Prenatal symptoms of anxiety and depression associated with sex differences in both maternal perceptions of one year old infant temperament and researcher observed infant characteristics.

BACKGROUND: Sex differences in the behaviour of children exposed to prenatal maternal depression and anxiety have been reported. This study compared depression and anxiety symptoms reported by mothers at term with maternal perceptions of one year old male and female infant temperament and with researcher observed infant characteristics, identifying differences for males and females with both approaches. METHODS: Infant behaviour and temperament was assessed via maternally completed questionnaires including Infant Behavioural Questionnaire Revised - Short form and by researcher administered subcomponents of Laboratory Temperament Assessment Battery and Bayley Scales of Infant Development III. RESULTS: For female infants, higher prenatal scores for depression and anxiety were associated with maternal perceptions of lower bonding, higher aggression and negativity, and lower soothability (n = 67 mother-infant dyads). In the laboratory assessment, intensity of escape was the only female infant factor significantly associated with maternal mood (n = 41). For male infants, there was minimal association between prenatal mood scores and maternal perceptions (n = 46) whereas in the laboratory assessment (n = 35) depression scores were associated with expressive language, facial interest and facial fear while anxiety scores were associated with expressive and receptive language, parent behaviour and facial fear. LIMITATIONS: Findings may be restricted to a single ethnicity or mode of delivery. Fewer infants attended the infant assessment. A laboratory setting may mask symptomatology in females. CONCLUSIONS: Atypical maternal perceptions may present a barrier to the early identification of male infants impacted by maternal depression and anxiety.

Anti-oxidant treatment for shock: vitamin E but not vitamin C improves survival.

Anti-oxidant therapy has been effective for treatment of experimental shock. In this study, the efficacy of Trolox (Aldrich Chemical Co., Milwaukee, WI), a water-soluble vitamin E analogue, and ascorbic acid (vitamin C) was evaluated in a rat model of hemorrhagic shock and resuscitation. In two prospective trials, rats were phlebotomized (27 mL/kg) and left in shock for 45 minutes. Resuscitation was then instituted by continuous IV infusion with lactated Ringer's (LR) (54 mL/kg) over 60 min. In Trial 1, rats were randomized to receive either placebo (LR) or Trolox (50 mg/kg) in LR. In Trial 2, rats were randomized to LR alone or ascorbic acid (50 mg/kg) in LR. Survival for ascorbic acid-treated rats (35 per cent) was not different than for control rats (35 per cent). However, the addition of Trolox to infusion significantly improved 72 hour survival, 75 per cent versus 40 per cent respectively, for Trolox-treated and control animals. These data demonstrate that Trolox is of survival benefit when added to resuscitation in this model. This benefit does not appear to be related to blood pressure or white cell adhesion. Trolox is more effective than ascorbic acid in this model.

Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock.

OBJECTIVE: Lisofylline is an enantiomer-specific, alkyl-substituted methylxanthine, which has specific and potent activity in down-regulating leukocyte activation. This study was designed to test the efficacy of lisofylline in the resuscitation of rats subjected to experimental hemorrhagic shock. DESIGN: Prospective, randomized, and blinded survival studies were performed with two lisofylline dosing regimens added to fluid resuscitation in a shock model. In addition, white cell adhesiveness was measured to assess the effects of lisofylline. SETTING: Animal laboratory. SUBJECTS: Sixty Sprague-Dawley rats. INTERVENTIONS: Lisofylline or placebo was added to the resuscitation regimen, either as a single dose or over 24 hrs. MEASUREMENTS AND MAIN RESULTS: The 72-hr survival rate, white blood cell count, and platelet adhesiveness were determined. When a single 1-hr infusion of lisofylline was added to the initial resuscitation regimen, the 72-hr survival rate increased from 20% in controls to 50% (p < .009). When repeated doses of lisofylline were given over 24 hrs, the 72-hr survival rate increased from 40% in controls to 70% (p < .02). Control animals significantly increased leukocyte adhesiveness after shock and resuscitation. This increased adhesiveness was completely eliminated by lisofylline infusion. Platelet adhesiveness was not affected by lisofylline. CONCLUSIONS: Lisofylline improves survival in this model of hemorrhagic shock. Its beneficial effect may be related to down-regulation of leukocyte adhesiveness.

Increasing nitric oxide production improves survival in experimental hemorrhagic shock.

UNLABELLED: The purpose of this study was to evaluate the importance of nitric oxide (NO) upon outcome following hemorrhagic shock. L-Arginine, an NO precursor, and L-NMMA, an inhibitor of NO synthesis, were added to resuscitation in a prospective, randomized, and double-blinded experimental model, and the effects upon blood pressure and survival were measured. METHODS: 60 Sprague-Dawley rats were anesthetized and subjected to phlebotomy to induce hemmorrhagic shock. After a 45 min shock period, animals were resuscitated with either lactated Ringer's alone (control), L-NMMA in lactated Ringer's or L-arginine in lactated Ringer's. Blood pressure was monitored, and animals were observed for survival. As an additional control experiment, 15 additional animals underwent the same protocol, but underwent sham shock, i.e. were not haemorrhaged. RESULTS: L-NMMA increased blood pressure transiently following sham shock, but increased blood pressure to a greater extent and for a longer duration following hemorrhage. However, L-NMMA had no effect upon survival. L-Arginine had no measurable effect upon blood pressure, but significantly increased survival. CONCLUSION: NO may play an important role following hemorrhage. The effectiveness of L-NMMA as a pressor suggests that NO contributes to hypotension following hemorrhage. However, reversing hypotension with L-NMMA did not improve survival in this model. In contrast, L-arginine did not further lower blood pressure, but had significant survival benefit. This suggests a possible protective effect of NO after hemorrhage, perhaps by improving the distribution of capillary blood flow and/or by decreasing platelet aggregation and leukocyte adhesion within the microcirculation.

Ethanol added to resuscitation improves survival in an experimental model of hemorrhagic shock.

Ethyl alcohol induces systemic vasodilation, decreases platelet aggregation, and inhibits neutrophil activation in vivo. Alcohol may thus be of potential benefit in resuscitation from shock by improving microcirculation. The purpose of this study was to test the effects of ethanol (ETOH) in resuscitation from hemorrhagic shock. Blood pressure, tissue pO2, white blood cell (WBC) and platelet adhesiveness, and survival were measured for 60 male Sprague-Dawley rats in a blinded and randomized study. Anesthetized animals were phlebotomized to 60 per cent of their blood volume, and maintained in shock for 45 minutes. Resuscitation was by continuous infusion of Lactated Ringers (LR) at 2 x shed blood volume over 1 hour. The experimental group received LR and ETOH (1.25 mL/kg). Control rats received LR and placebo. Mean arterial pressure was not significantly different, nor was WBC adhesiveness index different. However, postresuscitation platelet adhesiveness index was significantly higher in control rats than in ETOH rats. Postresuscitation total platelet arterial-venous difference was also greater in controls than in ETOH rats. Average tissue pO2 for ETOH rats (47 +/- 8.2 mm Hg) was significantly higher than controls (39.0 +/- 9.8 mm Hg) during resuscitation (P = 0.0001). Survival for ETOH rats (70%) was significantly higher than controls (20%) (P = 0.003). Our data suggests that ETOH added to resuscitation from shock improves survival by inhibiting platelet activation and increasing tissue perfusion.

The effect of Polyethylene Glycol-Superoxide Dismutase on gastric mucosa and survival in shock with tissue injury.

Oxygen-derived free radicals may play an important role in the pathogenesis of organ injury and death following hemorrhagic shock. This study was designed to test the effects of Polyethylene Glycol-Superoxide Dismutase (PEG-SOD) on gastric mucosal injury and survival in an animal model of hemorrhagic shock and tissue trauma. Reproducible tissue trauma was produced by IM injection of turpentine (1.4 microliters/g). A standardized hemorrhagic shock model with an LD 90 was employed. This model consisted of the following sequence of events: phlebotomy to 60 per cent blood volume, 45-minute shock period, resuscitation using Lactated Ringers (LR) at two times shed volume over 60 minutes. Twenty rats were randomly assigned to receive LR (control) or PEG-SOD (5.36 mg/kg). Immediately following the death or at 72 hours, the stomach was removed. Computer image analysis was used to determine the lesion area as a per cent of total gastric mucosal surface area. Our results show no statistical difference in gastric mucosal lesion area between groups (1.83% vs 1.75%, respectively). Survival at 72 hours was significantly higher for PEG-SOD animals vs controls (70% vs 10%, P = 0.0001). This data suggests that IV administration of PEG-SOD during resuscitation is a potentially effective means of improving survival following severe hemorrhagic shock and tissue injury.

Soluble cytokine receptors and receptor antagonists are sequentially released after trauma.

Cytokine receptors and receptor antagonists (RAs) have been identified in trauma patients. We hypothesized that after traumatic injury, a sequential release of soluble cytokine receptors and RAs may exist that mirrors the release of the primary cytokines themselves. Twenty-two patients were included in the study: 14 males and 8 females. The mean age was 30.1 +/- 12.5 (range, 19 to 71), and the mean Injury Severity Score was 28.7 +/- 12.6 (range, 4 to 57). There were 15 survivors and 7 nonsurvivors. Samples were collected on arrival to the emergency department and at serial intervals for up to 7 days. Monoclonal antibody enzyme-linked immunosorbent assay kits to tumor necrosis factor (TNF), soluble TNF-receptor (sTNF-R) 55 kd and 75 kd, interleukin (IL)-1 and IL-1 RA, and IL-2 and IL-2r were used. Sera from 22 healthy individuals were used as normal controls. No TNF, IL-1, or IL-2 could be detected in any patient sera after injury. Control levels for the soluble cytokine receptors and RAs were as follows: sTNF-R 55 kd, 607 +/- 89 pg/mL; sTNF-R 75 kd, 2,141 +/- 169 pg/mL; IL-1 RA, 291 +/- 35 pg/mL; and IL-2r, 426 +/- 53 U/mL. In trauma patients, both 55 kd and 75 kd sTNF-R were significantly elevated on arrival to the emergency department, with values of 2,441 +/- 506 pg/mL (p < 0.001) and 4,736 +/- 537 pg/mL (p < 0.001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-MgCl2 added to resuscitation improves survival in an experimental model of hemorrhagic shock.

The administration of ATP-MgCl2 may be of benefit in the treatment of shock by improving cellular metabolic function during resuscitation. Prior studies have reported data from hemorrhage models in which heparinized shed blood is returned both during shock and in resuscitation. The purpose of this study was to test the effects of ATP-MgCl2 therapy upon blood pressure and survival in an animal model of hemorrhagic shock utilizing crystalloid (Lactated Ringer's) resuscitation. Adult male Sprague-Dawley rats (340-360 g) were bled 27 cc/kg and maintained in shock for 45 min. At the end of the shock period, animals were resuscitated with crystalloid at twice the original hemorrhage volume. A blinded three-arm study was conducted and animals were assigned to receive either Lactated Ringer's (LR) with placebo, LR with MgCl2, or LR with ATP-MgCl2. Blood pressure was monitored throughout the procedure and survival time was noted. Post-resuscitation MAP was increased in animals treated with ATP-MgCl2. ATP-MgCl2 added to resuscitation significantly improved 72-h survival over that of control (LR) animals, and animals treated with MgCl2 alone.

Trauma causes sustained elevation of soluble tumor necrosis factor receptors.

BACKGROUND: Soluble tumor necrosis factor receptors (sTNF-R) are thought to modulate the systemic effects of tumor necrosis factor (TNF) by binding to serum TNF and preventing its interaction with target organs. Recently, it has been shown that traumatic injury causes the early release of the soluble forms of the 55 and 75 kDa membrane receptors for TNF. This study was done to determine the magnitude of TNF receptor elevation after trauma, to delineate the duration of this elevation, and to determine if sTNF-R levels correlate with severity of injury and outcome. STUDY DESIGN: One hundred injured patients treated at a Level I Trauma Center were included in the study (74 males, 26 females, mean age of 29.4 years [range of ten to 72 years], mean injury severity score of 16.8 [range of zero to 75]). Serum samples were drawn from these patients beginning within one hour of injury and continuing for as many as 15 days. Samples were analyzed using polyclonal ELISA assays for TNF and sTNF 55 and 75 kDa receptor levels; control levels of receptor were determined from healthy volunteers. RESULTS: Tumor necrosis factor was not measurable, but trauma caused immediate elevation of both receptor levels (within one hour of injury). Receptor levels remained elevated for as many as 15 days after injury. Late variations in levels were related to complications, that is, hypoxia, infection, and sepsis. Levels were significantly more elevated in critically ill patients and nonsurvivors. CONCLUSIONS: We conclude that sTNF-R levels are significantly elevated after trauma, in the absence of measurable TNF. Levels are elevated for variable periods of time, which seem to depend on the severity of injury and complications.

Amrinone improves survival in hemorrhagic shock.

Amrinone is a noncatecholamine inotropic agent used clinically in the management of heart failure. The purpose of this study was to determine if intravenous (i.v.) infusion of amrinone has beneficial effects during resuscitation from experimental hemorrhagic shock. Effectiveness was defined as significantly improved survival rate. Mean arterial pressure (MAP) and tissue oxygen tension (pO2) were measured to assess the physiologic effects of amrinone. Two separate randomized and blinded survival trials were conducted. In each trial, rats were randomly assigned to either a control group (n = 10) or an experimental group (n = 10). All animals were bled 27 ml/kg over 2 minutes and maintained in shock for 45 minutes before resuscitation. Resuscitation in placebo (control) animals was with 54 ml/kg (2 times the hemorrhage volume) Lactated Ringer's solution over 1 hour, whereas resuscitation in drug-treated animals was with a 0.75 mg/kg bolus amrinone over 3 minutes followed by 54 ml/kg Lactated Ringer's solution and 5 ug/kg/min infusion over 1 hour. Results were that resuscitation with amrinone significantly increased MAP, tissue pO2, and survival over resuscitation with Lactated Ringer's alone (P < 0.05). In both trials, survival rates increased by more than 66 per cent in the amrinone groups.

A method to determine the adequacy of resuscitation using tissue oxygen monitoring.

The change in tissue PO2 in response to an increased inspired O2 challenge may be related to the state of cellular oxygenation, and hence the adequacy of resuscitation. To test this hypothesis, we measured tissue PO2 during inspired O2 challenges in 29 injured patients during acute resuscitation or intensive care unit monitoring. The O2 challenge test had 100% sensitivity and specificity in detecting flow-dependent O2 consumption in invasively monitored patients in the intensive care unit. During acute resuscitation, 60% of patients had negative initial O2 challenge test results, indicating that flow-dependent O2 consumption might have been present. Of nine such patients, five had subsequent positive O2 challenge test results after fluid resuscitation, indicating successful resuscitation. Four patients (27% of acute resuscitations), however, had repeatedly negative findings, possibly indicating persistent inadequate cellular oxygenation despite fluid resuscitation. Other commonly measured variables did not differentiate these patients. Monitoring of tissue PO2 during an inspired O2 challenge may be a useful test for determining the adequacy of resuscitation from hypovolemic shock.