Time dependence of Na-nitroprusside administration in the prevention of neutrophil infiltration in the rat ischemic kidney.

The aim of this study was to determine the ideal time of administration of Na-nitroprusside to prevent neutrophil infiltration in ischemically damaged kidneys. Sprague-Dawley rats were subjected to 75 min of renal warm ischemia and contralateral nephrectomy. The animals were divided into 7 groups: the ischemic control (IC), which received normal saline, the sham group without warm ischemia and the experimental groups, which received intravenous Na-nitroprusside (NP) (5 mg/kg) at 75, 30, 15, and 5 min prior to reperfusion. Another experimental group was given verapamil (V) (5 mg/kg) as a NO-independent vasodilator 5 min prior to reperfusion. The final evaluation included survival at seven days, serum creatinine (SCr) and blood urea nitrogen (BUN) daily for 3 days, and neutrophil infiltration determined by the presence of myeloperoxidase (MPO) in renal tissue at 2 hr after reperfusion. Histological damage was assessed at 24 hr. There were significant improvements in all parameters when the Na-NP was administered at 75, 30, and 15 min prior to reperfusion when compared with the control group (p < 0.05). There were no differences either in survival or renal function when the 5 min group was compared with the IC or V groups. It is concluded then, that Na-NP can be administered as late as 15 min before reperfusion and still have a protective effect. It appears that the mechanism of protection of Na-NP is due to blocking of one of the steps of the interaction between leukocytes and endothelium--migration. Furthermore, the verapamil (a NO-independent vasodilator) and Na-NP5 (a NO-dependent vasodilator) groups did not show a beneficial effect in these severely ischemically damaged kidneys, which might be one more reason to believe that Na-NP could be interacting at the level of leukocyte-endothelial cell interaction.

Role of P-selectin in total hepatic ischemia and reperfusion.

BACKGROUND: Ischemia and reperfusion of the liver are associated with changes in the interaction of leukocyte-endothelium cells. The role of an adhesion molecule, P-selectin, is studied in ischemia and reperfusion injury of the liver. STUDY DESIGN: Total hepatic ischemia was produced in the rat for 90 minutes, using a portosystemic shunt. To determine the role of P-selectin in ischemia and reperfusion, a murine IgG1 monoclonal antibody to P-selectin (1 mg/kg) was used at different times (30 minutes before and at reperfusion and five minutes and 24 hours after reperfusion). Rats survived for seven days, and tests showing hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies were analyzed at four hours postreperfusion. RESULTS: Survival improved from 15 percent for the rats in the ischemia control group to 55 percent for those in the group receiving anti-P-selectin antibody given 30 minutes before reperfusion (p < 0.05). We observed an improved statistically significant difference in tests demonstrating hepatic injury, myeloperoxidase in hepatic tissue, and histologic studies in the treated and ischemia control groups. The other groups did not show consistent significant differences. CONCLUSIONS: P-selectin has a significant role in ischemia and reperfusion injury of the liver. Early modulation of the interaction between P-selectin and its ligand decreased neutrophil adhesion and migration and consequently diminished damage to the liver.

Role of sialyl Lewis(x) in total hepatic ischemia and reperfusion.

BACKGROUND: Neutrophil adhesion and migration is associated with hepatic ischemia and reperfusion. The role of a Sialyl Lewis(x) (SLe)(x) oligosaccharide, a ligand for selections, was studied in hepatic ischemia and reperfusion injury. STUDY DESIGN: Total hepatic ischemia was produced in rats for 90 minutes using an extracorporeal portosystemic shunt. To assess the role of SLe(x) in hepatic ischemia and reperfusion injury, 25 mg/kg of an SLe(x) analog, CY-1503, was given five minutes before reperfusion or at reperfusion. Biochemical tests of hepatic injury, myeloperoxidase activity in hepatic tissue, and histologic studies, including neutrophil infiltration determined by the naphthol esterase technique, were analyzed six hours after reperfusion. RESULTS: Significantly improved protection in biochemical hepatic injury tests (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) was noted between the ischemic and the SLe(x) treated groups. Myeloperoxidase activity and polymorphonuclear cell infiltration in hepatic tissue were decreased in the SLe(x) groups. Histologic protection from hepatic damage was observed in the treated groups. CONCLUSIONS: The SLe(x) oligosaccharide analog, CY-1503, had an important protective role in hepatic ischemia and reperfusion injury. Modulation of SLe(x) in the neutrophil decreased the adhesion of polymorphonuclear cells and their subsequent migration after hepatic ischemia and reperfusion.

[Nitric oxide, its importance in gastroenterology and surgery]. / Oxido nítrico, su importancia en gastroenterología y cirugía.

Nitric oxide is an important element that has been found in multiple biological systems, including the gastrointestinal tract. The nitric oxide function is reviewed, and its possible clinical use is commented.

Mechanism of protection of verapamil by preventing neutrophil infiltration in the ischemic rat kidney.

In this study, we tested if the mechanism of protection of a calcium channel blocker, Verapamil (VER), was due to modulation of neutrophil infiltration after ischemia/reperfusion injury, in a rat renal ischemic model. Forty-four Sprague-Dawley rats were subjected to 75 min of warm ischemia and immediate contralateral nephrectomy. The animals were divided into two groups: the ischemic control (IC) group, which received normal saline, and the experimental group that received VER 1.25 mg/kg. The drug was administrated intravenously after ligation of the renal pedicle, before reperfusion. Survival was followed for 7 days. Laboratory tests included renal function tests, with serum creatinine (SCr) and blood urea nitrogen (BUN), light histology and neutrophil infiltration, measured by the myeloperoxidase test in renal tissue. Better survival rate was observed in the VER group (85% at 7 days vs control 50%) (P = 0.08). SCr and BUN at 48 and 72 hr showed a statistical significant difference between the two groups (VER lower than IC P < 0.05). Histological damage was significantly less in the VER group (P < 0.05). Neutrophil infiltration was significantly decreased in the VER group when compared to the IC group (P < 0.05). We concluded then, that VER had a downregulating effect on neutrophil infiltration and this might be an important mechanism of protection during the development of renal ischemic damage.