Biomedical subjects

Chau-Fong Chen

Publications and source records attributed to Chau-Fong Chen.

At least 19 recordsLinked to original sources

PubMed2006

Transient limb ischemia induces remote preconditioning in liver among rats: the protective role of heme oxygenase-1.

BACKGROUND: We have reported the protective role of heme oxygenase-1 (HO-1) in the mechanism of hypoxic preconditioning. We wish to investigate the role of HO-1 in remote preconditioning (RP) against hepatic ischemia/reperfusion (I/R) injury in rats. METHODS: The remote preconditioning was produced by four cycles of 10-min ischemia-reperfusion of the hind limb of rats. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 240 min of reperfusion. Zinc-protoporphyrin IX (ZnPP), a specific inhibitor of HO enzymatic activity, was intra-peritoneally injected 1 hr before the ischemia-reperfusion injury in separate groups of RP rats. Serum alanine transaminase (ALT) levels, expression of hepatic HO-1 protein and mRNA, immunohistochemical staining and HO enzymatic activity were measured. RESULTS: HO-1 was induced in the livers of rats 4 hr after the RP stimuli, and the overexpression persisted for 24 hr. Immunohistochemical staining demonstrated induction of HO-1 in the hepatocytes. The peripheral lymphocytes did not express HO-1 after RP. RP diminished the elevation of serum ALT levels 4 hr after I/R injury (283.7+/-167.4 U L) when compared with controls (1297.7+/-729.3 U L) and RP+ ZnPP pretreated groups (1429.9+/-750.9 U L). The heme oxygenase activity in treated rats also correlated these results (286.8+/-34.3 pmol mg protein hr for the RP group, 156.3+/-27.5 pmol mg protein hr for the RP+ ZnPP pretreated group, and 170.6+/-19.4 pmol mg protein hr for the control group, 144.8+/-7.8 pmol mg protein hr for the control+ ZnPP pretreated group). CONCLUSION: Our results indicated that the induction of HO-1 in remote preconditioning played a protective role against hepatic I/R injury.

Alanine Transaminase↗

PubMed2006

Characterization of pegylated copolymeric micelles and in vivo pharmacokinetics and biodistribution studies.

The aim of this study was to evaluate the influence of pegylated copolymeric micelle carrier on the biodistribution of drug in rats. The copolymers were synthesized via a modified ring-opening copolymerization of lactone monomers (epsilon-caprolactone, delta-valerolactone, L-lactide) and poly(ethylene glycol) (PEG(10,000) and PEG(4000)). The molecular weights and the polydispersities of synthesized copolymers were in the range of 15,000-31,000 g/mol and 1.7-2.7, respectively. All of the pegylated amphiphilic copolymers were micelles formed with low CMC values in the range of 10(-7)-10(-8)M. The drug-loaded micelles were prepared via a dialysis method. The average particle size of micelles was around 150-200 nm. The cytotoxicity in terms of cell viability after treated with PCL-PEG, PVL-PEG, and PLA-PEG micelles was insignificant. PCL-PEG and PVL-PEG micelles without branch side chain in structures had higher drug loading than PLA-PEG micelles. In vitro release profiles indicated the release of indomethacin from these micelles exhibited a sustained release behavior. The similar phenomenon was also observed in vivo in rats. The pegylated copolymeric micelles not only decreased drug uptake by the liver and kidney, but also prolonged drug retention in the blood.

Animals↗

PubMed2006

Changes in nitric oxide production in the rat kidney due to CaOx nephrolithiasis.

AIMS: The aim of the study was to test the hypothesis that the renal nitric oxide (NO) system is involved in the animal model of nephrolithiasis by evaluating the relationship between nitric oxide synthase (NOS) and oxidative stress. METHODS: Deposition of renal calculi was induced by adding 0.75% ethylene glycol (EG) to the drinking water of male Wistar rats. After 42 days of treatment, urinary biochemistry and urinary levels of oxalate, NO metabolites (nitrate and nitrite), cGMP, and lipid peroxides, and markers for renal damage and oxidative stress in the kidney were examined. In the second part of the experiment, two diuretic stimuli (intrarenal infusion of l-arginine or saline loading) were applied to test the renal NO system response. Finally, levels of three isoforms of NOS in renal tissues were evaluated by immunostaining. RESULTS: In the EG-treated rats, increased urinary excretion of enzymes and lipid peroxides and increased nitrotyrosine levels and oxidative injury markers in the kidneys indicated that peroxynitrite formation occurred during oxidative stress, while the 24-hr urinary excretion of NO metabolites and cGMP remained unchanged. In contrast to control rats, urinary excretion and NO metabolites and cGMP excretion were unresponsive to intrarenal l-arginine infusion; in response to saline loading, an increase in these factors was seen, but the increase was only 50% of that seen in the identically treated control group. A significant decrease in eNOS expression and increase in iNOS expression were observed in the renal medulla of the EG-treated group, whereas expression of nNOS was not affected. CONCLUSIONS: Although basal renal NO production remained unchanged, excessive peroxynitrite formation in the kidney was noted in this model. A decreased response of the NOS system was noted when diuretic stimuli were applied. How the imbalance between eNOS and iNOS expression influences CaOx stone formation requires detailed evaluation.

Animals↗

PubMed2006

Enhanced expression of glucose transporter 1 on erythrocyte membrane in hemodialysis patients: the possible role in erythrocyte ascorbate recycling.

BACKGROUND: Human erythrocytes can take up dehydroascorbate on the glucose transporter 1 (GLUT 1) and reduce it to ascorbate. Intraerythrocyte ascorbate was proved to be directly responsible for decreased oxidation of extraerythrocytic ascorbate. In addition to spontaneous and irreversible loss of ascorbate in plasma, the hemodialysis (HD) process itself consumes plasma ascorbate. However, intraerythrocyte ascorbate status in uremic patients during HD has yet to be reported. METHODS: Plasma and intraerythrocyte ascorbate, dehydroascorbate, GLUT 1 expression on erythrocyte membranes, and in vitro studies of "erythrocyte ascorbate recycling" were investigated in age- and sex-matched healthy subjects (control group) and HD patients (HD group). RESULTS: Intraerythrocyte ascorbate concentrations decreased after 1 HD session compared with pre-HD and recovered to pre-HD values 2 days later, whereas plasma ascorbate concentrations did not recover. In vitro studies suggested that erythrocytes of HD patients have a stronger ability to maintain intracellular ascorbate concentrations compared with healthy subjects. This ability could be inhibited by cytochalasin B (GLUT 1 inhibitor). We also found increased GLUT 1 expression (P = 0.002) on erythrocyte membranes in the HD group compared with the control group. CONCLUSION: Erythrocytes of uremic patients lost large amounts of ascorbate during HD, but regained it to the pre-HD level 2 days later. Enhanced GLUT 1 expression on erythrocyte membranes for HD patients may contribute to better preservation of intracellular ascorbate compared with healthy subjects.

Aged↗

PubMed2005

Protection "outside the box" (skeletal remote preconditioning) in rat model is triggered by free radical pathway.

BACKGROUND: Remote preconditioning (RPC) for myocardial protection had been demonstrated in several organs, such as the kidney and mesentery artery. The aim of study was to investigate the effect of skeletal ischemia/reperfusion on coronary artery occlusion-induced myocardial infarction and to investigate the role of the free radicals. MATERIAL AND METHODS: RPC was performed in rats by a repeated four-cycle 10-min ischemia-reperfusion of femoral artery. Four experimental groups were included: I, sham group; II, RPC only; III, infarction only; and IV, which incorporated both RPC and infarction. A chemiluminescence study showed significant elevation of free radicals in groups with RPC, and pretreated mercaptopropionyl-glycine (MPG), a free radical scavenger, abolished the production of free radicals. RESULTS: The infarct size was significantly reduced for group IV (24.7 +/- 8.8%) compared with group III (51.4 +/- 9.1%; P < 0.001), and the effect was abolished by pretreatment with MPG (49.2 +/- 6.3% in MPG + III versus 50.1 +/- 8.2% in MPG + IV; P > 0.05). Cardiac enzymes also revealed significant decrease in the level for group IV compared with group III, and the protective effect could be abolished by MPG. Western blotting of heat shock protein (HSP) revealed that consistent elevation of HSP 25 and 70 in groups II, III, and IV, and the elevation can be abrogated by pretreatment with MPG. The expression of the antioxidant enzymes, Mn-superoxidase dismutase and glutathione peroxidase, in the area of risk were consistently elevated in groups II, III, and IV, similar to HSP. CONCLUSIONS: The skeletal RPC in rats can produce a protective effect in an infarction model that may be triggered through free radical pathway, and the protective effect was associated with HSP and antioxidant enzymes.

Animals↗

PubMed2005

Dynamic changes in reactive oxygen species and antioxidant levels in retinas in experimental glaucoma.

We investigated the balance of free radicals in retinas at various time points after chronically elevating intraocular pressures in rats. The left eyes of female Wistar rats were divided into five intraocular pressure elevation (IOPE) subgroups after cauterization of three episcleral veins (1 day, 3 days, 1 week, 3 weeks, and 5 weeks) and time-related sham controls. Chemiluminescence levels were examined in isolated retinas. The nitroblue tetrazolium (NBT) incubation method was also performed to confirm the superoxide expression. The activities of antioxidant enzymes and lipid peroxides in isolated retinas were detected by spectrophotometry. In the IOPE group, the intraocular pressure after cauterization was around 22-30 mm Hg; chemiluminescence levels of isolated retinas were significantly elevated on day 3 and week 1; there were more NBT-positive retinal ganglion cells on day 1 and day 3; lipid peroxidation also increased significantly from day 1 and came back to the baseline on week 5; the activities of superoxide dismutases and catalase rose on week 1. Intraocular pressure elevation was shown to change the free radical balance. We suggest that free radicals and their oxidative stresses may play a role in the early stage of glaucoma in causing retinal ganglion cell death in our rat model.

Animals↗

PubMed2004

The protective role of heme oxygenase-1 on the liver after hypoxic preconditioning in rats.

BACKGROUND: Hypoxic preconditioning (HP) confers cytoprotection against ischemia/reperfusion (I/R) injury. This effect is in part attributable to the induction of heme oxygenase (HO)-1. This experiment evaluates liver cell damage after I/R injury in HP rats. METHODS: HP rats were prepared by exposure (15 hr/day) to an altitude chamber (5500 m) for 2 weeks. Partial hepatic ischemia was produced in the left lobes for 45 min followed by 180 min of reperfusion. Zinc (Zn) protoporphyrin (PP), a specific inhibitor of HO enzymatic activity, was subcutaneously injected 1 hr before the I/R injury into separate groups of sea-level (SL) control and HP rats. Serum alanine aminotransferase (ALT) levels, liver HO-1 mRNA and protein, and HO enzymatic activity were measured. RESULTS: HO-1 was induced in the livers of rats exposed to HP. The levels of HO-1 mRNA and protein were obviously overexpressed after 2 weeks of HP. HP diminished the elevation of serum ALT levels after I/R injury (83.7+/- 4.9 U/L) when compared with SL controls (280.8+/-19.4 U/L) and HP+ZnPP-pretreated groups (151.3+/-4.4 U/L). The HO activity in treated rats also was correlated with these results (237.9+/-19.8 pmol/mg of protein per hour for the HP group, 164.3+/-12.7 pmol/mg of protein per hour for the HP+ZnPP group, and 182.6+/-8 pmol/mg of protein per hour for the SL controls). CONCLUSIONS: The authors' results indicated that the induction of HO-1 in hypoxic preconditioning played a protective role against hepatic I/R injury.

Animals↗

PubMed2004

Differentiation of ketamine effects on renal nerve activity and renal blood flow in rats.

BACKGROUND: A biphasic pattern in the effects of increasing dose of ketamine on mean arterial blood pressure (MBP) and renal sympathetic nerve activities (RSNA) was shown in previous study. We hypothesized that if renal vascular resistance (RVR) and renal blood flow (RBF) are mainly controlled by RSNA, they will show a similar biphasic pattern under increasing doses of ketamine. METHODS: 16 female Wistar rats anesthetized with urethane were studied for ketamine at 0.5, 1, 2 mg/kg, i.v. at 30 min intervals. Multifiber RSNA recording was studied in 8 rats and RBF (by electromagnetic flowmeter) and RVR were studied in the other 8 rats with intact renal nerves. RESULTS: Our results showed that although incremental doses of ketamine brought about a biphasic pattern in MBP and RSNA, the decrease in RBF and the increase in RVR went a dose-related way. CONCLUSIONS: We concluded that there was a differentiation of ketamine effects on renal nerve activity and renal blood flow in rats. The changes of RBF and RVR can not only be attributed to the effects of sympathetic nerve activities.

Animals↗

PubMed2003

Hypoxia preconditioning attenuates bladder overdistension-induced oxidative injury by up-regulation of Bcl-2 in the rat.

We explored whether hypoxic preconditioning minimizes oxidative injury induced by overdistension/emptying in the rat bladder. For hypoxic preconditioning, female Wistar rats were placed in a hypobaric chamber (380 Torr) 15 h day(-1) for 28 days. Overdistension was induced by infusion of two times the threshold volume of saline into the bladder and was maintained for 1 or 2 h, followed by drainage/emptying. During overdistension (ischaemia) and emptying (reperfusion) periods, a bursting increase of reactive oxygen species (ROS) from the bladder was originated from the large numbers of infiltrating leucocytes and scattered resident cells, including urothelial, submucosal, and smooth muscle cells. ROS impaired the voiding function by a reduction of bladder afferent and efferent nerve activity and bethanecol- or ATP-induced detrusor contraction. ROS enhanced pro-apoptotic mechanisms, including increases in the Bax/Bcl-2 ratio, CPP32 expression, and poly(ADP-ribose) polymerase (PARP) fragments with subsequent apoptotic cell formation in the insulted bladders. Hypoxia preconditioning up-regulated Bcl-2 expression in the bladder and significantly reduced the levels of ROS and apoptosis detected in the overdistension/emptying bladders and preserved partial voiding function. Bcl-2 up-regulation by hypoxia preconditioning contributes protection against overdistension/emptying-induced oxidative stress and injury in the bladder.

Animals↗

PubMed2003

Hypoxic preconditioning enhances renal superoxide dismutase levels in rats.

Renal ischaemia releases reactive oxygen species (ROS) in the kidneys. We hypothesized that the kidneys are more resistant to the insult of ROS in chronically hypoxic rats. We thus compared rats kept at sea level (SL) and those that had been adapted to hypoxia (hypoxia adapted, HA) by exposure to an altitude of 5500 m in an altitude chamber for 15 h day-1 for 4 weeks. Xanthine (X, 0.75 mg kg-1) and xanthine oxidase (XO, 24.8 mU kg-1) were injected intrarenally. A lucigenin-enhanced chemiluminescence method was employed to detect the amount of free radicals in renal venous blood samples and on the kidney surface. In the renal venous blood samples, 26.05 (+/- 4.36) x 104 and 10.98 (+/- 1.79) x 104 counts were detected in the SL and HA rats, respectively, after X-XO treatment; these figures were significantly different. On the kidney surface of the SL rats, the free radical count amounted to 12.77 (+/- 1.64) x 104, while that in the HA rats was 8.47 (+/- 0.42) x 104; these figures were also significantly different. There was a significant increase in urine volume and urinary excretion of Na+, K+ and protein after X-XO administration in both groups of rats. However, the effect was greater for the SL rats than for the HA rats. The lipid peroxidation of the kidneys was not significantly different in the two groups of rats. Finally, we found that the activity of superoxide dismutase (SOD) and SOD mRNA were higher in the renal tissue of HA rats. We conclude that the renal response to free radicals is attenuated after chronic hypoxia in rats, and that SOD might play an important role in protecting HA rats from oxidative stress.

Altitude↗

PubMed2003

Changes in renal hemodynamics and urodynamics in rats with chronic hyperoxaluria and after acute oxalate infusion: role of free radicals.

AIMS: The aim of this study was to evaluate possible changes in renal hemodynamic and urodynamic parameters in rats with chronic hyperoxaluria and after acute oxalate challenge. We also evaluated the possible association between free radical (FR) production, hyperoxaluria, and calcium oxalate (CaOx) calculi formation. METHODS: Chronic hyperoxaluria was induced by adding 0.75% ethylene glycol (EG) to the drinking water of male Wistar rats. After 7, 21, and 42 days of treatment, urinary biochemistry, oxalate levels, and lipid peroxides were measured. Kidney calculi were examined by polarizing microscopy. In the second part of the experiments, 1, 10, 20, and 30 mg kg(-1) hr(-1) oxalate was infused, by means of an intrarenal arterial catheter (IRA), into normal rats sequentially. Superoxide dismutase (SOD) infusion by means of IRA, in addition to oxalate, was also performed to check its influence on the altered renal function after oxalate infusion. In both the acute and chronic groups, renal blood flow (RBF), cortical microvascular blood flow (CMVBF), glomerular filtration rate (GFR), urine flow (UV), and urinary sodium excretion (U(Na)V) were measured, and chemiluminescence (CL) was examined in the renal venous blood. RESULTS: Levels of urinary lipid peroxides and enzymuria had increased since day 7, and increased the size of numbers of CaOx crystals in the kidney were noted beginning on day 21, but elevated CL was detectable only on day 7 after 0.75% EG treatment. Decreased UV and U(Na)V were noted in the 42-day EG group, although the 24-hr creatinine clearance values were normal in all experimental groups. On the other hand, RBF, GFR, and CMVBF were attenuated with elevated FR when the oxalate concentration was higher than 10 mg kg(-1) hr(-1) in the acute oxalate infusion group. With SOD pretreatment, the decreased RBF, GFR, and CMVBF could be reversed at 10 mg kg(-1) hr(-1) of oxalate, and be partially reversed at 20. FR also could be reduced significantly at 10 and 20 mg kg(-1) hr(-1) of oxalate. CONCLUSIONS: Decreased urine flow and sodium excretion were the main renal functions affected by chronic hyperoxaluria. However, that only the 42-day EG group had a decreased tubular function cannot be fully explained by the persistent tubular enzymuria and increased lipid peroxides that began on day 7 after EG treatment. With acute oxalate infusion, the major insult to renal function was renal hemodynamics. Pretreated SOD could reverse the attenuated hemodynamics and reduce the elevated FR partly, which suggested that FR is responsible for oxalate toxicity.

Acute Disease↗

PubMed2003

Lipid peroxidation and its correlations with urinary levels of oxalate, citric acid, and osteopontin in patients with renal calcium oxalate stones.

OBJECTIVES: To determine whether lipid peroxidation plays a role in patients with calcium oxalate kidney stones and to determine the correlation of lipid peroxidation with tubular damage and the major urinary risk factors. We also used the isoenzymes of glutathione S-transferase (GST) to examine which parts of the renal tubules were injured in patients with renal stones. METHODS: This clinical study included two study groups. Group 1 included 32 normal volunteers, and group 2 included 32 patients with calcium oxalate kidney stones. A 24-hour urine sample was collected from each subject, and the levels of Ca, P, Mg, oxalate, citrate, N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (GAL), alphaGST, piGST, osteopontin (OPN), thiobarbituric acid-reactive substances (TBARS), and malondialdehyde (MDA) were examined. RESULTS: Hyperoxaluria, hypocitraturia, and low urinary OPN were the major abnormalities found in the patients with stones. Elevated urinary alphaGST, NAG, and GAL were also noted in the patients with stones; however, urinary piGST showed no statistically significant difference compared with the controls. Urinary TBARS and MDA had statistically significant correlations with alphaGST, GAL, NAG, Ca, and oxalate, but had no correlation with piGST, citrate, OPN, Mg, and P. Urinary citrate had a negative, linear, and statistically significant correlation with alphaGST, GAL, and NAG. CONCLUSIONS: Lipid peroxidation correlated with hyperoxaluria and renal tubular damage, indicating that hyperoxaluria can induce tubular cell injury and that this injury may be due to the production of free radicals in patients with calcium oxalate stones. Renal tubular damage in patients with stones may be limited to the proximal tubules.

Acetylglucosaminidase↗

PubMed2003

The effect of an intestinal ischemia-reperfusion injury on renal nerve activity among rats.

An intestinal ischemia-reperfusion injury (IIR) may induce renal tubular dysfunction and a reduction in renal blood flow that may be related to the alteration of renal-nerve activity. A rat model of IIR injury was established. The superior mesenteric artery was clamped for 120 min, constituting the ischemic period, and was then released for 60 min, thus constituting the reperfusion period. Renal-nerve activity, renal function, and hemodynamic changes were recorded during the different periods. The levels of calcitonin gene-related peptide (CGRP) in portal-vein blood and intestinal tissue were investigated here. In the reperfusion period, the efferent renal-nerve activity (ERNA) was markedly elevated (94.3% +/- 21.6% higher than the baseline value), such an elevation being only partially reversed by fluid expansion (29.3% +/- 5.2% higher than the baseline value). The elevation of ERNA contributed to the renal blood-flow reduction from 6.8 +/- 0.3 mL/min/g to 2.0 +/- 0.4 mL/min/g, and decreased diuretic and natriuretic responses. The afferent renal nerve activity (ARNA) was markedly depressed (45.7% +/- 8.1% lower than the baseline value) during the reperfusion period. This depression was not reversed by fluid expansion, suggesting that the baroreflex was not responsible for this effect. The blunted ARNA also contributed to the elevation of ERNA by way of a renorenal reflex. The potent vasodilator neuropeptide in the gut, CGRP, revealed an increased level in the portal-vein blood (92.2 +/- 4.4 pg/mL vs. 57.8 +/- 0.6 pg/mL) and also in intestinal tissue (655.8 +/- 115.9 pg/mL vs. 60.5 +/- 9.4 pg/mL) with a time-matched related pattern with the change to renal-nerve activity, suggesting CGRP's role regarding changes in renal-nerve activity. This study indicates that the elevated ERNA level associated with IIR injury is related to a systemic hypotension-induced baroreflex, the contra-lateral inhibition of ARNA, and possibly also gut-released CGRP. In regards to an IIR injury, the depressed ARNA reflects the involvement of a renal sensory- impairment mechanism.

Afferent Pathways↗

PubMed2003

Hypoxic preconditioning prevents cortical infarction by transient focal ischemia-reperfusion.

One of the proposed pathologic actions underlying brain infarction is excess free radicals resulting from reoxygenation. In this paper we report an investigation of the neuroprotective effect of hypoxic preconditioning on transient focal ischemia-reperfusion injuries in rat brain. Female Wistar rats were subjected to 380 mmHg in an altitude chamber for 15 hours/day. Our ex vivo studies showed that auto-oxidation and iron-induced lipid peroxidation of brain homogenates of the four-week hypoxia-preconditioned rats were significantly lower than those of the normoxic rats. A focal infarction in the cerebral cortex of normoxic rats was consistently observed 24 hours after a 60-minute transient ischemic occlusion of the right middle cerebral artery and bilateral common carotid arteries. Hypoxic preconditioning in fact attenuated cortical infarction in a duration-dependent manner. Induction of the neuroprotection required two weeks of hypoxic preconditioning. Four weeks of hypoxic preconditioning significantly reduced the cortical infarcted area, the elevated lipid peroxidation, and resulted in an acute increase in cytosolic cytochrome c in the infarcted cortex of normoxic rats. The protective effect of four weeks of hypoxic preconditioning lasted seven days under a renormoxic condition. Our data suggest that oxidative stress may result in apoptosis in the transient focal ischemia-reperfusion injuries. Furthermore, hypoxic preconditioning attenuated cortical infarction in the rat brain. Although supplementation of antioxidants may encounter difficulty at the blood-brain barrier, hypoxic preconditioning is very likely to protect CNS targets from oxidative injuries without any barrier.

Animals↗

PubMed2003

Fluid administration prevents renal dysfunction during hypotension under spinal anesthesia in a rat model.

BACKGROUND: Severe hypotension deteriorates renal functions and renal hemodynamics especially renal cortical blood flow. Systemic hypotension following high level spinal anesthesia may impair renal functions in spite of the blockade of renal sympathetic nerves that may help prevent vasoconstriction. Fluid loading is clinically applied for preventing hypotension but the effects on the changes of renal functions have not been studied. This study was designed to investigate the effects of fluid loading on systemic hemodynamics, renal hemodynamics and functions especially the blood distribution to renal cortex. METHODS: A rat model was used in our study. Intravenous normal saline infusion was started in both control group (5 ml/kg/h, 8 rats) and fluid loading group (15 ml/kg/h, 8 rats) 30 min before spinal anesthesia. A high level (above T4) spinal anesthesia was conducted via a preset intrathecal catheter with 0.5% hyperbaric bupivacaine. Blood pressure, heart rate and renal cortical microvascular blood flow (CMBF) were measured via a laser Doppler probe firmly contacted on renal cortex and recorded continuously after spinal anesthesia. Renal functions including glomerular filtration rates (GFR, by inulin clearance), effective renal plasma flow (ERPF, by P-aminohippurate clearance), urine flow rate (UFR) and electrolytes excretion were measured every 30 min after spinal anesthesia. RESULTS: Severe hypotension was notable within 5-10 min after intrathecal anesthesia and recovered with 30 min in both groups but the difference was not significant between groups. In the control group, GFR and ERPF decreased significantly in the first 30 min by 51.9 +/- 19.8% and 44.3 +/- 13.7% respectively (P < 0.05) and recovered after 60 min. Also the deteriorations of UFR and CMBF were significantly longer (over 60 min). In fluid loading group, ERPF, UFR and CMBF could maintain throughout the experiment but only GFR was affected in the first 30 min. CONCLUSIONS: Fluid administration did not prevent hypotension following high level spinal anesthesia but might have beneficial effects on renal hemodynamics especially on the renal cortical circulation and urine flow rate.

Anesthesia, Spinal↗

PubMed2002

Simple methods to elevate pulmonary arterial pressure by pre- and post-tricuspid shunts in rats.

BACKGROUND: Arteriovenous shunt in the rat is an extremely useful experimental animal model for investigating cardiac hypertrophy as well as the hemodynamics and endocrine aspects of chronic heart failure. AIMS: The present study was to develop 2 pre-tricuspid and 1 post-tricuspid models of arteriovenous shunt to induce right ventricular hypertrophy and increase pulmonary blood flow in growing rats. METHODS: In the first model, an arteriovenous shunt was created from the common iliac artery to the inferior vena cava (ICS). The second model was shunted from the common carotid artery to the external jugular vein (CJS). A post-tricuspid shunt (the third model) was made by introducing the right common carotid artery into the right ventricular outflow tract (CVS). RESULTS: Four weeks after the shunt surgery, the pulmonary artery pressure was 14.4 +/- 0.5 mmHg in the control group, 15.8 +/- 0.8 mmHg in the ICS group, 21.2 +/- 0.7 mmHg in the CJS group, and 20.2 +/- 1.1 mmHg in the CVS group. The percentage of increasing pulmonary blood flow was 33.0 +/- 1.0% in the CJS group and 26.9 +/- 1.3% in the ICS group four weeks after shunt operation. The oxygen partial pressure of pulmonary artery blood was 30.9 +/- 0.7 mmHg in the control group, 33.6 +/- 1.0 mmHg in the ICS group, 43.7 +/- 1.4 mmHg in the CJS group and 41.1 +/- 2.5 mmHg in the CVS group. The CJS and CVS groups had significant right ventricle hypertrophy. CONCLUSIONS: These three models can provide for study of the flow-pressure effect of the right heart and pulmonary circulation.

Animals↗

PubMed2002

Enhanced expression of nitric oxide synthase in the early stage after increased pulmonary blood flow in rats.

OBJECTIVE: Evidence that vasodilator nitric oxide mediates normal pulmonary vascular tone has led to the hypothesis that endothelial injury induced by congenital heart disease with increased pulmonary blood flow disrupts these regulatory mechanisms and its associated altered vascular reactivity. Therefore, we hypothesized that increased pulmonary blood flow results in altered expression of endothelial nitric oxide synthase (eNOS). METHODS: We created an arteriovenous shunt in female Wistar (5-week-old) and measured the change of pulmonary blood flow and pressure immediately after and 1 month after the shunt operation. The protein levels of eNOS in the lung tissues of rats were assessed. RESULTS: The shunt immediately resulted in a significant increase in pulmonary blood flow (16.5 +/- 11.8% , pulmonary artery pressure (2.3 +/- 0.7 mm Hg), and blood O(2) saturation (16.1 +/- 11.8%) in the pulmonary artery. After 4 weeks, there was a significant increase in pulmonary blood flow (30.7 +/- 1.6%), pulmonary artery pressures (4.3 +/- 1.1 mm Hg), and blood O(2) content (43.3 +/- 17.5%). Western blot analysis demonstrated that eNOS protein was increased in the shunt lung 72 h after surgery and recovered to the control level 1 week later. CONCLUSION: This simple shunt model can induce early upregulation of eNOS expression with increased pulmonary blood flow and pulmonary artery pressure in rats.

Analysis of Variance↗

PubMed2002

Melatonin attenuates the neuronal NADPH-d/NOS expression in the nodose ganglion of acute hypoxic rats.

Excessive production of nitric oxide (NO) may play a detrimental role in the process of hypoxia-related neuropathology. This study explored whether treatment with melatonin would attenuate the neuropathological changes in the vagal ganglia following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment, young adult rats were pre-treated with melatonin at 5. 25 or 100 mg/kg injected intraperitoneally. Hypoxia was achieved by subjecting the rats to a barometric pressure of 0.2 atm (PO2 = 43 Torr) for 4 hr in an altitude chamber. Nicotinamine adenine dinucleotide phosphatediaphorase (NADPH-d) histochemistry combined with the neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to detect the NADPH-d/nNOS reactivity in the nodose ganglion (NG) at various time points following the hypoxic exposure. In normal untreated rats, about 43% of the neurons in the NG displayed NADPH-d/nNOS reactivity. Following hypoxic exposure, both the percentage and the staining intensity of NADPH-d/nNOS positive neurons in the NG were markedly increased, but these were reduced in longer surviving animals. Quantitative analysis of cell counts revealed that about 17% of the neurons died at 14 days after hypoxia treatment. However, in hypoxic rats given different doses of melatonin pretreatment, neuronal death as well as the frequency and staining intensity of NADPH-d/nNOS reactivity of the nodose neurons were significantly decreased. The effect of melatonin on neuronal survival and NADPH-d/ nNOS expression was dose-dependent. It is therefore suggested that melatonin exerts a neuroprotective effect and may serve as a potential therapeutic strategy for prevention and/or reducing the susceptibility of nodose neurons to NO-mediated hypoxic neuropathy.

Animals↗