Biomedical subjects

Loring W Rue

Publications and source records attributed to Loring W Rue.

At least 19 recordsLinked to original sources

PubMed2007

17beta-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage.

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17beta-estradiol (E(2)) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-alpha and ER-beta) and the endothelium-localized downstream mechanisms of actions of E(2) remain unclear. We hypothesized that E(2) attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-beta-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E(2) treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E(2), propylpyrazole triol (PPT, ER-alpha agonist), and diarylpropionitrile (DPN, ER-beta agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E(2) normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-beta agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-alpha agonist PPT was ineffective. Moreover, the vasorelaxing effects of E(2) were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E(2). Thus, E(2) administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-beta-mediated pathway that is dependent on endothelium-derived NO synthesis.

Animals↗

PubMed2006

Mitochondria play an important role in 17beta-estradiol attenuation of H(2)O(2)-induced rat endothelial cell apoptosis.

Studies have shown salutary effects of 17beta-estradiol following trauma-hemorrhage on different cell types. 17beta-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17beta-estradiol will maintain mitochondrial function and will have protective effects against H(2)O(2)-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H(2)O(2), a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17beta-estradiol. Flow cytometry analysis revealed H(2)O(2)-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17beta-estradiol resulted in an approximately 40% reduction in apoptosis. This protective effect of 17beta-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17beta-estradiol-mediated attenuation of H(2)O(2)-induced mitochondrial condensation. Western blot analysis demonstrated that H(2)O(2)-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17beta-estradiol. These findings suggest that 17beta-estradiol attenuated H(2)O(2)-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria.

Animals↗

PubMed2006

Estrus cycle: influence on cardiac function following trauma-hemorrhage.

Since cardiac function is depressed in males but not in proestrus (PE) females following trauma-hemorrhage (T-H), we examined whether different estrus cycles influence cardiac function in female rats under those conditions. We hypothesized that females in the PE cycle only will have normal cardiac function following T-H and resuscitation. Sham operation or T-H was performed in five groups of rats (250-275 g) including PE, estrus (E), metestrus (ME), diestrus (DE), and ovariectomized (OVX) females (n = 6-7 per group). Cardiac function was determined 2 h after T-H, following which cardiomyocytes were isolated and nuclei extracted. Cardiomyocyte IL-6 and NF-kappaB expressions were measured using Western blotting. Moreover, plasma IL-6, estradiol, and progesterone levels were measured using ELISA or EIA kits. Results (1-way ANOVA) indicated that following T-H, 1) cardiac function was depressed in DE, E, ME, and OVX groups but maintained in the PE group; 2) the PE group had the highest plasma estrogen level; 3) plasma IL-6 levels increased significantly in DE, E, ME, and OVX groups, but the increase was attenuated in the PE group; 4) cardiomyocyte IL-6 protein level increased significantly in DE, E, ME and OVX groups after TH, but the increase was attenuated in the PE group; and 5) cardiomyocyte NF-kappaB expression increased significantly but was attenuated in the PE group. These data collectively suggest that the estrus cycle plays an important role in cardiac function following TH. The salutary effect seen in PE following TH is likely due to a decrease in NF-kappaB-dependent cardiac IL-6 pathway.

Animals↗

PubMed2006

Mechanism of IL-6-mediated cardiac dysfunction following trauma-hemorrhage.

Cardiac function is depressed and circulating IL-6 levels increase following trauma-hemorrhage (T-H). Although sustained elevated IL-6 after T-H correlate with poor outcome, the mechanism by which IL-6 produces cardiac dysfunction remains unknown. We hypothesized that IL-6-mediated cardiac depression is due to upregulation of NF-small ka, CyrillicB, ICAM, CINC and neutrophil infiltration. Six groups of male adult rats (275-300 g) were used: sham/T-H + vehicle, sham/T-H + IgG, sham/T-H + anti-IL-6mAb. Following midline laparotomy, 60% of the circulating blood was withdrawn and after 90 min, crystalloid fluid resuscitation was provided. Either normal goat IgG or anti-rat IL-6mAb (16.7 microg/kg BW) was administered intraperitoneally at 30 min after the onset of resuscitation. Two hours after resuscitation, cardiac function was measured, blood samples collected, cardiomyocytes isolated and intracellular IL-6 levels measured by flow cytometry. Cardiac IL-6, IL-6R, gp130, NF-small ka, CyrillicB, Ismall ka, CyrillicB-alpha, and ICAM-1 protein levels were measured in freshly isolated hearts by immunoblotting. Moreover, cardiac MPO activity and CINC-1 and -3 were measured. Cardiac function was depressed and cardiac IL-6, NF-small ka, CyrillicB, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after T-H. Administration of anti-IL-6mAb following T-H: 1) improved cardiac output (P<0.05); 2) downregulated cardiac IL-6 levels (P<0.05); 3) attenuated cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity (P<0.05). Administration of IgG, however, did not significantly influence these parameters. Thus, IL-6-mediated upregulation of cardiac NF-small ka, CyrillicB, ICAM-1, CINC-1, -3, and MPO activity likely contributes to altered cardiac function following T-H and neutralization of IL-6 therefore appears to be an effective and novel adjunct for improving organ/cell function under those conditions.

Animals↗

PubMed2006

The contribution of opiate analgesics to the development of infectious complications in burn patients.

BACKGROUND: Immune and infectious complications are associated with burn injury. Opiate analgesics also can induce similar complications, however, their impact on postburn infectious complications is unknown. METHODS: A retrospective survey of records from 1997 to 2002 from an academic burn center was conducted. Information on all opiate analgesic use was obtained and expressed as opiate equivalents (OEs). Total OEs were summed for each patient and then compared between cases and controls. RESULTS: Patients who developed infections were more likely to be in the high OE group. This association was modified by burn severity. Patients with small burns and infection were more likely to be in the high OE group, whereas patients with moderate to large burns and infections were not associated significantly with opiate use. CONCLUSIONS: The results of this preliminary study suggest that opiate analgesics can contribute to the development of postburn infectious complications when the burn injury is of a less severe nature.

Analgesics, Opioid↗

PubMed2006

Androstenediol ameliorates alterations in immune cells cytokine production capacity in a two-hit model of trauma-hemorrhage and sepsis.

Although administration of androstenediol (a metabolite of dehydroepiandrosterone) following trauma-hemorrhage (T-H) produces beneficial effects on inflammatory cytokines and organ function, it remains unknown whether this metabolite has any salutary effects in preventing alterations in immune cell cytokine production following a combined insult of T-H and sepsis. To examine this, male rats underwent laparotomy, hemorrhagic shock (mean BP 40 mmHg for 90 min) and resuscitation or sham operation. Androstenediol (1 mg/kg BW i.v.) or vehicle was administered at the end of resuscitation. Twenty hrs after T-H or sham operation, sepsis was induced by cecal ligation and puncture (CLP). Five hours thereafter, plasma cytokine levels and cytokine production of various immune cells were determined. In a separate set of experiments, survival was monitored for 10 days after the induction of sepsis. Administration of androstenediol markedly decreased plasma IL-6 and TNF-alpha levels following T-H and CLP. Furthermore, it prevented the increased production of IL-6 and TNF-alpha by Kupffer cells and alveolar macrophages and attenuated the decrease in IL-6 and TNF-alpha production by splenic macrophages; however, it had no significant effects on the depressed IL-6 and TNF-alpha production by PBMC following T-H and CLP. The depressed IL-2 and IFN-gamma production by splenocytes under those conditions was attenuated by the administration of androstenediol. Furthermore, survival rate following T-H and subsequent sepsis was improved by androstenediol treatment. Since androstenediol administration following T-H attenuated cytokine production and reduced mortality in a double-hit model of T-H and sepsis, this agent appears to be a novel and useful adjunct for maintaining the immune cell functions following T-H and for decreasing the mortality rate from subsequent susceptibility to sepsis.

Anabolic Agents↗

PubMed2006

Motor vehicle restraint system use and risk of spine injury.

OBJECTIVE: Motor vehicle collision (MVC)-related spinal injury is a severe and often permanently disabling injury. In addition, strain injuries have been reported as a common outcome of MVCs. Although advances in automobile crashworthiness have reduced both fatalities and severe injuries, the impact of varying occupant restraint systems (seatbelts and airbags) on thoracolumbar spine injuries is unknown. This study examined the relationship between the occurrence of mild to severe cervical and thoracolumbar spine injury and occupant restraint systems among front seat occupants involved in frontal MVCs. METHODS: A retrospective cohort study was conducted among subjects obtained from the 1995-2004 National Automotive Sampling System. Cases were identified based on having sustained a spine injury of >/=1 on the Abbreviated Injury Scale (AIS), 1990 Revision. Risk risks (RRs) and 95% confidence intervals (CIs) were computed comparing occupant restraint systems with unrestrained occupants. RESULTS: We found an overall incidence of AIS1 cervical (11.8%) and thoracolumbar (3.7%) spinal injury. Seatbelt only restraints were associated with increased cervical AIS1 injury (RR = 1.40, 95% CI 1.04-1.88). However, seatbelt only restraints showed the greatest risk reduction for AIS2 spinal injuries. Airbag only restraints reduced thoracolumbar AIS1 injuries (RR = 0.29, 95% CI 0.08-1.04). Seatbelt combined with airbag use was protective for cervical AIS3+ injury overall (RR = 0.29, 95% CI 0.14-0.58), cervical neurological injury (RR = 0.19, 95% CI 0.05-0.81), and thoracolumbar AIS3+ injury overall (RR = 0.20, 95% CI 0.05-0.70). CONCLUSIONS: The results of this study suggest that seatbelts alone or in combination with an airbag increased the incidence of AIS1 spinal injuries, but provide protection against more severe injury to all regions of the spine. Airbag deployment without seatbelt use did not show increased protection relative to unrestrained occupants.

Abbreviated Injury Scale↗

PubMed2006

Trauma center resource consumption and mortality.

Studies suggesting that increased trauma center (TC) patient volume leads to improved patient outcomes have produced inconsistent results. It is possible that the combination of TC patient volume and TC resources has a greater influence over outcomes than TC volume alone. Patients admitted to 131 TCs from 1994 to 2002 were included. TC density was calculated as the ratio of TC adult beds to patient volume and categorized into quartiles. Adjusted risk ratios (RRs) and 95 per cent confidence intervals (CIs) compared mortality of groups (Q1 [low density]-Q4 [high density]). Relative to Q4 TCs, for penetrating injuries with ISS < 15, elevated mortality was seen for Q2 (low-moderate density) TCs (RR 1.47, CI 1.09-1.99) and Q3 (high-moderate density) TCs (RR 1.81, CI 1.36-2.41); but for ISS > or = 15, mortality was lowest for Q1 (RR 0.78, CI 0.68-0.89). For blunt injury, mortality was similar for low- and high-density TCs but elevated for low-moderate- and high-moderate-density TCs. Mortality at low-density TCs was decreased overall and for penetrating injuries specifically but similar for blunt injuries when compared with high-density TCs. Enhanced resources measurements will clarify the relationship between patient volume, resources, and mortality.

Adolescent↗

PubMed2005

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Animals↗

PubMed2005

PGC-1 upregulation via estrogen receptors: a common mechanism of salutary effects of estrogen and flutamide on heart function after trauma-hemorrhage.

Flutamide, an androgen receptor antagonist, is thought to improve cardiovascular function by blocking the androgen receptor after trauma-hemorrhage (T-H). Although 17beta-estradiol (E2) and flutamide improve cardiac function after T-H, whether E2 and flutamide produce their salutary effect via the same or a different mechanism is unknown. We hypothesized that E2 and flutamide mediate their effects via estrogen receptor (ER)-mediated upregulation of peroxisome proliferator-activated receptor coactivator 1 (PGC-1). PGC-1, a key regulator of cardiac mitochondrial function, induces mitochondrial genes by activating transcription factors such as nuclear respiratory factor 2 (NRF-2), which regulates mitochondrial proteins [i.e., mitochondrial transcription factor A (Tfam), cytochrome-c oxidase subunit IV, and beta-ATP synthase]. Adult male rats underwent T-H [5-cm midline incision and hemorrhage (blood pressure = 40 mmHg for approximately 90 min)] and resuscitation. At the onset of resuscitation, rats received vehicle, flutamide (25 mg/kg), or E2 (50 microg/kg). Another group received the ER antagonist ICI-182780 (3 mg/kg) with or without flutamide. Flutamide or E2 administration after T-H restored depressed cardiac function. Moreover, E2 and flutamide normalized expression of cardiac PGC-1, NRF-2, Tfam, cytochrome-c oxidase subunit IV, and the mitochondrial DNA-encoded gene cytochrome-c oxidase subunit I and beta-ATP synthase, mitochondrial ATP, and cytochrome-c oxidase activity. However, if the ER antagonist ICI-182780 was administered with flutamide, flutamide-mediated PGC-1 upregulation was totally abolished. These results indicate that E2 and flutamide upregulate PGC-1 via the ER. Thus PGC-1 upregulation appears to be the common mechanism by which E2 and flutamide mediate their salutary effects on cardiac function after T-H.

Animals↗

PubMed2005

Mechanism of salutary effects of estradiol on organ function after trauma-hemorrhage: upregulation of heme oxygenase.

A growing body of evidence indicates that heme degradation products may counteract the deleterious consequences of hypoxia and/or ischemia-reperfusion injury. Because heme oxygenase (HO)-1 induction after adverse circulatory conditions is known to be protective, and because females in the proestrus cycle (with high estrogen) have better hepatic function and less hepatic damage than males after trauma-hemorrhage, we hypothesized that estrogen administration in males after trauma-hemorrhage will upregulate HO activity and protect the organs against dysfunction and injury. To test this hypothesis, male Sprague-Dawley rats underwent 5-cm laparotomy and hemorrhagic shock (35-40 mmHg for 93 +/- 2 min), followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-Estradiol and/or the specific HO enzyme inhibitor chromium mesoporphyrin (CrMP) were administered at the end of resuscitation, and the animals were killed 24 h thereafter. Trauma-hemorrhage reduced cardiac output, myocardial contractility, and serum albumin levels. Portal pressure and serum alanine aminotransferase levels were markedly increased under those conditions. These parameters were significantly improved in the 17beta-estradiol-treated rats. Estradiol treatment also induced increased HO-1 mRNA expression, HO-1 protein levels, and HO enzymatic activity in cardiac and hepatic tissue compared with vehicle-treated trauma-hemorrhage rats. Administration of the HO inhibitor CrMP prevented the estradiol-induced attenuation of shock-induced organ dysfunction and damage. Thus the salutary effects of estradiol administration on organ function after trauma-hemorrhage are mediated in part via upregulation of HO-1 expression and activity.

Alanine Transaminase↗

PubMed2005

Seatbelt use during pregnancy: a comparison of women in two prenatal care settings.

OBJECTIVES: This study examines knowledge of proper automobile restraint use during pregnancy and attitudes toward restraint use. This manuscript, the second in a series, compares knowledge and attitudes in two populations of pregnant women, those receiving prenatal care at several county clinics and those receiving care in a private practice. METHODS: A survey requesting demographic information and frequency and knowledge of proper automobile restraint use was administered during prenatal visits. RESULTS: County clinic patients (n = 450, 70% black) were younger and less educated than private practice patients (n = 203, 75% non-Hispanic white). Fewer county patients (49%) always wore seatbelts prior to the pregnancy than private practice patients (88%). Correct use was reported by fewer county clinic patients (67%) than private practice patients (83%). Few (25-28%) in either setting reported receiving information on seatbelt use. CONCLUSIONS: Despite existing knowledge with respect to the consequences of seatbelt non-use in pregnant women, the proportion of women receiving information about correct seatbelt use during pregnancy appears to be low, regardless of care source.

Adolescent↗

PubMed2005

Motor vehicle mismatch-related spinal injury.

BACKGROUND/OBJECTIVE: Motor vehicle collision (MVC)-related spinal cord injury (SCI) is the most prevalent etiology of SCI. Few studies have defined SCI risk factors. Vehicle mismatch occurs in 2-vehicle MVCs in which there are significant differences in vehicle weight, stiffness, and height. This study examined SCI risk and vehicle mismatch. METHODS: A matched case-control study using the 1995 to 2003 National Automotive Sampling System (NASS). Study subjects were identified from 2-vehicle MVCs. Cases were occupants who had suffered a cervical, thoracic, or lumbar SCI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: There were 101,682 cases of SCI matched to 805,091 controls. Occupants of passenger vehicles involved in MVCs with a light truck or van (LTV) were at increased risk for SCI (OR = 1.87, 95% CI = 1.07-3.24) and this risk was greatest for thoracic SCI (OR = 5.09, 95% CI = 2.33-11.13). In addition, occupants of LTVs involved in MVCs with passenger vehicles were at significant increased risk for cervical (OR = 1.39) and lumbar (OR = 2.65) SCI; and occupants of LTVs involved in MVCs with other LTVs were at increased risk of any SCI (OR = 2.02, 95% CI = 1.52-2.69). For these subjects, significant increased risks were seen for all spine regions: cervical (OR = 1.41), thoracic (OR = 2.86), and lumbar (OR = 2.38). CONCLUSIONS: The results of this study suggest that occupants of passenger vehicles are at increased SCI risk when involved in 2-vehicle MVCs with LTVs; and that occupants of LTVs are at increased SCI risk, regardless.

Adult↗

PubMed2005

Unusual job activities as a risk factor for occupational injuries.

BACKGROUND: Based upon our clinical observation, many job-related injuries occur as a consequence of workers performing a task or engaging in an activity for which they have not been trained. METHODS: A case-crossover study was used to evaluate unusual job tasks, unusual tools and unusual work locations as triggers for occupational injuries. Data on work activities on the day of the injury and 7 days prior to injury were collected via in-person interview. RESULTS: All the 33 subjects enrolled were male, 23 were white and 10 were black, with a mean age of 34.9 years. The most common mechanisms of injury were falls and burns. The most common injuries were fractures and closed head injuries. Unusual job tasks [odds ratio (OR) 27.0, 95% confidence interval (CI) 3.1-235.3] and unusual tools (OR 13.3, 95% CI 1.4-125.4) were associated with the injury. CONCLUSIONS: Workers should be extra cautious and they should be provided with training for new tasks and new tools.

Accidents, Occupational↗

PubMed2005

The association between restraint system and upper extremity injury after motor vehicle collisions.

OBJECTIVES: This study was designed to investigate the relationship between upper extremity (UE) injuries and occupant restraint systems among front seat occupants who were involved in frontal motor vehicle collisions (MVCs). DESIGN: Case-control. SETTING: The 1995 through 2002 National Automotive Sampling System (NASS) Crashworthiness Data System (CDS). PARTICIPANTS: Subjects were identified from the NASS-CDS. All cases sustained an UE injury with a > or = 2 Abbreviated Injury Scale Score. OUTCOMES: Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated comparing risk of UE in 3 mutually exclusive restraint system groups (seatbelt-only, airbag-only, seatbelt-airbag-combined) to the unrestrained group. Data analysis was adjusted for significant occupant, vehicle, and collision characteristics. RESULTS: Seatbelt-only occupants had a reduced UE injury risk (OR, 0.41; 95% CI, 0.22-0.76). Near null associations were found for airbag-only (OR, 1.1; 95% CI, 0.68-1.76) and seatbelt-airbag-combined (OR, 0.97; 95% CI, 0.56-1.69). CONCLUSION: The results of this study suggest that UE injuries may become more common as a result of MVCs as the proportion of airbags in motor vehicles increases.

Abbreviated Injury Scale↗

PubMed2005

Gender differences in acute response to trauma-hemorrhage.

To understand the pathogenesis of a disease, experimental models are needed. A good experimental model is the one that simulates responses observed in the clinical setting. In recent years, clinical studies have indicated that gender might be a factor that plays a significant role in the outcome of patients with shock, trauma, and sepsis. These observations are now being evaluated in experimental setting. Studies performed in a rodent model of trauma-hemorrhage have concluded that alterations in immune and cardiac functions after trauma-hemorrhage are more markedly depressed in adult males, and ovariectomized and aged females. However, both are maintained in castrated males and in proestrus females. Moreover, the survival rate of proestrus females subjected to sepsis after trauma-hemorrhage is significantly higher than age-matched males or ovariectomized females. Although these observations suggest gender-specific response after trauma-hemorrhage, the mechanisms responsible for gender specificity remain largely unknown. Furthermore, in other injuries such as burn, experimental studies dealing with sexual dimorphism are limited. Therefore, more studies in clinical and experimental settings are required to determine whether gender-specific responses are global across the injuries or are observed in specific injury situations. Studies are also needed to delineate underlying mechanisms responsible for differences between males and females after trauma-hemorrhage. The information gained from the experimental studies will help in designing innovative therapeutic approaches for the treatment of trauma patients.

Animals↗

PubMed2005

Cecal ligation and puncture.

The model of cecal ligation and puncture (CLP) in rodents has been used extensively to investigate the clinical settings of sepsis and septic shock. This model produces a hyperdynamic, hypermetabolic state that can lead to a hypodynamic, hypometabolic stage, and eventual death. Blood cultures are positive for enteric organisms very early after CLP. The model has been widely used over the past 26 years and is highly versatile in adapting to a range of severity and testing objectives. It is inexpensive to prepare and technically straightforward. Aspects of sepsis research investigated using CLP include energetics, metabolism, resuscitation, antibiotic therapy, microbial factors, cardiovascular responses, immune function, mediator release, and cytokine expression patterns. The challenge of the small circulating blood volume in rodents can be overcome by using micromethods that enable analysis of small volumes, or alternatively, by using a large number of animals to obtain serial samples.

Animals↗

PubMed2005

The impact of combined trauma and burns on patient mortality.

BACKGROUND: Combined trauma and burn injuries are uncommon and seldom studied. There is a presumption that these patients fare worse than their trauma- and burn-only counterparts, but the mortality risk has not been quantified. METHODS: This was a retrospective cohort study using the 1994 to 2002 National Trauma Data Bank. Trauma- and burn-only patients were categorized according to Injury Severity Score (ISS) and burn severity (percentage body surface area burned [BSAB]), respectively, and combined trauma-burn patients were similarly categorized. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated comparing combined trauma-burn mortality to trauma-only and burn-only patients by corresponding trauma or burn severity. RRs were adjusted for age, gender, and ISS or burn severity. RESULTS: Compared with minor trauma-only patients (ISS of 1-15), patients with minor trauma, when combined with burn injury, had significantly increased mortality (RR, 4.04; 95% CI, 3.51-4.66). Similarly, relative to minor burn-only patients (BSAB of 1-25%), combined trauma-burn patients with minor burns (RR, 5.00; 95% CI, 3.54-7.06) had significantly increased mortality. For combined trauma-burn patients with more severe burns or trauma, small but significant increased mortality risks were seen relative to major trauma-only patients (ISS of 26+; RR, 1.26; 95% CI, 1.05-1.51) and major burn-only patients (BSAB of 76+; RR, 1.45; 95% CI, 1.15-1.82). CONCLUSION: The large increased risk of death for those with combined minor injuries is of clinical interest because the majority of combined patients fall into this category. Future research should characterize specific causes and types of injury of increased mortality in the patient with combined injuries.

Adolescent↗