Female sex hormones protect red blood cells from damage after trauma-hemorrhagic shock

BACKGROUND: Trauma/hemorrhagic shock (T/HS) is known to cause changes in red blood cell (RBC) deformability and resting shape. Our previous studies have shown that proestrus female rats are more protected from shock-induced RBC damage than diestrus females or males. However, it is unclear whether female or male sex hormones can influence the severity of these alterations. METHODS: Red blood cell deformability and shape were examined in proestrus female rats, and oophorectomized female rats, as well as in castrated and non-castrated male rats (5-10 animals per group) subjected to T/HS. Red blood cell deformability was measured by laser ektacytometry whereas erythrocyte shape was evaluated by scanning electron microscopy. RESULTS: Proestrus female rats subjected to T/HS did not show either significant RBC deformability changes (decrease in elongation index) or shape alterations (increase in the percentage of reversibly and irreversibly changed cells). Oophorectomized rats demonstrated more severe RBC changes than did non-oophorectomized rats. The degree of RBC damage was the same in castrated and non-castrated males, which was significantly worse than in proestrus females. CONCLUSIONS: Removal of female sex hormones increases the severity of T/HS-induced RBC changes, indicating that female sex hormones protect against RBC damage. In contrast, male sex hormones do not appear to modulate T/HS RBC dysfunction.     

The gut as source of sepsis after hemorrhagic shock

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.     

Early treatment with diltiazem reduces delayed cerebral vascular narrowing after subarachnoid hemorrhage

Using a primate model of subarachnoid hemorrhage, we have demonstrated the ability of diltiazem to reduce delayed, experimental narrowing of cerebral vessels under clinically realistic conditions. Twelve monkeys were treated identically, except that six received oral diltiazem (20 mg/kg t.i.d.) starting 24 hours after a subarachnoid hemorrhage (SAH) and continuing for 5 days. Neurological examination showed that all untreated monkeys were hyperreflexic and hypotonic on the side contralateral to the SAH. Only two of the six of the diltiazem-treated monkeys had a similar deficit. Control angiograms taken before the SAH were compared with those taken 5 days later. The average vessel diameter at six standard sites in monkeys without diltiazem was 61% of control, whereas the average diameter at the same positions in the diltiazem-treated monkeys was 92% of control (P less than 0.01). In each group, the diameter of the most narrowed artery of each monkey was compared with values at the same site before SAH. The average diameter in the untreated group was 22% of control, significantly smaller than the corresponding value from the diltiazem-treated group, which was 68% (P less than 0.005). Delaying diltiazem treatment until 24 hours after hemorrhage still provides some protection, but less than that given by pretreatment with the drug. This suggests that the processes that eventually result in chronic cerebral vascular narrowing are initiated during the 24-hour period immediately after SAH. We propose that there is initially an acute, severe, calcium-dependent contraction of vascular smooth muscle and associated injury to the vessel wall, including its innervation.(ABSTRACT TRUNCATED AT 250 WORDS)     

小肠移植后肠管早期吸收功能的研究

目的探讨小肠移植后早期移植肠管吸收功能状况。方法采用改良的Ｍｏｎｃｈｉｋ法施行大鼠节段性原位小肠移植。分为对照组（ＷｉｓｔｅｒＷｉｓｔｅｒ）和排斥反应组（ＢＮＷｉｓｔｅｒ）。移植后定期测量体重、血糖吸收值及病理组织学检查。结果麦芽糖吸收试验显示各组在移植３０分钟后血糖吸收值明显下降（Ｐ＜０．０５）,然后逐渐恢复;急性排斥反应发生时,与对照组相比血糖吸收值明显下降（Ｐ＜０．０５）。病理学检查再灌注后肠管粘膜呈再灌注损伤性改变;急性排斥反应组于移植后４日前与对照组相同,之后逐渐出现粘膜层炎性细胞浸润、肠管淋巴结肿大、结构破坏。结论小肠移植后早期,移植肠管存在着吸收功能,由于再灌注损伤,吸收功能低下。移植后１周左右肠管吸收功能基本上得到恢复。     

Apoptosis in organs of rats in early stage after polytrauma combined with shock.

OBJECTIVE: Apoptosis in organs of rats in early stage after polytrauma combined with shock was researched. METHODS: Sixty Sprague-Dawley rats were divided into six groups: normal control (A, n = 6), sham-operation (N, n = 6), single hemorrhagic shock (S, n = 6), two-site trauma/shock (B, n = 6), four-site trauma/shock (C, n = 6), and six-site trauma/shock (D, n = 30). Shock was kept 60 min by blood withdrawal. Polytrauma was performed by clamping different sites of limbs to make fractures according to different groups: B at both femurs; C at femurs and tibias; and D at femurs, tibias, and humeri. The animals of A were totally normal without any operation. The rats of N, S, B, and C were killed at 6 hours after resuscitation, and the rats of D were killed at 1, 3, 6, 12, and 24 hours, respectively. Then, DNA agarose gel electrophoresis, in situ end-labeling (ISEL), and light and electron microscopy were performed and the percentage of DNA fragmentation was detected to assess apoptosis. RESULTS: In B, C, and D, the special ladder patterns for apoptosis were seen in thymus, spleen, liver, lung, and intestine, but not in heart, kidney, and brain. However, positive responses were observed in all these eight organs by ISEL. At 6 hours after resuscitation, the percentages of DNA fragmentation in thymus, spleen, liver, lung, and intestine all increased together with the severity of trauma. In D, the percentages of DNA fragmentation in these five organs all increased significantly at 1 hour after resuscitation. At 3 hours, the percentages in spleen, liver, lung, and intestine reached peak, and declined gradually afterward, whereas those in thymus continued increasing after 3 hours and kept stable from 6 hours to 24 hours. It was shown by morphologic examination that the majority of apoptotic cells lay in cortex of thymus, in growth center of white pulp of spleen, in border area of hepatic lobule and portal area of liver, and at the base of crypts of intestine. In lung, multiple kinds of cells, including alveolar epithelial cells, vascular endothelial cells, and polymorphonuclear neutrophils, induced apoptosis. CONCLUSION: Apoptosis was induced in thymus, spleen, liver, lung, and intestine in early stage after polytrauma combined with shock, which may play partial roles in the development of multiple organ failure.     

Quality of life in patients with chronic anal fissure after topical treatment with diltiazem

AIM: To assess the physical and mental health of fissure patients before and after topical treatment with diltiazem.METHODS: Consecutive patients were enrolled prospectively into the study. Quality of life was measured with the short-forum 36 health survey (SF-36) before and after 6-wk treatment with diltiazem. Patients scored symptoms of pain, bleeding, and irritation using numeral rating scales at the initial and follow-up visits. Fissure healing was assessed and side effects were noted.RESULTS: Fissures healed in 21 of 30 (70%) patients. There were significant reductions in the scores of pain, bleeding, and irritation after 1 wk of treatment, respectively. Four patients experienced perianal itching and one patient reported headache. When measured at baseline, pain and irritation showed a negative impact on two of the eight subscales on the SF-36, respectively (bodily pain and social functioning for pain; vitality and mental health for irritation). Repeating the SF-36 showed an improvement in bodily pain (P = 0.001). Patients whose fissures healed reported an improvement in bodily pain, health-perception, vitality, and mental health (P < 0.05).CONCLUSION: Successful treatment of chronic anal fissure with topical diltiazem leads to improvement in health-related quality of life.     

创伤及休克肠道细菌移位的研究

研究创伤失血性休克肠道细菌移位的发生率。设计兔创伤失血性休克试验模型，实验组３０只兔，腹部皮肤撕脱１００ｍｍ×９０ｍｍ，并行股动脉放血致休克，对照组１０只兔，腹部撕脱同实验组，不放血致休克。对照组术后１小时、３小时、５小时取标本均未发现肠道细菌移位，实验组术后１小时采标本已有肠道细菌移位，３小时、５小时组细菌移位达３０％。认为创伤失血性休克早期即有肠道细菌移位，并讨论了其临床意义     

Nutritional condition and absorptive capacity of 14 infants with short bowel syndrome

We examined the absorptive capacity and the nutritional condition of 14 infants with short bowel syndrome, whose residual small intestine was 90 cm or less. Their age ranged from 1 year to 18 years. Examined items were body weight, height, serum albumin, total cholesterol, triglyceride, fat soluble vitamins, trace elements and rapid turn over protein as markers of the nutritional condition. Fecal fat, fecal bile acid, d-xylose absorption test, sugar-, amino acid-evoked potential difference in the small intestine and disaccharidase activity of the mucosa were examined as markers of the absorptive capacity. Our results showed that the body weight was below the normal range in the patients with small intestine of less than 50 cm. Most nutritional markers were within normal range, however, cholesterol and vitamin D were low in the patients with fat malabsorption, especially in patients with less than 50 cm of small intestine. Fecal bile acid was higher than the normal range in all the patients. Potential difference was in normal range or slightly lower than normal in all the patients. We concluded that infants with less than 50 cm of small intestine had malabsorption of sugar, protein and fat. Therefore, prolonged nutrient support, especially fat, is necessary.     

Mechanism responsible for the salutary effects of flutamide on cardiac performance after trauma-hemorrhagic shock: Upregulation of cardiomyocyte estrogen receptors

BACKGROUND: Although flutamide (FTM), an androgen-receptor antagonist, normalizes the depressed immune and cardiac function in males after trauma hemorrhage (T-H), the mechanism responsible for its salutary effects remains unknown. We hypothesized that the salutary effects of FTM are mediated via upregulation of estrogen receptors (ERs). METHODS: Male Sprague-Dawley rats underwent T-H (laparotomy and 90 minutes of hemorrhage (35-40 mm Hg) and then resuscitated with 4x the volume of shed blood in the form of Ringer's lactate). FTM (25 mg/kg) or vehicle (propanediol) was injected subcutaneously 30 minutes before the end of resuscitation. At 2 hours after T-H or sham operation, cardiac output, stroke volume, heart rate, mean arterial pressure, +/- dp/dt, and total peripheral resistance were measured (n = 6 rats per group). Immediately after the measurement of cardiac function, cardiomyocytes were isolated, RNA was extracted, and expression of ER-alpha, ER-beta, and androgen-receptor (AR) mRNA in cardiomyocytes was determined by quantitative real-time polymerase chain reaction. ER-alpha, ER-beta, and AR protein levels in cardiomyocytes were also measured by Western blot analysis. RESULTS: The depressed cardiac output, stroke volume, and +/- dp/dt after T-H were significantly improved in the FTM-treated T-H group. Moreover, the decrease in expression of ER-alpha and ER-beta mRNA and protein in cardiomyocytes in the T-H group was prevented with FTM treatment after T-H. However, expression of cardiomyocytes AR mRNA and protein were not significantly different between the T-H or sham group with or without FTM treatment. CONCLUSIONS: These findings collectively suggest that, in addition to blockade of androgen receptors, flutamide-mediated ER upregulation is likely to play a role in mediating the salutary effect of flutamide on cardiac function after trauma hemorrhage.     

Stair-climbing test to evaluate maximum aerobic capacity early after lung resection.

BACKGROUND: The aim of this study was to investigate the extent of reduction in maximum oxygen consumption in the early postoperative period after lung resection for lung carcinoma. METHODS: A total of 115 patients who underwent lung resection (95 lobectomies, 20 pneumonectomies) performed a maximal stair-climbing test the day before operation and the day of discharge from the hospital (8 +/- 3.3 days after the operation). RESULTS: The postoperative test showed a 15% reduction in maximum oxygen consumption (VO2max) with respect to the preoperative test (Student's t test, p < 0.0001). This reduction was greater after pneumonectomy (21.4%) than after lobectomy (14%) (Student's t test, p < 0.05). A multiple regression analysis showed that the only significant independent predictors of both preoperative and postoperative VO2max were the age of the patient and the level of arterial oxygen content. CONCLUSIONS: The early postoperative reduction in VO2max was greater after pneumonectomy than after lobectomy and the exercise performance was significantly influenced by the level of arterial oxygen content both before and early after the operation.     

Acute lung injury after hemorrhagic shock is dependent on gut injury and sex

Recent studies have established gut-derived lymph rather than portal blood as the major source of toxic mediators after hemorrhagic shock that causes distant organ injury. Similarly, emerging data have identified sex as a major modifier of the response to injury and illness. Thus we tested the hypothesis that female rats would be more resistant to shock-induced lung injury than male rats because females are more resistant to shock-induced gut injury and produce mesenteric lymph that is less toxic to endothelial cells. Male and female rats were subjected to sham or hemorrhagic shock and lung permeability was quantitated by Evans blue dye and protein extravasation into the alveolar space. Next, mesenteric lymph collected from shocked and sham-shocked rats of both sexes was incubated with human umbilical vein endothelial cells (HUVECs) and assayed for toxicity. Trypan blue dye exclusion and the release of lactate dehydrogenase assessed HUVEC viability and injury respectively. Lastly, sections of the terminal ileum were histologically examined for evidence of shock-induced mucosal injury. Male rats but not female rats subjected to hemorrhagic shock had evidence of increased lung permeability and produced mesenteric lymph that was cytotoxic to HUVECs. Shock caused gut injury in the male rats whereas histological evidence of gut injury was not observed in the female rats. Hemorrhagic shock-induced lung injury depends on gut injury and mesenteric lymph appears to be the route by which gut-derived toxic factors exit the gut to cause lung injury. The resistance of female rats to shock-induced lung injury appears to be secondary to their resistance to shock-induced gut injury.     

Altered coagulation after albumin supplements for treatment of oligemic shock.

Coagulation and need for postoperative blood and plasma therapy were studied in 94 injured patients requiring massive transfusions (average = 14.4); 46 patients, by random selection, received supplemental albumin. Albumin therapy increased total protein concentration (6.4 vs 5.8 g/dL), serum albumin level (4.2 vs 2.9 g/dL), and plasma volume (3,895 vs 3,579 mL) but not RBC volume (1,520 vs 1,530 mL). During the initial five postoperative days, patients receiving albumin required more transfusions (7.1 vs 3.8) and plasma (455 vs 317 mL). This increased need for blood and plasma correlated with a significant decrease in fibrinogen (238 vs 405 mg/dL) and prolongation of the prothrombin time (2.6 vs 1.4 seconds). The partial thromboplastin time was prolonged and the platelet concentration was decreased in albumin-treated patients, but not significantly. Deficiencies in specific coagulation factors have not yet been identified but are being studied. Impaired coagulation is another potential hazard of supplemental albumin therapy, which is probably contraindicated in injured patients.