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Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs), primarily 14,15-EET. EETs are derived from arachidonic acid via P-450 epoxygenases and are cardioprotective. We tested the hypothesis that sEH deficiency and pharmacological inhibition elicit tolerance to ischeniia via EETmediated STAT3 signaling in vitro and in vivo. In addition, the relevance of single nucleotide polymorphisms (SNPs) of EPHX2 (the gene encoding sEH) on tolerance to oxygen and glucose deprivation and reoxygenation and glucose repletion (OGD/RGR) was assessed in male C57BL\6J (WT) or sEH knockout (sEHKO) cardiomyocytes by using transactivator of transcription (TAT)-mediated transduction with sEH mutant proteins. Cell death and hydrolase activity was lower in Arg287Gln EPHX2 mutants vs. nontransduced controls. Excess 14,15-EET and SEH inhibition did not improve cell survival in Arg287Gln mutants. In WT cells, the putative EET receptor antagonist, 14,15-EEZE, abolished the effect of 14,15-EET and sEH inhibition. Cotreatment with 14,15-EET and SEH inhibition did not provide increased protection. In vitro, STAT3 inhibition blocked 14,15-EET cytoprotection, but not the effect of SEH inhibition. However, STAT3 small interfering RNA (siRNA) abolished cytoprotection by 14,15-EET and sEH inhibition, but cells pretreated with JAK2 siRNA remained protected. In vivo, STAT3 inhibition abolished 14,15-EET-mediated infarct size reduction. In summary, the Arg287Gln mutation is associated with improved tolerance against ischemia in vitro, and inhibition of sEH preserves cardiomyocyte viability following OGD/RGR via an EET-dependent mechanism. In vivo and in vitro, 14,15-EET-mediated protection is mediated in part by STAT3. [ABSTRACT FROM AUTHOR]

Motoki A, Merkel MJ, Packwood WH, Cao Z, Liu L, Iliff J, Alkayed NJ, Van Winide DM. Soluble epoxide hydmlase inhibition and gene deletion are pmtective against myocardial ischemia-reperfusion injury in vivo. Am J Physiol Heart Circ Physiol 295: H2128-H2134, 2008. First published October 3, 2008; doi: 10.1152/ajpheart.00428.2008. -Soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL\6J wildtype or sEH knockout mice were subjected to 40 mm of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-y1-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 mm before LCA occlusion or during ischemia 10 mm before reperfusion. 14,15EET, the main substrate for sEH, was administered intravenously 15 mm before LCA occlusion or during ischemia 5 mm before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 mm before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and tnphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

There is evidence for differences in the response to the treatment of cardiovascular disease in men and women. In addition, there are conflicting results regarding the effectiveness of pharmacologically induced protection or ischemic preconditioning in females. We investigated whether the ability of Met5-enkephalin (ME) to reduce cell death after oxygen-glucose deprivation (OGD) is influenced by the presence of 17β-estradiol (E2) in a nitric oxide (NO)- and estrogen receptor-dependent manner. On postnatal day 7 to 8, murine cardiomyocytes from wild-type or inducible NO synthase (iNOS) knockout mice were separated by sex, isolated by collagenase digestion, cultured for 24 h, and subjected to 90 min OGD and 180 min reoxygenation at 37°C (n = 4 to 5 replicates). Cell cultures were incubated in E2 for IS min or 24 h before OGD. ME was used to increase cell survival. Cell death was assessed by propidium iodide. More than 300 cells were examined for each treatment. Data are presented as means ± SE. As a result, in both sexes, ME-induced cell survival was lost in the presence of E2, and the ability of ME to improve cell survival was restored after treatment with the estrogen receptor antagonist ICI-182780. Furthermore, iNOS was necessary for ME to increase cell survival following OGD in vitro. We conclude that ME-induced reduction in cell death is abolished by E2 in a sex-independent manner via activation of estrogen receptors, and this interaction is dependent on iNOS. [ABSTRACT FROM AUTHOR]

The article discusses the research showing that the elective, real-time, ultrasound-guided cannulation of the subclavian vein may be more effective than the landmark-guided technique when performed by an experienced operator. The use of ultrasound guidance for subclavian vein cannulation may reduce the rate of mechanical complications, decrease insertion time, and improve the overall success rate of the procedure as compared with the landmark-guided technique.

Purpose A study was conducted using high-fidelity electronic health record (EHR)–based simulations with incorporated eye tracking to understand the workflow of critical care pharmacists within the EHR, with specific attention to the data elements most frequently viewed. Methods Eight critical care pharmacists were given 25 minutes to review 3 simulated intensive care unit (ICU) charts deployed in the simulation instance of the EHR. Using monitor-based eye trackers, time spent reviewing screens, clinical information accessed, and screens used to access specific information were reviewed and quantified to look for trends. Results Overall, pharmacists viewed 25.5 total and 15.1 unique EHR screens per case. The majority of time was spent looking at screens focused on medications, followed by screens displaying notes, laboratory values, and vital signs. With regard to medication data, the vast majority of screen visitations were to view information on opioids/sedatives and antibiotics. With regard to laboratory values, the majority of views were focused on basic chemistry and hematology data. While there was significant variance between pharmacists, individual navigation patterns remained constant across cases. Conclusion The study results suggest that in addition to medication information, laboratory data and clinical notes are key focuses of ICU pharmacist review of patient records and that navigation to multiple screens is required in order to view these data with the EHR. New pharmacy-specific EHR interfaces should consolidate these elements within a primary interface. [ABSTRACT FROM AUTHOR]

What We Already Know About This Topic: Electromagnetic interference from monopolar electrosurgery may disrupt implantable cardioverter defibrillators.Current management recommendations by the American Society of Anesthesiologists and Heart Rhythm Society are based on expert clinical opinion since there is a paucity of data regarding the risk of electromagnetic interference to implantable cardioverter defibrillators during surgery.What This Article Tells Us That Is New: With protocolized electrosurgery dispersive electrode positioning in patients with implantable cardioverter defibrillators, the risk of clinically meaningful electromagnetic interference was 7% in above-the-umbilicus noncardiac surgery and 0% in below-the-umbilicus surgery. In cardiac surgery, clinically meaningful electromagnetic interference with use of an underbody dispersive electrode was 29%.Despite protocolized dispersive electrode positioning, the risk of electromagnetic interference in above-the-umbilicus surgery is high, supporting recommendations to suspend antitachycardia therapy when monopolar electrosurgery is used above the umbilicus.With protocolized dispersive electrode positioning, the risk of electromagnetic interference in below-the-umbilicus surgery is negligible, implying that suspending antitachycardia therapy might be unnecessary in these cases.With an underbody dispersive electrode, the risk of electromagnetic interference in cardiac surgery is high.Background: The goal of this study was to determine the occurrence of intraoperative electromagnetic interference from monopolar electrosurgery in patients with an implantable cardioverter defibrillator undergoing surgery. A protocolized approach was used to position the dispersive electrode.Methods: This was a prospective cohort study including 144 patients with implantable cardioverter defibrillators undergoing surgery between May 2012 and September 2016 at an academic medical center. The primary objectives were to determine the occurrences of electromagnetic interference and clinically meaningful electromagnetic interference (interference that would have resulted in delivery of inappropriate antitachycardia therapy had the antitachycardia therapy not been programmed off) in noncardiac surgeries above the umbilicus, noncardiac surgeries at or below the umbilicus, and cardiac surgeries with the use of an underbody dispersive electrode.Results: The risks of electromagnetic interference and clinically meaningful electromagnetic interference were 14 of 70 (20%) and 5 of 70 (7%) in above-the-umbilicus surgery, 1 of 40 (2.5%) and 0 of 40 (0%) in below-the-umbilicus surgery, and 23 of 34 (68%) and 10 of 34 (29%) in cardiac surgery. Had conservative programming strategies intended to reduce the risk of inappropriate antitachycardia therapy been employed, the occurrence of clinically meaningful electromagnetic interference would have been 2 of 70 (2.9%) in above-the-umbilicus surgery and 3 of 34 (8.8%) in cardiac surgery.Conclusions: Despite protocolized dispersive electrode positioning, the risks of electromagnetic interference and clinically meaningful electromagnetic interference with surgery above the umbilicus were high, supporting published recommendations to suspend antitachycardia therapy whenever monopolar electrosurgery is used above the umbilicus. For surgery below the umbilicus, these risks were negligible, implying that suspending antitachycardia therapy is likely unnecessary in these patients. For cardiac surgery, the risks of electromagnetic interference and clinically meaningful electromagnetic interference with an underbody dispersive electrode were high. Conservative programming strategies would not have eliminated the risk of clinically meaningful electromagnetic interference in either noncardiac surgery above the umbilicus or cardiac surgery. [ABSTRACT FROM AUTHOR]