Reduction of risk following endotoxin injection in unilaterally nephrectomized rats.

In this study the consequences of unilateral nephrectomy on the survival rate of rats were examined under severe pathological conditions including injection of a lethal dose of endotoxin (exogenic LPS), cecal puncture (endogenic LPS), injection of LPS concomitantly with renal ischemia as well as a simultaneous injection of LPS and glycerol to the leg muscle in order to induce acute renal failure. Sham operated rats did not exhibit higher survival rates than the nephrectomized rats. In most cases there was even a decrease in the percent age rate of deaths in the nephrectomized rats. Improvement in the resistance of the nephrectomized rats to pathophysiological stress occurred when stress was induced immediately following nephrectomy as well as when stress was induced 30 days following nephrectomy. No significant differences were found in blood pressure, heart rate, hematocrit, rate of respiration and body temperature in the nephrectomized rats as compared to rats that did not undergo nephrectomy. A possible explanation for our results is that the solitary kidney excretes more LPS into the urine.

Unilateral renal ischemia reperfusion in the rat: effect of blood volume trapped in the kidney, sucrose infusion, and antioxidant treatments.

This study was carried out in order to examine whether the severity of acute renal failure observed during the four hours following a 45 min period of unilateral occlusion of the renal pedicle could be reduced by various treatments. These include intrarenal flush with saline immediately before the occlusion, by sucrose infusion immediately before reperfusion, or by injection of NAO (natural antioxidant) and vitamin E before the occlusion. After renal pedicle occlusion, creatinine levels increased to 165% of their pre-ischemic values. Urine flow, GFR, renal cortex blood flow and NADH decreased by 99%, 99%, 50% and 36%, respectively. A decrease in the Na and K reabsorption (15% and 32%, respectively) was also observed. Partial protection of renal function against ischemic damage was observed when kidney tissue remained blood-free, by exposing it to saline throughout the period of ischemia. Significant protection was observed after treatment with sucrose, vitamin E and NAO. This study demonstrates that it is possible to attenuate the injury to the ischemic kidney by inducing ischemia in a bloodless kidney, by inducing diuresis in the first phase of reperfusion, or by antioxidant treatment, such as vitamin E or NAO.

Increased sensitivity to bilateral nephrectomy in rat caused by endotoxemia.

In this study the possibility that the kidneys play a role in the removal of endotoxin from the blood was examined. This was carried out by an IP injection of endotoxin (at a dosage of 1 mg/100 gr) to rats that had undergone bilateral nephrectomy, and examining the times of death following various treatments. Furthermore, the rats underwent treatment for endotoxin tolerance or received treatment with the antioxidants superoxide dismutase (SOD) and natural antioxidant (NAO) or were injected with an inhibitor of the enzyme NOS (NGmethyl l-arginine 1-NMA). The endotoxin concentration in the plasma was also measured. The results of this study indicate the rats were more sensitive to bilateral nephrectomy in the presence of endotoxin. This increased sensitivity in the binephrectomized rat decreases following treatment inducing tolerance to endotoxin, or following treatment with an antioxidant or with the inhibitor of NOS. A possible explanation for the increased sensitivity following endotoxin injection is that it apparently results from an increased concentration of endotoxin in the blood due to the impossibility of removing the endotoxin via the kidneys. Therefore, endotoxin tolerance or abolishing the potential injuries that may be caused by endotoxin negate the sensitivity in the binephrectomized rats injected with endotoxin.

Reduction of risk following endotoxin injection in unilaterally nephrectomized rats.

In this study the consequences of unilateral nephrectomy on the survival rate of rats were examined under severe pathological conditions including injection of a lethal dose of endotoxin (exogenic LPS), cecal puncture (endogenic LPS), injection of LPS concomitantly with renal ischemia as well as a simultaneous injection of LPS and glycerol to the leg muscle in order to induce acute renal failure. Sham operated rats did not exhibit higher survival rates than the nephrectomized rats. In most cases there was even a decrease in the percent age rate of deaths in the nephrectomized rats. Improvement in the resistance of the nephrectomized rats to pathophysiological stress occurred when stress was induced immediately following nephrectomy as well as when stress was induced 30 days following nephrectomy. No significant differences were found in blood pressure, heart rate, hematocrit, rate of respiration and body temperature in the nephrectomized rats as compared to rats that did not undergo nephrectomy. A possible explanation for our results is that the solitary kidney excretes more LPS into the urine.

The effects of food and drink on the survival of binephrectomized rats.

Previous studies have shown that the survival time of rats following binephrectomy is between 48 and 120 hours. The aim of the present study was to examine the assumption that the eating and drinking protocol before and after binephrectomy affects the survival time following surgery in male, female and young rats. In this study we used protocols which included various combinations of eating and drinking or their prevention before and after binephrectomy. Survival time was determined by examining the kinetics of death following binephrectomy. Examination of the azotemia and physiological condition of the rat was performed by testing BUN, creatinine, plasma Na and K concentrations as well as the hematocrit. All rats that had eaten and drunk before and after binephrectomy, in various combinations, died within 48 hours. Rats that did not eat or drink before and after binephrectomy died within 72 hours (p < 0.001). Rats that did not eat before and after the binephrectomy but had free access to drink died within 90 hours of the surgery (p < 0.001). From this study it can be concluded that the eating and drinking protocol before and after binephrectomy affects the survival time of male, female and young rats. The effect varies between a survival time of 48 and 90 hours following binephrectomy. A possible explanation for this effect is that the eating and drinking protocol affects the rate of azotemia formation.

Glycerol-induced augmentation of sensitivity to endotoxin in rats.

Combined sepsis and rhabdomyolysis result in a mortality rate much higher than that caused by each process alone. An analogous rat model is obtained by simultaneous i.p. administration of a nonlethal dose of lipopolysaccharide (LPS 0.025 mg/100 g) and a nonlethal i.m. injection of glycerol (1 ml/100 g). The aim of this study was to determine the factors contributing to the high mortality rate in this rat model. The factors examined include: Dehydration, plasma volume expansion, 'immunization' to glycerol, induction of LPS tolerance and the effect of free radicals formed in this model. Neither dehydration nor volume expansion affected mortality. 'Immunization' with glycerol was also not effective. In contradistinction, tolerance to LPS achieved by a daily injection with gradual increasing doses of LPS (from 0.05 mg/100 g to 1 mg/100 g) for 6 days reduced the mortality rate by 60% (P < 0.001). Moreover, decreasing free radical activity using the natural antioxidant (NAO) (5 mg/100 g) reduced mortality rates by 50%. A different antioxidant, dimethylthiourea (DMTU) (50 mg/100 g) failed to reduce mortality rates. This study suggests that the synergism between glycerol and LPS is apparently due to an increase in the rats' sensitivity to endotoxin following glycerol injection. However, endotoxin apparently does not enhance sensitivity to glycerol in the rat. The new antioxidant NAO significantly reduced the high mortality rate.