The effect of hyperosmolar infusions on survival after hemorrhage

Hyperglycemia has previously been reported beneficial for survival after hemorrhage. In the present investigation, rats depleted of liver glycogen after 24 h food deprivation were infused either A: isotonic NaCl (300 mosm/kg H2O), B: glucose (1,800 mosm/kg), C: Xylose (2,000 mosm/kg) or D: NaCl (1,800 mosm/kg), during 60 min hemorrhage, and observed for recovery or death for seven days. During hemorrhage, all animals given hyperosmolar infusions had higher serum osmolality and greater plasma refill compared to group A. Increments in serum osmolality correlated inversely to hematocrit developments, p less than 0.05. Only 2/18 animals given isotonic NaCl survived, while survival in the other groups were 14/18 (glucose infused), 20/22 (xylose infused) and 20/20 (hypertonic NaCl). Best survival was noted in the groups with the highest final osmolality, and largest reduction in hematocrits; groups C and D, while significantly more animals given glucose died compared to group D. It is concluded that induction of hyperosmolality during the early phase of hemorrhage is associated with increased survival in hemorrhage, irrespective of hyperosmolar agent infused. The benefits of hyperglycemic hyperosmolality is primarily related to the osmolar properties of this solute, and not the immediate need for glucose as substrate.     

Pharmacologic interventions in acute mesenteric ischemia: improved survival with intravenous glucagon, methylprednisolone, and prostacyclin

An experimental model of acute mesenteric ischemia following 85 minutes of superior mesenteric artery (SMA) occlusion in male Wistar rats was used in this investigation. Untreated control animals had a 48-hour survival rate of 38% (n = 26), whereas sham laparotomy resulted in a 100% 48-hour survival rate (n = 10). Study groups received intravenous infusions of normal saline solution (16.6 ml/kg/hr; n = 26) or similar volumes of normal saline solution with the addition of glucagon (1.6 micrograms/kg/min; n = 26), dopamine (3.2 micrograms/kg/min; n = 26), or prostacyclin (PGI2) (10.7 ng/kg/min; n = 26). Infusions were begun 15 minutes after initiating 85 minutes of SMA occlusion and were continued for a total of 90 minutes. Glucagon increased the 48-hour survival rate to 85%, significantly greater than both control survival (p less than 0.001) and normal saline solution group survival rates (p less than 0.025). Neither normal saline solution alone nor dopamine significantly increased the 48-hour survival rate, which was 54% in both groups. The PGI2 group survival rate, 65% at 48 hours, was significantly greater than the control rate (p less than 0.05), was not statistically different from the normal saline solution group survival rate, and was 20% less than the glucagon group survival rate, the latter difference approaching statistical significance (p = 0.10). Methylprednisolone (40 mg/kg; n = 26) administered as an intravenous bolus 15 minutes after initiating SMA occlusion significantly increased the 48-hour survival rate to 73% (p less than 0.01), whereas neither intravenous heparin (150 U/kg; n = 26) nor superoxide dismutase (11,900 U/kg; n = 26) were beneficial. Glucagon, methylprednisolone, and PGI2 improved the survival rate in this model of acute mesenteric ischemia.     

Effect of prostaglandin and leukotriene antagonists in acute mesenteric artery occlusion

Superior mesenteric artery occlusion leads to mesenteric ischemia, activation of arachidonic acid metabolism and release of endotoxins into the systemic circulation. The effect of leukotriene and prostaglandin antagonists on hemodynamic response and survival of rats after superior mesenteric artery (SMA) occlusion was investigated. The animals were divided into five groups: in group 1 (n = 105) the SMA was clamped for 2 h and mortality assessed after 24 h. Group 2 animals (n = 20) were pretreated with 5 mg/kg indomethacin and the SMA clamped similarly to group 1, group 3 animals (n = 15) were pretreated with 5 mg/kg Voltaren, group 4 animals (n = 20) received 20 mg/kg BW 755C before mesenteric artery occlusion, and group 5 animals (n = 50) were pretreated with 100 mg diethylcarbamazine. The blood pressure and pulse response as well as histologic appearance of the bowel 1 h after declamping was similar in all five groups. The mortality rate after 24 h was 34% in the control group, 36% with indomethacin treatment, 36% with voltaren, 47% with BW 755C and 40% with diethylcarbamazine. The mortality rate in all the treated groups was not significantly different from the control group. Plasma thromboxane B2 levels were inhibited significantly by indomethacin and Voltaren and to a lesser extent by BW 755C. There was a paradoxical rise in thromboxane B2 following diethylcarbamazine treatment. It is concluded that inhibition of the cyclooxygenase and/or the lipoxygenase pathways of arachidonic acid did not alter the hemodynamic response and mortality following 2 h of acute superior mesenteric artery occlusion.     

The effect of glucose infusion on survival after acute mesenteric ischemia/reperfusion

Perfusion of ischemic tissue with glucose has been shown to be deleterious to heart, spinal cord, and kidney. Observations that glucagon improves survival after acute mesenteric ischemia, however, suggest that hyperglycemia may not be deleterious during bowel ischemia. This experiment examined the effect of glucose infusion on survival in an established rat model of acute mesenteric ischemia. The superior (cranial) mesenteric artery (SMA) was occluded for 85 min in 36 anesthetized Sprague-Dawley rats. Animals were randomized to receive 5% glucose in normal saline (n = 15; 16.5 mL/kg.min iv), normal saline alone (n = 13; 16.4 mL/kg.min iv), or no intravenous fluid (n = 8). Ninety-minute intravenous infusions were initiated 10 min after SMA occlusion. Survival to 48 h was 47% in glucose-saline-treated rats, 31% in saline-only-treated rats, and 12.5% in control rats. These results demonstrate no deleterious effect of glucose infusion on mortality after acute mesenteric ischemia in this model.     

The effect of polycythemia and hyperviscosity on bowel ischemia

Recent clinical reports suggest that newborn infants with polycythemia and other causes of hyperviscosity may be at risk for developing necrotizing enterocolitis (NEC). This study evaluates the relationship of polycythemia and increased blood viscosity on survival and bowel integrity and an ischemic bowel model in rats. Ninety-nine weanling Sprague Dawley rats underwent one-minute occlusion of the superior mesenteric artery. Animals were divided into five treatment groups. Group 1 (n = 40) ischemic controls had a mean hematocrit (HCT) of 44.3 +/- 3.3%. Group 2 (n = 19) rats were transfused with whole blood from donor rats followed by a dose of lasix (2mg/kg) intravenously (IV) 20 hours prior to ischemic injury, raising the HCT to 53.6 +/- 3.2%. Group 3 (n = 19) animals were transfused with whole blood X 2 and given lasix at 20 and 4 hours before operation, raising the HCT to 63.0 +/- 1.6%. Group 4 (n = 16) (HCT 68.6 +/- 2.55%) and group 5 (n = 15) rats (HCT 71.6 +/- 2.07%) were prepared with multiple blood transfusions and given lasix as group 3 animals to achieve those hematocrit levels. Animals were kept in individual cages and fed rat chow and water ad libitum. Survival, length of survival, and evidence of bowel perforation or necrosis were recorded at seven days following the ischemic insult. Blood viscosity was determined in each group. Survival at one week was 65% in group 1, 63% in group 2, and 63% in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of rhabdomyolysis in the diabetic state.

To evaluate the determinants of rhabdomyolysis in the diabetic state, we compared biochemical and clinical features of diabetic patients with (group 1, 41 patients) and without (group 2, 36 patients) rhabdomyolysis. There was no difference in values for serum potassium, bicarbonate, phosphate and calcium between the two groups. Nineteen patients in group 2 and 21 patients in group 1 were hypokalemic. The mean serum sodium level was higher (p less than 0.001) in group 1 patients (148.8 +/- 2.1 mEq/l) than in group 2 patients (135.0 +/- 1.1 mEq/l). Only 1 patient was hypernatremic in group 2, whereas 24 patients had hypernatremia in group 1. Linear regression of the creatine phosphokinase values versus serum sodium levels suggested a high correlation (p less than 0.001). The mean blood glucose level was higher (p less than 0.05) in group 1 patients (640.8 +/- 80.3 mg/dl) when compared to group 2 patients (436.0 +/- 56.7 mg/dl). There was a linear association (p less than 0.05) between the levels of blood glucose and creatine phosphokinase values in the patients with rhabdomyolysis. The mean serum osmolality was 350.3 +/- 8.2 mosm/kg in group 1 patients as compared to 304.9 +/- 3.6 mosm/kg in group 2 patients (p less than 0.001). There was also a significant correlation (p less than 0.001) between the serum osmolality levels and the serum creatine phosphokinase values in group 1 patients. We conclude that serum sodium, serum osmolality and blood glucose are major determinants for the occurrence of rhabdomyolysis in the diabetic state.     

The role of endothelin in radiocontrast nephropathy

In the present study we investigated the role of endothelin and AT II in radiocontrast nephropathy induced in rats with reduced renal mass (70–75%). Thirty-five male Wistar albino rats weighing between 280 and 400 g were anaesthetized with ketamine (130 mg/kg b.w.) and right total, left 50% nephrectomy were performed. After this operation, the rats were kept under observation for six to eight weeks and then they were randomly separated into three groups. Group I rats were infused with 8.9 ml/kg (or 2.9 g of iodine/kg body weight) Na diatrizoate (Urovision, 1500 mosm/kg). Group II rats were infused with 0.9% NaCl in an equal volume with the radiocontrast material. Group III rats were given 4.5% NaCl that had the same volume and osmolality as the radiocontrast material. Two hours after the drug infusions, blood and accumulated urine samples were collected from all the rats and tested for endothelin, AT II, BUN, creatinine, uric acid, electrolytes, calcium and phosphorus. We found that the plasma endothelin levels in Group I (77.64±29.62 pg/ml) were significantly higher than in Group II (20.52±5.83 pg/ml) and Group III (15.04±5.15 pg/ml) (t=8.34 and t=9.14, respectively, p<0.001). Therefore elevation in circulating endothelin might have been an additional factor leading to the radiocontrast-induced nephrotoxicity.     

Comparison of single-dose antithrombotic agents in the prevention of microvascular thrombosis.

A model of thrombosis was used to evaluate the efficacy of single-dose heparin, hemodilution, and 40,000 milliwatts dextran in the prevention of microvascular thrombosis. Forty Lewis rats (275 gm body weight) were divided into four groups (n = 10): hemodilution (6 ml NS), single-dose heparin (1 mu/gm), 40,000 mw dextran (0.3 gm/100 gm), and control (0.275 ml NS). After exposure of the superficial femoral arteries, a model of arterial crush with arteriotomy followed by an intimal abrasion was used. The animals randomly received one of the four solutions above. Experimental results included patency rates of 90% at 20 minutes and 10% at 24 hours in the hemodilution group, 100% at 20 minutes, and 70% at 24 hours in the single-dose heparin group, and 100% at both 20 minutes and 24 hours in the dextran group. A 100% thrombosis rate was observed in the control group at 20 minutes and 24 hours. Single-dose heparin and dextran significantly improved patency in comparison to both the control and hemodilution groups at 24 hours (p less than 0.01). Scanning electron microscopy of the vessels revealed thrombus deposition consistent with these findings. These results indicate that single-dose heparin and single-dose dextran reduce thrombosis in this model of microvascular injury.     

Ethanol inhibition of glucose absorption in isolated, perfused small bowel of rats

There is evidence for both humans and rats that malnutrition frequently occurs when ethanol is chronically ingested. Small bowel 14C-labelled glucose absorption was measured with an ex vivo system in which the small bowel of the rat was surgically removed and then arterially perfused with an artificial medium. Glucose absorption for a control group of seven rats was 248 +/- 8 microM/min/gm dry weight of small bowel (mean +/- SEM). This was significantly greater than the value 112 +/- 12 microM/min/gm dry weight (P less than 0.005) for a group of five rats in which a competitive inhibitor of glucose absorption, phlorizin (0.2 mM), was added to the bowel lumen. In the presence of 3% ethanol within the gut lumen of five rats, glucose absorption was also reduced (to 131 +/- 12 microM/min/gm dry weight) compared to absorption in the control group (P less than 0.005). The calculated amount of glucose absorbed was corrected for metabolism to lactate and carbon dioxide. We conclude that both phlorizin and ethanol inhibit glucose absorption in the isolated and perfused small bowel of rats and that probably at least part of the malnutrition in ethanol-fed rats is due to glucose malabsorption.     

卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。     

Ischemic bowel: the protective effect of free-radical anion scavengers

Recent data indicates that the free-radical anion superoxide (O2-), an unstable cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel following reperfusion after low flow states. This report evaluates the effect of free radical scavengers on survival in an animal model with bowel ischemia. At laparotomy, the superior mesenteric artery (SMA) of 79 weanling rats (90 g) was occluded for one minute and released. Animals were divided into three experimental groups: group I acted as controls (n = 41), group II, received thiopental 5 mg/kg IV (n = 19), group III, received methohexital 2.5 mg/kg IV (n = 19). At one week animals were evaluated for mortality, mean survival time, evidence of bowel necrosis or perforation, and bowel appearance on scanning electron microscopy (EM). Mortality was 63.5% (26/41) in group I, 19 had necrotic bowel and 7 had gross perforation; 31.6% in group II (6/19) (p less than .05 versus control), with one necrotic bowel and 5 perforations; and 57.9% in group III (11/19) where 7 had necrotic bowel and 4 had perforations (p NS v control). Survival time (mean +/- SD in days) post SMA occlusion was 3.2 +/- 1.9 for group I; 4.0 +/- 1.7 for group II; and 2.5 +/- 2.0 for group III. EM showed mucosal destruction worsened by the duration of reperfusion, decreased by thiopental but not by methohexital. Thiopental, a free radical anion scavenger was cytoprotective in this animal model, as it decreased mortality and the incidence of bowel necrosis and perforation. These data support the thesis that following low flow states bowel ischemia may be related to a reperfusion injury due to the release of toxic free radical anions.     

Controlled reperfusion of the regionally ischemic myocardium with leukocyte-depleted blood reduces stunning, the no-reflow phenomenon, and infarct size.

Open-chest sheep underwent 90 minutes' occlusion of the diagonal branch of the left anterior descending coronary artery, followed by vented cardiopulmonary bypass. After 30 minutes of cardioplegic arrest, simulating distal anastomoses, the occlusion on the coronary artery branch was released. Controlled reperfusion (40 to 50 mm Hg, 135 to 150 ml/min) for the first 20 minutes was delivered at the aortic root with either unmodified whole blood (control, n = 7) or blood passed through leukocyte filters (filters, n = 7). Serial measurements were made during 3 additional hours reperfusion off cardiopulmonary bypass. During ischemia, the major determinants of infarct size, which include area at risk, collateral myocardial blood flow, and rate-pressure product were not significantly different between groups. Overall, during reperfusion, mean left ventricular stroke work index in the filter group was greater than in the control group (28.7 +/- 5.8 versus 12.6 +/- 6.4 x 10(3) erg/gm, p less than 0.05), as was mean rate of rise of left ventricular pressure (1900 +/- 260 versus 1348 +/- 279 mm Hg/sec, p less than 0.05). Myocardial blood flow to the area at risk at 3 1/2 hours of reperfusion in the filter group was also significantly better than in the control group (0.57 +/- 0.15 versus 0.27 +/- 0.05 ml/min/gm, p less than 0.05), as was necrotic area as a percentage of area at risk (40% +/- 6% versus 70% +/- 5%, p less than 0.05). These results demonstrate amelioration of myocardial stunning and the no-reflow phenomenon, as well as decreased infarct size. We conclude that controlled reperfusion with leukocyte-depleted blood is superior to whole-blood reperfusion for the surgical treatment of acute regional ischemia.     

Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats

Hepatic steatosis is one of the two principal hepatic complications of total parenteral nutrition (TPN), the other being cholestasis. While the cause is uncertain, an excess of carbohydrate calories in rats leads to an elevated portal insulin/glucagon (I/G) molar ratio, periportal fatty infiltration, and increased total hepatic lipid content. Insulin causes fatty acid biosynthesis, whereas glucagon causes hepatic release and inhibition of fatty acid synthesis. Thus we attempted to add glucagon to lower the I/G to see if this would affect the degree of hepatic fatty infiltration by encouraging hepatic fat mobilization. Adult rats (n = 21) received internal jugular catheters; Group 1 (n = 7) was given saline solution (3 ml/h) and chow ad libitum; Group 2 (n = 7), 25% dextrose-base (D25W) TPN solution; Group 3 (n = 7), D25W TPN + 33 micrograms/100 gm/day glucagon. At 7 days portal and peripheral venous blood samples were drawn for insulin and glucagon radioimmunoassay and blood glucose determination; livers were removed for histologic study and lipid determination. Blood glucose did not differ in any group. Hepatic lipid and peripheral and portal venous I/G were increased and periportal fatty infiltration was extensive in Group 2, whereas hepatic lipid and I/G were decreased and periportal fatty infiltration was absent in glucagon-infused rats (Group 3). An abnormally high I/G ratio in portal blood elicited by high-glucose TPN may be responsible, at least in part, for hepatic steatosis. By increasing hepatic lipid export, addition of glucagon to TPN may play a major role in decreasing hepatic steatosis.     

Therapeutic action of fructose-1,6-diphosphate in traumatic shock

Traumatic shock was induced in 130 rats by tumbling them in a Noble-Collip drum for a total of 600 revolutions at 40 rotations/min. The experimental protocol was designed to evaluate the therapeutic effectiveness of fructose 1,6-diphosphate (FDP) in reducing the mortality rate when given both prior to and following the trauma, or only following the trauma. In the first group (n=50) in which the treatment was given prior to and after trauma, the animals were randomly assigned to 3 subgroups as follows: 20 rats received 350 mg/kg of FDP prior to and an additional 350 mg/kg after trauma; 20 other rats received in the same manner equal amounts of glucose; and 10 rats received no treatment. In the group treated only after inflicting the injury (n=80), 35 rats received 350 mg/kg of FDP after trauma; another 35 received glucose; and 10 received no treatment. The rats from the different subgroups were tumbled at the same time. Survival rates in the pretreated subgroups were 85% for those receiving FDP, 30% for glucose-treated animals (p< 0.005), and 20% for the nontreated ones. In the animals that were treated after trauma, there was also a significant increase in survival rate for the FDP-treated ones (66%), while for those receiving glucose it was 31% (p<0.01), and 20% for the nontreated ones. The results of the present study and those obtained in other etiological types of shock indicate that FDP has profound antishock therapeutic activity. This action appears to be metabolically mediated by augmenting the endogenous energy production via glycolysis.     

Ischemic preconditioning protects intestine from prolonged ischemia

Ischemic preconditioning (IP), obtained by exposure to brief periods of vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of this study was to evaluate the effects of IP on intestinal morphology. Forty rats were subjected to sham surgery (n = 20, group I) or intestinal preconditioning (n = 20, group II) with a cycle of brief ischemia/reperfusion (10-minute occlusion of superior mesenteric artery [SMA], followed by 10-minute reperfusion) before prolonged ischemia produced by SMA occlusion (45 minutes). Five animals in each group were sacrificed 2, 12, 24, and 48 hours after reperfusion. Intestinal samples were processed for light and electron microscopy. A TUNEL assay was performed to detect apoptosis. Statistical analysis used Student t test and Kaplan-Meier survival curves. The overall mortality for the sham-operated group was 15%, while no animals of group II died (NS). Histological evaluation showed early detachment of epithelial cells from villous stroma accompanied by marked congestion and edema. Successive morphological changes were represented by leukocyte infiltration, focal necrosis, and marked villus denudation or loss. Group II animals showed significantly reduced inflammatory infiltrates in the lamina propria and a greater villus height compared to group I. The maximum number of apoptotic nuclei was observed in both groups, Following 2 hours of reperfusion group II animals showed significantly, greater apoptosis at 2 and 12 hours after reperfusion (P <.05). Electron microscopy showed severe mitochondrial and basement membrane damage. The findings from this study confirm that IP preconditioning attenuates morphological alterations that are invariably present after prolonged ischemia and reperfusion.     

Superoxide: a critical oxygen-free radical in ischemic bowel injury

The radical anions of molecular oxygen reduction, superoxide (O2), hydrogen peroxide (H2O2), and hydroxyl radical (OH), have been implicated in a number of disease processes, including ischemic bowel injury. This report evaluates the effect of superoxide dismutase (SOD), catalase (CAT), dimethyl sulfoxide (DMSO), selenium treatment, and selenium deficiency on bowel integrity and survival in experimental intestinal ischemia in rats. Ischemic bowel injury was produced in 204 male Sprague-Dawley rats (wt 90 to 100 g) by a one-minute occlusion of the superior mesenteric artery (SMA) with a microaneurysm clip. Experiment I treatment animals (n = 20) received 2.5 mg/kg SOD dissolved in Ringer's lactate, and control animals (n = 71) received Ringer's lactate alone. Experiment II treatment animals (n = 16) received 1 cc of 100% DMSO gavage, and control animals (n = 11) received no treatment. Experiment III treatment animals (n = 17) received 25 mg/kg CAT dissolved in phosphate buffered saline, and control animals (n = 11) received nothing. Experiment IV treatment animals (n = 14) received 300 micrograms of sodium selenate by gavage dissolved in deionized water, and control animals (n = 15) receiving nothing. Experiment V treatment animals (n = 20) were raised from 35 to 50 g size on a selenium deficient diet, and control animals were raised (n = 20) on a normal rat chow diet, until they weighed 100 g when ischemia was induced. At seven days, survival, incidence of bowel perforation or necrosis, and length of survival were compared in each experiment between control and treatment groups using chi 2 analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of hypertonic (3%) saline with and without furosemide on plasma osmolality, sodium concentration, and brain water content after closed head trauma in rats

Adding furosemide (F) to mannitol causes a greater decrease of brain volume, intracranial pressure, and brain water content (BW) as compared with mannitol alone. We examined whether adding F to hypertonic saline (HS) causes less increase of BW early after closed head trauma (CHT) as compared with HS alone. With institutional approval, 125 rats underwent sham surgery or CHT and then immediately received no treatment, HS (1.2 g/kg, 3% solution), or HS + F (2 mg/kg). In groups 1-10 (n = 8/group), the percent BW content was determined at 30, 60, or 120 minutes. In groups 11-14 (n = 8/group), physiologic values were determined at 0, 30, 60, and 120 minutes. At 120 minutes, the increase of BW caused by CHT (sham = 78.9 +/- 0.6% and CHT = 81.5 +/- 2.2%, mean +/- SD) was prevented by HS + F (78.0 +/- 0.8%) but not by HS (80.7 +/- 2.2%). Both HS and HS + F similarly increased plasma osmolality and sodium concentration. Post-CHT hypotension and acidosis (30 and 60 minutes) and decrease of hemoglobin concentration (120 minutes) were less with HS + F than with HS. We conclude that adding F to HS decreases BW without causing more increase of osmolality and Na than that caused by HS alone.     

Attenuation of ischemic renal injury with fructose 1,6-diphosphate

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.     

Prevention of peritoneal adhesions in rats with trimetazidine

The effect of trimetazidine (an antianginal drug that acts as a scavenger of oxygen radicals) in the prevention of peritoneal adhesions induced by complete vascular obstruction of an ileal segment for 30 minutes followed by reperfusion was investigated in rats. Group A (n = 20) acted as controls. Group B (n = 20) received trimetazidine intravenously in a dose of 2.5 mg/kg 30 minutes before the induction of ischaemia. Group C (n = 20) received the same dose of trimetazidine for 5 days before the experiment, twice a day intraperitoneally, and also intravenously 30 minutes before the induction of ischaemia. Group D (n = 20) received the same dose of trimetazidine intravenously immediately after reperfusion had started. Ten days later adhesions had developed in 90% of the animals of group A, 40% of those in group B (p less than 0.001), 5% of those in group C (p less than 0.001), and 60% of those in group D (p less than 0.05). The severity of adhesions was significantly less in the treated groups than in the control animals. Release of creatine phosphokinase during ischaemia and reperfusion significantly increase in groups A, B, and D. These results suggest that trimetazidine reduces the incidence and severity of peritoneal adhesion formation induced by ileal ischaemia and reperfusion, treatment before induction of ischaemia gave better results than treatment given afterwards.     

Beneficial effects of fructose 1,6 diphosphate on hemorrhagic shock in rats

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