RESUMEN
When determining extracorporeal oxygen transfer (V ML O 2 ) during venovenous extracorporeal membrane oxygenation (VV ECMO) dissolved oxygen is often considered to play a subordinate role due to its poor solubility in blood plasma. This study was designed to assess the impact of dissolved oxygen on systemic oxygenation in patients with acute respiratory distress syndrome (ARDS) on VV ECMO support by differentiating between dissolved and hemoglobin-bound extracorporeal oxygen transfer. We calculated both extracorporeal oxygen transfer based on blood gas analysis using the measuring energy expenditure in extracorporeal lung support patients (MEEP) protocol and measured oxygen uptake by the native lung with indirect calorimetry. Over 20% of V ML O 2 and over 10% of overall oxygen uptake (VO 2 total ) were realized as dissolved oxygen. The transfer of dissolved oxygen mainly depended on ECMO blood flow (BF ML ). In patients with severely impaired lung function dissolved oxygen accounted for up to 28% of VO 2 total . A clinically relevant amount of oxygen is transferred as physically dissolved fraction, which therefore needs to be considered when determining membrane lung function, manage ECMO settings or guiding the weaning procedure.
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Oxigenación por Membrana Extracorpórea , Oxígeno , Síndrome de Dificultad Respiratoria , Oxigenación por Membrana Extracorpórea/métodos , Humanos , Oxígeno/sangre , Oxígeno/metabolismo , Síndrome de Dificultad Respiratoria/terapia , Persona de Mediana Edad , Masculino , Femenino , Adulto , Análisis de los Gases de la Sangre/métodos , Anciano , Consumo de Oxígeno/fisiología , SolubilidadRESUMEN
BACKGROUND: Mechanical ventilation is an essential component in the treatment of patients with acute respiratory distress syndrome. Prompt adaptation of the settings of a ventilator to the variable needs of patients is essential to ensure personalised and protective ventilation. Still, it is challenging and time-consuming for the therapist at the bedside. In addition, general implementation barriers hinder the timely incorporation of new evidence from clinical studies into routine clinical practice. RESULTS: We present a system combing clinical evidence and expert knowledge within a physiological closed-loop control structure for mechanical ventilation. The system includes multiple controllers to support adequate gas exchange while adhering to multiple evidence-based components of lung protective ventilation. We performed a pilot study on three animals with an induced ARDS. The system achieved a time-in-target of over 75 % for all targets and avoided any critical phases of low oxygen saturation, despite provoked disturbances such as disconnections from the ventilator and positional changes of the subject. CONCLUSIONS: The presented system can provide personalised and lung-protective ventilation and reduce clinician workload in clinical practice.
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Respiración Artificial , Síndrome de Dificultad Respiratoria , Animales , Proyectos Piloto , Volumen de Ventilación Pulmonar/fisiología , Pulmón , Respiración , Síndrome de Dificultad Respiratoria/terapiaRESUMEN
Measurement of oxygen uptake (VO 2 ) and carbon dioxide removal (VCO 2 ) on membrane lungs (MLs) during extracorporeal membrane oxygenation (ECMO) provides potential for improved and safer therapy. Real-time monitoring of ML function and degradation, calculating caloric needs as well as cardiac output, and weaning algorithms are among the future possibilities. Our study compared the continuous measurement of the standalone Quantum Diagnostics System (QDS) with the published Measuring Energy Expenditure in ECMO patients (MEEP) approach, which calculates sequential VO 2 and VCO 2 values via blood gas analysis and a physiologic gas content model. Thirty-nine datasets were acquired during routine venovenous ECMO intensive care treatment and analyzed. VO 2 was clinically relevant underestimated via the blood-sided measurement of the QDS compared to the MEEP approach (mean difference -42.61 ml/min, limits of agreement [LoA] -2.49/-87.74 ml), which could be explained by the missing dissolved oxygen fraction of the QDS equation. Analysis of VCO 2 showed scattered values with wide limits of agreement (mean difference 54.95 ml/min, LoA 231.26/-121.40 ml/min) partly explainable by a calculation error of the QDS. We described potential confounders of gas-sided measurements in general which need further investigation and recommendations for enhanced devices.
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Oxigenación por Membrana Extracorpórea , Humanos , Pulmón/metabolismo , Oxígeno , Dióxido de Carbono , Gasto CardíacoRESUMEN
Infarction-related cardiogenic shock is the most severe complication of an acute coronary syndrome, that still bears a high mortality up to 50â% and wastes a lot of resources of an intensive care unit, especially if extracorporeal assist devices are used.In contrast to the adverse short-term outcome, patients fare a surprisingly well in the long range, both for survival and quality of life. Same as for the acute disease, which needs specific cardiologic and intensive care measures, long-term follow-up care needs a lot of medical and lifestyle interventions and treatments to obtain the best possible result for the patients. Since there is good evidence for cardiologic therapies from randomized controlled trials, high quality data to treat long-term sequalae of the stay on intensive care unit, are sparse.Overall, follow-up care of survivors of infarction related cardiogenic shock includes the best available treatment of the coronary artery disease, intensified heart failure therapy of left and right heart dysfunction and evaluation for the risk of sudden cardiac death and treatment of sequelae of the intensive-care-unit stay.
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Síndrome Coronario Agudo , Choque Cardiogénico , Síndrome Coronario Agudo/complicaciones , Estudios de Seguimiento , Humanos , Calidad de Vida , Choque Cardiogénico/etiología , Choque Cardiogénico/terapiaRESUMEN
BACKGROUND: Models of hypoxemic lung injury caused by lavage-induced pulmonary surfactant depletion are prone to prompt recovery of blood oxygenation following recruitment maneuvers and have limited translational validity. We hypothesized that addition of injurious ventilation following surfactant-depletion creates a model of the acute respiratory distress syndrome (ARDS) with persistently low recruitability and higher levels of titrated "best" positive end-expiratory pressure (PEEP) during protective ventilation. METHODS: Two types of porcine lung injury were induced by lung lavage and 3 h of either protective or injurious ventilation, followed by 3 h of protective ventilation (N = 6 per group). Recruitment maneuvers (RM) and decremental PEEP trials comparing oxygenation versus dynamic compliance were performed after lavage and at 3 h intervals of ventilation. Pulmonary gas exchange function, respiratory mechanics, and ventilator-derived parameters were assessed after each RM to map the course of injury severity and recruitability. RESULTS: Lung lavage impaired respiratory system compliance (Crs) and produced arterial oxygen tensions (PaO2) of 84±13 and 80±15 (FIO2 = 1.0) with prompt increase after RM to 270-395 mmHg in both groups. After subsequent 3 h of either protective or injurious ventilation, PaO2/FIO2 was 104±26 vs. 154±123 and increased to 369±132 vs. 167±87 mmHg in response to RM, respectively. After additional 3 h of protective ventilation, PaO2/FIO2 was 120±15 vs. 128±37 and increased to 470±68 vs. 185±129 mmHg in response to RM, respectively. Subsequently, decremental PEEP titration revealed that Crs peaked at 36 ± 10 vs. 25 ± 5 ml/cm H2O with PEEP of 12 vs. 16 cmH2O, and PaO2/FIO2 peaked at 563 ± 83 vs. 334 ± 148 mm Hg with PEEP of 16 vs. 22 cmH2O in the protective vs. injurious ventilation groups, respectively. The large disparity of recruitability between groups was not reflected in the Crs nor the magnitude of mechanical power present after injurious ventilation, once protective ventilation was resumed. CONCLUSION: Addition of transitory injurious ventilation after lung lavage causes prolonged acute lung injury with diffuse alveolar damage and low recruitability yielding high titrated PEEP levels. Mimicking lung mechanical and functional characteristics of ARDS, this porcine model rectifies the constraints of single-hit lavage models and may enhance the translation of experimental research on mechanical ventilation strategies.
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To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19-related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)-related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18-58 d) versus 16 days (IQR, 19-39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6-28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9-27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7-25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.
RESUMEN
Cardiogenic shock as a complication of myocardial infarction (5-10%) increases the mortality of uncomplicated myocardial infarction from less than 10% to 40%. This is due to the development of multiple organ dysfunction syndrome triggered by the extensive shock-induced impairment of organ perfusion. Therefore, guideline-based treatment should not only be restricted to reopening of the occluded coronary artery and management of complications of the infarction: important for survival are also guideline-driven optimization of organ perfusion by inotropic and vasoactive substances and, with well-defined indications, by temporary mechanical circulatory support but not by intra-aortic counterpulsation. Equally important, however, are shock-specific intensive care measures to prevent or attenuate organ dysfunction, such as lung protective ventilation in cases where ventilation is obligatory.
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Infarto del Miocardio , Choque Cardiogénico , Humanos , Contrapulsador Intraaórtico , Insuficiencia Multiorgánica , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapiaRESUMEN
PURPOSE: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. METHODS: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. RESULTS: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 ± 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. CONCLUSION: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes.
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Óxido Nítrico , Respiración , Administración por Inhalación , Humanos , Reproducibilidad de los Resultados , Respiración Artificial , Ventiladores MecánicosRESUMEN
The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow () to cardiac output (). Thermodilution-based measurements of may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of and Rf on classic thermodilution-based measurements of in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow () at the aortic root. Rf was quantified with the ultrasound dilution technique. was set to 0-125% of and was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated () at all settings compared to . The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between and increased with an of 75-125%/ compared to QEC <50%/. Overestimation of was highest when resulted in a high Rf. Thus, thermodilution-based measurements can overestimate cardiac output during VV ECMO. The degree of overestimation of depends on the EC/ ratio and the recirculation fraction.
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Oxigenación por Membrana Extracorpórea , Termodilución , Animales , Gasto Cardíaco/fisiología , Oxigenación por Membrana Extracorpórea/métodos , Hemodinámica , Pulmón , Porcinos , Termodilución/métodosRESUMEN
BACKGROUND: In cases of hypertrophic obstructive cardiomyopathy (HOCM), the systolic anterior motion of the mitral valve apparatus results in an obstruction of the left ventricular outflow tract (LVOT), which is known as the SAM [systolic anterior motion] phenomenon. Hypothetically, a pathological obstruction of the LVOT of a different etiology would result in a comparable hemodynamic instability, which would be refractory to inotrope therapy, and may be detectable through echocardiography. CASE PRESENTATION: We observed a severely impaired left ventricular function due to a combination of a thrombotic LVOT obstruction and distinctive mitral regurgitation in a 56-year-old Caucasian, female patient after massive transfusion with aggressive procoagulant therapy. Initially, the patient had to be resuscitated due to cardiac arrest after a long-distance flight. The resuscitation attempts in combination with lysis therapy due to suspected pulmonary artery embolism were initially successful but resulted in traumatic liver injury, hemorrhagic shock and subsequent acute respiratory distress syndrome (ARDS). Oxygenation was stabilized with veno-venous extracorporeal membrane oxygenation (ECMO), but the hemodynamic situation deteriorated further. Transesophageal echocardiography (TEE) showed a massive, dynamic LVOT obstruction. Two thrombi were attached to the anterior leaflet of the mitral valve, resulting in a predominantly systolic obstruction. Unfortunately, the patient died of multiple-organ failure despite another round of lysis therapy and escalation of the ECMO circuit to a veno-venoarterial cannulation for hemodynamic support. CONCLUSION: Massive transfusion with aggressive procoagulant therapy resulted in mitral valve leaflet thrombosis with dynamic, predominantly systolic LVOT obstruction, comparable to the SAM phenomenon. The pathology was only detectable with a TEE investigation.
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Cardiomiopatía Hipertrófica , Insuficiencia de la Válvula Mitral , Choque Hemorrágico , Obstrucción del Flujo Ventricular Externo , Femenino , Humanos , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Choque Hemorrágico/etiología , Choque Hemorrágico/terapia , Obstrucción del Flujo Ventricular Externo/diagnóstico por imagen , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/terapiaRESUMEN
BACKGROUND: The second edition of the German-Austrian S3 guideline contains updated evidence-based recommendations for the treatment of patients with infarction-related cardiogenic shock (ICS), whose mortality is several times higher than that of patients with a hemodynamically stable myocardial infarction (1). METHODS: In five consensus conferences, the experts developed 95 recommendations-including two statements-and seven algorithms with concrete instructions. RESULTS: Recanalization of the coronary vessel whose occlusion led to the infarction is crucial for the survival of patients with ICS. The recommended method of choice is primary percutaneous coronary intervention (pPCI) with the implantation of a drug-eluting stent (DES). If multiple coronary vessels are diseased, only the infarct artery (the "culprit lesion") should be stented at first. For cardiovascular pharmacotherapy-primarily with dobutamine and norepinephrine-the recommended hemodynamic target range for mean arterial blood pressure is 65-75 mmHg, with a cardiac index (CI) above 2.2 L/min/m2. For optimal treatment in intensive care, recommendations are given regarding the type of ventilation (invasive rather than non-invasive, lungprotective), nutrition (no nutritional intake in uncontrolled shock, no glutamine supplementation), thromboembolism prophylaxis (intravenous heparin rather than subcutaneous prophylaxis), und further topics. In case of pump failure, an intra-aortic balloon pump is not recommended; temporary mechanical support systems (Impella pumps, veno-arterial extracorporeal membrane oxygenation [VA-ECMO], and others) are hemodynamically more effective, but have not yet been convincingly shown to improve survival. CONCLUSION: Combined cardiological and intensive-care treatment is crucial for the survival of patients with ICS. Coronary treatment for ICS seems to have little potential for further improvement, while intensive-care methods can still be optimized.
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Stents Liberadores de Fármacos , Infarto del Miocardio , Austria , Humanos , Contrapulsador Intraaórtico , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapiaRESUMEN
Various animal models exist to study the complex pathomechanisms of the acute respiratory distress syndrome (ARDS). These models include pulmo-arterial infusion of oleic acid, infusion of endotoxins or bacteria, cecal ligation and puncture, various pneumonia models, lung ischemia/reperfusion models and, of course, surfactant depletion models, among others. Surfactant depletion produces a rapid, reproducible deterioration of pulmonary gas exchange and hemodynamics and can be induced in anesthetized pigs using repeated lung lavages with 0.9% saline (35 mL/kg body weight, 37 °C). The surfactant depletion model supports investigations with standard respiratory and hemodynamic monitoring with clinically applied devices. But the model suffers from a relatively high recruitability and ventilation with high airway pressures can immediately reduce the severity of the injury by reopening atelectatic lung areas. Thus, this model is not suitable for investigations of ventilator regimes that use high airway pressures. A combination of surfactant depletion and injurious ventilation with high tidal volume/low positive end-expiratory pressure (high Tv/low PEEP) to cause ventilator induced lung injury (VILI) will reduce the recruitability of the resulting lung injury. The advantages of a timely induction and the possibility to perform experimental research in a setting comparable to an intensive care unit are preserved.
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Modelos Animales de Enfermedad , Surfactantes Pulmonares , Respiración Artificial/efectos adversos , Síndrome de Dificultad Respiratoria/etiología , Animales , Hemodinámica , Pulmón , Masculino , Intercambio Gaseoso Pulmonar , PorcinosRESUMEN
Despite advances in the treatment of acute myocardial infarction with subsequent mortality reduction, which are mainly caused by the early timing of revascularization, cardiogenic shock still remains the leading cause of death with mortality rates still approaching 40 to 50%. Cardiogenic shock is characterized by a multiorgan dysfunction syndrome, often complicated by a systemic inflammatory response syndrome that affects the outcome more than the reduction of the cardiac contractile function. However, both European and American guidelines on myocardial infarction focus on interventional or surgical aspects only. Therefore, experts from eight German and Austrian specialty societies including the German Society for Thoracic and Cardiovascular Surgery published the German-Austrian S3 guideline "cardiogenic shock due to myocardial infarction: diagnosis, monitoring, and treatment" to provide evidence-based recommendations for the diagnosis and treatment of infarction-related cardiogenic shock in 2010 covering the topics of early revascularization, revascularization techniques, intensive care unit treatment including ventilation, transfusion regimens, adjunctive medical therapy, and mechanical support devices. Within the last 3 years, this guideline was updated as some major recommendations were outdated, or new evidence had been found. This review will therefore outline the management of patients with cardiogenic shock complicating acute myocardial infarction according to the updated guideline with a major focus on evidence-based recommendations which have been found relevant for cardiac surgery.
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Infarto del Miocardio , Choque Cardiogénico , Austria , Humanos , Contrapulsador Intraaórtico , Infarto del Miocardio/complicaciones , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/etiología , Choque Cardiogénico/terapia , Resultado del TratamientoRESUMEN
Acute kidney injury (AKI) corrupts the outcome of about 50% of all critically ill patients. We investigated the possible contribution of the pathology acidemia on the development of AKI. Pigs were exposed to acidemia, acidemia plus hypoxemia or a normal acid-base balance in an experimental setup, which included mechanical ventilation and renal replacement therapy to facilitate biotrauma caused by extracorporeal therapies. Interestingly, extensive histomorphological changes like a tubular loss of cell barriers occurred in the kidneys after just 5 hours exposure to acidemia. The additional exposure to hypoxemia aggravated these findings. These 'early' microscopic pathologies opposed intra vitam data of kidney function. They did not mirror cellular or systemic patterns of proinflammatory molecules (like TNF-α or IL 18) nor were they detectable by new, sensitive markers of AKI like Neutrophil gelatinase-associated lipocalin. Instead, the data suggest that the increased renal proton excretion during acidemia could be an 'early' first hit in the multifactorial pathogenesis of AKI.
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Desequilibrio Ácido-Base/complicaciones , Lesión Renal Aguda/etiología , Riñón/fisiopatología , Animales , Hipoxia , Túbulos Renales/patología , Protones , PorcinosRESUMEN
BACKGROUND: Monocytes can be differentiated by the presence of CD14 and CD16 (CD14++CD16-, classical; CD14++CD16+, intermediate and CD14 + CD16++, non-classical monocytes). Recent studies have reported conflicting results regarding an association between subtypes of monocytes as defined by the expression of these two surface markers in atherosclerosis. METHODS: We investigated subtypes of monocytes in n = 994 patients with angiographically documented coronary artery disease (CAD). We compared total numbers of monocyte subgroups stratified by tertiles with the occurrence of the pre-defined combined endpoint (non-fatal myocardial infarction, cardiovascular death and non-haemorrhagic cerebral insult). Patients were followed up for a minimum of 52 weeks. Classical risk factors of coronary heart disease were included in multivariate analysis. RESULTS: The primary endpoint occurred 134 times at a median time of 34.5 weeks (IR 10.6/59.6). Intermediate (p = 0.813), non-classical (p = 0.725) and the number of total monocytes (p = 0.626) stratified by tertiles showed no significant association with the combined endpoint. However, a higher absolute number of classical monocytes divided in tertiles was associated with incidence of the combined endpoint {T1 = 8.9% vs T2 = 14.2% vs T3 = 16.0% (p = 0.021)}. When comparing the third with the first tertile of Mo1 population, multivariate analysis showed a hazard ratio of 1.646 (CI: 1.005-2.699, p = 0.048). CONCLUSIONS: The absolute counts of classical monocytes divided in tertiles are predictive of major adverse cardiac events in patients with CAD. A tremendous shift from classical to intermediate monocytes was also confirmed in patients with CAD. These data highlight the importance of CD14++ monocytes in cardiovascular diseases.
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Aterosclerosis/metabolismo , Enfermedades Cardiovasculares/inmunología , Enfermedad de la Arteria Coronaria/inmunología , Monocitos/inmunología , Anciano , Aterosclerosis/fisiopatología , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Comorbilidad , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Proteínas Ligadas a GPI/inmunología , Humanos , Receptores de Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Receptores de IgG/inmunología , Factores de RiesgoRESUMEN
KEY POINTS: Carbonic anhydrase (CA) inhibitors such as acetazolamide inhibit hypoxic pulmonary vasoconstriction (HPV) in humans and other mammals, but the mechanism of this action remains unknown. It has been postulated that carbonic anhydrase may act as a nitrous anhydrase in vivo to generate nitric oxide (NO) from nitrite and that this formation is increased in the presence of acetazolamide. Acetazolamide reduces HPV in pigs without evidence of any NO generation, whereas nebulized sodium nitrite reduces HPV by NO formation; however; combined infusion of acetazolamide with sodium nitrite inhalation did not further increase exhaled NO concentration over inhaled nitrite alone in pigs exposed to alveolar hypoxia. We conclude that acetazolamide does not function as either a nitrous anhydrase or a nitrite reductase in the lungs of pigs, and probably other mammals, to explain its vasodilating actions in the pulmonary or systemic circulations. ABSTRACT: The carbonic anhydrase (CA) inhibitors acetazolamide and its structurally similar analogue methazolamide prevent or reduce hypoxic pulmonary vasoconstriction (HPV) in dogs and humans in vivo, by a mechanism unrelated to CA inhibition. In rodent blood and isolated blood vessels, it has been reported that inhibition of CA leads to increased generation of nitric oxide (NO) from nitrite and vascular relaxation in vitro. We tested the physiological relevance of augmented NO generation by CA from nitrite with acetazolamide in anaesthetized pigs during alveolar hypoxia in vivo. We found that acetazolamide prevents HPV in anaesthetized pigs, as in other mammalian species. A single nebulization of sodium nitrite reduces HPV, but this action wanes in the succeeding 3 h of hypoxia as nitrite is metabolized and excreted. Pulmonary artery pressure reduction and NO formation as measured by exhaled gas concentration from inhaled sodium nitrite were not increased by acetazolamide during alveolar hypoxia. Thus, our data argue against a physiological role of carbonic anhydrase as a nitrous anhydrase or nitrite reductase as a mechanism for its inhibition of HPV in the lung and blood in vivo.
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Vasos Sanguíneos/metabolismo , Anhidrasas Carbónicas/metabolismo , Pulmón/irrigación sanguínea , Óxido Nítrico/metabolismo , Vasoconstricción , Acetazolamida/farmacología , Animales , Vasos Sanguíneos/efectos de los fármacos , Vasos Sanguíneos/fisiología , Inhibidores de Anhidrasa Carbónica/farmacología , Masculino , Óxido Nitroso/metabolismo , Oxidación-Reducción , Oxidorreductasas/metabolismo , Oxígeno/metabolismo , PorcinosRESUMEN
BACKGROUND: Observational studies suggest there are gender based differences in the treatment of coronary artery disease, with women receiving evidence based therapy less frequently than suggested by current guidelines. The aim of our study was to evaluate gender based differences in the use of DES. METHODS: We analysed prospectively collected data from 100704 stent implantations in the PCI registry of the ALKK between 2005 and 2009. RESULTS: The usage of DES increased from 16.0 to 43.9%. Although women had smaller vessel sizes, they received DES less often compared to men (28.2 vs. 31.3%), with an adjusted odds ratio of 0.93 (95% confidence interval 0.89-0.97) at the age of 75, and an adjusted odds ratio of 0.89 (95% confidence interval 0.84-0.94) at the age of 80. CONCLUSION: Despite having smaller vessels than men, women were treated less often with DES. These findings apply to women above the age of 75 years. These findings support previous reports, that elderly women with coronary artery disease are treated differently to men.
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Enfermedad de la Arteria Coronaria/terapia , Stents Liberadores de Fármacos , Disparidades en Atención de Salud , Intervención Coronaria Percutánea/instrumentación , Evaluación de Procesos, Atención de Salud , Factores de Edad , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Femenino , Alemania , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Intervención Coronaria Percutánea/efectos adversos , Diseño de Prótesis , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Resultado del TratamientoRESUMEN
Various animal models of lung injury exist to study the complex pathomechanisms of human acute respiratory distress syndrome (ARDS) and evaluate future therapies. Severe lung injury with a reproducible deterioration of pulmonary gas exchange and hemodynamics can be induced in anesthetized pigs using repeated lung lavages with warmed 0.9% saline (50 ml/kg body weight). Including standard respiratory and hemodynamic monitoring with clinically applied devices in this model allows the evaluation of novel therapeutic strategies (drugs, modern ventilators, extracorporeal membrane oxygenators, ECMO), and bridges the gap between bench and bedside. Furthermore, induction of lung injury with lung lavages does not require the injection of pathogens/endotoxins that impact on measurements of pro- and anti-inflammatory cytokines. A disadvantage of the model is the high recruitability of atelectatic lung tissue. Standardization of the model helps to avoid pitfalls, to ensure comparability between experiments, and to reduce the number of animals needed.
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Modelos Animales de Enfermedad , Síndrome de Dificultad Respiratoria/terapia , Animales , Lavado Broncoalveolar , Humanos , Pulmón , Tensoactivos , Porcinos , Irrigación TerapéuticaRESUMEN
BACKGROUND: Arterial hypertension is a common disease with high prevalence in the general population. Left ventricular hypertrophy (LVH) is an independent risk factor in arterial hypertension. Electrocardiographic indices like the Sokolow-Lyon index (SLI) are recommended as diagnostic screening methods for LVH. We assessed the diagnostic performance of the SLI in a cohort of a large general population. METHODS: We used electrocardiographic and echocardiographic data from the prospective, population-based cohort study CARdio-vascular Disease, Living and Ageing in Halle (CARLA). Linear and logistic regression models were used to assess the association of SLI with LVH. To assess the impact of the body-mass-index (BMI), we performed interaction analyses. RESULTS: AUC of SLI to predict LVH was 55.3 %, sensitivity of the SLI was 5 %, specificity 97 %. We found a significant association of SLI after covariate-adjustment with echocardiographically detected LVH (increase of left-ventricular mass index, LVMI 7.0 g/m(2) per 1 mV increase of SLI, p < 0.0001). However, this association was mainly caused by an association of SLI with the left-ventricular internal diameter (LVIDd, increase of 0.06 cm/m(2) per 1 mV increase of SLI, p < 0.0001). In obese (BMI > 30 kg/m(2)) we found the strongest association with an increase of 9.2 g/m(2) per 1 mV. CONCLUSIONS: Although statistically significant, relations of SLI and echocardiographic parameters of LVH were weak and mainly driven by the increase in LVIDd, implicating a more eccentric type of LVH in the collective. The relations were strongest when obese subjects were taken into account. Our data do not favour the SLI as a diagnostic screening test to identify patients at risk for LVH, especially in non-obese subjects without eccentric LVH.
Asunto(s)
Envejecimiento/patología , Ecocardiografía/normas , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Alemania Oriental/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Intensive therapy demanding diseases (organ failure or sepsis) are assumed to be the etiology behind a decreased biocompatibility of extracorporeal systems for renal replacement therapy (RRT). There are also potential interactions between different components of the overall therapy. Volume substitutes are known to influence hemorheology and coagulation. To define a potential net effect of volume substitutes on the hemocompatibility of an RRT, we chose an animal model without interfering pathophysiologies. According to the problem of early filter failure and coagulation disorders in critically ill patients, we focused on the hypothesized interaction between RRT and different volume substitutes with respect to blood cell counts, coagulation parameters and required heparin dose. Forty-eight pigs were assigned to four groups of fluid therapy with either normal saline (NaCl), 6%HES130kD/0.4 (HES130), 6%HES200kD/0.5 (HES200) or 4%gelatin (GEL). Six pigs of each fluid group underwent continuous venovenous hemofiltration (CVVH), the remaining six served as the control group. Anticoagulation was performed with continuous heparin infusion. CVVH was run in a recirculation-mode for 4.5 h to force hemocompatibility reactions, thereafter in a standard-mode for 2 h. During the CVVH-treatment GEL reduced platelet counts and fibrinogen concentration and additionally lowered ATIII levels. Heparin requirements did not differ between different volume substitutes or CVVH and control groups. Severe pathophysiologies are not the only reason for a reduced hemocompatibility of CVVH treatment. Interaction of a particular volume substitute with CVVH should be considered when interpreting study results and evolving new strategies.