Aromatase is increased in astrocytes in the presence of elevated pressure.

After traumatic brain injury (TBI), a progressive injury and death of neurons and glia leads to decreased brain function. Endogenous and exogenous estrogens may protect these vulnerable cells. In this study, we hypothesized that increased pressure leads to an increase in aromatase expression and estrogen production in astrocytes. In this study, we subjected rat glioma (C6) cells and primary cortical astrocytes to increased pressure (25 mm Hg) for 1, 3, 6, 12, 24, 48, and 72 h. Total aromatase protein and RNA levels were measured using Western analysis and RT-PCR, respectively. In addition, we measured aromatase activity by assaying estrone levels after administration of its precursor, androstenedione. We found that increased pressure applied to the C6 cells and primary cortical astrocytes resulted in a significant increase in both aromatase RNA and protein. To extend these findings, we also analyzed aromatase activity in the primary astrocytes during increased pressure. We found that increased pressure resulted in a significant (P < 0.01) increase in the conversion of androstenedione to estrone. In conclusion, we propose that after TBI, astrocytes sense increased pressure, leading to an increase in aromatase production and activity in the brain. These results may suggest mechanisms of brain estrogen production after increases in pressure as seen in TBI patients.

What is the optimal chest compression-ventilation ratio?

PURPOSE OF REVIEW: Despite a more widespread knowledge of basic cardiopulmonary resuscitation maneuvers in the community, the survival rate for patients with cardiac arrest has remained essentially unchanged in the past 30 years. Over the past few decades, many different compression-ventilation ratios have been studied in terms of best coronary and cerebral oxygen delivery, restoration of spontaneous circulation, and neurologic outcome. This article summarizes the recent evidence presented at the International Consensus on Resuscitation Science in January 2005. RECENT FINDINGS: Recent data from animal and mathematical models suggest a move to a higher compression-ventilation ratio to maximize coronary and cerebral oxygen delivery during cardiac arrest and long-term neurologic outcome. Prospective randomized human data on alternative compression-ventilation ratios are missing and new evidence seems to indicate the inadequacy of both lay and professional rescuers in providing chest compression and ventilating the victim in cardiac arrest. Finally, observational and animal studies highlight the hidden danger of inadvertent hyperventilation during advanced cardiac life support as a reduction of both coronary and perfusion pressure secondary to increased intrathoracic pressure and decreased venous return. SUMMARY: The optimal compression-ventilation ratio is still unknown and the best tradeoff between oxygenation and organ perfusion during cardiopulmonary resuscitation is probably different for each patient and scenario. A discrepancy between what is recommended by the current guidelines and the 'real world' of cardiopulmonary resuscitation has resulted in a near flat survival rate from cardiac arrest in the past few years.

The effects of different mouth-to-mouth ventilation tidal volumes on gas exchange during simulated rescue breathing.

UNLABELLED: The American Heart Association recommends tidal volumes of 700 to 1000 mL during mouth-to-mouth ventilation, but smaller tidal volumes of 500 mL may be of advantage to decrease the likelihood of stomach inflation. Because mouth-to-mouth ventilation gas contains only 17% oxygen, but 4% carbon dioxide, it is unknown whether 500-mL tidal volumes given during rescue breathing may result in insufficient oxygenation and inadequate carbon dioxide elimination. In a university hospital research laboratory, 20 fully conscious volunteer health care professionals were randomly assigned to breathe tidal volumes of 500 or 1000 mL of mouth-to-mouth ventilation gas (17% oxygen, 4% carbon dioxide, 79% nitrogen), or room air control (21% oxygen, 79% nitrogen) for 5 min. Arterial blood gases were taken immediately before, and after breathing 5 min of the experimental gas composition. When comparing 500 versus 1000 mL of mouth-to-mouth ventilation tidal volumes with 500 mL of room air, 500 mL of mouth-to-mouth ventilation tidal volume resulted in significantly (P < 0.05) lower mean +/- SEM arterial oxygen partial pressure (70 +/- 1 versus 85 +/- 2 versus 92 +/- 3 mm Hg, respectively), and lower oxygen saturation (94 +/- 0.4 versus 97 +/- 0.2 versus 98 +/- 0.2%), but increased arterial carbon dioxide partial pressure (46 +/- 1 versus 40 +/- 1 versus 39 +/- 1 mm Hg, respectively). Sixteen of 20 volunteers had to be excluded from the experiment with 500 mL of mouth-to-mouth ventilation gas after about 3 min instead of after 5 minutes as planned because of severe nervousness, sweating, and air hunger. We conclude that during simulated mouth-to-mouth ventilation, only large (approximately 1000 mL), but not small (approximately 500 mL) tidal volumes were able to maintain both sufficient oxygenation and adequate carbon dioxide elimination. IMPLICATIONS: To provide efficient mouth-to-mouth ventilation, it is important to administer tidal volumes of 1000 mL; tidal volumes of 500 mL were not adequate.

Murine natural killer cell activation receptors.

Natural killer (NK) cells express two types of receptors involved in target recognition: inhibitory receptors for target cell MHC class I molecules and activation receptors. While there has been significant progress in understanding the inhibitory receptors, less is known about the activation receptors. Detailed analysis of several mouse NK-cell activation receptors provides insight into the physiologic relevance of these receptors in the innate immune response.

The respiratory system during resuscitation: a review of the history, risk of infection during assisted ventilation, respiratory mechanics, and ventilation strategies for patients with an unprotected airway.

The fear of acquiring infectious diseases has resulted in reluctance among healthcare professionals and the lay public to perform mouth-to-mouth ventilation. However, the benefit of basic life support for a patient in cardiopulmonary or respiratory arrest greatly outweighs the risk for secondary infection in the rescuer or the patient. The distribution of ventilation volume between lungs and stomach in the unprotected airway depends on patient variables such as lower oesophageal sphincter pressure, airway resistance and respiratory system compliance, and the technique applied while performing basic or advanced airway support, such as head position, inflation flow rate and time, which determine upper airway pressure. The combination of these variables determines gas distribution between the lungs and the oesophagus and subsequently, the stomach. During bag-valve-mask ventilation of patients in respiratory or cardiac arrest with oxygen supplementation (> or = 40% oxygen), a tidal volume of 6-7 ml kg(-1) ( approximately 500 ml) given over 1-2 s until the chest rises is recommended. For bag-valve-mask ventilation with room-air, a tidal volume of 10 ml kg(-1) (700-1000 ml) in an adult given over 2 s until the chest rises clearly is recommended. During mouth-to-mouth ventilation, a breath over 2 s sufficient to make the chest rise clearly (a tidal volume of approximately 10 ml kg(-1) approximately 700-1000 ml in an adult) is recommended.

Effects of inspired gas content during respiratory arrest and cardiopulmonary resuscitation.

Mouth-to-mouth and bag-valve-mask ventilation have been an indispensable part of cardiopulmonary resuscitation (CPR). However, only recently have the effects of different tidal volumes on arterial oxygenation been reported for mouth-to-mouth and bag-valve-mask ventilation. Currently recommended tidal volumes (10-15 mL/kg) are associated with an increased risk of gastric inflation because they produce high peak inspiratory pressures. An animal model of ventilation with an unprotected airway showed that a smaller tidal volume (6 mL/kg) is as effective as a larger tidal volume (12 mL/kg) in maintaining Sao2 at >96%. However, a smaller tidal volume with exhaled gas ventilation produced a mean Sao2 of 48%, which is ineffective. Ventilation gas mixtures have been studied in models of cardiac arrest and CPR. One study showed that ventilation with air during 6 mins of CPR resulted in a return of spontaneous circulation in 10 of 12 animals compared with only 5 of 12 animals ventilated with exhaled gas (p<.04). Arterial and mixed-venous Po2 were significantly higher, and Pco2 was significantly lower in the air ventilation group. Investigations of the cardiovascular effects of mouth-to-mouth ventilation during CPR suggest that there are adverse effects during low blood flow states. However, mouth-to-mouth ventilation during respiratory arrest is lifesaving and should continue to be taught and emphasized in basic life support courses.

Smaller tidal volumes with room-air are not sufficient to ensure adequate oxygenation during bag-valve-mask ventilation.

The European Resuscitation Council has recommended decreasing tidal volume during basic life support ventilation from 800 to 1200 ml, as recommended by the American Heart Association, to 500 ml in order to minimise stomach inflation. However, if oxygen is not available at the scene of an emergency, and small tidal volumes are given during basic life support ventilation with a paediatric self-inflatable bag and room-air (21% oxygen), insufficient oxygenation and/or inadequate ventilation may result. When apnoea occurred after induction of anaesthesia, 40 patients were randomly allocated to room-air ventilation with either an adult (maximum volume, 1500 ml) or paediatric (maximum volume, 700 ml) self-inflatable bag for 5 min before intubation. When using an adult (n=20) versus paediatric (n=20) self-inflatable bag, mean +/-SEM tidal volumes and tidal volumes per kilogram were significantly (P<0.0001) larger (719+/-22 vs. 455+/-23 ml and 10.5+/-0.4 vs. 6.2+/-0.4 ml kg(-1), respectively). Compared with an adult self-inflatable bag, bag-valve-mask ventilation with room-air using a paediatric self-inflatable bag resulted in significantly (P<0.01) lower paO(2) values (73+/-4 vs. 87+/-4 mmHg), but comparable carbon dioxide elimination (40+/-2 vs. 37+/-1 mmHg; NS). In conclusion, our results indicate that smaller tidal volumes of approximately 6 ml kg(-1) ( approximately 500 ml) given with a paediatric self-inflatable bag and room-air maintain adequate carbon dioxide elimination, but do not result in sufficient oxygenation during bag-valve-mask ventilation. Thus, if small (6 ml kg(-1)) tidal volumes are being used during bag-valve-mask ventilation, additional oxygen is necessary. Accordingly, when additional oxygen during bag-valve-mask ventilation is not available, only large tidal volumes of approximately 11 ml kg(-1) were able to maintain both sufficient oxygenation and carbon dioxide elimination.

Survey of effects of anesthesia protocols on hemodynamic variables in porcine cardiopulmonary resuscitation laboratory models before induction of cardiac arrest.

OBJECTIVE: An advantage of animal models in cardiopulmonary resuscitation (CPR) research is the possibility to control confounding variables that may be impossible to standardize in clinical trials. A neglected effect of the anesthesia protocol in porcine CPR studies may be its impact on hemodynamic variables before induction of cardiac arrest. Accordingly, the purpose of the study reported here was to evaluate published CPR reports with regard to their anesthesia protocol. METHODS: Of 100 articles that reported on laboratory models simulating cardiac arrest between 1987 and 1997 in peer-reviewed journals, 25 met inclusion criteria and were analyzed for values of coronary perfusion pressure, mean arterial pressure, heart rate, temperature, and cardiac index before induction of cardiac arrest. Subsequently, mean values for all animals in a given report were calculated and corrected for group size; statistical analysis was not performed since this was a survey only. RESULTS: Different anesthesia protocols resulted in a widely distributed pattern of hemodynamic variables prior to induction of cardiac arrest. Ranges compared with reference values were: heart rate, 100 to 122 beats/min versus 105+/-11 beats/min; mean arterial pressure, 68 to 130 mm Hg versus 102+/-9 mm Hg; coronary perfusion pressure, 55 to 114 mm Hg (no reference value); cardiac index, 69 to 152 ml/kg/min versus 147+/-22 ml/kg/min; body temperature, 37 to 38.5 degrees C versus 38.5+/-0.7 degrees C. CONCLUSION: The anesthesia protocol may have an impact on hemodynamic variables before induction of cardiac arrest in CPR studies.

The natural killer gene complex genetic locus Chok encodes Ly-49D, a target recognition receptor that activates natural killing.

Previously, we established that natural killer (NK) cells from C57BL/6 (B6), but not BALB/c, mice lysed Chinese hamster ovary (CHO) cells, and we mapped the locus that determines this differential CHO-killing capacity to the NK gene complex on chromosome 6. The localization of Chok in the NK gene complex suggested that it may encode either an activating or an inhibitory receptor. Here, results from a lectin-facilitated lysis assay predicted that Chok is an activating B6 NK receptor. Therefore, we immunized BALB/c mice with NK cells from BALB.B6-Cmv1(r) congenic mice and generated a mAb, designated 4E4, that blocked B6-mediated CHO lysis. mAb 4E4 also redirected lysis of Daudi targets, indicating its reactivity with an activating NK cell receptor. Furthermore, only the 4E4(+) B6 NK cell subset mediated CHO killing, and this lysis was abrogated by preincubation with mAb 4E4. Flow cytometric analysis indicated that mAb 4E4 specifically reacts with Ly-49D but not Ly-49A, B, C, E, G, H, or I transfectants. Finally, gene transfer of Ly-49DB6 into BALB/c NK cells conferred cytotoxic capacity against CHO cells, thus establishing that the Ly-49D receptor is sufficient to activate NK cells to lyse this target. Hence, Ly-49D is the Chok gene product and is a mouse NK cell receptor capable of directly triggering natural killing.

Effects of smaller tidal volumes during basic life support ventilation in patients with respiratory arrest: good ventilation, less risk?

OBJECTIVE: When ventilating an unintubated patient in cardiac or respiratory arrest, smaller tidal volumes of 500 ml instead of 800-1200 ml may be beneficial to decrease peak airway pressure, and to minimise stomach inflation. The purpose was to determine the effects of small (approximately 500 ml) versus large (approximately 1000 ml) tidal volumes given with paediatric versus adult self-inflatable bags and approximately 50% oxygen on respiratory parameters in patients during simulated basic life support ventilation. METHODS: While undergoing induction of anaesthesia, patients were randomised to three minutes of ventilation with either an adult (n = 40) or paediatric (n = 40) self-inflatable bag. RESULTS: When compared with an adult self-inflatable bag, the paediatric bag resulted in significantly lower mean (+/- standard deviation) exhaled tidal volume (365 +/- 55 versus 779 +/- 122 ml; P < 0.0001), peak airway pressure (20 +/- 2 versus 25 +/- 5 cm H2O; P < 0.0001), but comparable oxygen saturation (97 +/- 1% versus 98 +/- 1%; NS (nonsignificant)). Stomach inflation occurred in five of 40 patients ventilated with an adult self-inflatable bag, but in no patients who were ventilated with a paediatric self-inflatable bag (P = 0.054). CONCLUSION: Administering smaller tidal volumes with a paediatric instead of an adult self-inflatable bag in unintubated adult patients with respiratory arrest maintains good oxygenation and carbon dioxide elimination while decreasing peak airway pressure, which makes stomach inflation less likely.

Respiratory system compliance decreases after cardiopulmonary resuscitation and stomach inflation: impact of large and small tidal volumes on calculated peak airway pressure.

The purpose of the present study was to evaluate respiratory system compliance after cardiopulmonary resuscitation (CPR) and subsequent stomach inflation. Further, we calculated peak airway pressure according to the different tidal volume recommendations of the European Resuscitation Council (7.5 ml/kg) and the American Heart Association (15 ml/kg) for ventilation of an unintubated cardiac arrest victim. After 4 min of ventricular fibrillation, and 6 min of CPR, return of spontaneous circulation (ROSC) after defibrillation occurred in seven pigs. Respiratory system compliance was measured at prearrest, after ROSC, and after 2 and 4 l of stomach inflation in the postresuscitation phase; peak airway pressure was subsequently calculated. Before cardiac arrest the mean (+/- S.D.) respiratory system compliance was 30 +/- 3 ml/cm H2O, and decreased significantly (P < 0.05) after ROSC to 24 +/- 5 ml/cm H2O, and further declined significantly to 18 +/- 4 ml/cm H2O after 2 l, and to 13 +/- 3 ml/cm H2O after 4 l of stomach inflation. At prearrest, the mean +/- S.D. calculated peak airway pressure according to European versus American guidelines was 9 +/- 1 versus 18 +/- 3 cm H2O, after ROSC 12 +/- 2 versus 23 +/- 4 cm H2O, and 15 +/- 2 versus 30 +/- 5 cm H2O after 2 l, and 22 +/- 6 versus 44 +/- 12 cm H2O after 4 l of stomach inflation. In conclusion, respiratory system compliance decreased significantly after CPR and subsequent induction of stomach inflation in an animal model with a wide open airway. This may have a significant impact on peak airway pressure and distribution of gas during ventilation of an unintubated patient with cardiac arrest.

Genetic control of natural killing and in vivo tumor elimination by the Chok locus.

The molecular mechanisms underlying target recognition during natural killing are not well understood. One approach to dissect the complexities of natural killer (NK) cell recognition is through exploitation of genetic differences among inbred mouse strains. In this study, we determined that interleukin 2-activated BALB/c-derived NK cells could not lyse Chinese hamster ovary (CHO) cells as efficiently as C57BL/6-derived NK cells, despite equivalent capacity to kill other targets. This strain-determined difference was also exhibited by freshly isolated NK cells, and was determined to be independent of host major histocompatibility haplotype. Furthermore, CHO killing did not correlate with expression of NK1.1 or 2B4 activation molecules. Genetic mapping studies revealed linkage between the locus influencing CHO killing, termed Chok, and loci encoded within the NK gene complex (NKC), suggesting that Chok encodes an NK cell receptor specific for CHO cells. In vivo assays recapitulated the in vitro data, and both studies determined that Chok regulates an NK perforin-dependent cytotoxic process. These results may have implications for the role of NK cells in xenograft rejection. Our genetic analysis suggests Chok is a single locus that affects NK cell-mediated cytotoxicity similar to other NKC loci that also regulate the complex activity of NK cells.

Severe ventilatory compromise due to gastric distention during pediatric cardiopulmonary resuscitation.

We describe a child in cardiac arrest with severe ventilatory compromise due to gastric distention. During cardiopulmonary resuscitation (CPR), positive pressure ventilation may lead to gastric insufflation because of decreased pulmonary compliance and decreased lower esophageal sphincter tone. Essentially, gas delivered will follow the path of least resistance, which may be to the stomach. In our patient, gastric distention precluded effective ventilation and gastric decompression relieved ventilatory compromise. The values and pitfalls of clinical evaluation and capnography are presented.

Influence of tidal volume on the distribution of gas between the lungs and stomach in the nonintubated patient receiving positive-pressure ventilation.

OBJECTIVES: When ventilating a nonintubated patient in cardiac arrest, the European Resuscitation Council has recently recommended a decrease in the tidal volume from 0.8 to 1.2 L to 0.5 L, partly in an effort to decrease peak flow rate, and therefore, to minimize stomach inflation. The purpose of the present study was to examine the validity of the European Resuscitation Council's recommendation in terms of gas distribution between lungs and stomach in a bench model that simulates ventilation of a nonintubated patient with a self-inflatable bag representing tidal volumes of 0.5 and 0.75 L. DESIGN: A bench model of a patient with a nonintubated airway was used consisting of face mask, manikin head, training lung (lung compliance, 50 mL/cm H2O; airway resistance, 5 cm H2O/L/sec), adjustable lower esophageal sphincter pressure (LESP) and simulated stomach. SETTING: University hospital laboratory. SUBJECTS: Thirty healthcare professionals. INTERVENTIONS: Healthcare professionals performed 1-min bag-mask ventilation at each LESP level of 5, 10, and 15 cm H2O at a rate of 12 breaths/min, using an adult and pediatric self-inflating bag, respectively. Volunteers were blinded to the LESP, which was randomly varied. MEASUREMENTS AND MAIN RESULTS: Both types of self-inflating bags induced stomach inflation, with higher stomach and lower lung tidal volumes when the LESP was decreased. Lung tidal volume with the pediatric bag was significantly (p < .05) lower at all LESP levels when compared with the adult bag, and ranged between 240 mL at an LESP of 15 cm H2O and 120 mL at an LESP of 5 cm H2O. Stomach tidal volume with the adult bag ranged between 250 mL at an LESP of 15 cm H2O and increased to 550 mL at an LESP of 5 cm H2O. Stomach tidal volume with the pediatric bag was significantly lower (p < .05) at all LESP levels when compared with the adult bag and ranged between 70 mL at an LESP of 15 cm H2O and 300 mL at an LESP of 5 cm H2O. CONCLUSIONS: Our data support the recommendation of the European Resuscitation Council to decrease tidal volumes to 0.5 L when ventilating a cardiac arrest victim with an unprotected airway. A small tidal volume may be a better trade-off in the basic life support phase, as this may provide reasonable ventilation while avoiding massive stomach inflation.