Abstract 14456: Rethinking The Treatment Of Cardiac Arrest To Include Non-oxygen Metabolite Supplementation: Plasma Lysophosphatidylcholine Level Maintenance After Cardiac Arrest Is Critical For Survival

Cardiac arrest (CA) is a loss of circulation that curtails the supply of oxygen and non-oxygen metabolites to the whole body resulting in ischemia and death. Subsequent resuscitation is vital for survival, but also causes reperfusion injury. Oxygen deprivation as one arm of ischemia-reperfusion injury and its relationship with death is well-established, but its counterpart, metabolite dysfunction, is overlooked and poorly understood. We have previously shown that many metabolites are not normalized as efficiently or rapidly after resuscitation especially, particularly those that are severely decreased after CA. As such, we hypothesize that appropriate replenishment of certain metabolites is essential for survival. Lysophosphatidylcholine (LPC), an important family of phospholipids, is an example of such non-oxygen metabolites required post-CA. With multifactorial roles for maintaining homeostasis, such as acting as an energy substrate, maintaining membrane integrity, and functioning in inter- and intra-cellular signaling, decreased levels of LPC post-CA disrupts the various physiologic responsibilities resulting in profound systemic effects causing cellular and organ system injury. In this analysis, 1) phospholipid screening using HPLS-MS on plasma samples obtained from asphyxial-CA rats and human CA patients shows that LPC significantly decreases post-CA, especially during the reperfusion phase, and is strongly correlated with the duration of preceding CA and poor neurological/survival outcomes, and 2) individual supplementation of three species of LPC (LPC 18:0, LPC 18:1, and LPC 22:6) following resuscitation after 10 and 12 min rat CA helps improve survival and brain function as compared with vehicle. Overall, our study highlights that LPC is an essential, non-oxygen metabolite that is necessary to help promote survival after CA in rats that has therapeutic potential for human translation.

Induction of Viable but Nonculturable Salmonella in Exponentially Grown Cells by Exposure to a Low-Humidity Environment and Their Resuscitation by Catalase

ABSTRACTSalmonella is a major cause of foodborne disease that sometimes occurs in massive outbreaks around the world. This pathogen is tolerant of low-humidity conditions. We previously described a method for induction of viable but nonculturable (VBNC) Salmonella enterica serovar Enteritidis by treatment with hydrogen peroxide (H2O2) and subsequent resuscitation with 0.3 mM sodium pyruvate. Here, we report a new method for the induction of the VBNC state in Salmonella Enteritidis cells, one involving dehydration. Exposure of Salmonella Enteritidis cells to dehydration stress under poor nutritional conditions (0.9% [wt/vol] NaCl) and 10 to 20% relative humidity at room temperature decreased the presence of culturable population to 0.0067%, but respiratory and glucose uptake active populations were maintained at 0.46 and 1.12%, respectively, meaning that approximately 1% may have entered the VBNC state. Furthermore, these VBNC cells could be resuscitated to acquire culturability by incubation with catalase in M9 minimal medium without glucose in a manner dependent on the dose of catalase but not sodium pyruvate. These results suggest that a low-humidity environment could cause Salmonella Enteritidis cells to enter the VBNC state and the cells could then be resuscitated for growth by treatment with catalase, suggesting a potential risk of Salmonella Enteritidis to survive in low water activity foods in the VBNC state and to start regrowth for foodborne illness.

Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

Acute ethanol intoxication increases the production of reactive oxygen species (ROS). Hemorrhagic shock with subsequent resuscitation (H/R) also induces ROS resulting in cellular and hepatic damagein vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.). Then, rats were hemorrhaged to a mean arterial blood pressure of30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.). Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE) and nitrosative (3-nitrotyrosine, 3-NT) stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

Statistics and Sudden Infant Death Syndrome

To the Editor.— Drs Oren, Kelly, and Shannon1 used an uncorrected χ2 test to analyze their data. All of the probability tables would have expected values of less than 5.2 Thus, either a Yates correction should be used or the Fisher exact test2 should be used. (To avoid numerical overflow on small computers taking the logarithm of the Fisher equation prior to computation and the antilog of the calculated probability after calculation is helpful.) With more appropriate statistics (1) the comparison of infants requiring subsequent resuscitation by mouth-to-mouth or vigorous stimulation v those not requiring such subsequent resuscitation would have P < .02 instead of < .007;

Care of Infants With Near-Miss Sudden Infant Death Syndrome

The purpose of this study was to evaluate the effectiveness of home management of life-threatening apnea in infants with near-miss sudden infant death syndrome (SIDS). A total of 84 infants were monitored with apnea monitors for an average of seven months (range, 1 to 27). A group of 27 infants had episodes of apnea requiring resuscitation during home monitoring, all of whom were successfully resuscitated by their parents on at least one occasion using bag and mask resuscitation, and 17 infants required more than one resuscitation. Subsequent resuscitation was unsuccessful with four infants. Infants who experienced more than ten episodes of prolonged sleep apnea (apnea longer than 20 seconds) during home monitoring had a significantly increased risk of requiring resuscitation than other infants being studied. With the use of home monitoring of these infants and parents trained in cardiopulmonary resuscitation, the survival rate was 93.4%.