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BACKGROUND: Guidelines on myocardial revascularization define recommendations for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. Only little information exists on long-term follow-up and quality of life (QoL) after CABG preceded by PCI. The aim of our study was to evaluate the impact of prior PCI on outcome and QoL in patients with stable coronary artery disease who underwent CABG. METHODS: In our retrospective study, CABG patients were divided in: CABG preceded by PCI: PCI-first (PCF), and CABG-only (CO) groups. The PCF group was further divided in guideline-conform (GCO) and guideline nonconform (GNC) subgroups, according to the SYNTAX score (2014 European Society of Cardiology [ESC]/European Association for Cardio-Thoracic Surgery [EACTS] guidelines). Thirty days mortality, major adverse cardiac events, and QoL using the European Quality-of-Life-5 Dimensions were evaluated. RESULTS: A total of 997 patients were analyzed, of which 784 underwent CABG without (CO), and 213 individuals with prior PCI (PCF). The latter group consisted of 67 patients being treated in accordance (GCO), and 24 in discordance (GNC) to the 2014 ESC/EACTS guidelines. Reinfarction (PCF: 3.8% vs. CO: 1.0%; p = 0.024), re-angiography (PCF: 17.6% vs. CO: 9.0%; p = 0.004), and re-PCI (PCF: 10.4% vs. CO: 3.0%; p < 0.001) were observed more frequently in PCF patients. Also, patients reported better health status in the CO compared to PCF group (CO: 72.48 ± 19.31 vs. PCF: 68.20 ± 17.86; p = 0.01). Patients from the guideline nonconform subgroup reported poorer health status compared to the guideline-conform group (GNC: 64.23 ± 14.56 vs. GCO: 73.42 ± 17.66; p = 0.041) and were more likely to require re-PCI (GNC: 18.8% vs. GCO: 2.4%; p = 0.03). Also, GNC patients were more likely to have left main stenosis (GCO: 19.7% vs. GNC: 37.5%; p < 0.001) and showed higher preinterventional SYNTAX score (GCO: 18.63 ± 9.81 vs. GNC: 26.67 ± 5.07; p < 0.001). CONCLUSION: PCI preceding CABG is associated with poorer outcomes such as reinfarction, re-angiography, and re-PCI, but also worse health status and higher rehospitalization. Nevertheless, results were better when PCI was guideline-conformant. This data should impact the Heart Team decision.
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BACKGROUND: Heart surgery with extracorporeal circulation (ECC) often leads to postoperative delirium (POD). This is associated with increased morbidity resulting in longer hospital stay and associated costs. The purpose of our study was to analyze the effect of intraoperative mannitol application on POD in patients undergoing elective aortic valve replacement (AVR). MATERIALS AND METHOD: s In our retrospective single-center study, 259 patients underwent elective AVR, using Bretschneider cardioplegic solution for cardiac arrest, between 2014 and 2017. Patients were divided in mannitol (n = 188) and nonmannitol (n = 71) groups. POD was assessed using the confusion assessment method for the intensive care unit (ICU). Statistical significance was assumed at p < 0.05. RESULTS: Baseline patient characteristics did not differ between the groups. Incidence of POD was significantly higher in the nonmannitol group (33.8 vs. 13.8%; p = 0.001). These patients required longer ventilation time (24.1 vs. 17.1 hours; p = 0.021), higher reintubation rate (11.3 vs. 2.7%; p = 0.009), ICU readmission (12.7 vs. 4.8%; p = 0.026), prolonged ICU (112 vs. 70 hours; p = 0.040), and hospital stay (17.8 vs. 12.6 days; p < 0.001), leading to higher expenses (19,349 vs. 16,606 , p < 0.001). A 30-day mortality was not affected, but nonmannitol group showed higher Simplified Acute Physiology Score II score (32.2 vs. 28.7; p < 0.001). Mannitol substitution was independently associated with lower incidence of POD (odds ratio: 0.40; 95% confidence interval: 0.18-0.89; p = 0.02). CONCLUSION: Treatment with mannitol during ECC was associated with decreased incidence of POD. This was accompanied by shorter ventilation time, ICU and hospital stay, and lower treatment expenses.
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Valva Aórtica , Delírio , Valva Aórtica/cirurgia , Delírio/diagnóstico , Delírio/etiologia , Delírio/prevenção & controle , Parada Cardíaca Induzida/efeitos adversos , Humanos , Manitol/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Ischemic cardiomyopathy leads to inflammation and left ventricular (LV) dysfunction. Animal studies provided evidence for cardioprotective effects of the endocannabinoid system, including cardiomyocyte adaptation, inflammation, and remodeling. Cannabinoid type-2 receptor (CB2) deficiency led to increased apoptosis and infarctions with worsened LV function in ischemic cardiomyopathy. The aim of our study was to investigate a possible cardioprotective effect of endocannabinoid anandamide (AEA) after ischemia and reperfusion (I/R). Therefore, fatty acid amide hydrolase deficient (FAAH)-/- mice were subjected to repetitive, daily, 15 min, left anterior descending artery (LAD) occlusion over 3 and 7 consecutive days. Interestingly, FAAH-/- mice showed stigmata such as enhanced inflammation, cardiomyocyte loss, stronger remodeling, and persistent scar with deteriorated LV function compared to wild-type (WT) littermates. As endocannabinoids also activate PPAR-α (peroxisome proliferator-activated receptor), PPAR-α mediated effects of AEA were eliminated with PPAR-α antagonist GW6471 i.v. in FAAH-/- mice. LV function was assessed using M-mode echocardiography. Immunohistochemical analysis revealed apoptosis, macrophage accumulation, collagen deposition, and remodeling. Hypertrophy was determined by cardiomyocyte area and heart weight/tibia length. Molecular analyses involved Taqman® RT-qPCR and immune cells were analyzed with fluorescence-activated cell sorting (FACS). Most importantly, collagen deposition was reduced to WT levels when FAAH-/- mice were treated with GW6471. Chemokine ligand-2 (CCL2) expression was significantly higher in FAAH-/- mice compared to WT, followed by higher macrophage infiltration in infarcted areas, both being reversed by GW6471 treatment. Besides restoring antioxidative properties and contractile elements, PPAR-α antagonism also reversed hypertrophy and remodeling in FAAH-/- mice. Finally, FAAH-/--mice showed more substantial downregulation of PPAR-α compared to WT, suggesting a compensatory mechanism as endocannabinoids are also ligands for PPAR-α, and its activation causes lipotoxicity leading to cardiomyocyte apoptosis. Our study gives novel insights into the role of endocannabinoids acting via PPAR-α. We hypothesize that the increase in endocannabinoids may have partially detrimental effects on cardiomyocyte survival due to PPAR-α activation.
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Canabinoides , Cardiomiopatias , Doença da Artéria Coronariana , Isquemia Miocárdica , Disfunção Ventricular Esquerda , Camundongos , Animais , Endocanabinoides/metabolismo , Ligantes , Amidoidrolases/metabolismo , Alcamidas Poli-Insaturadas/farmacologia , Alcamidas Poli-Insaturadas/metabolismo , Receptores de Canabinoides , PPAR alfa/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Inflamação , Reperfusão , Colágeno , HipertrofiaRESUMO
Mitochondria play a crucial role in cell physiology and pathophysiology. In this context, mitochondrial dynamics and, subsequently, mitochondrial ultrastructure have increasingly become hot topics in modern research, with a focus on mitochondrial fission and fusion. Thus, the dynamics of mitochondria in several diseases have been intensively investigated, especially with a view to developing new promising treatment options. However, the majority of recent studies are performed in highly energy-dependent tissues, such as cardiac, hepatic, and neuronal tissues. In contrast, publications on mitochondrial dynamics from the orthopedic or trauma fields are quite rare, even if there are common cellular mechanisms in cardiovascular and bone tissue, especially regarding bone infection. The present report summarizes the spectrum of mitochondrial alterations in the cardiovascular system and compares it to the state of knowledge in the musculoskeletal system. The present paper summarizes recent knowledge regarding mitochondrial dynamics and gives a short, but not exhaustive, overview of its regulation via fission and fusion. Furthermore, the article highlights hypoxia and its accompanying increased mitochondrial fission as a possible link between cardiac ischemia and inflammatory diseases of the bone, such as osteomyelitis. This opens new innovative perspectives not only for the understanding of cellular pathomechanisms in osteomyelitis but also for potential new treatment options.
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Dinâmica Mitocondrial , Osteomielite , Humanos , Mitocôndrias/fisiologia , Dinâmica Mitocondrial/fisiologia , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Osteoblastos/metabolismo , Osteomielite/metabolismoRESUMO
Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and ß-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function.NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to ß-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.
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Apoptose , Pós-Condicionamento Isquêmico/métodos , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/terapia , Função Ventricular Esquerda , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Citocinas/genética , Citocinas/metabolismo , Feminino , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Injeções Intraperitoneais , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/genética , Cadeias Pesadas de Miosina/metabolismo , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/farmacologia , Oligodesoxirribonucleotídeos/uso terapêutico , Inibidores Teciduais de Metaloproteinases/genética , Inibidores Teciduais de Metaloproteinases/metabolismo , Receptor Toll-Like 9/agonistasRESUMO
BACKGROUND: Revascularization strategy in coronary artery bypass grafting (CABG) surgery usually depends on coronary dimension and stenosis severity. Little is known about the relation of preoperative evaluation of scarcely or invisibly chronic occluded coronary arteries (chronic total occlusion [CTO]) and revascularization rate or anastomosis quality. We aimed to evaluate the success rates of CTO revascularization in CABG surgery and determine the influence of coronary lumen visibility and collateralization in preoperative angiograms on revascularization rates, bypass blood flow, and target vessel diameter. METHOD: Preoperative coronary angiograms were evaluated for 938 consecutive patients who underwent isolated CABG surgery between 2014 and 2016 and screened for occluded coronary arteries. The occluded vessels were scored for visibility using the Rentrop grading of collateral filling. Intraoperatively, dimensions of the occluded arteries were measured using conventional vessel probes, and anastomosis quality was assessed by transit time flow measurement. RESULTS: A total of 404 (43.1%) patients were identified with at least one CTO. Revascularization rates differed from 96.2% in the left anterior descending artery, to 85.0% in left circumflex artery-dependent vessels, and 78.8% in right coronary artery territory. Coronary visibility and grade of collateralization in the preoperative angiogram had no influence on intraoperatively measured coronary diameter. Bypass blood flow in grafts revascularizing CTOs lacking collateralization were not significantly lower than those grafts leading to CTOs with higher Rentrop scores. CONCLUSION: Preoperative coronary assessment often differs from intraoperative findings. Our study confirms that even patients with scarcely collateralized CTOs and impaired visibility in the coronary angiogram have a high chance of complete revascularization during CABG surgery.
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Angiografia Coronária , Ponte de Artéria Coronária , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/cirurgia , Idoso , Doença Crônica , Tomada de Decisão Clínica , Circulação Colateral , Ponte de Artéria Coronária/efeitos adversos , Circulação Coronária , Oclusão Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Crystalloid priming is a cost-effective, free from immunological reactions, and independent from human plasma delivery. However, there is some debate on the negative impact of low plasma colloid pressure and higher incidence of systemic inflammatory response syndrome (SIRS). The aim of the study was to rule out any adverse effects of crystalloid priming on the postoperative outcome. METHODS: We investigated 520 consecutive patients, including emergencies, who had isolated on-pump coronary artery bypass grafting in 2009 by retrospective analysis in our clinic. Crystalloid priming (n = 294) was introduced as an alternative to albumin (n = 226). Reviewing patient charts and IT-based data generated a dataset of perioperative parameters. RESULTS: There were no differences with respect to demographical data and preexisting comorbidities between both groups. Despite equal perfusion times, more volume had to be substituted during extracorporeal circulation following crystalloid priming. However, this did not influence the inhospital outcomes. According to the definition of the "Sepsis-3 Guidelines," the incidence of SIRS was similar. There was no difference in the need for a vasopressor treatment, and only transient higher serum lactate levels were found in the crystalloid group. The incidence of neurologic and organ-related adverse events, as well as 30-day mortality was comparable. CONCLUSION: The use of crystalloid priming is safe in coronary artery bypass grafting surgery in adults. However, there might be a greater need for crystalloid fluids during surgery.
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Albuminas/administração & dosagem , Soluções Cardioplégicas/administração & dosagem , Ponte de Artéria Coronária , Circulação Extracorpórea/instrumentação , Máquina Coração-Pulmão , Compostos de Potássio/administração & dosagem , Idoso , Albuminas/efeitos adversos , Soluções Cardioplégicas/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Circulação Extracorpórea/efeitos adversos , Circulação Extracorpórea/mortalidade , Feminino , Alemanha/epidemiologia , Glucose/administração & dosagem , Glucose/efeitos adversos , Máquina Coração-Pulmão/efeitos adversos , Humanos , Incidência , Masculino , Manitol/administração & dosagem , Manitol/efeitos adversos , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/efeitos adversos , Compostos de Potássio/efeitos adversos , Procaína/administração & dosagem , Procaína/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Patients with acute myocardial infarction (AMI) are at high risk when undergoing emergency coronary artery bypass graft (CABG)-surgery. Their outcome remains poor despite increased use of extracorporeal membrane oxygenation (ECMO). We investigated the impact of timing for perioperative ECMO-support in these patients. METHODS: In this retrospective double-center study, we evaluated 201 patients with AMI undergoing CABG, dividing them into the following groups: No-ECMO (n = 101), preoperative ECMO (pre-ECMO, n = 6), intraoperative ECMO (ECC-ECMO, n = 67), and postoperative ECMO (post-ECMO, n = 27). We evaluated the impact of ECMO timing on postoperative mortality, organ function, and length of stay, comparing these to predicted outcome using different risk-scores. RESULTS: Post-ECMO patients showed lowest 30-day-survival (40.7%), while earlier ECMO-start was associated with better outcome (50.7% in extracorporeal circulation [ECC]-ECMO and 66.7% in pre-ECMO patients). On admission, only pre-ECMO and ECC-ECMO patients showed higher surgery- and intensive-care-unit (ICU)-related risk-scores. In pre- and ECC-ECMO patients, the first significant increase in lactate-levels (>4 mmol/L) was observed preoperatively, while this occurred 1 hour postoperatively in post-ECMO patients. Bilirubin was increased in all patients, decreasing after 3 and 12 days in pre- and ECC-ECMO patients, respectively, but only after 18 days in post-ECMO patients. Multiple ICU risk-scores did not discriminate survival-probability correctly. Only the ECMO-related survival after veno-arterial-ECMO-score correctly predicted the significantly lower survival in post-ECMO patients. CONCLUSION: Our study shows that timely ECMO-support is associated with earlier bilirubin-downtrend and higher survival in patients with AMI after CABG. Lactate-increase greater than 4 mmol/L seems to be a helpful threshold to trigger the timely onset of ECMO-therapy, providing better survival.
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Ponte de Artéria Coronária , Oxigenação por Membrana Extracorpórea/mortalidade , Infarto do Miocárdio/cirurgia , HumanosRESUMO
Background Transcatheter valve-in-ring strategies have been developed to treat recurrent mitral regurgitation (MR) after failing surgical annuloplasty. However, suboptimal THV expansion with consecutive paravalvular leakage (PVL) is a procedure-immanent issue. Methods A rigid, saddle-shaped ring was cut at four locations. The segments were reconnected with pull-springs, rearranged to the original shape, and covered with a sewing cuff. The length of the annuloplasty ring construct, including extended pull-springs, was defined by the perimeter of an appropriate THV. We deployed a Sapien XT within the new ring, expanded it to its maximum extent, and investigated the geometrical changes. Results Fluoroscopy confirmed oval, saddle-shaped ring before dilation. After THV implantation, the ring segments spread apart and pull-springs were stretched. The extended ring changed its configuration from "oval" to "round" and anchored the THV leaving no paravalvular or central gaps as potential source for PVL. Conclusion We developed an expandable annuloplasty ring that is perfectly concerted to THV implantation. This proof-of-concept study revealed no PVL and good oversizing ability that might impact future annuloplasty ring design. Further studies have to evaluate durability and device safety.
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Cateterismo Cardíaco/instrumentação , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Anuloplastia da Valva Mitral/instrumentação , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Anuloplastia da Valva Mitral/efeitos adversos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Falha de Prótese , Fatores de Risco , Resultado do TratamentoRESUMO
To compare stroke volumes (SV) in small hearts assessed by real-time three-dimensional echocardiography (3DE) with SV measured by transpulmonary thermodilution (TPTD) and continuous pulse contour analysis (PC) under various hemodynamic conditions. In thirteen anesthetized piglets (range 3.6-7.1 kg) SV were measured by 3DE, TPTD and PC at baseline and during phenylephrine and esmolol administration. 3DE and TPTD measurements were done successively while SV calculated by PC was documented at the time of 3DE. 3DE and TPTD showed a good correlation (r2 = 0.74) and a bias of -1.3 ml (limits of agreement -4.1 to 1.5 ml). While TPTD measured higher SV than 3DE, both methods tracked SV changes with a concordance rate of 91 %. PC and 3DE showed a lower correlation coefficient of r2 = 0.57 and a bias of -2.1 ml (limits of agreement -5.9 to 1.8 ml). Inter- and intra-observer variability of SV measured by 3DE was good with a mean bias <5 %. SV3DE showed a small variance and tracked acute small changes in SV in acceptable concordance with TPTD. PC measured SV with a higher variance and mean difference compared to 3DE. In an experimental setting 3DE has the possibility to offer non-invasive assessments of ventricular volumes volume changes. To determine whether 3DE could be used for SV assessment in a clinical routine our results need confirmation in a clinical setting.
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Ecocardiografia Tridimensional/métodos , Coração/fisiologia , Volume Sistólico , Termodiluição/métodos , Animais , Feminino , Frequência Cardíaca , Hemodinâmica , Modelos Animais , Variações Dependentes do Observador , Pediatria , Fenilefrina/administração & dosagem , Propanolaminas/administração & dosagem , Reprodutibilidade dos Testes , Suínos , Sístole , Fatores de Tempo , Disfunção Ventricular Esquerda , Função Ventricular EsquerdaRESUMO
BACKGROUND: Unresolved inflammation resulting in capillary leakage with endothelial barrier dysfunction is a major contributor to postoperative morbidity and mortality after coronary artery bypass graft (CABG). Angiopoietins (ANGs) are vascular growth factors, also mediating inflammation and disruption of the endothelium, thus inducing capillary leakage. We hypothesized that changes in the relative serum levels of ANG1 and ANG2 influence endothelial barrier function and perioperative morbidity after CABG. METHODS: After approval and informed consent, serum samples (n = 28) were collected pre CABG surgery, 1, 6, and 24 h after aortic de-clamping. ANG1, ANG2, soluble ANG receptor TIE2 (sTIE2), and IL-6 serum concentrations were analyzed by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with patient serum and FITC-dextran permeability was assessed. Furthermore, ANG2 secretion of HPMECs was analyzed after incubation with IL-6-containing patient serum. RESULTS: CABG induced an early and sustained increase of ANG2/ANG1 ratio (5-fold after 24 h compared to pre-surgery). These changes correlated with elevated serum lactate levels, fluid balance, as well as the duration of mechanical ventilation. Permeability of HPMECs significantly increased after incubation with post-surgery serum showing a marked shift of ANG2/ANG1 balance (18-fold) compared to serum with a less pronounced increase (6-fold). Furthermore, CABG resulted in increased IL-6 serum content. Pre-incubation with serum containing high levels of IL-6 amplified the ANG2 secretion by HPMECs; however, this was not influenced by blocking IL-6. CONCLUSIONS: CABG affects the balance between ANG1 and ANG2 towards a dominance of the barrier-disruptive ANG2. Our data suggest that this ANG2/ANG1 imbalance contributes to an increased postoperative endothelial permeability, likewise being reflected by the clinical course. The results strongly suggest a biological effect of altered angiopoietin balance during cardiac surgery on endothelial permeability.
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Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Ponte de Artéria Coronária/mortalidade , Células Endoteliais/metabolismo , Permeabilidade , Idoso , Idoso de 80 Anos ou mais , Angiopoietina-1/sangue , Angiopoietina-2/sangue , Feminino , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Receptor TIE-2/metabolismo , Estatística como AssuntoRESUMO
Polyunsaturated fatty acids such as DHA have known anti-inflammatory properties. The therapeutic implication highlights the importance of accurate serum measurements. Sample preservation is challenging when performed parallel to the clinical obligations. Impact of time between sample collection and processing regarding concentration alterations of fatty acids in human blood remains to be elucidated. Therefore, more information is required with respect to the stability and storage options in the context of potential degradation and concentration changes. This study investigates the stability of DHA in serum samples over time, given the challenges of timely sample analysis in clinical settings. Blood samples from three patients were collected and stored at +4 °C. Concentrations were analysed between 6 h and 7 days post-collection. Our data indicate that DHA concentrations remained unchanged during the observational period. Our results suggest that storage duration up to 7 days before sample processing does not affect accuracy of the results. DHA measurements is crucial for ongoing and future research in cardiovascular and inflammatory diseases. Our results reveal that DHA stability remains consistent over one week. This information is important for further clinical studies investigating PUFA concentrations, providing researches the option to postpone processing of samples if required along the clinical obligations.
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Right ventricular failure (RVF) after cardiac surgery is associated with an in-hospital mortality rate of up to 75%. Microaxial flow pumps are one of the mechanical circulatory supports (MCS) options available for the treatment of RVF, however the specifics of timing and indication for MCS, as well as predictors for survival, remain unclear due to a dearth of published data. We evaluated the clinical outcome of patients treated with Impella-RP for predictors of mortality and the hemodynamic effects of the pump. This is a single-center retrospective observational study involving adult patients who underwent cardiac surgery with cardiopulmonary bypass between January 2019 and December 2020 in cardiac surgery and required therapeutic management of RVF with an Impella-RP. Overall, 18 patients were included and analyzed for factors that could be associated with mortality, or that could be predictors of patient outcomes for this population. Treatment of RVF with Impella-RP improved the patient hemodynamics significantly and had a survival rate of 61% within 30 days. Patients with isolated CABG or better liver function before implantation had a better survival rate, which may indicate that underlying disease and timing of implantation are significant for successful treatment of RVF.
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Procedimentos Cirúrgicos Cardíacos , Insuficiência Cardíaca , Adulto , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Complicações Pós-Operatórias , Selênio , Choque Cardiogênico , Humanos , Choque Cardiogênico/mortalidade , Choque Cardiogênico/terapia , Masculino , Feminino , Selênio/administração & dosagem , Selênio/uso terapêutico , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/prevenção & controle , Coração Auxiliar , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/prevenção & controle , Insuficiência de Múltiplos Órgãos/etiologiaRESUMO
BACKGROUND: Severe aortic stenosis (sAS) is associated with acquired von Willebrand syndrome (AVWS) by loss of high-molecular-weight multimers (HMWM) of von Willebrand factor (VWF), potentially resulting in perioperative bleeding. Analysis of VWF multimers remains challenging. Recently, the new, rapid Hydragel 5 assay has been developed, using electrophoretic protein separation for dividing VWF-multimers into low (LMWM), intermediate (IMWM), and HMWM, the hemostatically active part of VWF. Here, we evaluated its impact on predicting blood loss in presence of AVWS after surgical aortic valve replacement (SAVR). METHODS: We prospectively examined 52 patients (age: 68 ± 7 years; 54 % male) admitted to SAVR. They were divided in two groups (A: normal VWF, n = 28; B: abnormal VWF, n = 24, defined as VWF-activity/antigen (VWF:Ac/Ag)-ratio < 0.7 and/or HMWM loss). Blood samples and echocardiographic data were collected before, seven days and three months after SAVR. Blood loss and transfusions were recorded. RESULTS: Baseline characteristics and clinical data were similar in both groups. HMWM loss was present in 38.5 % of all patients. HMWM, the VWF:Ac/Ag- and HMWM/(IMWM+LMWM)-ratios were significantly decreased preoperatively in group B but normalized after SAVR. Bleeding, re-thoracotomy and transfusion rates were comparable. HMWM loss was inversely correlated with the peak aortic gradient (Pmax) and positively with the aortic valve area (AVA), while HMWM/(IMWM+LMWM)-ratio negatively correlated with the mean aortic gradient (Pmean). CONCLUSION: HMWM and HMWM/(IMWM+LMWM)-ratio inversely correlate with severity of AS and normalize after SAVR. The Hydragel-5 assay's might be valuable for routine diagnostics to assess bleeding risk and postoperative normalization of AS and VWF abnormalities in SAVR patients.
Assuntos
Estenose da Valva Aórtica , Fator de von Willebrand , Humanos , Masculino , Fator de von Willebrand/análise , Idoso , Feminino , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Implante de Prótese de Valva Cardíaca/métodos , Doenças de von Willebrand/sangue , Doenças de von Willebrand/diagnóstico , Valva Aórtica/cirurgiaRESUMO
Previous studies demonstrated an important role of oxidative stress in the pathogenesis of cardiovascular disease (CVD) in diabetic patients due to hyperglycemia. CVD remains the leading cause of premature death in the western world. Therefore, diabetes mellitus-associated oxidative stress and subsequent inflammation should be recognized at the earliest possible stage to start with the appropriate treatment before the onset of the cardiovascular sequelae such as arterial hypertension or coronary artery disease (CAD). The pathophysiology comprises increased reactive oxygen and nitrogen species (RONS) production by enzymatic and non-enzymatic sources, e.g., mitochondria, an uncoupled nitric oxide synthase, xanthine oxidase, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). Considering that RONS originate from different cellular mechanisms in separate cellular compartments, adequate, sensitive, and compartment-specific methods for their quantification are crucial for early detection. In this review, we provide an overview of these methods with important information for early, appropriate, and effective treatment of these patients and their cardiovascular sequelae.
Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Sistema Cardiovascular/metabolismo , NADPH Oxidases/metabolismoRESUMO
Large epidemiological studies have shown that traffic noise promotes the development of cardiometabolic diseases. It remains to be established how long these adverse effects of noise may persist in response to a noise-off period. We investigated the effects of acute aircraft noise exposure (mean sound level of 72 dB(A) applied for 4d) on oxidative stress and inflammation mediating vascular dysfunction and increased blood pressure in male C57BL/6 J mice. 1, 2 or 4d of noise cessation after a 4d continuous noise exposure period completely normalized noise-induced endothelial dysfunction of the aorta (measured by acetylcholine-dependent relaxation) already after a 1d noise pause. Vascular oxidative stress and the increased blood pressure were partially corrected, while markers of inflammation (VCAM-1, IL-6 and leukocyte oxidative burst) showed a normalization within 4d of noise cessation. In contrast, endothelial dysfunction, oxidative stress, and inflammation of the cerebral microvessels of noise-exposed mice did not improve at all. These data demonstrate that the recovery from noise-induced damage is more complex than expected demonstrating a complete restoration of large conductance vessel function but persistent endothelial dysfunction of the microcirculation. These findings also imply that longer noise pauses are required to completely reverse noise-induced vascular dysfunction including the resistance vessels.
RESUMO
AIMS: Environmental stressors such as traffic noise represent a global threat, accounting for 1.6 million healthy life years lost annually in Western Europe. Therefore, the noise-associated health side effects must be effectively prevented or mitigated. Non-pharmacological interventions such as physical activity or a balanced healthy diet are effective due to the activation of the adenosine monophosphate-activated protein kinase (α1AMPK). Here, we investigated for the first time in a murine model of aircraft noise-induced vascular dysfunction the potential protective role of α1AMPK activated via exercise, intermittent fasting, and pharmacological treatment. METHODS AND RESULTS: Wild-type (B6.Cg-Tg(Cdh5-cre)7Mlia/J) mice were exposed to aircraft noise [maximum sound pressure level of 85 dB(A), average sound pressure level of 72 dB(A)] for the last 4 days. The α1AMPK was stimulated by different protocols, including 5-aminoimidazole-4-carboxamide riboside application, voluntary exercise, and intermittent fasting. Four days of aircraft noise exposure produced significant endothelial dysfunction in wild-type mice aorta, mesenteric arteries, and retinal arterioles. This was associated with increased vascular oxidative stress and asymmetric dimethylarginine formation. The α1AMPK activation with all three approaches prevented endothelial dysfunction and vascular oxidative stress development, which was supported by RNA sequencing data. Endothelium-specific α1AMPK knockout markedly aggravated noise-induced vascular damage and caused a loss of mitigation effects by exercise or intermittent fasting. CONCLUSION: Our results demonstrate that endothelial-specific α1AMPK activation by pharmacological stimulation, exercise, and intermittent fasting effectively mitigates noise-induced cardiovascular damage. Future population-based studies need to clinically prove the concept of exercise/fasting-mediated mitigation of transportation noise-associated disease.
Traffic noise, e.g. from aircraft, significantly contributes to an increased risk of cardiovascular or metabolic diseases in the general population by brain-dependent stress reactions leading to higher levels of circulating stress hormones and vasoconstrictors, all of which cause hypertension, oxidative stress, and inflammation. With the present experimental studies, we provide for the first time molecular mechanisms responsible for successful noise mitigation: Physical exercise, intermittent fasting, and pharmacological activation of the adenosine monophosphate-activated protein kinase (AMPK), a metabolic master regulator protein, prevent cardiovascular damage caused by noise exposure, such as hypertension, endothelial dysfunction, and reactive oxygen species formation (e.g. free radicals) and inflammation.These beneficial mitigation manoeuvers are secondary to an activation of the endothelial AMPK, thereby mimicking the antidiabetic drug metformin.
Assuntos
Endotélio Vascular , Ruído dos Transportes , Humanos , Camundongos , Animais , Endotélio Vascular/metabolismo , Estresse Oxidativo , Ruído dos Transportes/efeitos adversos , Jejum , Aeronaves , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologiaRESUMO
Non-communicable diseases (NCDs) are fatal for more than 38 million people each year and are thus the main contributors to the global burden of disease accounting for 70% of mortality. The majority of these deaths are caused by cardiovascular disease (CVD). The risk of NCDs is strongly associated with exposure to environmental stressors such as pollutants in the air, noise exposure, artificial light at night, and climate change, including heat extremes, desert storms, and wildfires. In addition to the traditional risk factors for CVD such as diabetes, arterial hypertension, smoking, hypercholesterolaemia, and genetic predisposition, there is a growing body of evidence showing that physicochemical factors in the environment contribute significantly to the high NCD numbers. Furthermore, urbanization is associated with accumulation and intensification of these stressors. This comprehensive expert review will summarize the epidemiology and pathophysiology of environmental stressors with a focus on cardiovascular NCDs. We will also discuss solutions and mitigation measures to lower the impact of environmental risk factors with focus on CVD.
Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Diabetes Mellitus , Doenças não Transmissíveis , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Doenças não Transmissíveis/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologiaRESUMO
BACKGROUND: Diabetic vasculopathy plays an important role in the pathophysiology of coronary artery disease (CAD) with oxidative stress as a strong mediator. This study aims to elucidate the underlying pathomechanisms of diabetic cardiac vasculopathy leading to coronary disease with an emphasis on the role of oxidative stress. Therefore, novel insights into antioxidant pathways might contribute to new strategies in the treatment and prevention of diabetic CAD. METHODS: In 20 patients with insulin-dependent or non-insulin dependent diabetes mellitus (IDDM/NIDDM) and 39 non-diabetic (CTR) patients, myocardial markers of oxidative stress, vasoactive proteins, endothelial nitric oxide synthase (eNOS), activated phosphorylated eNOS (p-eNOS), and antioxidant enzymes, e.g., tetrahydrobiopterin generating dihydrofolate reductase (DHFR), heme oxygenase (HO-1), as well as serum markers of inflammation, e.g., E-selectin, interleukin-6 (IL-6), and lipid metabolism, e.g., high- and low-density lipoptrotein (HDL- and LDL-cholesterol) were determined in specimens of right atrial tissue and in blood samples from type 2 diabetic and non-diabetic patients undergoing coronary artery bypass graft (CABG) surgery. RESULTS: IDDM/NIDDM increased markers of inflammation (e.g., E-selectin, p = 0.005 and IL-6, p = 0.051), decreased the phosphorylated myocardial p-eNOS (p = 0.032), upregulated the myocardial stress response protein HO-1 (p = 0.018), and enhanced the serum LDL-/HDL-cholesterol ratio (p = 0.019). However, the oxidative stress markers in the myocardium and the expression of vasoactive proteins (eNOS, DHFR) showed only marginal adverse changes in patients with IDDM/NIDDM. CONCLUSION: Dyslipidemia and myocardial inflammation seem to be the major determinants of diabetic CAD complications. Dysregulation in pro-oxidative enzymes might be attributable to the severity of CAD and oxidative stress levels in all included patients undergoing CABG.