EFEITOS DA INFUSAO CONTINUA DO PROPOFOL SOBRE A FUNCAO RENAL DO CAO. ESTUDO COMPARATIVO COM O PENTOBARBITAL SODICO

Little research has been done with propofol in relation to renal function. The aim of this study was to evaluate the effects of the continuous infusion of propofol on renal function in dogs. Sixteen dogs, previously anesthetized with pentobarbital sodium (30 mg.kg-1) for surgical preparation, catheterism and monitoring, were studied. The dogs were mechanically ventilated with air and received alcuronium (0.2 mg.kg-1 in bolus and 0.06 mg.kg-1 - maintenance). The following parameters were studied: heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), aortic blood flow (A(o)BF - by electromagnetic flowmeter installed in the ascending aortic), aortic vascular resistance index (A(o)VRI), renal plasma flow (ERPF - by para-aminohipurate clearance), glomerular filtration rate (GFR - by creatinine clearance), effective renal blood flow (ERBF = ERPF/1 - hematocrit), urinary volume (UV), renal vascular resistance (RVR = MAP.80/ERBF.10-3), urinary sodium excretion (UE(Na)), fractionated sodium excretion (FE(Na)), osmolar clearance (C(osm)) and free water clearance (C(H2O)). These parameters were studied at 15 (M1), 30 (M2), 45 (M3) and 60 (M4) min after beginning pentobarbital sodium infusion (5 mg.kg-1.h-1). The dogs were allocated into two groups of eight animals each: G1 (control-pentobarbital sodium) and G2 (propofol). In G1, pentobarbital was given at the four times studied. G2 dogs received the same treatment as G1 dogs at M1 and M2; infusion of pentobarbital was substituted by propofol (3 mg.kg-1 bolus, followed by 12 mg.kg-1.h-1 continuous infusion) at M3 and M4. Profile Analysis was used to analyze the results statistically. In G1 (pentobarbital), there was a significant increase in RVR (M1 < M4) and a decrease in ERPF and ERBF (M1 > M4). In G2 (propofol) there was only a significant increase in A(o)BF (M1 < M2 = M3). In comparison among groups, these was a significant alteration of FE(Na) at M3 (pentobarbital > propofol). It was observed that the continuous infusion of propofol in dogs, at the given doses, did not alter the basic variables of renal function and hemodynamics studied. We concluded that propofol can be one of the drugs of choice to provide base anesthesia in studies of renal function in dogs.

EFEITOS DO SULFATE DE MAGNESIO NA HEMODINAMICA E FUNCAO RENAL DE CAES ANESTESIADOS CORN PENTOBARBITAL SODICO

Background and objectives - The use of magnesium sulphate for the prevention of seizures in pre-eclampsia may induce hypermagnesemia. Clinical and experimental studies are not in agreement about the effects of magnesium on the renal hemodynamics and function. We therefore studied the effects of hypermagnesemia on the renal hemodynamics and function of dogs anesthetized with pentobarbitone. Methods - Sixteen mongrel dogs were anesthetized with pentobarbitone 30 mg.kg-1 and submitted to extracellular ) and mechanical ventilation with room air. The dogs were volume expansion with Ringer's solution (0.4 ml.kg.min allocated into two groups of 8 animals, for the study of renal hemodynamics and function following the administration of 5 mg.kg-1 of pentobarbitone (Group 1 - control or of pentobarbitone associated with magnesium sulphate in the dose (Group 2). The parameters studied were: PAH of 140 mg.kg, administered in 15 minutes, followed by 80 mg.kg-1.h-1 clearance, creatinine clearance, osmolar clearance, free water clearance, renal blood flow, renal vascular resistance, filtration fraction, urinary volume, plasmatic and urinary osmolarity, urinary and fractionary excretion of sodium and potassium, measured at five moments: 15 (M1), 30 (M2), 60 (M3) and 75 (M4) minutes after the first supplementary dose of pentobarbitone and 15 minutes (M5) after the second supplementary dose in Group 1. In Group 2, the moments M3, M4, M5 were 15, 30 and 60 minutes after the priming dose of magnesium sulphate and during the maintenance dose. Results - In Group I no significant changes were observed in renal hemodynamic parameters and creatinine clearance. The extracellular volume expansion increased urinary volume and decreased urinary osmolarity as a consequence of sodium, potassium and free water clearance. The fractionary excretion of sodium was maintained. The plasmatic osmolarity increased. In Group 2, renal hemodynamic parameters and creatinine clearance were also maintained. There was an increase in renal sodium clearance, as detected by the increase in the fractionary excretion of sodium. Conclusions - Magnesium sulphate did not produce significant changes in renal hemodynamics and facilitated the renal excretion of sodium in dogs anesthetized with pentobarbitone.

On a dual role for clonidine stimulation of the ventromedial nucleus of the hypothalamus in sodium and potassium renal excretions of rats

The effects of clonidine on sodium and potassium excretions were examined after previous administration of prazosin (an α 1-adrenergic receptor antagonist) and yohimbine (an α 2-adrenergic receptor antagonist) into the ventromedial nucleus of the hypothalamus of conscious rats. Clonidine injected into the ventromedial nucleus of the hypothalamus induced inhibitory and facilitatory effects on the urinary sodium and potassium excretions. The results suggest that facilitatory effects of clonidine on natriuresis and kaliuresis are mediated through activation of α 1-adrenoceptors and that inhibitory effects require α(2A)-adrenoceptors.

Effects of cyclosporine on adriamycin induced nephropathy

The effect of cyclosporine on adriamycin nephropathy was studied over both short (6 weeks) and long (26 weeks) periods. In the short-term study, cyclosporine was introduced 2 weeks after nephritis induction and in the long-term study, 14 weeks after the first adriamycin injection. The animals with adriamycin nephropathy treated with cyclosporine, studied for 6 weeks, developed proteinuria with increased renal size and glomerular area. The nephrotic animals treated with cyclosporine showed less proteinuria than the nephrotic control animals. There were no differences in glomerular area, creatinine clearance or serum creatinine and kidney weight between the treated nephrotic group and the health control group. The nephrotic animals, studied for the longer period, developed intense proteinuria, decreased creatinine clearance, glomerular necrosis and sclerosis, severe tubulointerstitial nephritis, increased hydroxyproline concentration and tubulointerstitial area. No difference was observed between the nephrotic animals treated with cyclosporine and those not treated. In conclusion, Cyclosporine A reduced proteinuria, glomerular hypertrophy and kidney weight in rats with short-term nephropathy but had no effect on the established nephropathy.

Tempo de latencia e duracao do efeito do brometo de rocuronio no paciente submetido ao transplante renal

Background and Objectives - Successful cadaver kidney transplantation relies on a fast procedure. Patients with chronic renal failure may present with a delayed gastric emptying making it critical a fast tracheal intubation and airway maintenance. Rocuronium a recently introduced nondepolarizing neuromuscular blocker with a fast onset. The aim of this study was to evaluate onset time and duration of rocuronium effects in patients undergoing renal transplantation. Methods - Sixty patients were allocated into two groups of 30: Group R (GR) = patients undergoing renal transplantation and Group N (GN) = patients with normal renal function. All patients were premedicated with oral midazolam (15 mg) and anesthesia was induced with 30 μg.kg-1 alfentanil, 0.3 mg.kg-1 etomidate and 0.6 mg.kg-1 rocuronium injected through a central venous catheter. neuromuscular block was monitored by acceleromyography in the ulnar nerve pathway. The following parameters were evaluated: time between administration of rocuronium and first twitch reduction to 5% after supra-maximal stimulation (T1) (onset time = OT); time for first twitch to return to 25% (clinical duration = R25); time elapsed between 25% and 75% recovery of first twitch (relaxation recovery time = R25-75). Heart rate (HR) and mean blood pressure (MBP) were recorded in 6 moments. Results - Median OT was 31 sec. in GR and 47 sec. in GN. Median R25 was 51.5 min in GR and 33.5 min in GN. Median R25-75 was 28 min in GR and 20 min in GN. MBP and HR were higher in GR. Tracheal intubation conditions were excellent for most patients in both groups. Conclusions - These results open the possibility of 0.6 mg.kg-1 rocuronium being injected through a central venous catheter when a faster onset is needed. Due to wide differences in individual responses, monitoring of neuromuscular block is recommended.

Haemodynamic effects of hypothalamic disconnection in anaesthetized rats

The aim of the present study was to analyse the haemodynamic effects induced by the hypothalamic disconnection (HD) caudal or rostral to the paraventricular nucleus of the hypothalamus (PVN). Mean arterial pressure (MAP), hindlimb, renal and mesenteric blood flow and vascular conductance (HVC, RVC and MVC, respectively) were measured in urethane (1.2 g/kg, i.v.) anesthetized rats for 60 min after disconnection. HD caudal to the PVN was performed with a double-edged microknife of bayonet shape (R=1 mm, H=2 mm) stereotaxically placed, lowered 2.8 mm caudal to the bregma along the midline. The cut was achieved by rotating the microknife 90° right and 90° left. HD rostral to the PVN was performed with the knife placed 0.8 mm caudal to the bregma. Thirty minutes after the hypothalamic disconnection caudal (HD-C), a decrease in MAP was observed (-14±3 mm Hg), reaching a 60-min decrease of 30±3 mm Hg. Hindlimb conductance increased 10 min after HD (156±14%) and remained elevated throughout the experimental period. On the contrary, we observed a transitory renal vasoconstriction (82±9%, ≤20 min) and a late mesenteric vasodilation, starting at 30 min (108±4%) and reaching 138±6% at 60 min. In rats with HD rostral to the PVN, we only observed minor changes in the cardiovascular parameters. In the MAP, there was a slight decrease 60 min after the hypothalamic disconnection rostral (HD-R) (-9±4 mm Hg). There were no significant changes in HVC. RVC and MVC were increased 60 min after the HD-R (116±12% and 124±11%, respectively). These results suggest that vasodilation in the hindlimb and in the mesenteric bed could contribute to the observed decrease in MAP in HD caudal to PVN rats. © 2002 Elsevier Science B.V. All rights reserved.

Acute and short-term insulin-induced molecular adaptations of GLUT2 gene expression in the renal cortex of diabetic rats

Increased GLUT2 gene expression in the renal proximal tubule of diabetic rats is an adaptive condition, which may be important in the diabetic nephropathy development. We investigated the effects of insulin treatment upon the renal GLUT2 overexpression of diabetic rats. Acute treatment, surprisingly, induced a rapid further increase in GLUT2 mRNA content. Twelve hours after insulin injection, GLUT2 mRNA was twice the value of saline-injected rats (P < 0.001), when GLUT2 protein remained unchanged. In response to short-term treatment, both GLUT2 mRNA and protein were increased in 1-day treated rats (P < 0.05 versus saline-injected), decreasing after that, and reaching, within 6 days, values close to those of non-diabetic rats. Concluding, insulin treatment induced: initially, an additional upregulation of GLUT2 gene expression, involving posttranscriptional modulation; thereafter, downregulation of GLUT2 expression, which returns to non-diabetic levels. The former may be related to increased insulin concentration, the latter may be due to glycemic control. © 2005 Elsevier B.V. All rights reserved.

Efeitos da ciclosporina a sobre a função renal de cães da raça Golden Retriever normais ou afetados pela distrofia muscular

The muscular dystrophy of Golden Retriever is a degenerative miopaty caused by the absence of dystrophy and it is genetically homologue of the Duchenne muscular dystrophy in humans, so, these dogs are considerably experimental models for studies on cellular therapy. Their successful depends of the adequate immunosuppression. Cyclosporin A is indicated for that and the monitoring of blood concentration and adverse effects are essential to viabilise the therapy. It was studied GRMD dogs, and normal dogs from the same breed, submitted for therapy with CsA, associated, on GRMD, of cell transplantation. It was evaluated the possible effects of the drug on renal functions. It has been considerate the clinic manifestations, urinalisis, testis of glomerular function and blood concentrations of urea, cretinine, sodium and potassium. In our results we found a discrete increase of blood urea on booth groups; increased levels of urine's cylinders and protein and also increase of urinary density on GRMD group. CsA therapy could make acute lesions on renal tubules, especially on GRMD. These dogs also have different reactions than normal dogs on relation of ions homeostasis and renal function. However, earlier diagnosis and adequate treatment could prevent the development of renal diseases.

Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epithelia

Bites from snake (Bothrops genus) cause local tissue damage and systemic complications, which include alterations such as hemostatic system and acute renal failure (ARF). Recent studies suggest that ARF pathogenesis in snakebite envenomation is multifactorial and involves hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. The aim of the work was to investigate the effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV (10 μg/mL) reduced the perfusion pressure at 90 and 120 min. The renal vascular resistance (RVR) decreased at 120 min of perfusion. The effect on urinary flow (UF) and glomerular filtration rate (GFR) started 30 min after BlV infusion, was transient and returned to normal at 120 min of perfusion. It was also observed a decrease on percentual tubular transport of sodium (%TNa+) at 120 min and of chloride (%TCl-) at 60 and 90 min. The treatment with BlV caused decrease in cell viability to the lowest concentration tested with an IC50 of 1.25 μg/mL. Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by necrosis. However, a cell death process may involve apoptosis in lower concentrations. BlV treatment (1.25 μg/mL) led to significant depolarization of the mitochondrial membrane potential and, indeed, we found an increase in the expression of cell death genes in the lower concentrations tested. The venom also evoked an increase in the cytosolic Ca2+ in a concentration dependent manner, indicating that Ca2+ may participate in the venom of B. leucurus effect. The characterization of the effects in the isolated kidney and renal tubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism. © 2012.

Evaluation of the effects of nicorandil and its molecular precursor (without radical NO) on proliferation and apoptosis of 786-cell

Nicorandil is a nitric oxide (NO) donor used in the treatment of angina symptoms. It has also been reported to protect cells and affect the proliferation and death of cells in some tissues. The molecules that interfere with these processes can cause dysfunction in healthy tissues but can also assist in the therapy of some disorders. In this study we examined the effect of nicorandil and of the molecular precursor that does not have the NO radical (N-(beta-hydroxyethyl) nicotinamide) on the cell proliferation and death of human renal carcinoma cells (786-O) under normal oxygenation conditions. The molecular precursor was used in order to analyze the effects independents of NO. In the cytotoxicity test, nicorandil was shown to be cytotoxic at very high concentrations and it was more cytotoxic than its precursor (cytotoxic at concentrations of 2,000 and 3,000 μg/mL, respectively). We propose that the lower cytotoxicity of the precursor is due to the absence of the NO radical. In this study, the cells exposed to nicorandil showed neither statistically significant changes in cell proliferation nor increases in apoptosis or genotoxicity. The precursor generated similar results to those of nicorandil. We conclude that nicorandil causes no changes in the proliferation or apoptosis of the cell 786-O in normal oxygenation conditions. Moreover, the lack of NO radical in the precursor molecule did not show a different result, except in the cell cytotoxicity. © 2013 Springer Science+Business Media Dordrecht.

Inhibitory mechanism of the nucleus of the solitary tract involved in the control of cardiovascular, dipsogenic, hormonal, and renal responses to hyperosmolality

The nucleus of the solitary tract (NTS) is the primary site of visceral afferents to the central nervous system. In the present study, we investigated the effects of lesions in the commissural portion of the NTS (commNTS) on the activity of vasopressinergic neurons in the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, plasma vasopressin, arterial pressure, water intake, and sodium excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats with 15-20 days of sham or electrolytic lesion (1 mA; 10 s) of the commNTS were used. CommNTS lesions enhanced a 2 M NaCl intragastrically induced increase in the number of vasopressinergic neurons expressing c-Fos in the PVN (28 ± 1, vs. sham: 22 ± 2 c-Fos/AVP cells) and SON (26 ± 4, vs. sham: 11 ± 1 c-Fos/AVP cells), plasma vasopressin levels (21 ± 8, vs. sham: 6.6 ± 1.3 pg/ml), pressor responses (25 ± 7 mmHg, vs. sham: 7 ± 2 mmHg), water intake (17.5 ± 0.8, vs. sham: 11.2 ± 1.8 ml/2 h), and natriuresis (4.9 ± 0.8, vs. sham: 1.4 ± 0.3 meq/1 h). The pretreatment with vasopressin antagonist abolished the pressor response to intragastric 2 M NaCl in commNTS-lesioned rats (8 ± 2.4 mmHg at 10 min), suggesting that this response is dependent on vasopressin secretion. The results suggest that inhibitory mechanisms dependent on commNTS act to limit or counterbalance behavioral, hormonal, cardiovascular, and renal responses to an acute increase in plasma osmolality. © 2013 the American Physiological Society.

Effects of magnesium sulphate on the pharmacodynamics of rocuronium in patients aged 60 years and older: A randomised trial

BACKGROUND There is little information on the interaction between magnesium sulphate (MgSO4) and rocuronium in elderly patients. With a growing number of older patients who need surgical procedures, it is increasingly important to study this age group. OBJECTIVE To evaluate the effects of MgSO4 administration on the pharmacodynamics of rocuronium in patients aged 60 years or older. DESIGN A randomised controlled trial. SETTING A tertiary care hospital. PATIENTS Sixty-four patients, aged 60 years or older, American Society of Anesthesiologists (ASA) physical status classes I to III, scheduled for elective oncological head and neck surgery. Exclusion criteria were severe renal insufficiency (calculated creatinine clearance <30 ml min-1), preoperatorive serum magnesium concentration of more than 1.25 mmol l1 and patients receiving drugs known to affect neuromuscular function. INTERVENTIONS Patients were randomly allocated to one of two groups: in the magnesium group, patients received MgSO4 30mgkg1 intravenously, for 10 min, and then a continuous intravenous infusion at a rate of 1 g h-1. The control group received the same volume of physiological saline. Neuromuscular function was evaluated continuously in both groups. MAIN OUTCOME MEASURES Total recovery time was the primary outcome. Onset time, clinical duration, recovery index and recovery time were considered as secondary endpoints. Values are given as mean [SD]. RESULTS Total recovery time from neuromuscular block (NMB) was 113 [36] min in the magnesium group and 101 [39] min in the control group. Clinical duration was 69 [23] min in the magnesium group and 59 [28] min in the control group. Recovery index was 19 [36] min in the magnesium group and 17 [6] min in the control group. Recovery timewas 44 [22] min in the magnesium group and 42 [18] min in the control group. There were no statistically significant differences between the groups in any of the recovery indices. In the magnesium group, the mean onset time was 144 [58] s, significantly shorter than the onset time in the group that received physiological saline, which was 187 [90] s (P-0.03). Group variances were compared using an F test: onset time varied significantly less in the magnesium group (P-0.02). CONCLUSION In oncology patients of 60 or more years of age, preadministration of MgSO4, with the doses used in this study, significantly reduced the onset time of NMB induced by rocuronium. © 2013 European Society of Anaesthesiology.

Potenciais evocados auditivos de tronco encefálico e emissões otoacústicas evocadas transientes: achados em pacientes com doença renal crônica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do DMSO (dimetilsulfóxido), administrado por via intravenosa, sobre as funções renal e hepática, perfil hidrossalino e hemograma de cães sadios

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da taxa de filtração glomerular e excreção fracionada de eletrólitos de cães com doença renal crônica tratados com dimetilsulfóxido (DMSO)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)