Biomedical subjects

M K Angele

Publications and source records attributed to M K Angele.

At least 19 recordsLinked to original sources

PubMed2006

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage.

Several studies indicate that cell-mediated immune responses, i.e., macrophage (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after trauma-hemorrhage in male mice. Testosterone has been shown to be responsible for the depression of MPhi cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic MPhi was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in MPhi from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss.

Androgen Antagonists↗

PubMed2005

Tumour size is an important predictor for the outcome after liver transplantation for hepatocellular carcinoma.

AIMS: Recently, there is a tendency to expand tumour sizes qualifying for OLT. The present study re-evaluates tumour size and histopathological features as selection criteria for OLT. METHODS: Retrospective analysis of 93 adult HCC patients underwent OLT between June 1985 and December 2003. Median follow-up was 28 months (1-222 months). The Milan criteria were routinely applied since 1994. RESULTS: Five year survival rate of HCC patients was significantly lower than in patients transplanted for benign diseases, 41 and 71%, respectively (p<0.0001). Multivariate analysis revealed that the presence of vascular invasion represents the most significant predictor (p<0.001) affecting the survival rate. Survival was also significantly impaired when the tumour size was >5 cm (p<0.05), whereas the number of nodules had no significant effect on survival. Consequently, the survival rate for HCC fulfilling the Milan criteria histologically improved to 70% since 1994. CONCLUSION: Tumour size has been shown to be the most important pre-operatively detectable predictor for patient survival after OLT.

Adolescent↗

PubMed2005

[Laparoscopic incisional hernia repair -- an alternative to the conventional procedure?].

INTRODUCTION: Tension-free incisional hernia repair using alloplastic material increasingly replaces conventional repair techniques. The aim of the present study was to evaluate the early and long-term complications as well as patients' satisfaction. METHODS: Laparoscopic hernia repair with intraperitoneal mesh implantation (PTFE) was performed on 28 patients at the Klinikum Grosshadern between 2000 and 2003 (16 males, 12 females, average age 61.2). Intra- and postoperative complications were registered retrospectively. In addition, 25 patients were evaluated for recurrence, postoperative pain and patient contentment (median follow-up 383 days). RESULTS: A low complication rate was observed in our patient collective. One trocar bleeding occurred. 2 patients presented with wound hematoma. The recurrence rate was 8 % (2/25). 60 % of the patients were free of pain postoperatively. 88 % would once again choose the laparoscopic approach for incisional hernia repair. DISCUSSION: The laparoscopic technique was associated with a low recurrence rate, a small rate of wound infections and high patient comfort. Thus, the laparoscopic approach for mesh implantation appears to be a safe and effective method for the treatment of incisional hernias. The efficiency of laparoscopic intraperitoneal mesh implantation, however, should be evaluated within a prospectively randomized multicenter trial.

Adult↗

PubMed2005

Immunomodulation during sepsis in organ transplanted children.

Newer immunosuppressive agents have dramatically reduced the rates of acute graft rejection over the last decade but may have exacerbated the problem of post-transplant infections. Causes of early mortality include graft dysfunction and sepsis. Late mortality occurs mainly due to sepsis. An excessive inflammatory response followed with a dramatic paralysis of cell-mediated immunity has been documented in septic patients. In transplanted individuals the pathophysiological changes of the immune response are further complicated by immunosuppressive agents. This article will focus on the effect of immunosuppressive agents and sepsis on cell-mediated immune responses. Moreover, potentially promising immunomodulatory approaches, i.e. human activated protein C, immunomodulatory diets containing L-arginine and fish oil, selective cytokine blockade, platelet-activating factor receptor antagonist, LPS receptor CD14 blockade and G-CSF, for the treatment of immunodysfunction in septic patients will be outlined in this review article. Most of them, however, have not been tested in the clinical arena in transplanted patients. Thus, the main part of the article, immunomodulation during sepsis in organ transplanted children is quite speculative and based on immunomodulatory strategies in other non-transplanted septic patients.

Age Factors↗

PubMed2004

Differences in the expression of LPS-receptors are not responsible for the sex-specific immune response after trauma and hemorrhagic shock.

Several studies demonstrated a sex-specific cytokine secretion by macrophages following trauma-hemorrhage (T-H) and incubation with lipopolysaccharide A (LPS). Although LPS is known to act via the receptors CD14 and TLR4 on macrophages, it remains unknown whether differences in LPS receptor expression in males and females may be responsible for the gender-specific LPS induced cytokine response following (T-H). To study this, male and proestrus female mice (C3H/HeN) were subjected to trauma (laparotomy) followed by hemorrhage or sham operation. At 2 h thereafter, SMphi and PMphi were harvested and cultured for 2 h. The expression of CD14 and TLR4 was measured by flow cytometry on unstimulated SMphi and PMphi as well as after LPS stimulation. The results indicate that the expression of CD14 and TLR4 on SMphi and PMphi from female and male mice was similar in sham-operated animals and after (T-H). Incubation of macrophages with LPS did not alter CD14 and TLR4 expression in the study groups. Thus, the sex specific LPS induced cytokine secretion after (T-H) is not caused by differences in LPS receptor expression on Mphi of male and female mice.

Animals↗

PubMed2003

Rifampin and Triclosan but not silver is effective in preventing bacterial infection of vascular dacron graft material.

OBJECTIVES: To evaluate the efficacy of silver- or Triclosan-coated prosthetic material compared to Rifampin bonded Dacron concerning their resistance to infection following subcutaneous implantation and contamination with Staphylococcus aureus. DESIGN: Animal experimental study in mice. MATERIAL AND METHODS: Thirty-six C3H/HcN mice (Charles River Lab., Sulzfeld, Germany) with a weight between 24 and 27 g were randomised into six groups counting six animals each. Group I: control, gel-sealed dacron graft, group II: gel-sealed dacron graft and local contamination, group III: Intergard-Silver-prosthesis and contamination, group IV: silver/gel-sealed dacron prosthesis (test graft) and contamination, group V: Rifampin-bonded gel-sealed graft and contamination, group VI: Triclosan/collagen-coated dacron graft and contamination. Dacron graft material 0.8x1 cm was subcutaneously implanted in mice. Local contamination with 2x10(7)/0.2 ml S. aureus ATCC 25923 was carried out in groups II to VI. On day 14 the animals were killed and the grafts were explanted. The microscopic, histologic and microbiological evaluation of the graft material and the perigraft tissue was performed. RESULTS: In control group I no case of infection was detected. In group II, 6 of 6 animals showed infection. In group III (Intergard-Silver) and group IV (silver/gel-test graft) were 6 of 6, in group V (Rifampin) only 1 of 6 grafts and in group VI (Triclosan) 4 of 6 grafts were infected. The difference between the low rate of infection in group V (Rifampin) in comparison to the completely infected groups III and IV (Silver) as well as the control group II was significant. Treatment of grafts with Triclosan could prevent infection only in 1/3 of the cases in group IV. CONCLUSION: Silver coating failed to prevent graft infection material. A potential antimicrobial property was evident for Triclosan whereas Rifampin-bonded grafts exhibit a significantly reduced infection rate. Thus, silver-coated vascular grafts cannot ensure protection from vascular graft infection.

Animals↗

PubMed2003

[Experimental examination concerning the efficacy of silver-coated Dacron prostheses in vascular graft infections following subcutaneous implantation in a standardized infection model].

UNLABELLED: It was the aim of the study to examine the efficacy of silver coated prostheses in comparison to Rifampin in impregnated prostheses in the prevention of vascular graft infections. MATERIAL AND METHODS: 24 C3H/HcN mice with a bodyweight between 24 and 27 grams were assigned to four different groups. GROUP I: control gel-sealed Dacron graft (Uni-Graft DV) (6), GROUP II: gel-sealed Dacron graft (Uni-Graft DV) contaminated locally with 2 x 10(7) CFU/1.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP III: silver prosthesis (Intergard Silver) contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6), GROUP IV: Rifampin impregnated prosthesis contaminated locally with 2 x 10(7) CFU/0.2 ml Staphylococcus aureus ATCC 25923 (6). 14 days after primary operation all animals were euthanized and the grafts harvested. Specimens were examined for signs of infections by histology and microbiology. RESULTS: At termination of the trial on day 14 none of the grafts of group I were contaminated. 6 out of 6 grafts in group II, 6 out of 6 grafts in group III and 1 out of 6 grafts in group IV presented with infected grafts. The use of antimicrobial Rifampin could significantly prevent infection after bacterial challenge in group IV. CONCLUSION: The silver protected prosthesis (Intergard Silver) seems to be not effective in protecting vascular infection in vivo. However, the Rifampin group showed excellent results. In conclusion Rifampin bonded gelatin-sealed Dacron grafts are significantly more resistant to bacteremic infection than are silver/collagen-coated Dacron grafts.

Animals↗

PubMed2002

Recent advances in minimally invasive colorectal cancer surgery.

Laparoscopy has improved surgical treatment of various diseases due to its limited surgical trauma and has developed as an interesting therapeutic alternative for the resection of colorectal cancer. Despite numerous clinical advantages (faster recovery, less pain, fewer wound and systemic complications, faster return to work) the laparoscopic approach to colorectal cancer therapy has also resulted in unusual complications, i.e. ureteral and bladder injury which are rarely observed with open laparotomy. Moreover, pneumothorax, cardiac arrhythmia, impaired venous return, venous thrombosis as well as peripheral nerve injury have been associated with the increased intraabdominal pressure as well as patient's positioning during surgery. Furthermore, undetected small bowel injury caused by the grasping or cauterizing instruments may occur with laparoscopic surgery. In contrast to procedures performed for nonmalignant conditions, the benefits of laparoscopic resection of colorectal cancer must be weighed against the potential for poorer long-term outcomes of cancer patients that still has not been completely ruled out. In laparoscopic colorectal cancer surgery, several important cancer control issues still are being evaluated, i.e. the extent of lymph node dissection, tumor implantation at port sites, adequacy of intraperitoneal staging as well as the distance between tumor site and resection margins. For the time being it can be assumed that there is no significant difference in lymph node harvest between laparoscopic and open colorectal cancer surgery if oncological principles of resection are followed. As far as the issue of port site recurrence is concerned, it appears to be less prevalent than first thought (range 0-2.5%), and the incidence apparently corresponds with wound recurrence rates observed after open procedures. Short-term (3-5 years) survival rates have been published by a number of investigators, and survival rates after laparoscopic surgery appears to compare well with data collected after conventional surgery for colorectal cancer. However, long-term results of prospective randomized trials are not available. The data published so far indicate that the oncological results of laparoscopic surgery compare well with the results of the conventional open approach. Nonetheless, the limited information available from prospective studies leads us to propose that minimally invasive surgery for colorectal cancer surgery should only be performed within prospective trials.

Colorectal Neoplasms↗

PubMed2002

[Surgical therapy of advanced gallbladder carcinoma].

The use of surgery for the treatment of advanced gall bladder cancer is controversially discussed. This retrospective study included 204 patients who were subjected to surgery due to advanced gall bladder cancer at the Klinikum Grosshadern. Mean survival time of all patients was 4.5 months. Advancement of the tumor stage resulted in a decreased percentage of possible R0 resections (T3 n = 48, R0 31%, T4 n = 87, R0 13%). Nonetheless, R0 resections of T3 tumors significantly increased the survival rate compared to R1 and R2 resections (mean survival 20.2 vs. 4.5 months). R0 resections of T4 tumors also significantly attenuated the survival rate (18.1 vs. 2.4 months compared to R1 and R2 resections). Thus, diagnostic procedures have to focus on identifying patients with possible R0 resections and perform extensive resections on those patients.

Cholecystectomy↗

PubMed2001

Testosterone and estrogen differently effect Th1 and Th2 cytokine release following trauma-haemorrhage.

The object of the study was to determine whether male and female sex steroids produce divergent effects on Th1 and Th2 cytokine release following trauma-haemorrhage. Recent studies indicate that androgens are responsible for the depressed splenocyte Th1 cytokine release in males following trauma-haemorrhage. In contrast, female mice maintain their Th1 cytokine release capacity following trauma-haemorrhage. Nonetheless, the effect of male and female sex steroids on Th1 and Th2 cytokine release following trauma-haemorrhage remains unknown. Male C3H/HeN mice were castrated and treated with pellets containing either vehicle, 5alpha-dihydrotestosterone (DHT), 17beta-estradiol (estradiol), or a combination of both steroid hormones, for 14 days prior to soft-tissue trauma (i.e. laparotomy) and haemorrhagic shock (35+/-5 mmHg for 90 min followed by adequate fluid resuscitation) or sham operation. Untreated male and female mice, as well as DHT treated female mice, served as control groups. Twenty-four hours later the animals were sacrificed, plasma obtained and splenocytes harvested. Plasma DHT and estradiol levels in treated animals were comparable with intact male and female mice, respectively. A significant depression of splenocyte Th1 cytokines, i.e. IL-2, IFN-gamma, was observed in DHT treated castrated animals, DHT treated females, and untreated males following trauma-haemorrhage, as opposed to maintained Th1 cytokine release in estradiol treated and estradiol/DHT treated castrated animals and females. The release of the anti-inflammatory cytokine IL-10 was markedly increased in DHT treated mice and males subjected to trauma-haemorrhage compared to shams, but decreased in estrogen treated mice and females under such conditions. These results suggest that male and female sex steroids differentially affect the release of Th1 and Th2 cytokines following trauma-haemorrhage and should be further studied for their potential to modulate splenocyte function in trauma victims.

Animals↗

PubMed2001

[Dissection techniques in liver surgery].

The first liver resection was performed in 1888. Since then a wide variety of dissection techniques have been introduced. The blunt dissection was replaced by novel methods, i.e. the CUSA technique and the Jet Cutter for major liver resections. These methods represent selective dissection techniques; whereas non-selective methods include the scalpel, scissors, linear stapling cutter, high-frequency coagulation, and the laser technique. The aim of this review article is the comparison of the different resection techniques in liver surgery, focussing on blood loss and resection time.

Blood Loss, Surgical↗

PubMed2001

Acute ischemia of the upper extremity: long-term results following thrombembolectomy with the Fogarty catheter.

OBJECTIVE: In 1962, the procedure of arterial thrombembolectomy with the Fogarty catheter was established. Numerous studies have been published studying thrombembolectomies of the lower extremities. Limited information, however, is available following thrombembolectomy of the upper extremity after arterial occlusion. The aim of the present study, therefore, was to determine long-term results (3-5 years after thrombembolectomy) following thrombembolectomy of the upper extremity with the Fogarty catheter in a large retrospective clinical study. DESIGN: In the present study, 251 patients were encountered. Over a period of 20 years, 283 thrombembolectomies with the Fogarty catheter were performed on the upper extremity at the surgical department of the University of Munich. MAIN OUTCOME MEASUREMENTS: The appearance of local and general complications in the postoperative phase, as well as long-term results, were evaluated. RESULTS: The results indicate that general complications - i.e., cardiac insufficiency, cerebral ischemia, etc. - occurred in 18 patients (7.2%). Local complications - i.e., wound infection, persistence of ischemia, or hematoma - were evident in 51 patients (20.3%). Re-occlusion following thrombembolectomy was found in 21 patients (8.8%). The affected extremity had to be amputated in five cases (2.0%), and 14 patients (5.6%) died during the postoperative phase. As a result of multimorbidity of the patients and average age at the time of surgery (73 years), 40% of the patients had died before the date of examination. Nonetheless, 111 patients of the 117 living patients showed no complaints or minor coldness and pain following heavy exercise. CONCLUSIONS: The results of the present study indicate that, in most cases, thrombembolectomy with the Fogarty catheter represents a successful surgical method for the acute treatment of arterial occlusion of the upper extremity.

Adult↗

PubMed2001

The acute phase response following implantation of triclosan-bonded vascular prostheses.

OBJECTIVE: Infection of prosthetic material is a major complication of vascular surgery. Therapy for it includes implantation of antimicrobial prostheses bonded with different antimicrobial agents. These agents may, however, induce an acute phase reaction following implantation in the host, thus compromising follow-up of the infection. It is not known whether the antimicrobial agent triclosan induces a significant acute phase reaction when bonded to vascular prostheses. METHODS: To study this, 34 adult swine weighing 20-30 kg were allotted randomly to the following groups: (1) controls with untreated prostheses, (2) control group with triclosan-bonded prostheses, (3) therapy group with untreated prostheses, local infection with Staphylococcus aureus surgical revision, and exchange with new, untreated prostheses, and (4) therapy group with untreated prostheses, local infection with S. aureus, surgical revision, and exchange with triclosan-bonded prostheses. Serum C-reactive protein (CRP) and haptoglobin values were determined during the 28-day period after surgery. The study was performed at the Institute for Surgical Research of the Ludwig Maximilian University School of Medicine in Munich. RESULTS: Normal ranges of serum CRP and haptoglobin values were 10.7+/-1.4 microg/ml and 2.5+/-0.3 mg/ml, respectively. Following implantation of untreated and triclosan-bonded vascular prostheses, significantly elevated serum CRP and haptoglobin values were observed. No significant differences between results with triclosan-bonded and untreated prostheses were observed in control or treatment groups. No correlation was found between acute phase reaction and the absence or presence of infection. CONCLUSIONS: Triclosan is the only antimicrobial agent that bonds to vascular prosthetic material without the need of a sealant. Our data indicate that vascular prosthesis implantation, whether untreated and triclosan-bonded, results in a significant acute phase reaction. No differences between antimicrobial and untreated prostheses were observed, independently of the absence or presence of infection. The antimicrobial agent itself did not induce a severe acute phase response and may, therefore, be used in patients at risk of infection.

Acute-Phase Proteins↗

PubMed2001

17 beta-Estradiol normalizes immune responses in ovariectomized females after trauma-hemorrhage.

Recent studies indicate that immune responses in proestrus females are maintained after trauma-hemorrhage but markedly depressed in ovariectomized females under such conditions. The current study tested the hypothesis that the decreased estrogen levels after ovariectomy are responsible for this immune depression. To study this hypothesis, ovariectomized female CBA/J mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 +/- 5 mmHg for 90 min, then resuscitated) or sham operation. The mice received either 17 beta-estradiol (E2; 100 microg/25 g body wt) or vehicle subcutaneously during resuscitation. Immune cells were isolated 24 h thereafter. Splenocyte proliferation and interferon-gamma, interleukin (IL)-2, and IL-3 release were significantly depressed after trauma-hemorrhage in vehicle-treated mice, whereas these functions were maintained in E2-treated mice. Peritoneal macrophage IL-1 beta and IL-6 release and splenic macrophage IL-6 and IL-12 release were also significantly depressed in vehicle-treated mice after trauma-hemorrhage, and release of these cytokines was restored by E2 treatment. In summary our findings indicate that the depressed splenic and peritoneal immune responses after trauma-hemorrhage can be normalized by a single dose of E2. Thus estrogen appears to be the causative factor in the maintenance of immunocompetence in females after trauma-hemorrhage, and its administration to ovariectomized or postmenopausal females should be helpful in preventing immune depression under such conditions.

Animals↗

PubMed2001

[Supportive sepsis therapy: what is still valid today?].

Following several disappointing approaches to decrease the mortality of septic patients using various adjuncts, protein C is the first substance leading to a significant reduction of the mortality rate (PROWESS). The increased risk for bleeding complications in patients receiving protein C, however, limits its use in septic surgical patients. Administration of AT III in septic patients (KYBERSEPT) reduced the mortality rate solely in patients which were not treated with heparin. Although hydrocortisone reduced the amount of vasoactive katecholamines the effect of hydrocortisone administration on the survival rate remains unknown. In summary, early intervention to eliminate the septic focus and the use of antibiotics according to an antibiogramm still remains the most efficient basis for the treatment of septic patients.

Antithrombin III↗

PubMed2000

Do female sex steroids adversely or beneficially affect the depressed immune responses in males after trauma-hemorrhage?

HYPOTHESIS: Administration of female sex steroids in males after trauma-hemorrhage has salutary effects on the depressed immune responses. DESIGN: Randomized laboratory experiment. INTERVENTIONS: Male C3H/HeN mice were subjected to midline laparotomy and hemorrhagic shock (35+/-5 mm Hg for 90 minutes, then resuscitation) or sham operation and received subcutaneous 17beta-estradiol (40 microg/kg body weight) or corn oil vehicle at the beginning of resuscitation. MAIN OUTCOME MEASURES: At 24 hours after hemorrhage, the animals were killed and plasma 17beta-estradiol and IL-6, splenocyte interleukin (IL) 2, IL-3, and IL-10 production as well as splenic and peritoneal macrophage IL-1beta, IL-10, and IL-6 release were measured. RESULTS: Splenocyte IL-2 and IL-3 release were significantly depressed after hemorrhage in vehicle-treated mice (P<.05, analysis of variance). Treatment with 17beta-estradiol after hemorrhage led to the restoration of splenocyte IL-2 and IL-3 release. The depressed proinflammatory cytokine (IL-1 and IL-6) release seen in splenic and peritoneal macrophages was restored in the 17beta-estradiol-treated hemorrhage group. In contrast, the sustained release of the anti-inflammatory cytokine IL-10 by splenocytes and splenic and peritoneal macrophages in vehicle-treated mice after hemorrhage was decreased in 17beta-estradiol-treated mice. The increase in circulating IL-6 levels after hemorrhage was significantly attenuated in 17beta-estradiol-treated mice. Although administration of 17beta-estradiol increased plasma 17beta-estradiol levels by approximately 100% in sham as well as hemorrhage groups, improved immune responses were seen only in posthemorrhage 17beta-estradiol-treated mice. There was no adverse effect of 17beta-estradiol treatment in the sham or posthemorrhage groups. CONCLUSION: Since administration of a single dose of 17beta-estradiol in males after trauma-hemorrhage restores the immune functions and decreases circulating levels of IL-6, hormones with estrogenic properties should be considered as safe and novel therapeutic agents for restoring the immune responsiveness in male trauma victims.

Adjuvants, Immunologic↗

PubMed2000

Immune dysfunction following trauma-haemorrhage: influence of gender and age.

Recent studies indicate that young female proestrus mice show an enhanced immune response following trauma-haemorrhage, as opposed to the immunodepression observed in males of comparable age. Testosterone is suggested as the cause of immunodepression in males, whereas oestradiol seems to be responsible for the enhanced immune response in females, however, sex hormone levels decrease with age. To determine if the sexual dimorphism in immune responses observed in young mice following trauma-haemorrhage changes with age, young (2-3 months) and aged (18-19 months) male and female CBA/J NIA mice were subjected to soft-tissue trauma (laparatomy) and haemorrhage (35+5 mmHg for 90 min and fluid resuscitation) or sham operation. Mice were killed 24 h later, and whole blood, as well as splenic and peritoneal macrophages (Mstraight phi) obtained. Plasma 17beta-oestradiol and free testosterone decreased in aged females and males, respectively. Mstraight phi from young females had enhanced IL-1beta and suppressed IL-10 production following trauma-haemorrhage, while aged females had unchanged production IL-1beta and IL-6 production and enhanced IL-10 release. In contrast, IL-1beta and IL-6 production by Mbeta from young males was suppressed and IL-10 production enhanced following trauma-haemorrhage, whereas Mstraight phi from aged males produced elevated levels of IL-1beta and IL-6 and suppressed levels of IL-10 following trauma-haemorrhage. Thus, the gender-related changes in the immune response to trauma-haemorrhage were reversed in aged mice.

Age Factors↗

PubMed2000

L-arginine attenuates trauma-hemorrhage-induced liver injury.

OBJECTIVES: Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions. DESIGN: A prospective, controlled animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, four times the maximum shed blood volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L-arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation, rats were killed, blood was obtained, and the liver was fixed for histology (hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of liver damage), L-arginine, citrulline, and ornithine concentrations were assessed. MEASUREMENTS AND MAIN RESULTS: The increased concentrations of plasma glutathione S-transferase observed in vehicle-treated hemorrhage animals were normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophil infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were increased in L-arginine-treated rats. CONCLUSIONS: Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.

Animals↗