anterograde and retrograde Wenckebach thresholds; slow and fast pathway effective refractory periods (ERPs); accessory pathway ERP; right atrial and ventricular ERPs; blood pressure; and serum magnesium were evaluated before and after administration of MgSO(4) during sustained tachycardia. AVN reentry was induced in 14 patients and atrioventricular reentry was induced in 9; 1 of the latter had dual AVN physiology with tachycardia using the slow pathway. Serum magnesium level increased from 0.88 +/- 0.11 to 1.79 +/- 0.14 mmol/L (p <0.0001). Magnesium increased tachycardia cycle length to a greater extent in those with dual AVN physiology than those without: 340 +/- 54 to 370 +/- 57 ms versus 347 +/- 29 to 350 +/- 30 ms (p = 0.01). This was associated with greater increase in AH interval in those with dual AVN physiology than in those without: 241 +/- 59 to 270 +/- 60 ms versus 144 +/- 16 to 140 +/- 20 ms (p = 0.003). Presence of dual AVN physiology was more frequently associated with reversion to sinus rhythm: 5 of 15 versus 0 of 8 (p = 0.06). MgSO(4) did not alter other measured parameters. In conclusion, magnesium increases tachycardia cycle length and AH interval in patients with dual AVN physiology through a dominant effect on the slow AVN pathway.     

The methionine connection: homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats

Increased intrahepatic resistance in cirrhotic livers is caused by endothelial dysfunction and impaired formation of two gaseous vasodilators, nitric oxide (NO) and hydrogen sulfide (H(2)S). Homocysteine, a sulfur-containing amino acid and H(2)S precursor, is formed from hepatic methionine metabolism. In the systemic circulation, hyperhomocystenemia impairs vasodilation and NO production from endothelial cells. Increased blood levels of homocysteine are common in patients with liver cirrhosis. In this study, we demonstrate that acute liver perfusion with homocysteine impairs NO formation and intrahepatic vascular relaxation induced by acetylcholine in methoxamine-precontracted normal livers (7.3% +/- 3.0% versus 26% +/- 2.7%; P < 0.0001). In rats with mild, diet-induced hyperhomocystenemia, the vasodilating activity of acetylcholine was markedly attenuated, and incremental increases in flow induced a greater percentage of increases in perfusion pressure than in control livers. Compared with normal rats, animals rendered cirrhotic by 12 weeks' administration of carbon tetrachloride exhibited a greater percentage of increments in perfusion pressure in response to shear stress (P < 0.05), and intrahepatic resistance to incremental increases in flow was further enhanced by homocysteine (P < 0.05). In normal hyperhomocysteinemic and cirrhotic rat livers, endothelial dysfunction caused by homocysteine was reversed by perfusion of the livers with sodium sulfide. Homocysteine reduced NO release from sinusoidal endothelial cells and also caused hepatic stellate cell contraction; this suggests a dual mechanism of action, with the latter effect being counteracted by H(2)S. CONCLUSION: Impaired vasodilation and hepatic stellate cell contraction caused by homocysteine contribute to the dynamic component of portal hypertension.     

Beneficial effects of empagliflozin and liraglutide on the cerebral microcirculation of diabetic rats

Objectives

This study aimed to evaluate the effects of the antidiabetics liraglutide, a GLP-1 analog, and empagliflozin, an SGLT-2 inhibitor, on the brain microcirculation of diabetic rats.

Methods

Type 2 diabetes mellitus (DM) was experimentally induced in male Wistar rats by combining a high-fat diet and a low dose of streptozotocin (35 mg/kg). Liraglutide (100 μg/kg s.c.) and empagliflozin (10 mg/kg, oral) were administered for 5 weeks. Body weight was monitored periodically. Oral glucose tolerance, fasting glycemia, and blood triglycerides were evaluated after the treatments. Endothelial–leukocyte interactions in the brain microcirculation and structural capillary density were assessed.

Results

DM rats presented metabolic and cerebrovascular alterations. Liraglutide treatment decreased body weight and blood triglycerides of DM rats. Empagliflozin treatment improved glucose tolerance but only the combination therapy significantly reduced fasting blood glucose. Both treatments and their combination reduced leukocyte adhesion into the endothelium of brain venules. However, empagliflozin was more effective in preventing DM-induced microvascular rarefaction.

Conclusion

These findings suggest that chronic treatment with SGLT2 inhibitors and GLP-1 receptor agonists may serve as potential therapeutic approaches to prevent microvascular complications associated with diabetes.     

Anti-inflammatory effects of Aloe vera on leukocyte-endothelium interaction in the gastric microcirculation of Helicobacter pylori-infected rats

This research was aimed to investigate anti-inflammatory effects of Aloe vera on leukocyte-endothelium in the gastric microcirculation of Helicobacter pylori (H. pylori)-infected rats. Thirty-six male Sprague-Dawley rats were divided into 3 groups: control, H. pylori-infected, and A. vera-treated group (200 mg/kg b.w., twice daily). H. pylori-inoculation was induced in the rats by the administration of H. pylori solution. Intravital fluorescence videomicroscopy was used to examine leukocyte adhesion in postcapillary venules on the posterior surface of stomach area on different periods after administration of A. vera. Serum tumor necrosis factor-alpha (TNF-alpha) level was measured in blood collected at the end of experiment by using ELISA technique. The results showed that in H. pylori-infected group on day 8, the leukocyte adhesion was 13.40+/-1.00 cells/100 microm vessel length and the TNF-alpha was 76.76+/-23.18 pg/ml, which increased significantly (p < 0.05), compared with the control group (leukocyte adhesion(control) = 2.54+/-0.6 cells/100 microm vessel length and TNF-alpha(control) = 9.92+/-2.62 pg/ml). Treatment with A. vera reduced the leukocyte adhesion (5.5+/-0.5 cells/100 microm vessel length), and TNF-alpha (26.31+/-6.38 pg/ml) significantly (p < 0.05). In conclusion, H. pylori enhanced leukocyte-endothelium interaction in the posterior stomach area markedly. This enhancement in leukocyte-endothelium interaction could be improved by the treatment of A. vera, associated with reduction in TNF-alpha level.     

高血压病患者的甲襞微循环改变及吸烟对微循环的影响

目的 :了解高血压病患者甲襞微循环改变及吸烟对其甲襞微循环影响。方法 :10 6例高血压病患者均作甲襞微循环加权积分值测定 ,就有主要并发症 (脑血管意外、冠心病及糖尿病 )组与无并发症组作比较 ,并对其中 31例吸烟患者作吸烟前、后甲襞微循环动态定性比较。结果 :除伴糖尿病组微循环管周状态积分值无差异 (P>0 .0 5)外 ,其余各组各项指标均有非常显著差异 (P<0 .0 1或 P<0 .0 0 1)。吸烟后血管袢形态及流态绝大多数有不同程度改变。结论 :高血压病患者甲襞微循环改变能客观反映靶器官损害程度。吸烟试验前后微循环的动态改变 ,是一项证明吸烟对人体有害的直观指标     

Differential effects of pancreatic polypeptide on luteinizing hormone release in female rats

Observations that a pancreatic polypeptide-like substance is present in hypothalamus and may coexist with catecholamines prompted evaluation of its possible role in control of luteinizing hormone (LH) secretion. Intracerebroventricular administration of 0.5 or 2 micrograms of human pancreatic polypeptide to ovariectomized, hormonally untreated rats significantly decreased LH levels. However, when administered to ovariectomized rats pretreated with estradiol benzoate and progesterone, the neuropeptide significantly increased circulating LH in a dose-related manner. These results, which are similar to those reported for centrally administered norepinephrine, raise the possibility that pancreatic polypeptide, or a similar peptide, may participate in the physiologic regulation of LH release, either independently or perhaps as a neuromodulator or a cotransmitter with catecholamines.     

OPS imaging of human microcirculation: a short technical report

Despite the pivotal role of microcirculation in numerous diseases, techniques for the direct assessment of human microcirculation are limited. A new approach based on orthogonal polarization spectral (OPS) imaging (Cytoscan microscope) allows noninvasive observation of human microcirculation in all accessible tissue surfaces. Limitations remain: application of pressure with the instrument affects blood flow, lateral movement of tissue precludes continuous investigation of a given microvascular region, and blood flow velocities above 1 mm/s cannot be measured. We addressed these problems by (a) constructing an attachment to the probe, preventing direct contact of the instrument with the observed tissue area and allowing fixation of the tissue, and (b) implementing a double-flash spatial correlation technique extending the measuring range for blood flow velocities up to approximately 40 mm/s. The modified approach was tested in vitro and in vivo. Velocity readings correlated well with velocities of an external standard (r(2) = 0.99, range 1.9-33.8 mm/s). Pulsatile flow patterns synchronous with heart rate with maximal velocities of about 10 mm/s could be detected in arterioles of the human sublingual mucosa. The modified instrument may prove useful to investigate the microcirculation in the context of research, diagnosis and therapy control.     

Effects of oestradiol-17 beta on testicular microcirculation in rats

The effect of oestradiol-17 beta on testicular microcirculation in intact and hypophysectomized rats was studied before and after treatment with human chorionic gonadotrophin (hCG). Treatment of intact rats with oestradiol-17 beta for 5 days did not influence vasomotion but decreased testicular interstitial fluid volume (IFV). Treatment of intact rats with 50 IU hCG 8 h before the experiment began induced an increase in testicular IFV, abolished vasomotion and increased the accumulation of polymorphonuclear leucocytes in the testicular venules and interstitium. These changes were unaffected by pretreatment with oestradiol-17 beta, despite the decreased testosterone production. However, pretreatment with oestradiol-17 beta potentiated the hCG-induced migration of polymorphonuclear leucocytes to the interstitium. The interstitial fluid volume and number of polymorphonuclear leucocytes in blood vessels were decreased in hypophysectomized rats, and vasomotion was abolished. Daily treatment with 5 IU hCG increased the IFV and the number of polymorphonuclear leucocytes in blood vessels, and preserved vasomotion. Treatment of hypophysectomized rats with oestradiol-17 beta decreased testosterone production but did not influence basal IFV, vasomotion or the changes in IFV and vasomotion induced by 5 IU hCG. The present study shows that the regulation of testicular vascular permeability and vasomotion may not be directly related to testicular steroidogenesis, and that oestrogens are probably not involved as a mediator of the hCG-induced changes in testicular microcirculation.     

Effects of Yibei multi-active elements on mesenteric microcirculation in rats

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