Pressão arterial e manipulação tubular renal de sodio em um modelo de septicemia em ratos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2001

RESUMO

Acute renal failure is a frequent complication in septic patients associated with a high mortality rate. An important characteristic is a decrease in glomerular filtration rate, which is even present in situations where renal blood flow has been maintained. Prevailing hypothesis on the pathogenesis of renal failure suggest an inappropriate and uncontrolled release of various inflammatory mediators. Overwhelming sepsis, with or without septic shock, can be an extremely difficult clinical trouble to treat. Antibiotics clearly are a mainstay of therapy but are often inadequate in the immunocompromised host. Additionally, an adequate nutritional, pressure, fluid and electrolyte management is critical in the care of patients with sepsis. One such septicemia model that is frequently used is cecal ligation and puncture in rats. This model resembles human sepsis in several important aspects, such as an early phase of hyperdynamic, hypermetabolic sepsis followed by a late phase of hypodynamic sepsis. An intra-abdominal abscess causes the condition and devitalized tissue, which are common source of sepsis in-patients as well. Recent studies also suggest involvement of nitric oxide (NO), generated by inducible NO synthase (iNOS), in the pathogenesis of endotoxin-induced renal failure. Several studies have shown that the short-term administration of Nw-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis results in a prompt increase in the arterial pressure of rats, rabbits, and dogs. The immediate increase in arterial pressure reflects principally an increased vascular smooth muscle tone as a consequence of decreased NO synthesis. Increases in sympathetic nerve activity have been described after acute inhibition of NO synthesis, suggesting that neurogenic mechanisms may contribute to the rise in arterial pressure. Administration of an adequate volume of fluid is important for the hyperdynamic response and to keep the hemodynamic steady state after cecal ligation and puncture (CLP) in rats. In the present study, 5 milliliters per 100 grams of body weight of 0.15M NaCl solution were administered via subcutaneous, immediately after CLP, as recommended previously. The present study was performed to compare blood pressure behavior and renal sodium handling in three groups (experimental versus control group, n=10 each) of adult male Wistar-Hannover rats (weighting between 200-250 g) at 3, 6, 12 and 18 hour after cecal ligation and puncture (CLP): 1) CLP and sham-operated vehicle-treated, 2) CLP and sham-operated L-NAME-treated, and 3) CLP and sham-operated 0.15M NaCl-treated rats. Three series of experiment were performed between 3 to 18 hours once most of animals died after 24 hours post CLP. Arterial blood pressure and renal function study were measured 3, 6, 12 and 18-h after CLP in conscious rats by tail-cuff method and whole kidney creatinine and lithium clearances. The arterial pressure and renal function tests were performed in individual metabolic cages 7 days after the beginning of L-NAME administration (60mg/kg/day) and 3, 6, 12 and 18-h after 5ml 0.15M NaCl administration, and progressively increased arterial pressure from 127±3.5 mmHg to 149±13.0 mmHg (P<0.05%) in the sham-operated group and a significant blood pressure decrease to 96±8.0 mmHg 18-h after CLP. So, the development of hypertension was significantly delayed and attenuated in septic L-NAME-treated rats. By the 7th day of treatment the increased blood pressure was accompanied by a non-significant fall in creatinine clearance from 310±32ml/min/100 g to 305±23ml/min/100 g and no change in fractional urinary sodium excretion. In CLP group the treatment with L-NAME did not prevent the glomerular filtration fall (from 294±25ml/min/100 g to 185±16ml/min/100 g), as well as the proximal sodium rejection (43.7±4.4 % to 53.0±3.3 %) 18-h post sepsis induction. This was accompanied by a striking additional increase in fractional renal potassium excretion from 0.15±0.04% to 0.31±0,03% in sham-operated and septic rats respectively and an enhanced proximal followed by consecutive fall post-proximal sodium excretion compared to no-changed urinary sodium excretion the sham-operated group. Fluid replacement was performed with the view of obtaining the amelioration of circulation and renal function in septic rats. Administration of an adequate volume of fluid is important for the hemodynamic stability after CLP in rats. However, in the present study, 5 ml per 100 g of body weight of 0.15M NaCl solution administered subcutaneously did not improved significantly the survival rate and renal tubular function. Our results suggest that fluid resuscitation delayed and attenuated the blood pressure and glomerular filtration rate decrease, based upon current understanding of the pathophysiology of fluid imbalance, should be to ensure adequate oxygen delivery by optimizing blood oxygenation, perfusion pressure, and circulation volume independently of an additional increase in tubule sodium reabsorption in the whole segments of nephrons. Maintenance of higher values in venous pressure during fluid resuscitation might be recommended because adequate fluid resuscitation could sustain the renal function, and result in good outcome

ASSUNTO(S)

septicemia choque septico insuficiencia renal aguda oxido nitrico

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