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The pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients who had coronary heart disease served as "healthy controls". All patients underwent the necessary surgical procedure according to the diagnosed aortic disease in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1 and MMP9 and TIMP1 and TIMP2 as well. Vascularization was monitored by a CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found the smallest changes in the intima area at all. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In the case of arteriosclerotic changes, intima had a capillarization, but not in the media. An opposite pattern was found in the dissected aortas. There are differences in the vascularization between the aneurysm and dissection and the different layers, respectively. A different remodeling process of the ECM in comparison to the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, disturbed nutrition, and dysfunctional vasa vasorum remodeling must be assumed as causes of dissection.
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BACKGROUND: There is a paucity of evidence on people with thoracic aortic aneurysm and dissection. We aimed to determine the prevalence of genetic variants and their associations with phenotypes. METHODS: In this cross-sectional single-centre cohort study of consecutive patients who underwent endovascular or open-surgical repair of thoracic aortic aneurysm and dissection, genetic analysis was performed using four-stage Next Generation Sequencing, and findings were confirmed with Sanger sequencing. We collected personal and family history on comorbidities, clinical examination, anthropometrics, skeletal deformities, joint function, and ophthalmological measures. Cardiovascular risk and phenotype scores were calculated. RESULTS: Ninety-five patients were eligible (mean age 54 ± 9 years, 70% males, 56% aortic dissection). One-fifth had a family history of aortic disease. Furthermore, 95% and 54% had a phenotype score of ≤5 and ≤2, respectively. There were no significant differences in the distribution of phenotype characteristics according to age, sex, aortic pathology, or performed invasive procedures. Genetic variants of uncertain significance were detected in 40% of patients, with classic mutations comprising 18% of all variants. We observed no significant association with cardiovascular and phenotype scores but with higher joint function scores (p = 0.015). CONCLUSION: Genetic variants are highly present in clinically relevant aortic pathologies. Variants appear to play a larger role than previously described. The different variants do not correlate with specific phenotypes, age, pathology, sex, or family history.
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AIMS: The conditions of hypoxia are suggested to induce permanent atrial fibrillation (AF). The regulation of COX4I2 and COX4I1 depends on oxygen availability in tissues. A role of COX4I2 in the myocardium of AF patients is supposed for pathogenesis of AF and subsequent alterations in the electron transfer chain (ETC) under hypoxia. METHODS AND RESULTS: In vitro, influence of hypoxia on HeLa 53 cells was studied and elevated parts of COX 4I2 were confirmed. Myocardial biopsies were taken ex vivo from the patients' Right Atria with SR (n = 31) and AF (n = 11), respectively. RT- PCR for mRNA expresson, mitochondrial respiration by polarography and the protein content of cytochrome c oxidase (CytOx) subunit 4I1 and CytOx subunit 4I2 by ELISA were studied. Clinical data were correlated to the findings of gene expressions in parallel. Patients with permanent AF had a change in isoform 4I2/4I1 expression along with a decrease of isoform COX 4I1 expression. The 4I2/4I1 ratio of mRNA expression was increased from 0.630 to 1.058 in comparison. However, the protein content of CytOx subunit 4 was much lower in the AF group, whereas the respiration/units enzyme activity in both groups remained the same. CONCLUSIONS: This study describes a possible molecular correlate for the development of AF. Due to the known functional significance of COX 4I2, mitochondrial dysfunction can be assumed as a part of the pathogenesis of AF.
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Fibrilación Atrial , Complejo IV de Transporte de Electrones , ARN Mensajero , Femenino , Humanos , Masculino , Fibrilación Atrial/genética , Fibrilación Atrial/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/genética , Ensayo de Inmunoadsorción Enzimática , Células HeLa , ARN Mensajero/genéticaRESUMEN
Background: Advanced-stage lung cancers sometimes require an extensive surgical approach. There is a risk of severe bleeding due to injury to the cardiac atria. Due to the fact that in most cases the surgical planning does not involve the expertise of a heart surgeon or the availability of a heart lung machine, only rapid effective action can avert this life-threatening complication. Methods: In an experimental study of porcine heart-lung packs, three different methods were used to investigate the most effective way of controlling mass hemorrhage due to left atrial injury. In order to obtain a realistic model, the heart-lung packet was connected to a heart-lung machine after appropriate preparation and perfused with volume support. The damage control to the left atrial injury was either performed by manual compression, surgical clamping or balloon catheter occlusion. Results: In addition to manual compression and clamping, the use of a balloon catheter inserted into the atrial lesion was found to be the most effective method. The blood loss of 41.88±7.53 mL (vs. 105.00±31.74 and 106.00±50.67 mL) proved to be the lowest value. Conclusions: For extensive resections of lung carcinoma, balloon catheters of different sizes should be kept ready to rapidly control massive blood loss due to injury of the cardiac atria.
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Lung carcinomas infiltrate the aorta mostly on the left side and are altogether rare. As an initial step, complete staging is performed and the results are evaluated in an interdisciplinary tumor board. If the patient's general condition including cardiopulmonary reserves is sufficient, and if there is neither distant metastasis nor an N2 situation, surgical resection may be indicated. The option for neoadjuvant chemotherapy should always be taken into consideration. Depending on the anatomic tumor location, partial lung resection and resection of the affected aortic wall are performed employing a cardiopulmonary bypass. The resected aortic wall is replaced by a vascular prosthesis. In recent years, this proven procedure has partly been replaced by an alternative one, avoiding extracorporeal circulation. An endoaortic stent is implanted in the affected area followed by partial lung resection and resection of the diseased aortic wall. This new procedure has significantly reduced perioperative mortality and morbidity. With proper patient selection, long-term survival can be improved even in this complex malignoma.
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We evaluated the feasibility of hybrid percutaneous coronary intervention (PCI) and minimally invasive mitral valve surgery (MIMVS) in patients with concomitant coronary and mitral disease. Of 534 patients who underwent MIMVS at our institution between 2012 and 2018, those with combined mitral and single vessel coronary pathologies who underwent MIMVS and PCI were included. Patients were excluded if they had endocarditis or required emergency procedures. Preprocedural, procedural, and postprocedural data were retrospectively analyzed. In total, 10 patients (median age, 75 years; 7 males) with a median ejection fraction (EF) of 60% were included. Nine patients underwent PCI before and one after MIMVS. The success rate was 100% in both procedures. There were no postoperative myocardial infarctions or strokes. Two patients developed delirium and one required re-thoracotomy for bleeding. The median stay in intensive care and the hospital was 3 and 8 days, respectively. The 30-day survival rate was 100%. A hybrid PCI and MIMVS approach is feasible in patients with mitral valve and single vessel coronary disease. In combined pathologies, the revascularization strategy should be evaluated independent from the mitral valve pathology in the presence of MIMVS expertise. Extension of this recommendation to multivessel disease should be evaluated in future studies.
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Background: Thoracic endovascular aortic repair (TEVAR) is a well-established technique for the management of blunt thoracic aortic injury (BTAI). Despite improvements in vascular imaging, graft material properties, and implant techniques, stent-graft deployment artificially induces aortic stiffening. This study aimed to evaluate the midterm effect of thoracic endovascular aortic repair after blunt thoracic aortic injury on aortic stiffness and cardiac function in young patients using cardiovascular magnetic resonance (CMR) imaging. Patients and methods: From all patients who underwent TEVAR for BTAI between 2009 and 2019 in a single institution, 10 patients with no other comorbidities affecting arterial stiffness were sex-, age-, height-, and body surface area-matched to 10 healthy controls. Comprehensive CMR examination was performed in all controls and patients. The mean follow-up period was 5.4±1.8 years; the mean age at the time of TEVAR was 30.3±8.7 years. Results: Four patients who underwent TEVAR developed arterial hypertension. 4D flow CMR-based analysis demonstrated higher global pulse wave velocity (PWV) in TEVAR patients than in controls (p=0.012). Segmental analysis showed a higher PWV in the descending and abdominal aorta. The indexed diameter of the ascending aorta was larger in TEVAR patients than in controls (p=0.007). The CINE acquisitions demonstrated increased left ventricular myocardial thickness (p<0.001). The 3D global diastolic strain rate and diastolic longitudinal velocity (e') decreased, and the A-wave velocity increased. Native myocardial T1 values were significantly higher in TEVAR patients (p=0.037). Conclusions: Young patients with TEVAR after BTAI are at an increased risk of developing vascular and myocardial dysfunction due to increased aortic stiffness. CMR follow-up allows for a comprehensive and radiation-free evaluation of vascular stiffness and associated myocardial changes, especially at the early and subclinical stages.
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Implantación de Prótesis Vascular , Procedimientos Endovasculares , Lesiones del Sistema Vascular , Heridas no Penetrantes , Humanos , Adulto Joven , Adulto , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Análisis de la Onda del Pulso , Estudios Retrospectivos , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Implantación de Prótesis Vascular/efectos adversos , Imagen por Resonancia Magnética , Lesiones del Sistema Vascular/diagnóstico por imagen , Lesiones del Sistema Vascular/etiología , Lesiones del Sistema Vascular/cirugía , Aorta Abdominal , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/cirugía , Heridas no Penetrantes/etiología , Resultado del TratamientoRESUMEN
Background Cardiac non-Hodgkin's lymphoma is rare and has a poor prognosis. Here we report a rare case mimicking pulmonary embolism. Case Description A 38-year-old woman suffered from severe dyspnea after cesarean section. With the clinical picture of fulminant central pulmonary embolism, lysis therapy was initiated. Further deterioration necessitated extracorporeal membrane oxygenation (ECMO) support and cardiosurgical intervention. Intraoperatively, a massive intravascular tumor obstructed the pulmonary bifurcation and was found to be B-cell lymphoma. Aggressive excision and pulmonary tree reconstruction improved the critical condition and initiated convalescence. Conclusion High suspicion in central pulmonary embolism and early cardiosurgical therapy after ineffective lysis are essential.
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BACKGROUND: Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. MATERIALS AND METHODS: In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore group blood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. RESULTS: Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min (p = .005). CONCLUSION: The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.
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Soluciones Cardiopléjicas , Delirio del Despertar , Humanos , Incidencia , Delirio del Despertar/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Paro Cardíaco Inducido/métodos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , SodioRESUMEN
BACKGROUND: Stroke in the postoperative time course after heart surgery remains a serious risk. Cranial computer tomography (CCT) is the first line option to detect severe intracranial damage. However, only few data are available to predict neurological outcome. Using visual rating scales (VRSs), this study addresses reliability and effectivity to indicate neurological status and likelyhood of improvement. METHODS: In a single-center retrospective evaluation, 3719 patients underwent coronary bypass surgery. Because of a delayed recovery phase and neurologic deficits after cardiac surgery 109 patients had a cranial CT scan in the early postoperative period. The incidence of clinically relevant findings within the imaging was rated by an experienced neuroradiologist using two VRS, that is, the age-related white matter changes (ARWMCs) and the Mendes-Ribeiro visual rating scale (MRVRS). Both are computer-assisted measurement schemes to detect stroke-related intracranial damage. Follow-up was investigated with regard to clinical outcome and patient-related risk profiles. RESULTS: Of 109 patients with postoperative cranial CT scans due to prolonged recovery phases or proven neurological damage 44.5% had one cerebral defect in CCT imaging scans only. The others showed multiple defects. During hospital stay, 92.3% experienced neurological improvement exposing reduced ARWMC, while 7.1% had no improvement and correlating high scores. Of both scales, the ARWMC-VRS demonstrated superior accuracy and discrimination. The preoperative ejection fraction (EF), arteriosclerotic degeneration of carotid arteries, and reduced glomerular filtration rate were found to have a high correlation (r = 0.0005) with the latter group. In-hospital mortality of this cohort was 8.18%. CONCLUSION: Both the ARWMC and MRVRS were found to be appropriate. They reliably discriminate the groups of stroke patients after coronary artery bypass grafting (CABG) in the analysis of CCT images. When applied at the onset of neurological symptoms both scales are able to predict neurological reconvalescence upon hospital dismission. The ARWMC scale appeared superior as it demonstrated better accuracy and discrimination. The use of both VRS in patients with suspected stroke after CABG surgery can give insightful information toward a progression of neurological dysfunction or postoperative improvement.
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Puente de Arteria Coronaria , Accidente Cerebrovascular , Puente de Arteria Coronaria/métodos , Humanos , Complicaciones Posoperatorias/diagnóstico por imagen , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The pathogenesis of mitral valve insufficiency is not yet fully understood. Several studies stressed the role of matrix metalloproteinases (MMPs) in the emergence of valvular pathologies. The primary objective of the present study is to analyze the role of selected MMPs and their inhibitors in mitral valve insufficiency. PATIENTS AND METHODS: Eighty patients (33 female/47 male, mean age 67 years) underwent cardiopulmonary bypass surgery for mitral valve reconstruction between 2007 and 2015. All patients suffered from mitral insufficiency (MI) Stages iii and iv. When tissue resection was acquired specimens were taken immediately frozen and used for histological examination. Expression of MMP-1, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 was examined immunohistochemically and distribution was analyzed in regard to preoperative clinical, echocardiographic, and histopathological findings. RESULTS: A clear correlation between the MMP expression and the MI degree of severity could be shown. The expression of MMPs proved to be high in relation to mild insufficiencies and relatively weak in the case of severe ones. Additionally, the etiology of the MI was considered in the analysis and a significant difference in the expression of MMPs between the mitral valves with endocarditis and the ones featuring a degenerative disease could be shown. Within the group of valves with degenerative diseases, no significant difference could be established between the subgroups (myxoid and sclerosed valves). CONCLUSION: The increased expression of MMPs and their inhibitors in mild insufficiencies could prove that the molecular changes in the valve precede the macroscopical and thus the echocardiographically diagnosable changes. Hence, new options for early diagnosis and therapy of MIs should be examined in further studies, respectively. Herein, the correlation of the MMP blood levels with MMP tissue expression should be addressed for surgical therapeutical decisions.
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Insuficiencia de la Válvula Mitral , Anciano , Femenino , Humanos , Masculino , Metaloproteinasa 1 de la Matriz , Metaloproteinasa 9 de la Matriz , Metaloproteinasas de la Matriz/metabolismo , Insuficiencia de la Válvula Mitral/etiología , Insuficiencia de la Válvula Mitral/cirugía , Inhibidor Tisular de Metaloproteinasa-1 , Inhibidor Tisular de Metaloproteinasa-2 , Inhibidores Tisulares de Metaloproteinasas/metabolismoRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a frequent complication associated with on-pump cardiac surgery. Early recognition may alter their prognosis. Therefore, the urinary concentrations of TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor-binding protein) as predictors for AKI were studied. METHODS: Repetitive blood and urine samples were collected consecutively from 50 patients. Demographic, intra-, and postoperative data were recorded prospectively. To calculate the production of the TIMP-2 and IGFBP-7 protein concentrations, urinary samples were taken preoperatively, intraoperatively at 30 and 60 min after aortic clamping and at 0, 6, 12, and 24 h after admission to the intensive care unit (ICU). RESULTS: AKI occurred in 14 patients (28%), all of them at Kidney Disease: Improving Global Outcomes stage 1. Predictive value for [TIMP-2] × [IGFBP7] was shown at 0 and 24 h after admission to ICU. At 0 h, the sensitivity was 84.6% and the specificity 55.6% for an ideal calculated cutoff at 0.07. After 24 h, the ideal cutoff amounted to 0.35 with a sensitivity of 53.8% and a specificity of 88.2%. The receiver operating characteristic curves demonstrated areas under the curve of 0.725 and 0.718. The suggested cutoffs of 0.3 and 2.0 could not be confirmed. The serum creatinine was reached to the peak median within 48 h after admission to ICU. CONCLUSION: Postoperative risk assessment for the development of AKI can be established by [ TIMP - 2 ] × [ IGFBP 7 ] . Previously suggested cutoff values could not be confirmed. A correlation with urinary dilution parameters may enable the identification of more universal cutoffs.
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Lesión Renal Aguda , Procedimientos Quirúrgicos Cardíacos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Biomarcadores , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Inhibidor Tisular de Metaloproteinasa-2/orinaRESUMEN
BACKGROUND: Prospective, single-center trials have shown that the implementation of the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations in high-risk patients significantly reduced the development of acute kidney injury (AKI) after surgery. We sought to evaluate the feasibility of implementing a bundle of supportive measures based on the KDIGO guideline in high-risk patients undergoing cardiac surgery in a multicenter setting in preparation for a large definitive trial. METHODS: In this multicenter, multinational, randomized controlled trial, we examined the adherence to the KDIGO bundle consisting of optimization of volume status and hemodynamics, functional hemodynamic monitoring, avoidance of nephrotoxic drugs, and prevention of hyperglycemia in high-risk patients identified by the urinary biomarkers tissue inhibitor of metalloproteinases-2 [TIMP-2] and insulin growth factor-binding protein 7 [IGFBP7] after cardiac surgery. The primary end point was the adherence to the bundle protocol and was evaluated by the percentage of compliant patients with a 95% confidence interval (CI) according to Clopper-Pearson. Secondary end points included the development and severity of AKI. RESULTS: In total, 278 patients were included in the final analysis. In the intervention group, 65.4% of patients received the complete bundle as compared to 4.2% in the control group (absolute risk reduction [ARR] 61.2 [95% CI, 52.6-69.9]; P < .001). AKI rates were statistically not different in both groups (46.3% intervention versus 41.5% control group; ARR -4.8% [95% CI, -16.4 to 6.9]; P = .423). However, the occurrence of moderate and severe AKI was significantly lower in the intervention group as compared to the control group (14.0% vs 23.9%; ARR 10.0% [95% CI, 0.9-19.1]; P = .034). There were no significant effects on other specified secondary outcomes. CONCLUSIONS: Implementation of a KDIGO-derived treatment bundle is feasible in a multinational setting. Furthermore, moderate to severe AKI was significantly reduced in the intervention group.
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Lesión Renal Aguda/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Adhesión a Directriz/normas , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Paquetes de Atención al Paciente/normas , Guías de Práctica Clínica como Asunto/normas , Inhibidor Tisular de Metaloproteinasa-2/orina , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/orina , Anciano , Biomarcadores/orina , Europa (Continente) , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
INTRODUCTION: Acute kidney injury (AKI) is a frequent complication after cardiac surgery with adverse short-term and long-term outcomes. Although prevention of AKI (PrevAKI) is strongly recommended, the optimal strategy is uncertain. The Kidney Disease: Improving Global Outcomes (KDIGO) guideline recommended a bundle of supportive measures in high-risk patients. In a single-centre trial, we recently demonstrated that the strict implementation of the KDIGO bundle significantly reduced the occurrence of AKI after cardiac surgery. In this feasibility study, we aim to evaluate whether the study protocol can be implemented in a multicentre setting in preparation for a large multicentre trial. METHODS AND ANALYSIS: We plan to conduct a prospective, observational survey followed by a randomised controlled, multicentre, multinational clinical trial including 280 patients undergoing cardiac surgery with cardiopulmonary bypass. The purpose of the observational survey is to explore the adherence to the KDIGO recommendations in routine clinical practice. The second phase is a randomised controlled trial. The objective is to investigate whether the trial protocol is implementable in a large multicentre, multinational setting. The primary endpoint of the interventional part is the compliance rate with the protocol. Secondary endpoints include the occurrence of any AKI and moderate/severe AKI as defined by the KDIGO criteria within 72 hours after surgery, renal recovery at day 90, use of renal replacement therapy (RRT) and mortality at days 30, 60 and 90, the combined endpoint major adverse kidney events consisting of persistent renal dysfunction, RRT and mortality at day 90 and safety outcomes. ETHICS AND DISSEMINATION: The PrevAKI multicentre study has been approved by the leading Research Ethics Committee of the University of Münster and the respective Research Ethics Committee at each participating site. The results will be used to design a large, definitive trial. TRIAL REGISTRATION NUMBER: NCT03244514.
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Lesión Renal Aguda/prevención & control , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Adhesión a Directriz , Complicaciones Posoperatorias/prevención & control , Guías de Práctica Clínica como Asunto , Lesión Renal Aguda/epidemiología , Biomarcadores , Estudios de Factibilidad , Humanos , Cooperación Internacional , Participación del Paciente , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Factores de Tiempo , Extractos de TejidosRESUMEN
BACKGROUND: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend a bundle of different measures for patients at increased risk of acute kidney injury (AKI). Prospective, single-center, randomized controlled trials (RCTs) have shown that management in accordance with the KDIGO recommendations was associated with a significant reduction in the incidence of postoperative AKI in high-risk patients. However, compliance with the KDIGO bundle in routine clinical practice is unknown. METHODS: This observational prevalence study was performed in conjunction with a prospective RCT investigating the role of the KDIGO bundle in high-risk patients undergoing cardiac surgery. A 2-day observational prevalence study was performed in all participating centers before the RCT to explore routine clinical practice. The participating hospitals provided the following data: demographics and surgical characteristics, AKI rates, and compliance rates with the individual components of the bundle. RESULTS: Ninety-five patients were enrolled in 12 participating hospitals. The incidence of AKI within 72 hours after cardiac surgery was 24.2%. In 5.3% of all patients, clinical management was fully compliant with all 6 components of the bundle. Nephrotoxic drugs were discontinued in 52.6% of patients, volume optimization was performed in 70.5%, 52.6% of the patients underwent functional hemodynamic monitoring, close monitoring of serum creatinine and urine output was undertaken in 24.2% of patients, hyperglycemia was avoided in 41.1% of patients, and no patient received radiocontrast agents. The patients received on average 3.4 (standard deviation [SD] ±1.1) of 6 supportive measures as recommended by the KDIGO guidelines. There was no significant difference in the number of applied measures between AKI and non-AKI patients (3.2 [SD ±1.1] vs 3.5 [SD ±1.1]; P = .347). CONCLUSIONS: In patients after cardiac surgery, compliance with the KDIGO recommendations was low in routine clinical practice.
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Lesión Pulmonar Aguda/prevención & control , Procedimientos Quirúrgicos Cardíacos/métodos , Adhesión a Directriz/estadística & datos numéricos , Enfermedades Renales/terapia , Complicaciones Posoperatorias/prevención & control , Lesión Pulmonar Aguda/epidemiología , Adulto , Anciano , Estudios de Cohortes , Creatinina/sangre , Creatinina/orina , Femenino , Humanos , Incidencia , Enfermedades Renales/complicaciones , Pruebas de Función Renal , Tiempo de Internación , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Prevalencia , Estudios ProspectivosRESUMEN
BACKGROUND: Extracorporeal liver support therapies (ELS) are technical options (for bridge-to-recovery as well as bridge-to-transplant) in patients with acute liver dysfunction (e.g. acute liver failure (ALF), acute-on chronic liver failure (AoCLF) or decompensated chronic liver disease (decomp. CLD)) to reduce effects of failing hepatic detoxification functions. The present study investigates the real-life utilization of ELS (annual incidences), mortality rates as well as data regarding specific populations of liver transplantation in Germany. METHODS: Data on patient cases receiving extracorporeal liver support therapy were identified in a nationwide data set from the Federal statistical Office of Germany from 1 January 2007 through 31 December 2015 and analyzed regarding in-hospital mortality, age- and sex-specific distribution and use of ELS in the context of liver transplantation. Mortality rates in patients with primary acute liver dysfunction and secondary acute liver dysfunction (in the context of cardiothoracic surgery) were evaluated. RESULTS: Annual incidences of ELS use remained stable between 0.39/100.000 in 2007 and 0.47/100.000 ELS in 2015. In-hospital mortality rate was 51.49% in the 2886 evaluated patient cases. Mortality was higher in men (56.04%) than in women (43.70) in the observed time period between 2007 and 2015. ELS utilization and case-related liver transplantation rates were low (12.47%). Since 2012, the annual numbers for ELS therapy in cardiosurgical patients exceeded the frequency of ELS utilization in cases of primary liver dysfunction (mortality rates: 68.39% versus 40.63%). CONCLUSIONS: ELS utilization remained stable between 2007 and 2015. Mortality rates are high in this patient population of acute liver dysfunction, especially in combination with case-related cardiothoracic surgery. ELS is rarely used in the setting of liver transplantation. In 2015, more than 50% of all ELS cases in Germany were performed in the context of cardiothoracic surgery.
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Fallo Hepático Agudo/terapia , Hígado Artificial/estadística & datos numéricos , Complicaciones Posoperatorias/terapia , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Cardíacos , Niño , Preescolar , Femenino , Alemania/epidemiología , Mortalidad Hospitalaria , Humanos , Lactante , Recién Nacido , Fallo Hepático Agudo/mortalidad , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Plasmaféresis , Complicaciones Posoperatorias/mortalidad , Desintoxicación por Sorción/estadística & datos numéricos , Adulto JovenRESUMEN
Protamine sulfate (PS) is widely used in heart surgery as an antidote for heparin, albeit its pharmacological effects are not fully understood and applications are often accompanied by unwanted side effects. Here we show the effect of PS on mitochondrial bioenergetics profile resulting in mitochondrial reactive oxygen species (ROS) production. Polarographic measurements were performed in parallel to membrane potential and ROS measurements by FACS analyzer using tetramethylrhodamine ethyl ester and MitoSOX fluorescent dyes, respectively. PS inhibited intact rat heart mitochondrial respiration (stimulated by ADP) to 76% (P < 0.001) from the baseline of 51.6 ± 6.9 to 12.4 ± 2.3 nmol O2â min-1â ml-1 The same effect was found when respiration was inhibited by antimycin A (101.0 ± 8.9 vs. 38.0 ± 9.9 nmol O2 â min-1â ml-1, P < 0.001) and later stimulated by substrates of cytochrome oxidase (CytOx) i.e., ascorbate and tetramethyl phenylene diamine, suggesting that PS exerted its effect through inhibition of CytOx activity. Furthermore, the inhibition of mitochondrial respiration by PS was concentration dependent and accompanied by hyperpolarization of the mitochondrial membrane potential (Δψ m), i.e., 18% increase at 50 µg/ml and an additional 3.3% increase at 250 µg/ml PS compared with control. This effect was associated with a strong consequent increase in the production of ROS, i.e., 85% and 88.6% compared with control respectively. We propose that this excessive increase in ROS concentrations results in mitochondrial dysfunction and thus might relate to the "protamine reaction," contributing to the development of various cardiovascular adverse effects.
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Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Protaminas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Respiración de la Célula/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Complejo IV de Transporte de Electrones/metabolismo , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Miocardio/citología , Miocardio/metabolismo , Ratas , Ratas WistarRESUMEN
Induction of Heat Shock Proteins results in cytoprotection. Beneficial effect results from transcription and translational cellular components' involvement that defends metabolism and thus induce ischemic protection of the tissue. Mitochondrial respiration is also involved in stress- induced conditions. It is not a uniform process. Cytochrome c Oxidase (CytOx) representing complex IV of the Electron Transfer Chain (ETC) has a regulatory role for mitochondrial respiratory activity, which is tested in our study after hsp induction. Moreover, protein translation for mitochondrial components was probed by the detection of MT-CO1 for Subunit 1 of CytOx neosynthesis. Wistar rats were subjected to whole-body hyperthermia at 42.0-42.5⯰C for 15â¯min followed by a normothermic recovery period. Heat shock response was monitored time dependent from LV biopsies of all control and heat treated animals with PCR-analysis for hsp 32, 60, 70.1, 70.2, 90 and MT-CO1 expression at 15, 30, 45, 60, 120 and 360â¯min recovery (nâ¯=â¯5 in each group), respectively. Enzymatic activity of CytOx were evaluated polarographically. High energy phosphates were detected by chromatographic analysis. The mRNA expression of MT-CO1 peaked at 60â¯min and was accompanied by hsp 32 (râ¯=â¯0.457; pâ¯=â¯0.037) and hsp 70.2 (râ¯=â¯0.615; pâ¯=â¯0.003) upregulation. With hsp induction, mitochondrial respiration was increased initially. Enzymatic activity reconciled from active into relaxed status wherein CytOx activity was completely inhibited by ATP. Myocardial ATP content increased from stress induced point i.e. <â¯1⯵molâ¯g-1 protein w/w to finally 1.5⯱â¯0.53⯵molâ¯g-1 protein w/w at 120â¯min recovery interval. Hyperthermic, myocardial hsp- induction goes along with increased CytOx activity representing an increased "active" mitochondrial respiration. In parallel, de -novo holoenzyme assembly of CytOx begins as shown by MT-CO1 upregulation at 60â¯min recovery time crossing with a final return to the physiological "relaxed" state and ATP -inhibited respiration.
Asunto(s)
Proteínas de Choque Térmico/genética , Respuesta al Choque Térmico/fisiología , Hipertermia Inducida , Mitocondrias/metabolismo , Miocardio/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Respiración de la Célula , Complejo IV de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/metabolismo , Masculino , ARN Mensajero/metabolismo , Ratas WistarRESUMEN
BACKGROUND: Treatment of heart failure remains one of the most challenging task for intensive care medicine, cardiology and cardiac surgery. New options and better indicators are always required. Understanding the basic mechanisms underlying heart failure promote the development of adjusted therapy e.g. assist devices and monitoring of recovery. If cardiac failure is related to compromised cellular respiration of the heart, remains unclear. Myocardial respiration depends on Cytochrome c- Oxidase (CytOx) activity representing the rate limiting step for the mitochondrial respiratory chain. The enzymatic activity as well as mRNA expression of enzyme's mitochondrial encoded catalytic subunit 2, nuclear encoded regulatory subunit 4 and protein contents were studied in biopsies of cardiac patients suffering from myocardial insufficiency and dilated cardiomyopathy (DCM). METHODS: Fifty-four patients were enrolled in the study and underwent coronary angiography. Thirty male patients (mean age: 45 +/- 15 yrs.) had a reduced ejection fraction (EF) 35 ± 12% below 45% and a left ventricular end diastolic diameter (LVEDD) of 71 ± 10 mm bigger than 56 mm. They were diagnosed as having idiopathic dilated cardiomyopathy (DCM) without coronary heart disease and NYHA-class 3 and 4. Additionally, 24 male patients (mean age: 52 +/- 11 yrs.) after exclusion of secondary cardiomyopathies, coronary artery or valve disease, served as control (EF: 68 ± 7, LVEDD: 51 ± 7 mm). Total RNA was extracted from two biopsies of each person. Real-time PCR analysis was performed with specific primers followed by a melt curve analysis. Corresponding protein expression in the tissue was studied with immune-histochemistry while enzymatic activity was evaluated by spectroscopy. RESULTS: Gene and protein expression analysis of patients showed a significant decrease of subunit 4 (1.1 vs. 0.6, p < 0.001; 7.7 ± 3.1% vs. 2.8 ± 1.4%, p < 0.0001) but no differences in subunit 2. Correlations were found between reduced subunit 2 expression, low EF (r = 0.766, p < 0.00045) and increased LVEDD (r = 0.492, p < 0.0068). In case of DCM less subunit 4 expression and reduced shortening fraction (r = 0.524, p < 0.017) was found, but enzymatic activity was higher (0.08 ± 0.06 vs. 0.26 ± 0.08 U/mg, p < 0.001) although myocardial oxygen consumption continued to the same extent. CONCLUSION: In case of myocardial insufficiency and DCM, decreased expression of COX 4 results in an impaired CytOx activity. Higher enzymatic activity but equal oxygen consumption contribute to the pathophysiology of the myocardial insufficiency and appears as an indicator of oxidative stress. This kind of dysregulation should be in the focus for the development of diagnostic and therapy procedures.
Asunto(s)
Cardiomiopatía Dilatada/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Adulto , Cardiomiopatía Dilatada/complicaciones , Corazón/fisiopatología , Insuficiencia Cardíaca/etiología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Miocardio/patología , Consumo de Oxígeno/fisiología , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
BACKGROUND: The purpose of this single-center, retrospective study was to review the early outcome with defined endpoints of myocardial infarction, brain injury, and death after coronary bypass grafting and simultaneous carotid endarterectomy with or without combined valve replacement. METHODS: During the preoperative investigation 52 (44 males, 8 females) patients were examined by cardiac catheterization within the scope of their coronary status. In addition, all patients underwent echocardiography, CT angiography of the supra-aortic vessels, and full description of their neurologic status. Included were all patients with the need of coronary revascularization, valve disease, and either symptomatic or asymptomatic carotid artery stenosis with a maximal narrowing of >70%. RESULTS: There was one (2%) patient with a perioperative stroke and paresis of the upper limb. One (2%) patient experienced PRIND (2%). Eighteen (35%) patients suffered symptomatic transitory psychotic syndrome that fully recovered in all patients. One (2%) patient incurred a perioperative myocardial infarction that could be cured by percutaneous coronary stent implantation. Overall mortality was 4%. CONCLUSION: Simultaneous coronary bypass grafting as a single procedure or in combination with valve replacement and endarterectomy of severe carotid lesions with or without patients' history of previous stroke can be performed with a calculated low surgical risk. The complication rate for neurologic and myocardial events is low compared with the hazard of a single surgical repair. The in-hospital mortality is not significantly different to isolated procedures. The concomitant appearance of coronary stenosis and carotid artery disease is reasonable due to the nature of arteriosclerosis. In our opinion these patients benefit from a combined surgical approach.