Renal artery clipping attenuates the progression of adriamycin nephropathy

This study was designed to analyze the impact of diminished renal perfusion pressure due to renal clipping on the rat model of adriamycin nephropathy. Male Wistar rats, divided into four groups (n = 9 per group) were injected with saline as control (C), adriamycin 3 ml/kg (Ad), saline with the left renal artery clipped (Rv), and adriamycin plus clip (AdRv). After 24 weeks mean arterial pressure (MAP), inulin, and p-aminohippurate (PAH) clearances were performed to evaluate renal function. Morphologic analysis included histologic criteria of percentage of glomerulosclerosis and tubulointerstitial lesion index (TILI). The MAP (mm Hg) was similar between Rv (143 +/- 13) and AdRv (154 +/- 20), but higher (P < .05) than C (120 +/- 8) and Ad (124 +/- 11). Inulin clearance (mL/min/100 g) in Ad (0.2 +/- 0.05) was smaller than in C (0.53 +/- 0.17) and Rv (0.4 +/- 0.01) (P < .05), and was at an intermediate level in AdRv (0.33 +/- 0.2). The level of PAH (mL/min/100 g) was normal at 1.76 in C, and diminished more in Ad (0.58) than in Rv (1.06) and AdRv (1.18) (P < .05). Both Ad and the AdRv nonclipped kidneys had the highest degree of glomerulosclerosis (33% and 25%) and TILI (7% and 8%), respectively, compared with C and Rv (both 0%), whereas the clipped kidneys displayed intermediate degrees (9% and 5%) (P < .05 v nonclipped). The data suggest that diminished perfusion pressure of the clipped kidney, by decreasing the intraglomerular pressure, protects the glomerulus from damage and attenuates the evolution of adriamycin nephropathy. Am J Hypertens 1998;11:1124-1128 (C) 1998 American Journal of Hypertension, Ltd.

Vascular effects and electrolyte homeostasis of the natriuretic peptide isolated from Crotalus oreganus abyssus (North American Grand Canyon rattlesnake) venom

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cardiorespiratory and neuroendocrine changes induced by methadone in conscious and in isoflurane anaesthetised dogs

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

Efeitos do pentobarbital sódico sobre o fluxo sanguíneo renal. Estudo experimental no cão

In six dogs, previously anesthetized with sodium pentobarbital (30 mg/kg) for surgical preparation, catheterism and monitoring, the action of sodium pentobarbital (7,5 mg/kg) on renal flow was studied. Determinations of mean arterial pressure, venous pressure, cardiac rate, arterio-cava pressure gradient and renal arterial resistance were made. Pentobarbital doesn't change significantly the renal blood flow or any of the other parameters studied, with the exception of venous pressure in the inferior caval vein where the drug produces a significant fall.

Pressor, dipsogenic, natriuretic and kaliuretic responses to central carbachol in rats with lesion of the medial septal area

In the present study we investigated the effect of electrolytic lesion of the medial septal area (MSA) on the dipsogenic, natriuretic, kaliuretic and pressor responses elicited by intracerebroventricular (i.c.v.) injection of the cholinergic agonist carbachol. Freely moving rats with sham or MSA lesion (1-7 days and 14-18 days) and a stainless steel cannula implanted into the lateral ventricle were studied. In sham rats, i.c.v. injection of carbachol (7.5 nmol) produced an increase in water intake (10.2 ± 1.5 ml/h), mean arterial pressure (MAP) (35 ± 5 mmHg) and urinary Na+ and K+ excretion (551 ± 83 and 170 ± 17 μEq 120 min, resp.). The pressor (18 ± 3 and 14 ± 4 mmHg, resp.) and natriuretic responses (178 ± 58 and 172 ± 38 μEq 120 min) produced by i.c.v. carbachol in acute or chronic MSA-lesioned rats were reduced. No change was observed in urinary K+ excretion and a reduced water intake (5 ± 1.3 ml/h) was observed only in acute MSA-lesioned rats. These results suggest that the MSA plays an important role for the pressor and natriuretic responses induced by central cholinergic activation in rats. A small influence of this structure on water intake may also be suggested. © 1991.

Effect of AV3V lesion on the cardiovascular, fluid, and electrolytic changes induced by activation of the lateral preoptic area

In this study we investigated the effect of the anteroventral third ventricle (AV3V) lesion on the pressor, bradycardic, natriuretic, kaliuretic, and dipsogenic responses induced by the injection of the cholinergic agonist carbachol into the lateral preoptic area (LPOA) in rats. Male Holtzman rats with sham or electrolytic AV3V lesion were implanted with stainless steel cannula directly into the LPOA. Injection of carbachol (7.5 nmol) into the LPOA of sham rats induced natriuresis (405 ± 66 μEq/120 min), kaliuresis (234 ± 44 μEq/120 min), water intake (9.5 ± 1.7 ml/60 min), bradycardia (-47 ± 11 bpm), and increase in mean arterial pressure (28 ± 3 mmHg). Acute AV3V lesion (1-5 days) reduced the natriuresis (12 ± 4 μEq/120 min), kaliuresis (128 ± 27 μEq/120 min), water intake (1.7 ± 0.9 ml/60 min), and pressor responses (14 ± 4 mmHg) produced by carbachol into the LPOA. Tachycardia instead of bradycardia was also observed. Chronic (14-18 days) AV3V lesion reduced only the pressor response (10 ± 2 mmHg) induced by carbachol. These results showed that acute, but not chronic, AV3V lesion reduced the natriuretic, kaliuretic, and dipsogenic responses to carbachol injection into the LPOA. The pressor response was reduced in acute or chronic AV3V-lesioned rats. The results suggest that the lateral areas may control the fluid and electrolyte balance independently from the AV3V region in chronic AV3V-lesioned rats. © 1992.

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.

Papel da regiao AV3V no choque septico experimental em ratos tratados com NaCl 7,5%

The effect of intravenous infusion of hypertonic saline (HS) on the recovery of mean arterial pressure (MAP) during septic shock was studied in sham-operated rats and in rats with electrolytic lesion in the anteroventral third ventricle (AV3V) region. Our results show that intravenous HS infusion in rats treated with endotoxin (Etx) partially restores MAP, but when we have a severe shock produced by Etx, HS was not able to reverse the hypotension. We also show that the integrity of the AV3V region is essential for the protective action of HS in endotoxin shock. It is possible that NO production contributes to the deleterious effect of endotoxin. So, the unraveling of the release of NO by the vascular endothelium and their role as regulators of vascular tone is increasing our understanding of the physiology and pathophysiology of the cardiovascular system and will therefore enhance the possibilities of preventing and treating endotoxin shock.

Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia

Six Welsh gelding ponies (weight 246 ± 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.

Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol

We investigated the effects of losartan, an AT 1-receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/l μl) into the LV blocked the pressor response induced by ANG II (12 ng/l μl) and carbachol (2 nmol/l μl). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 ± 1 and 28 ± 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 ± 1 and 5 ± 2 mmHg, respectively). The injection of ramipril (12 ng/l μl) prior to carbachol blocked the pressor effect of carbachol to 7 ± 3 mmHg. These results suggest an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure.

Acute renal failure in renal allograft recipients and patients with native kidneys

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or non-normalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis ≤ 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.

Effect of α-tocopherol, taurine and selenium on the attenuation of ischemia/reperfusion injury of splanchnic organs

Background: Splanchnic artery occlusion shock is caused by increased capillary permeability and cellular injury precipitated by oxygen derived free radicals following ischemia and reperfusion of splanchnic organs. The purpose of this study was to assess the role of several well-known oxygen- derived free radical scavengers in ameliorating or preventing this syndrome. Study design: Anesthetized rats were subjected to periods of occlusion of the visceral arteries and reperfusion. Tocopherol, taurine, selenium or a 'cocktail' of these three agents was injected subcutaneously for 4 consecutive days prior to operation. Mean arterial blood pressure was measured throughout the experimental period. Fluorometry and technetium-99m pyrophosphate counting of the visceral organs were performed as well as a histologic grading system for intestinal viability. Results: Final mean arterial blood pressure associated with the 'cocktail' and selenium groups was 79.1 ± 27.4 mmHg and 83.6 ± 17.8 mmHg, respectively. These values were significantly higher than the control group, 40.8 ± 11.4 mmHg (P < 0.05). Similar patterns of the benefit of selenium in contrast with the other groups were obtained with fluorescein perfusion, radioisotopic activity and histologic analysis. Conclusion: Pretreatment with selenium of splanchnic ischemia and reperfusion in the rat improves mean arterial blood pressure and microcirculatory visceral perfusion. Further analysis of the precise protective mechanism of selenium for reperfusion injury will enable visceral organs to withstand the consequences of increased capillary leakage and oxidant injury.

Commissural NTS lesions and cardiovascular responses in aortic baroreceptor-denervated rats

Both acute (1 day) lesions of the commissural nucleus of the solitary tract (commNTS) and aortic baroreceptor denervation increase pressor responses to bilateral common carotid occlusion (BCO) during a 60-second period in conscious rats. In this study, we investigated the following: (1) the effects of commNTS lesions on basal mean arterial pressure (MAP) and heart rate (HR) of aortic denervated (ADNx) rats; (2) the effects of acute commNTS lesions on pressor responses to BCO in ADNx rats; and (3) the effects of chronic (10 days) commNTS lesions on the pressor response to BCO. ADNx increased basal MAP and HR in sham-lesioned rats. Acute commNTS lesions abolished the MAP and HR increases observed in ADNx rats. Acute commNTS lesions increased the pressor responses to BCO in rats with intact- baroreceptor innervation but produced no additional change in the pressor response to BCO in ADNx rats. Chronic commNTS lesions did not change the pressor responses to BCO in rats with intact-baroreceptor innervation. The data show that acute commNTS lesions abolish the MAP increase produced by aortic baroreceptor denervation. They also suggest that acute commNTS lesions enhance the pressor response to BCO by partial withdrawal of aortic baroreceptor inputs into the NTS. Chronically, reorganization in the remaining aortic baroreceptor or in the baroreflex function as a whole might produce normalization of the cardiovascular responses to BCO.

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.