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1.
Pediatr Crit Care Med ; 24(9): 775-781, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37260321

RESUMEN

OBJECTIVES: Report on the use of two statewide Medical Operations Coordination Centers (MOCCs) to manage a rapid surge in pediatric acute and critical care patient needs. DESIGN: Brief report. SETTING: The states of Washington and Oregon during the pediatric respiratory surge in November 2022/December 2022 which overwhelmed existing pediatric acute and critical care hospital capacity. PATIENTS: Pediatric patients requiring hospitalization in Washington and Oregon. INTERVENTIONS: Adaptations to the use of two existing statewide MOCCs to provide pediatric patient load balancing through surveillance, modifications of existing referral agreements, coordinated expansion of resources, activation of regional crisis standards of care, and integration of pediatric critical care physicians from Harborview Medical Center as subject matter experts (SMEs). MEASUREMENTS AND MAIN RESULTS: The Washington and Oregon MOCCs managed 183 pediatric requests from hospitals unable to transfer pediatric patients between November 1, 2022, and December 14, 2022. Sixteen percent of requests were for children younger than 3 months and 37% were for children between 3 months and 1 year; most had acute viral respiratory disease. Requests for children older than 13 years old were primarily intentional drug ingestions. Fifty-eight percent were for critically ill children and 17% originated from critical access hospitals. Washington's SMEs were utilized in nearly a quarter of cases with the disposition changing in 38% of these. CONCLUSIONS: Washington and Oregon statewide MOCCs have leveraged centralized coordination to effectively load balance a surge in pediatric patients which has overwhelmed existing pediatric hospital resources. Centralized coordination and surveillance informed pediatric hospitals and policy makers of unmet clinical needs and facilitated rapid expansion of clinical capacity and modifications to referral processes. Integration of pediatric SMEs enabled efficient triage of these resources. MOCCs provide an adaptable centralized resource for addressing surge and have been effective in managing overwhelmed pediatric hospital resources in Washington and Oregon.


Asunto(s)
Hospitalización , Hospitales Pediátricos , Niño , Humanos , Estados Unidos , Adolescente , Triaje , Washingtón , Derivación y Consulta , Capacidad de Reacción
2.
J Nurs Care Qual ; 36(2): 112-116, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33259469

RESUMEN

BACKGROUND: The COVID-19 pandemic resulted in the need for hospitals to plan for a potential "surge" of COVID-19 patients. PROBLEM: Prior to the onset of the COVID-19 pandemic, our hospital adult acute care capacity ranged 90% to 100%, and a potential hospital surge was projected for Oregon that would exceed existing capacity. APPROACH: A multidisciplinary team with stakeholders from nursing leadership, nursing units, nurse-led case management, and physicians from hospital medicine was convened to explore the conversion of an ambulatory surgical center to overflow patient acute care capacity. OUTCOMES: A protocol was rapidly created and implemented, ultimately transferring 12 patients to an ambulatory surgery unit. CONCLUSIONS: This project highlighted the ability for stakeholders and innovators to work together in an interprofessional, multidisciplinary way to rapidly create an overflow unit. While this innovation was designed to address COVID-19, the lessons learned can be applied to any other emerging infectious disease or acute care capacity crisis.


Asunto(s)
COVID-19/epidemiología , COVID-19/terapia , Planificación Hospitalaria/organización & administración , Innovación Organizacional , Grupo de Atención al Paciente/organización & administración , Humanos , Oregon/epidemiología
3.
Anesthesiology ; 130(4): 530-540, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30601218

RESUMEN

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.


Asunto(s)
Desfibriladores Implantables/normas , Electrodos Implantados/normas , Fenómenos Electromagnéticos , Electrocirugia/normas , Marcapaso Artificial/normas , Adulto , Anciano , Desfibriladores Implantables/efectos adversos , Electrodos Implantados/efectos adversos , Electrocirugia/instrumentación , Electrocirugia/métodos , Femenino , Cardiopatías/fisiopatología , Cardiopatías/terapia , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial/efectos adversos
4.
Anesth Analg ; 125(1): 58-65, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28319519

RESUMEN

BACKGROUND: Economic, personnel, and procedural challenges often complicate and interfere with efficient and safe perioperative care of patients with cardiovascular implantable electronic devices (CIEDs). In the context of a process improvement initiative, we created and implemented a comprehensive anesthesiologist-run perioperative CIED service to respond to all routine requests for perioperative CIED consultations at a large academic medical center. This study was designed to determine whether this new care model was associated with improved operating room efficiency, reduced institutional cost, and adequate patient safety. METHODS: We included patients with a CIED and a concurrent cohort of patients with the same eligibility criteria but without a CIED who underwent first-case-of-the-day surgery during the periods between February 1, 2008, and August 17, 2010 (preintervention) and between March 4, 2012, and August 1, 2014 (postintervention). The primary end point was delay in first-case-of-the day start time. We used multiple linear regression to compare delays in start times during the preintervention and postintervention periods and to adjust for potential confounders. A patient safety database was queried for CIED-related complications. Cost analysis was based on labor minutes saved and was calculated using nationally published administrative estimates. RESULTS: A total of 18,148 first-case surgical procedures were performed in 15,100 patients (preintervention period-7293 patients and postintervention period-7807 patients). Of those, 151 (2.1%) patients had a CIED in the preintervention period, and 146 (1.9%) had a CIED in the postintervention period. After adjustment for imbalances in baseline characteristics (age, American Society of Anesthesiologists physical status, and surgical specialty), the difference in mean first-case start delay between the postintervention and preintervention periods in the cohort of patients with a CIED was -16.7 minutes (95% confidence interval [CI], -26.1 to -7.2). The difference in mean delay between the postintervention and preintervention periods in the cohort without a CIED was -4.7 minutes (95% CI, -5.4 to -3.9). There were 3 CIED-related adverse events during the preintervention period and none during the postintervention period. Based on reduction in first-case start delay, the intervention was associated with cost savings (estimated institutional savings $14,102 annually, or $94.06 per CIED patient), with a return on investment ratio of 2.18 over the course of the postintervention period. CONCLUSIONS: Based on our experience, specially trained anesthesiologists can provide efficient and safe perioperative care for patients with CIEDs. Other centers may consider implementing a similar strategy as our specialty adopts the perioperative surgical home model.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Desfibriladores Implantables , Evaluación de Procesos y Resultados en Atención de Salud , Marcapaso Artificial , Atención Perioperativa/métodos , Centros Médicos Académicos , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Cardíacos/economía , Sistema Cardiovascular , Estudios de Cohortes , Femenino , Costos de la Atención en Salud , Humanos , Masculino , Persona de Mediana Edad , Quirófanos , Seguridad del Paciente , Periodo Perioperatorio , Medición de Riesgo , Factores de Tiempo
6.
Curr Opin Crit Care ; 20(5): 507-15, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25010460

RESUMEN

PURPOSE OF REVIEW: Therapeutic hypothermia following out-of-hospital cardiac arrest improves neurological recovery. Coupled with neurological benefit, multiple complications including infection have been associated with therapeutic hypothermia following out-of-hospital cardiac arrest. In this review, we will discuss therapeutic hypothermia, and more broadly, temperature management, as a risk for ICU infection. RECENT FINDINGS: The application of therapeutic hypothermia following out-of-hospital cardiac arrest has been associated with infectious complications. Studies of hypothermic animal models have provided useful insights into mechanisms by which therapeutic hypothermia confers neuroprotection. Ironically, the same mechanisms through which therapeutic hypothermia provides neuroprotection have been implicated in the risk of infection associated with therapeutic hypothermia. Studies have demonstrated types of infections, pathogens, and the impact of infections on mortality and neurological recovery. SUMMARY: Studies demonstrate increased rate of pneumonia and bacteremia but decreased rate of other infections, suggesting redistribution but no overall increased risk of infection per se. The diagnosis of infection during therapeutic hypothermia does not impact mortality or neurological recovery.


Asunto(s)
Temperatura Corporal , Infecciones Relacionadas con Catéteres/prevención & control , Hipotermia Inducida , Unidades de Cuidados Intensivos , Paro Cardíaco Extrahospitalario/terapia , Neumonía/prevención & control , Reanimación Cardiopulmonar , Infecciones Relacionadas con Catéteres/inmunología , Humanos , Hipotermia Inducida/efectos adversos , Fármacos Neuroprotectores , Paro Cardíaco Extrahospitalario/inmunología , Neumonía/inmunología , Factores de Riesgo
7.
Am J Health Syst Pharm ; 79(22): 2018-2025, 2022 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-35671342

RESUMEN

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.


Asunto(s)
Registros Electrónicos de Salud , Farmacéuticos , Humanos , Tecnología de Seguimiento Ocular , Flujo de Trabajo , Unidades de Cuidados Intensivos
8.
Am J Physiol Heart Circ Physiol ; 298(2): H679-87, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20008276

RESUMEN

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 ischemia via EET-mediated 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.


Asunto(s)
Epóxido Hidrolasas/antagonistas & inhibidores , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/prevención & control , Miocitos Cardíacos/patología , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/metabolismo , Animales , Supervivencia Celular/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Epóxido Hidrolasas/genética , Epóxido Hidrolasas/metabolismo , Quinasas Janus/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación/genética , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Polimorfismo de Nucleótido Simple/genética
10.
Respir Care ; 64(7): 743-751, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30967439

RESUMEN

BACKGROUND: Acute right ventricular dysfunction is a challenging problem in the immediate postoperative period following orthotopic heart transplantation. There are no prior reports of the use of inhaled iloprost in the setting of acute right ventricular dysfunction and acute pulmonary hypertension. Our hypothesis was that the use of inhaled iloprost in heart transplant recipients would be associated with a reduction in the duration of mechanical ventilation compared to patients being treated with continuous inhaled epoprostenol. Additionally, we hypothesized that the change in inhaled vasodilatory therapy would not be associated with a significant change in postoperative bleeding or use of vasoactive medications. METHODS: We reviewed charts of 80 consecutive patients undergoing heart transplantation at our institution between July 1, 2003, and August 8, 2008. From July 1, 2003 to March 13, 2006, epoprostenol was our primary vasodilator; subsequently epoprostenol was replaced with iloprost. We included 39 subjects who received epoprostenol and 40 subjects who received iloprost. Data were collected on the use of inhaled vasodilators, comparing periods before and after our institutional protocol change. Demographic data, hemodynamic values, drain output, and any requirement for vasoactive medication infusions were collected. Our primary end point was the natural logarithm of duration of mechanical ventilation. Secondary end points were hemodynamic values and length of ICU and hospital stay. RESULTS: Subjects treated with iloprost were mechanically ventilated for 0.36 ± 0.20 (adjusted mean ± SE) log days, which was shorter (P = .033) than the 1.00 ± 0.22 logdays for subjects treated with epoprostenol. This resulted in an estimated median number of mechanically ventilated days for subjects treated with epoprostenol that was approximately 1.9 times longer than the estimated median number of ventilated days for subjects treated with iloprost (95% CI 1.05-3.4, P = .033). There were no differences in safety end points or length of hospital stay. CONCLUSIONS: Use of inhaled iloprost was associated with shorter duration of mechanical ventilation compared to inhaled epoprostenol, without safety concerns.


Asunto(s)
Epoprostenol/administración & dosificación , Trasplante de Corazón/efectos adversos , Hipertensión Pulmonar , Iloprost/administración & dosificación , Complicaciones Posoperatorias , Disfunción Ventricular Derecha , Administración por Inhalación , Adulto , Femenino , Trasplante de Corazón/métodos , Hemodinámica/efectos de los fármacos , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/cirugía , Hipertensión Pulmonar/terapia , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/terapia , Respiración Artificial/métodos , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , Vasodilatadores/administración & dosificación , Disfunción Ventricular Derecha/etiología , Disfunción Ventricular Derecha/fisiopatología , Disfunción Ventricular Derecha/terapia
12.
ICU Dir ; 3(6): 271-278, 2012 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-23420469

RESUMEN

BACKGROUND: Therapeutic hypothermia (TH) has been established as an effective treatment for preserving neurological function after out of hospital cardiac arrest (CA). Use of TH has been limited in cardiac surgery patients in particular because of concern about adverse effects such as hemorrhage and dysrhythmia. Little published data describe efficacy or safety of TH in cardiac surgical patients who suffer unintentional CA. However, the benefits of TH are such as may suggest clinical equipoise, even in this high risk patient population. OBJECTIVE: To report a series of three patients in our institution's cardiac surgery intensive care unit who suffered unintentional CA within 48 hours of cardiac surgery and were treated with TH. METHODS: After institutional review board approval, study patients were identified by diagnosis of undesired intraoperative CA or arrest on ICU days 1-2, as well as having documented TH. The institution's electronic medical record and the Society of Thoracic Surgeons database were retrospectively reviewed for demographic information, comorbid diagnoses, surgical procedure, and outcomes including hemorrhage, re-warming dysrhythmias, infection, in-hospital mortality, and neurologic outcome were assessed. TH was initiated and monitored using active cooling pads according to written institutional protocol. RESULTS: Four patients received TH after perioperative arrest. One patient was inadequately cooled and had massive surgical bleeding, and was therefore excluded from this review. The remaining three patients had a predicted mortality of 14.6% (±13.3) based on Euroscore calculation, and were cooled for 17.6±4.0 hours after CA. Coagulopathy, hypovolemia, severe electrolyte abnormalities, and re-warming dysrhythmias were not identified in any patient. 2 patients were discharged home and 1 was discharged to a long-term care facility. CONCLUSION: Herein we report the safe and successful use of TH after unintentional perioperative CA in 3 cardiac surgery patients. These data suggest that further investigation of this therapy may be warranted given the potential benefit and apparent safety in a small series.

13.
Crit Care Clin ; 26(2): 365-82, table of contents, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20381726

RESUMEN

Echocardiography is a rapid, noninvasive, comprehensive cardiac assessment option for patients presenting with hemodynamic instability. In patients with septic shock, echocardiography can be used to guide fluid therapy by measuring collapsibility of the inferior vena cava. Sepsis-induced myocardial dysfunction can be diagnosed, and responses to therapy can be monitored with echo. Patients with persistent shock should be evaluated for right heart failure, dynamic left ventricular obstruction, or tamponade if they do not respond to resuscitation and norepinephrine. Unexpected or rare findings that affect management may be revealed using focused echocardiography. This article presents national and international competency statements regarding critical care echocardiography and training resources for intensivists.


Asunto(s)
Ecocardiografía/métodos , Choque Séptico/fisiopatología , Ecocardiografía/instrumentación , Fluidoterapia/métodos , Hemodinámica/fisiología , Humanos , Choque Séptico/diagnóstico , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiología
14.
Am J Physiol Heart Circ Physiol ; 295(1): H409-15, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18502904

RESUMEN

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 Met(5)-enkephalin (ME) to reduce cell death after oxygen-glucose deprivation (OGD) is influenced by the presence of 17beta-estradiol (E(2)) 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 degrees C (n = 4 to 5 replicates). Cell cultures were incubated in E(2) for 15 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 E(2), 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 E(2) in a sex-independent manner via activation of estrogen receptors, and this interaction is dependent on iNOS.


Asunto(s)
Encefalina Metionina/metabolismo , Estradiol/metabolismo , Glucosa/deficiencia , Miocitos Cardíacos/metabolismo , Oxígeno/metabolismo , Receptores Opioides delta/metabolismo , Animales , Animales Recién Nacidos , Muerte Celular , Hipoxia de la Célula , Supervivencia Celular , Células Cultivadas , Citoprotección , Inhibidores Enzimáticos/farmacología , Estradiol/análogos & derivados , Estradiol/farmacología , Antagonistas de Estrógenos/farmacología , Femenino , Fulvestrant , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Receptores Opioides delta/agonistas , Factores Sexuales
15.
Am J Physiol Heart Circ Physiol ; 295(5): H2128-34, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18835921

RESUMEN

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 wild-type or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. 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.


Asunto(s)
Adamantano/análogos & derivados , Inhibidores Enzimáticos/farmacología , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/deficiencia , Eliminación de Gen , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Urea/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/administración & dosificación , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/metabolismo , Adamantano/administración & dosificación , Adamantano/farmacología , Animales , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Epóxido Hidrolasas/genética , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/enzimología , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/enzimología , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/enzimología , Factores de Tiempo , Urea/administración & dosificación , Urea/farmacología
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