Early Emergency Medicine Milestone Assessment for Predicting First-Year Resident Performance.

Introduction: The Accreditation Council for Graduate Medical Education (ACGME) requires emergency medicine (EM) residency training programs to monitor residents' progress using standardized milestones. The first assessment of PGY 1 resident milestones occurs midway through the first year and could miss initial deficiencies. Early assessment of PGY 1 EM resident milestones has potential to identify at-risk residents prior to standard midyear evaluations. We developed an orientation syllabus for PGY 1 residents followed by a milestone assessment. Assessment scores helped predict future milestone scores and American Board of Emergency Medicine (ABEM) In-Training Examination (ITE) scores for PGY 1 residents. Methods: From 2013 to 2020, we developed and implemented Milestone Evaluation Day (MED), a simulation-based day and written exam assessing PGY 1 EM residents during their first month on the 23 ACGME 1.0 milestones. MED stations included a history and physical with verbal presentation, patient simulation, vascular access, wound management, and airway management. MED, Clinical Competency Committee-generated (CCC-generated) milestone, and ABEM ITE scores were averaged and compared utilizing Pearson's correlation coefficient. Results: Of 112 PGY 1 EM residents, 110 (98%) were analyzed over an 8-year period. We observed a moderate positive correlation of MED and CCC-generated milestone scores (r = .34, p < .001). There was a nonstatistically significant weak positive correlation of MED and ABEM ITE scores (r = .13, p = .17). Discussion: An early assessment of EM milestones in the PGY 1 year can assist in the prediction of CCC-generated milestone scores for PGY 1 residents.

LATIN AMERICAN RESIDENTS' SURGICAL EDUCATION AFTER THE PANDEMIC: WHAT STRATEGIES HAVE EMERGED FOR ADAPTING TO THIS NEW ERA?

BACKGROUND: The COVID-19 pandemic has had a negative effect on surgical education in Latin America, decreasing residents' surgical training and supervised clinical practice. AIMS: This study aimed to identify strategies that have been proposed or implemented to adapt surgical training and supervised clinical practice to COVID-19-related limitations in Latin America. METHOD: A literature review was performed between April and May 2021, divided into two searches. The first one sought to identify adaptation strategies in Latin America for surgical training and supervised clinical practice. The second one was carried out as a complement to identify methodologies proposed in the rest of the world. RESULTS: In the first search, 16 of 715 articles were selected. In the second one, 41 of 1,637 articles were selected. Adaptive strategies proposed in Latin America focused on videoconferencing and simulation. In the rest of the world, remote critical analysis of recorded/live surgeries, intrasurgical tele-mentoring, and surgery recording with postoperative feedback were suggested. CONCLUSIONS: Multiple adaptation strategies for surgical education during the COVID-19 pandemic have been proposed in Latin America and the rest of the world. There is an opportunity to implement new strategies in the long term for surgical training and supervised clinical practice, although more prospective studies are required to generate evidence-based recommendations.

Latin american residents' surgical education after the pandemic: what strategies have emerged for adapting to this new era? / Pandemia de covid-19 e educação cirúrgica de residentes da américa latina. que estratégias surgiram para se adaptar a esta nova era?

ABSTRACT BACKGROUND: The COVID-19 pandemic has had a negative effect on surgical education in Latin America, decreasing residents' surgical training and supervised clinical practice. AIMS: This study aimed to identify strategies that have been proposed or implemented to adapt surgical training and supervised clinical practice to COVID-19-related limitations in Latin America. METHOD: A literature review was performed between April and May 2021, divided into two searches. The first one sought to identify adaptation strategies in Latin America for surgical training and supervised clinical practice. The second one was carried out as a complement to identify methodologies proposed in the rest of the world. RESULTS: In the first search, 16 of 715 articles were selected. In the second one, 41 of 1,637 articles were selected. Adaptive strategies proposed in Latin America focused on videoconferencing and simulation. In the rest of the world, remote critical analysis of recorded/live surgeries, intrasurgical tele-mentoring, and surgery recording with postoperative feedback were suggested. CONCLUSIONS: Multiple adaptation strategies for surgical education during the COVID-19 pandemic have been proposed in Latin America and the rest of the world. There is an opportunity to implement new strategies in the long term for surgical training and supervised clinical practice, although more prospective studies are required to generate evidence-based recommendations.

RESUMO RACIONAL: A pandemia de COVID-19 teve um efeito negativo na educação cirúrgica na América Latina, diminuindo o treinamento cirúrgico dos residentes e a prática clínica supervisionada. OBJETIVOS: Identificar estratégias que foram propostas ou implementadas para adaptar o treinamento cirúrgico e a prática clínica supervisionada às limitações relacionadas ao COVID-19 na América Latina. MÉTODOS: Foi realizada revisão de literatura entre abril-maio de 2021, dividida em duas buscas. O primeiro procurou identificar estratégias de adaptação em América Latina para treinamento cirúrgico e prática clínica supervisionada. A segunda foi realizada como complemento para identificar metodologias propostas no resto do mundo. RESULTADOS: Na primeira busca, foram selecionados 16 dos 715 artigos. Na segunda, foram selecionados 41 dos 1.637 artigos. Estratégias adaptativas propostas na América Latina com foco em videoconferência e simulação. No resto do mundo, foram sugeridas análises críticas remotas de cirurgias gravadas/ao vivo, tele-mentoria intra-cirúrgica e gravação de cirurgia com feedback pós-operatório. CONCLUSÕES: Múltiplas estratégias de adaptação para educação cirúrgica durante a pandemia de COVID-19 foram propostas na América Latina e no resto do mundo. Há uma oportunidade de implementar novas estratégias a longo prazo para treinamento cirúrgico e prática clínica supervisionada, embora mais estudos prospectivos sejam necessários para gerar recomendações baseadas em evidências.

A prospective study to validate pulmonary blood mass changes on non-contrast 4DCT in pulmonary embolism patients.

PURPOSE: Limited diagnostic options exist for patients with suspected pulmonary embolism (PE) who cannot undergo CT-angiogram (CTA). CT-ventilation methods recover respiratory motion-induced lung volume changes as a surrogate for ventilation. We recently demonstrated that pulmonary blood mass change, induced by tidal respiratory motion, is a potential surrogate for pulmonary perfusion. In this study, we examine blood mass and volume change in patients with PE and parenchymal lung abnormalities (PLA). METHODS: A cross-sectional analysis was conducted on a prospective, cohort-study with 129 consecutive PE suspected patients. Patients received 4DCT within 48 h of CTA and were classified as having PLA and/or PE. Global volume change (VC) and percent global pulmonary blood mass change (PBM) were calculated for each patient. Associations with disease type were evaluated using quantile regression. RESULTS: 68 of 129 patients were PE positive on CTA. Median change in PBM for PE-positive patients (0.056; 95% CI: 0.045, 0.068; IQR: 0.051) was smaller than that of PE-negative patients (0.077; 95% CI: 0.064, 0.089; IQR: 0.056), with an estimated difference of 0.021 (95% CI: 0.003, 0.038; p = 0.0190). PLA was detected in 57 (44.2%) patients. Median VC for PLA-positive patients (1.26; 95% CI: 1.22, 1.30; IQR: 0.15) showed no significant difference from PLA-negative VC (1.25; 95% CI: 1.21, 1.28; IQR: 0.15). CONCLUSIONS: We demonstrate that pulmonary blood mass change is significantly lower in PE-positive patients compared to PE-negative patients, indicating that PBM derived from dynamic non-contrast CT is a potentially useful surrogate for pulmonary perfusion.

Clinical prediction rule for SARS-CoV-2 infection from 116 U.S. emergency departments 2-22-2021.

OBJECTIVES: Accurate and reliable criteria to rapidly estimate the probability of infection with the novel coronavirus-2 that causes the severe acute respiratory syndrome (SARS-CoV-2) and associated disease (COVID-19) remain an urgent unmet need, especially in emergency care. The objective was to derive and validate a clinical prediction score for SARS-CoV-2 infection that uses simple criteria widely available at the point of care. METHODS: Data came from the registry data from the national REgistry of suspected COVID-19 in EmeRgency care (RECOVER network) comprising 116 hospitals from 25 states in the US. Clinical variables and 30-day outcomes were abstracted from medical records of 19,850 emergency department (ED) patients tested for SARS-CoV-2. The criterion standard for diagnosis of SARS-CoV-2 required a positive molecular test from a swabbed sample or positive antibody testing within 30 days. The prediction score was derived from a 50% random sample (n = 9,925) using unadjusted analysis of 107 candidate variables as a screening step, followed by stepwise forward logistic regression on 72 variables. RESULTS: Multivariable regression yielded a 13-variable score, which was simplified to a 13-point score: +1 point each for age>50 years, measured temperature>37.5°C, oxygen saturation<95%, Black race, Hispanic or Latino ethnicity, household contact with known or suspected COVID-19, patient reported history of dry cough, anosmia/dysgeusia, myalgias or fever; and -1 point each for White race, no direct contact with infected person, or smoking. In the validation sample (n = 9,975), the probability from logistic regression score produced an area under the receiver operating characteristic curve of 0.80 (95% CI: 0.79-0.81), and this level of accuracy was retained across patients enrolled from the early spring to summer of 2020. In the simplified score, a score of zero produced a sensitivity of 95.6% (94.8-96.3%), specificity of 20.0% (19.0-21.0%), negative likelihood ratio of 0.22 (0.19-0.26). Increasing points on the simplified score predicted higher probability of infection (e.g., >75% probability with +5 or more points). CONCLUSION: Criteria that are available at the point of care can accurately predict the probability of SARS-CoV-2 infection. These criteria could assist with decisions about isolation and testing at high throughput checkpoints.

Quantifying pulmonary perfusion from noncontrast computed tomography.

PURPOSE: Computed tomography (CT)-derived ventilation methods compute respiratory induced volume changes as a surrogate for pulmonary ventilation. Currently, there are no known methods to derive perfusion information from noncontrast CT. We introduce a novel CT-Perfusion (CT-P) method for computing the magnitude mass changes apparent on dynamic noncontrast CT as a surrogate for pulmonary perfusion. METHODS: CT-Perfusion is based on a mass conservation model which describes the unknown mass change as a linear combination of spatially corresponding inhale and exhale HU estimated voxel densities. CT-P requires a deformable image registration (DIR) between the inhale/exhale lung CT pair, a preprocessing lung volume segmentation, and an estimate for the Jacobian of the DIR transformation. Given this information, the CT-P image, which provides the magnitude mass change for each voxel within the lung volume, is formulated as the solution to a constrained linear least squares problem defined by a series of subregional mean magnitude mass change measurements. Similar to previous robust CT-ventilation methods, the amount of uncertainty in a subregional sample mean measurement is related to measurement resolution and can be characterized with respect to a tolerance parameter τ . Spatial Spearman correlation between single photon emission CT perfusion (SPECT-P) and the proposed CT-P method was assessed in two patient cohorts via a parameter sweep of τ . The first cohort was comprised of 15 patients diagnosed with pulmonary embolism (PE) who had SPECT-P and 4DCT imaging acquired within 24 h of PE diagnosis. The second cohort was comprised of 15 nonsmall cell lung cancer patients who had SPECT-P and 4DCT images acquired prior to radiotherapy. For each test case, CT-P images were computed for 30 different uncertainty parameter values, uniformly sampled from the range [0.01, 0.125], and the Spearman correlation between the SPECT-P and the resulting CT-P images were computed. RESULTS: The median correlations between CT-P and SPECT-P taken over all 30 test cases ranged between 0.49 and 0.57 across the parameter sweep. For the optimal tolerance τ = 0.0385, the CT-P and SPECT-P correlations across all 30 test cases ranged between 0.02 and 0.82. A one-sample sign test was applied separately to the PE and lung cancer cohorts. A low Spearmen correlation of 15% was set as the null median value and two-sided alternative was tested. The PE patients showed a median correlation of 0.57 (IQR = 0.305). One-sample sign test was statistically significant with 96.5 % confidence interval: 0.20-0.63, P < 0.00001. Lung cancer patients had a median correlation of 0.57(IQR = 0.230). Again, a one-sample sign test for median was statistically significant with 96.5 percent confidence interval: 0.45-0.71, P < 0.00001. CONCLUSION: CT-Perfusion is the first mechanistic model designed to quantify magnitude blood mass changes on noncontrast dynamic CT as a surrogate for pulmonary perfusion. While the reported correlations with SPECT-P are promising, further investigation is required to determine the optimal CT acquisition protocol and numerical method implementation for CT-P imaging.

SPRINT Through Tasks: A Novel Curriculum for Improving Resident Task Management in the Emergency Department.

Introduction: The emergency department (ED) presents a challenging task-management environment to emergency medicine (EM) trainees. However, equipping residents with a tool to improve task switching (generically known as multitasking) could have positive impacts on patient care and physician emotional state. We designed a task-management tool and educational curriculum with the goal of improving emergency medicine resident task-switching ability. Methods: The task-management tool uses the acronym SPRINT: (1) stabilize critical patients, (2) perform procedures, (3) rack (see new patients in the chart rack), (4) in or out (reassess and disposition), (5) type it up (chart completion). These tasks and their order were decided on by two seasoned clinicians based on their years of experience in the ED. The SPRINT tool was taught to EM residents through a 1-hour curriculum consisting of an introductory video, a classroom-based workshop with multimedia didactics, and team learning with a card game simulating the use of the SPRINT tool on a shift. Residents were surveyed to evaluate their task-management confidence and perceived effectiveness of the curriculum. Results: A total of 34 EM residents participated in this training on the SPRINT tool. There was an improvement in resident confidence in task management, and residents reporting having a strategy for task prioritization 8 weeks after the workshop. Discussion: The SPRINT curriculum provides EM residents with a tool to manage the complex task-management environment of the ED. Further research in task-management education should focus on patient-oriented outcomes among physicians who have received this training.

An Emergency Medicine Milestone-Based Simulation Curriculum: Acute Ischemic Stroke.

Introduction: The emergency medicine (EM) resident's ability to make independent decisions in the setting of acute ischemic stroke has been reduced as a result of the involvement of multidisciplinary teams. This simulation was created to give EM residents the opportunity to independently manage the early stages of ischemic stroke and its complications. Methods: A solo learner was presented with a 55-year-old male with complaints consistent with an acute stroke. The resident had to calculate stroke severity; coordinate hospital resources; discuss risks, benefits, and alternatives to thrombolysis; and deal with subsequent complications. The learner had to keep a broad differential for sudden change in mental status and consider alternative interventions. Strategies to decrease intracranial pressure needed to be implemented while obtaining neurosurgical consultation. Debriefing included discussion of expected actions in the context of the Accreditation Council for Graduate Medical Education (ACGME) milestones. Residents' review of their video performance added additional self-reflection. Results: A total of 69 PGY 3 EM residents independently participated in this simulation over a 5-year period. Thirty-two completed a postsimulation evaluation. Nearly all learners felt that this case reflected an actual patient encounter and increased their confidence in managing stroke. The milestone-based feedback tool was completed with all learners. Anticipated actions linked to Level 1 and 2 milestones were regularly achieved while acquisition of Level 3 and 4 actions varied. Discussion: Case actions were uniquely characterized by the ACGME milestones, which helped to delineate learners' knowledge gaps and provided concrete areas for improvement.

Monthly Progression of Emergency Medicine Resident Efficiency: What Can We Expect of Our Residents Throughout Training?

BACKGROUND: Developing the capacity for efficient patient care is essential during emergency medicine (EM) residency training. Previous studies have demonstrated that resident efficiency improves during each year of training. OBJECTIVES: This study assessed the progression of EM resident efficiency monthly and sought to develop a model that describes this progression in terms of patients per hour (pts/h) weighted by month of training. METHODS: We performed a retrospective review of EM resident efficiency as determined by pts/h using EM resident monthly patient logs from a postgraduate year (PGY) 1-3 EM training program. Mean pts/h and standard deviation (SDs) were calculated based on month of training. One-way analysis of variance compared year-to-year training. We formulated several linear regression models to describe this progression. RESULTS: We analyzed 51 consecutive months of patient logs from 110 residents. The mean pts/h for PGY1 was 1.201 (n = 85, SD = 0.241), for PGY2 was 1.497 (n = 82, SD = 0.218), and for PGY3 was 1.676 (n = 80, SD = 0.224). Linear regression was used to describe patients seen per hour by the month of training. A significant regression was found with an R2 of 0.437 and p < 0.000. Over 36 months of training, a resident's predicted pts/h is equal to 1.113 + (0.018 × month of training). CONCLUSIONS: EM resident efficiency increases monthly, with most improvement occurring in the PGY1 year. Understanding this improvement may aid in resident performance evaluation and the understanding of predicted resident workflow.

Difficulty Breathing With a Rash: A Pediatric Simulation Case for Residents and Fellows.

INTRODUCTION: The purpose of the case is to teach health care professionals to recognize Henoch-Schönlein purpura (HSP), including rare and serious complications. The case includes a review of epidemiology, classification, clinical manifestations, and treatment of HSP. METHODS: Utilizing an adolescent simulation mannequin, we present the case of an 11-year-old female who presents to a pediatric emergency department with HSP and respiratory symptoms requiring intubation. This case reinforces the appearance of the characteristic rash and helps learners develop an algorithm for HSP management that includes the identification and management of abdominal pain associated with HSP, as well as the rare and serious complication of pulmonary vasculitis. We focus learners on managing severe respiratory distress in the HSP patient. Learners are assessed using standardized forms, and the learner outcome measurements include the recognition of HSP and successful management of abdominal pain and respiratory failure in this unique setting. RESULTS: This module has been used with pediatric residents, emergency medicine residents, pediatric emergency medicine fellows, and pediatric emergency medicine nurse practitioners. Approximately 30 learners have completed this module during seven separate sessions. All learners felt the case provided the opportunity to identify HSP as well as to manage a serious and rare complication of the disease. DISCUSSION: Overall, we have had positive feedback from the learners about this case, and it provides them the opportunity to see more rare complications during their training period. Learners leave the session with enhanced knowledge of HSP, as well as a review of respiratory failure and intubation.

PROGNOSTIC VALUE OF THE MULTIPLE MINI-INTERVIEW FOR EMERGENCY MEDICINE RESIDENCY PERFORMANCE.

BACKGROUND: The Multiple Mini-Interview (MMI) uses short, structured contacts, and is known to predict medical school success better than traditional interviews and application materials. Its utility in Emergency Medicine residency selection is untested. OBJECTIVES: We investigate whether it provides additional information regarding future first-year resident performance that can be useful in resident selection. METHODS: From three Emergency Medicine residency programs, 71 interns in their first month completed an MMI developed to focus on desirable resident characteristics. Application data were reviewed. First-year resident performance assessments covering the American Council for Graduate Medical Education (ACGME) core competencies, along with professionalism and performance concerns, were obtained. Multiple logistic regressions were employed and MMI correlations were compared with program rank lists and typical selection factors. RESULTS: An individual's score on the MMI correlated with overall performance (p < 0.05) in single logistic regression. MMI correlated with ACGME individual competencies patient care and procedural skills at a less robust level (p < 0.1), but not with any other outcomes. Rank list position correlated with the diagnostic skill competency (p < 0.05), but no others. Traditional selection factors correlated with overall performance, disciplinary action, patient care, medical knowledge, and diagnostic skills (p < 0.05). MMI was not correlated significantly with the outcomes when included in multiple ordinal logistic regression with other selection factors. CONCLUSIONS: MMI scores correlate with overall performance, but are not statistically significant when other traditional selection factors were considered. The MMI process seems potentially superior to program rank list at correlating with first-year performance. The MMI may provide additional benefit when examined using a larger and more diverse sample.

The multiple mini-interview for emergency medicine resident selection.

BACKGROUND: The Multiple Mini-Interview (MMI) uses multiple, short-structured contacts to evaluate communication and professionalism. It predicts medical school success better than the traditional interview and application. Its acceptability and utility in emergency medicine (EM) residency selection are unknown. OBJECTIVE: We theorized that participants would judge the MMI equal to a traditional unstructured interview and it would provide new information for candidate assessment. METHODS: Seventy-one interns from 3 programs in the first month of training completed an eight-station MMI focused on EM topics. Pre- and post-surveys assessed reactions. MMI scores were compared with application data. RESULTS: EM grades correlated with MMI performance (F[1, 66] = 4.18; p < 0.05) with honors students having higher scores. Higher third-year clerkship grades were associated with higher MMI performance, although this was not statistically significant. MMI performance did not correlate with match desirability and did not predict most other components of an application. There was a correlation between lower MMI scores and lower global ranking on the Standardized Letter of Recommendation. Participants preferred a traditional interview (mean difference = 1.36; p < 0.01). A mixed format (traditional interview and MMI) was preferred over a MMI alone (mean difference = 1.1; p < 0.01). MMI performance did not significantly correlate with preference for the MMI. CONCLUSIONS: Although the MMI alone was viewed less favorably than a traditional interview, participants were receptive to a mixed-methods interview. The MMI does correlate with performance on the EM clerkship and therefore can measure important abilities for EM success. Future work will determine whether MMI performance predicts residency performance.

A feasibility study of the sensitivity of emergency physician Dysphagia screening in acute stroke patients.

STUDY OBJECTIVE: To determine the sensitivity of dysphagia screening by emergency physicians on acute stroke patients. METHODS: To develop a 2-tiered dysphagia screen and performed it on a convenience sample of acute stroke patients. Tier 1 examined voice quality, swallowing complaints, facial asymmetry, and aphasia. Tier 2 involved a water swallow test, with evaluation for swallowing difficulty, voice quality compromise, and pulse oximetry desaturation (>or=2%). We classified patients passing both tiers as "low risk" and compared the screen's sensitivity to a formal assessment by speech language pathologists. To assess reproducibility, we performed 2 consecutive, blinded ED screens on a convenience sample of 32 patients. RESULTS: During 16 months, we enrolled a convenience sample of 103 patients, excluding 19 patients from data analysis for lack of a stroke discharge diagnosis (n=11), an incomplete speech language pathologist evaluation within 24 hours (n=7), or pneumonia on emergency department (ED) chest radiography (n=1). Of the 84 remaining patients, speech language pathologists identified dysphagia in 48. The sensitivity of the ED dysphagia screen was 96% (95% confidence interval [CI] 85% to 99%), with a negative likelihood ratio of 0.08 (95% CI 0.02 to 0.3). Reproducibility testing yielded a kappa for the overall screen result of 0.9 (95% CI 0.9-1.0) and a simple agreement of 97%. CONCLUSION: Preliminary data on the sensitivity and reliability of our ED dysphagia screening tool are promising. The simple screen provides an easy way for emergency physicians to identify acute stroke patients eligible for early oral medications and nutrition. Further validation and refinement of our screen are needed before its widespread adoption.

Intravenous fat emulsion: a potential novel antidote.

Intravenous fat emulsions (IFE) are traditionally used as a component of parenteral nutrition therapy. Recently, IFE was used to resuscitate severe local anesthetic drug toxicity. This review focuses on the potential role of IFE in treatment of toxicity due to local anesthetics and other lipid-soluble drugs. The general properties of IFE, metabolic fate, and associated adverse events are described. Cases of local anesthetic toxicity treated with IFE are presented along with a discussion of the possible antidotal mechanisms. Initial investigations into the antidotal use of IFE for lipophilic central nervous and cardiovascular drug toxicity are also reviewed.

The interaction of isoflurane and protein kinase C-activators on sarcolemmal KATP channels.

Protein kinase C (PKC)-dependent signaling pathways may be involved in the "memory" effect of anesthetic and ischemic preconditioning, which facilitates activation of cardioprotective adenosine triphosphate (ATP)-sensitive potassium channels during later ischemic challenge and ATP depletion. Using patch-clamp techniques, we found that exposure of isolated guinea pig cardiomyocytes to 1 mM of isoflurane after phorbol ester stimulation of PKC facilitates the induction of larger (P < or = 0.05) sarcolemmal K(ATP) channel currents (IKATP) during cell dialysis with 0.5, compared to 1.0, mM of ATP in the pipette (10 +/- 5 versus 2 +/- 1 pA/pF in five and six cells, respectively). A PKC inhibitor, bisindolylmaleimide, abolished the induction of IKATP by a second brief isoflurane exposure under these conditions. A diacylglycerol PKC activator applied via the pipette elicited concentration-related activation of IKATP. The diacylglycerol alone (0.5 microM) elicited I(KATP), averaging 5 +/- 3 pA/pF in nine cells. Briefly treating myocytes on the microscope stage with isoflurane, followed by washout and patching with the same diacylglycerol solution, elicited larger (P < or = 0.01) IKATP, averaging 40 +/- 9 pA/pF (10 cells), with an onset 48 +/- 2 min after anesthetic pretreatment. Facilitation of IKATP by isoflurane during the reduction of intracellular ATP is dependent on PKC, whereas "preconditioning" myocytes with isoflurane causes persistent changes in sarcolemmal KATP channel function, which enhance the induction of IKATP by a diacylglycerol.

Protein kinase C-epsilon primes the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to modulation by isoflurane.

BACKGROUND: Cardioprotection by volatile anesthetic-induced preconditioning is known to involve intracellular signaling pathways. Recent studies have shown that protein kinase C (PKC) plays an important role in anesthetic-induced preconditioning. In this study, the effects of the activation of specific isozymes of PKC, specifically PKC-epsilon and -delta, on the modulation of the sarcolemmal adenosine triphosphate-sensitive potassium (sarcKATP) channel by isoflurane were investigated. METHODS: The sarcKATP current was measured in ventricular myocytes isolated from guinea pig hearts using the whole cell configuration of the patch clamp technique. Peptides that induced the translocation of specific PKC isozymes were used to activate PKC-epsilon and PKC-delta. RESULTS: Under whole cell conditions, isoflurane alone was unable to elicit the opening of the sarcKATP channel. Pretreatment with the specific PKC-epsilon activator, PP106, primed the sarcKATP channel to open in the presence of isoflurane. The resulting sarcKATP current densities in the presence of 0.88 mm isoflurane were 6.5 +/- 6.0 pA/pF (n = 7) and 40.4 +/- 18.2 pA/pF (n = 7) after pretreatment with 100 and 200 nm PP106, respectively. The PKC-epsilon antagonist PP93 abolished this effect. A scrambled peptide of the PKC-epsilon activator PP105 did not prime the sarcKATP channel. The PKC-delta activator PP114 was significantly less effective in priming the sarcKATP channel. 5-Hydroxydecanoate significantly attenuated the effect of the PKC-epdsilon activator on the sarcKATP channel. In addition, immunohistochemical analysis showed that the PKC-epsilon isoform translocated to both the mitochondria and sarcolemma after anesthetic-induced preconditioning, whereas the PKC-delta isoform translocated to the mitochondria. CONCLUSION: The PKC-epsilon isozyme primed the sarcKATP channel to open in the presence of isoflurane. The PKC-delta isozyme was significantly less effective in modulating the isoflurane effect on this channel.