RESUMO
INTRODUCTION: Neurocognitive decline (NCD) is a common complication after cardiac surgery with implications for outcomes and quality of life. Identifying risk factors can help surgeons implement preventative measures, optimize modifiable risk factors, and counsel patients about risk and prognosis. METHODS: Prospective cohort study at a single academic center. 104 patients planned to undergo cardiac surgery were enrolled. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to measure neurocognitive function preoperatively, on postoperative day four, and postoperative day 30. NCD is defined as a change in RBANS scaled score of < -8 from baseline to postoperative day 4. Patient charts were reviewed for medication history: beta-blockers, angiotensin-converting enzyme and angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents, and psychoactive medications. Charts were also reviewed to calculate postoperative opioid usage. RESULTS: NCD was detected in 42.9% of patients. Incidence of NCD was significantly higher in patients taking a psychoactive medication (56.8%) than patients not (31.9%), P < 0.03. There was no relationship between historical use of beta-blocker, calcium-channel blocker, statin, or oral hypoglycemic medications and incidence of NCD. Simple linear regression showed no relationship between change in RBANS total scaled score and opioid usage. There was no difference in incidence of NCD at 1 mo. CONCLUSIONS: Patients with a history of taking psychoactive medications prior to cardiac surgery have an increased risk of acute postoperative NCD.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças não Transmissíveis , Humanos , Estudos Prospectivos , Analgésicos Opioides , Doenças não Transmissíveis/tratamento farmacológico , Qualidade de Vida , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Fatores de RiscoRESUMO
Pneumonia causes short- and long-term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia-elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long-term potentiation; and, (3) inhibit long-term potentiation dependent upon tau. Cytotoxic amyloid and tau species were recovered from the blood and the hippocampus following pneumonia, and they were present in the extracorporeal membrane oxygenation oxygenators of patients with pneumonia, especially in those who died. Introduction of immunopurified blood-borne amyloid and tau into either the airways or the blood of uninfected animals acutely and chronically impaired hippocampal information processing. In contrast, the infection did not impair long-term potentiation in tau knockout mice and the amyloid- and tau-dependent disruption in hippocampal signaling was less severe in tau knockout mice. Moreover, the infection did not elicit cytotoxic amyloid and tau variants in tau knockout mice. Therefore, pneumonia initiates a tauopathy that contributes to cognitive dysfunction.
Assuntos
Pneumonia/complicações , Tauopatias/etiologia , Adulto , Idoso , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Amiloide/metabolismo , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Feminino , Hipocampo/metabolismo , Humanos , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Pneumonia/metabolismo , Ratos , Tauopatias/metabolismo , Adulto Jovem , Proteínas tau/metabolismoRESUMO
BACKGROUND: Whether perioperative glycemic control is associated with neurocognitive decline (NCD) after cardiac surgery was examined. METHODS: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on postoperative day 4 (POD4). Indices of glucose control were examined. Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. RESULTS: A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p = .973) or elevated fasting blood glucose levels the morning of surgery (>126 mg/dl, p = .910), or a higher maximum blood glucose levels during CPB (>180 mg/dl, p = .252), or higher average glucose levels during CPB (>160 mg/dl, p = .639). Patients with postoperative leukocytosis (WBC ≥ 10.5) had more NCD when compared to their baseline function (p = .03). Patients with elevated IL-8 levels at 6 h postoperatively had a significant decline in NCD at POD4 (p = .04). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. CONCLUSIONS: Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. The profile of gene expression was altered in patients with NCD with or without diabetes.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Controle Glicêmico , Ponte Cardiopulmonar , Expressão Gênica , HumanosRESUMO
BACKGROUND: Transcatheter aortic valve replacement (TAVR) exposes patients to radiation. OBJECTIVES: We sought to identify factors associated with higher radiation exposure and to quantify their relative influence, which may inform reduction of this hazard. METHODS: All TAVR procedures at Rhode Island Hospital between March 20, 2012 and February 12, 2017 were included. Procedures were performed by two co-primary operators using a Siemens Artis Zeego system. Radiation metrics were generated by the imaging system. The primary metric was dose-area product (DAP, Gy*cm2 ), and secondary metrics were reference point air kerma (mGy) and fluoroscopy time (minutes). Data collected for the STS/ACC TVT Registry were utilized to develop a multivariable linear regression model predicting DAP. RESULTS: In 294 TAVRs, median DAP was 169 Gy*cm2 [interquartile range (IQR) 106-238]. The r2 values for the full 27-variable DAP model and reduced eight-variable model were 0.457 and 0.420, respectively. Valve area, aortic insufficiency, and procedure year (suggesting absence of a learning curve) were non-significant predictors in the full model, while increasing weight, cutdown transfemoral access, higher pre-procedure creatinine and hemoglobin, and vascular complications predicted higher DAP in both models. Results were unchanged when DAP was log-transformed. Secondary models for air kerma and fluoroscopy time revealed similar predictors. CONCLUSION: Factors associated with increased procedural complexity and duration as well as radiation attenuation and scatter predict increased patient radiation exposure during TAVR. Modification of procedural technique, especially using percutaneous femoral vascular access, may facilitate reduction in exposure.
Assuntos
Valva Aórtica/cirurgia , Doses de Radiação , Exposição à Radiação , Radiografia Intervencionista , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Feminino , Humanos , Masculino , Duração da Cirurgia , Segurança do Paciente , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Proteção Radiológica/métodos , Radiografia Intervencionista/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espalhamento de Radiação , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversosRESUMO
BACKGROUND: Transfusion of blood products commonly occur in patients undergoing repair of acute type A aortic dissection (AADA). MATERIALS AND METHODS: The medical records of 102 AADA patients were retrospectively reviewed and stratified into cohorts by packed red blood cell (PRBC) and platelet units received: PRBC ≤2 units (n = 68) versus PRBC >2 units (n = 34); platelets ≤1 unit (n = 74) versus platelets >1 unit (n = 28). Continuous and categorical variables were assessed by analysis of variance testing and chi-square or Fisher's testing as appropriate. Multivariate logistic regression was applied to derive P values for post-transfusion complications. Kaplan-Meier survival analyses were used to compare the hospital length of stay (LOS) and survival rate at 1 mo and 1 y. RESULTS: Patients receiving >2 units of PRBC had a median LOS of 14 d versus 9 d for those receiving ≤2 units (P < 0.002). Transfusion of >2 units of PRBC was a risk factor for postoperative infection (odds ratio [OR] = 5.4, 95% confidence interval [CI]: 1.5-19.0, P = 0.009). Survival at 1 mo was 91% versus 94% (P = 0.783) and 1 y survival was 82% versus 93% (P = 0.269) between the two groups. Patients receiving >1 unit of platelets had a median LOS of 15 d versus 10 d for those receiving ≤1 unit (P = 0.005). Transfusion of >1 unit of platelets was a risk factor for postoperative atrial fibrillation and acute kidney injury (OR = 2.9, 95% CI: 1.1-7.6, P = 0.031; OR = 3.3, 95% CI: 1.2-9.4, P = 0.025, respectively). Survival at 1 mo was 93% versus 93% (P = 0.872) and 1 y survival was 81% versus 92% (P = 0.582) between the two groups. CONCLUSIONS: Transfusion of PRBC and platelets above a threshold increases the incidence of postoperative complications and hospital LOS among patients undergoing repair of AADA.
Assuntos
Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Plaquetas/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Enxerto Vascular/efeitos adversos , Idoso , Dissecção Aórtica/mortalidade , Aneurisma da Aorta Torácica/mortalidade , Perda Sanguínea Cirúrgica , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Transfusão de Plaquetas/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Enxerto Vascular/métodosRESUMO
BACKGROUND: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. METHODS: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. RESULTS: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. CONCLUSIONS: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.
Assuntos
Permeabilidade Capilar , Coração Artificial , Hemorreologia , Junções Aderentes/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Bovinos , Edema , Endotélio Vascular/metabolismo , Feminino , Masculino , Microvasos/metabolismo , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/patologiaAssuntos
Oxigenação por Membrana Extracorpórea/efeitos adversos , Previsões/métodos , Hemorragia/diagnóstico , Aprendizado de Máquina/tendências , Trombose/diagnóstico , Distribuição de Qui-Quadrado , Estudos de Coortes , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Hemorragia/fisiopatologia , Humanos , Estudos Retrospectivos , Trombose/fisiopatologiaRESUMO
BACKGROUND: There has been an evolution in the disease severity and complexity of patients presenting to the cardiac intensive care unit (CICU). There are limited data evaluating the role of palliative care in contemporary CICU practice. METHODS: PubMed Central, CINAHL, EMBASE, Medline, Cochrane Library, Scopus, and Web of Science databases were evaluated for studies on palliative care in adults (≥18 years) admitted with acute cardiovascular conditions - acute myocardial infarction, cardiogenic shock, cardiac arrest, advanced heart failure, post-cardiac surgery, spontaneous coronary artery dissection, Takotsubo cardiomyopathy, and pulmonary embolism - admitted to the CICU, coronary care unit or cardiovascular intensive care unit from 1/1/2000 to 8/8/2022. The primary outcome of interest was the utilization of palliative care services. Secondary outcomes of included studies were also addressed. Meta-analysis was not performed due to heterogeneity. RESULTS: Of 5711 citations, 30 studies were included. All studies were published in the last seven years and 90 % originated in the United States. Twenty-seven studies (90 %) were retrospective analyses, with a majority from the National Inpatient Sample database. Heart failure was the most frequent diagnosis (47 %), and in-hospital mortality was reported in 67 % of studies. There was heterogeneity in the timing, frequency, and background of the care team that determined palliative care consultation. In two randomized trials, there appeared to be improvement in quality of life without an impact on mortality. CONCLUSIONS: Despite the growing recognition of the role of palliative care, there are limited data on palliative care consultation in the CICU.
RESUMO
Despite the importance of informed consent in healthcare, the readability and specificity of consent forms often impede patients' comprehension. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness. Consent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4's potential for generating de novo procedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review. Analysis of 15 academic medical centers' consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (all P < 0.05) following GPT-4-faciliated simplification. Readability improved from an average college freshman to an 8th-grade level (P = 0.004), matching the average American's reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review. This study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers.
RESUMO
BACKGROUND: Neurocognitive decline (NCD) is a common complication of cardiac surgery. Understanding risk factors helps surgeons counsel patients pre- and perioperatively about risk, prevention, and treatment. STUDY DESIGN: Patients undergoing cardiac surgery using cardiopulmonary bypass underwent pre- and postoperative neurocognitive testing. Neurocognitive data are presented as a change from baseline to either postoperative day 4 or to 1 month. The score is standardized with respect to age. RESULTS: Eighty-four patients underwent surgery and completed postoperative neurocognitive testing. There was no significant difference in baseline neurocognitive function. NCD was more common in female patients (71%) than male patients (26.4%) on postoperative day 4. By 1 month, the incidence of NCD is similar between female (15.0%) and male patients (14.3%). Of note, female patients differed from male patients in preoperative hematocrit, preoperative creatinine, and type of surgery. CONCLUSIONS: In the acute postoperative period, female patients are both more likely to experience NCD and experience a more severe change from baseline cognitive function. This difference between male and female patients resolves by the 1 month follow-up point. Female patients had a lower preoperative hematocrit and were more likely to receive intraoperative and perioperative blood transfusion. Lower preoperative hematocrit appears to mediate the difference in NCD between male and female patients.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças não Transmissíveis , Humanos , Masculino , Feminino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fatores de Risco , CogniçãoRESUMO
A 23-year-old man sustained blunt cardiac injury after a motor vehicle collision resulting in left ventricular septal avulsion, ruptured chordae tendineae, and moderate to severe tricuspid regurgitation that necessitated operative intervention. The patient underwent successful resection of a prolapsed avulsed septal wall segment and concomitant tricuspid valve repair.
Assuntos
Traumatismos Cardíacos , Contusões Miocárdicas , Insuficiência da Valva Tricúspide , Masculino , Humanos , Adulto Jovem , Adulto , Cordas Tendinosas/cirurgia , Insuficiência da Valva Tricúspide/cirurgia , Valva Tricúspide/cirurgia , Traumatismos Cardíacos/diagnóstico , Traumatismos Cardíacos/diagnóstico por imagem , Contusões Miocárdicas/complicaçõesRESUMO
BACKGROUND: The clinical applicability of machine learning predictions of patient outcomes following cardiac surgery remains unclear. We applied machine learning to predict patient outcomes associated with high morbidity and mortality after cardiac surgery and identified the importance of variables to the derived model's performance. METHODS: We applied machine learning to the Society of Thoracic Surgeons Adult Cardiac Surgery Database to predict postoperative hemorrhage requiring reoperation, venous thromboembolism (VTE), and stroke. We used permutation feature importance to identify variables important to model performance and a misclassification analysis to study the limitations of the model. RESULTS: The study dataset included 662,772 subjects who underwent cardiac surgery between 2015 and 2017 and 240 variables. Hemorrhage requiring reoperation, VTE, and stroke occurred in 2.9%, 1.2%, and 2.0% of subjects, respectively. The model performed remarkably well at predicting all 3 complications (area under the receiver operating characteristic curve, 0.92-0.97). Preoperative and intraoperative variables were not important to model performance; instead, performance for the prediction of all 3 outcomes was driven primarily by several postoperative variables, including known risk factors for the complications, such as mechanical ventilation and new onset of postoperative arrhythmias. Many of the postoperative variables important to model performance also increased the risk of subject misclassification, indicating internal validity. CONCLUSIONS: A machine learning model accurately and reliably predicts patient outcomes following cardiac surgery. Postoperative, as opposed to preoperative or intraoperative variables, are important to model performance. Interventions targeting this period, including minimizing the duration of mechanical ventilation and early treatment of new-onset postoperative arrhythmias, may help lower the risk of these complications.
RESUMO
BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.
Assuntos
Injúria Renal Aguda , Anemia , Procedimentos Cirúrgicos Cardíacos , Humanos , Estudos Prospectivos , Eritrócitos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Glutationa/farmacologia , Hipóxia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como AssuntoRESUMO
Background Mesenchymal stem cell-derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs. Methods and Results Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery. Subsequently, animals received either intramyocardial injection of vehicle-saline as controls; (ND-controls n=7, HFD-controls, n=6) or EVs; (ND-EVs n=10, HFD-EVs n=8) into the ischemic territory. Five weeks later, myocardial function, perfusion, vascular density, cell signaling, and gene expression were examined. EVs improved indices of myocardial contractile function, myocardial perfusion, and arteriogenesis in both dietary cohorts. Interestingly, quantification of alpha smooth muscle actin demonstrated higher basal arteriolar density in HFD swine compared with their ND counterparts; whereas EVs were associated with increased CD31-labeled endothelial cell density only in the ND tissue, which approached significance. Levels of total endothelial nitric oxide synthase, FOXO1 (forkhead box protein O1) , transforming growth factor-ß, phosphorylated VEGFR2 (vascular endothelial growth factor receptor 2), and phosphorylated MAPK ERK1/ERK2 (mitogen-activated protein kinase) were higher in ischemic myocardial lysates from ND-controls compared with HFD-controls. Conversely, HFD-control tissue showed increased expression of phosphorylated endothelial nitric oxide synthase, phosphorylated FOXO1, VEGFR2, and MAPK ERK1/ERK2 with respect to ND-controls. Preliminary gene expression studies indicate differential modulation of transcriptional activity by EVs between the 2 dietary cohorts. Conclusions HFD produces a profound metabolic disorder that dysregulates the molecular mechanisms of collateral vessel formation in the ischemic myocardium, which may hinder the therapeutic angiogenic effects of EVs.
Assuntos
Indutores da Angiogênese/farmacologia , Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Dieta Hiperlipídica/efeitos adversos , Vesículas Extracelulares/patologia , Isquemia Miocárdica/etiologia , Miocárdio/metabolismo , Animais , Doença Crônica , Circulação Coronária/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/etiologia , Neovascularização Patológica/metabolismo , Fosforilação , SuínosRESUMO
BACKGROUND: Hypercholesterolemia is prevalent in patients who experience myocardial ischemia-reperfusion injury (IR). We investigate the impact of dietary-induced hypercholesterolemia on the myocardium in the setting of acute IR. METHODS AND RESULTS: In normocholesterolemic (NC, n=7) and hypercholesterolemic (HC, n=7) Yucatan male pigs, the left anterior descending coronary artery was occluded for 60 minutes, followed by reperfusion for 120 minutes. Hemodynamic values were recorded, and TTC staining was used to assess necrosis. Oxidative stress was measured. Specific cell death and survival signaling pathways were assessed by Western blot and TUNEL staining. Infarct size was 45% greater in HC versus NC (42% versus 61%, P<0.05), whereas the area at risk (AAR) was similar in both groups (P=0.61). Whereas global LV function (+dP/dt, P<0.05) was higher during entire period of IR in HC versus NC, regional function deteriorated more following reperfusion in HC (P<0.05). Ischemia increased indices of myocardial oxidative stress such as protein oxidation (P<0.05), lipid peroxidation (P<0.05), and nitrotyrosylation in HC versus NC, as well as the expression of phospho-eNOS (P<0.05). The expression of myeloperoxidase, p38 MAPK, and phospho-p38 MAPK was higher in HC versus NC (all P<05). Ischemia caused higher expression of the proapoptotic protein PARP (P<0.05), and lower expression of the prosurvival proteins Bcl2 (P<0.05), phospho-Akt, (P<0.05), and phospho-PKCepsilon (P<0.05) in the HC versus NC. TUNEL-positive cell count was 3.8-fold (P<0.05) higher in the AAR of HC versus NC. CONCLUSIONS: This study demonstrates that experimental hypercholesterolemia is associated with increased myocardial oxidative stress and inflammation, attenuation of cell survival pathways, and induction of apoptosis in the ischemic territory, which together may account for the expansion of myocardial necrosis in the setting of acute IR.
Assuntos
Hipercolesterolemia/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Animais , Apoptose , Vasos Coronários/fisiopatologia , Hemodinâmica , Hipercolesterolemia/fisiopatologia , Lipídeos/sangue , Masculino , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Necrose , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Suínos , Fibrilação Ventricular/etiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: This study examined effects of diabetes mellitus (DM) on cellular proliferation associated with vascular endothelial growth factor (VEGF) signaling in endothelial progenitor cells (EPCs) and evaluated protein expression involved in cellular proliferation and proapoptotic signaling in chronically ischemic myocardium. METHODS: Insulin-dependent DM was induced in yucatan miniswine with alloxan. Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Seven weeks after ameroid constrictor, perfusion of ischemic territory was measured by isotope-labeled microspheres, and ischemic myocardium was harvested. Bone marrow (BM) samples were harvested from iliac bone and mononuclear cells (MNCs) were cryopreserved. EPCs were isolated from cryopreserved MNCs in control (n = 6) and DM swine (n = 6). EPC proliferation was assessed. RESULTS: EPC proliferation was decreased in DM as compared to control (1.02 ± 0.09, 0.40 ± 0.04, p < 0.01). VEGF-induced EPC proliferation was impaired in DM as compared to control (p < 0.01). Expression of ERK protein, an activator of VEGF-induced cell proliferation, was decreased. AKT activation, an inhibitor of apoptosis, was decreased, while Bad, an activator of proapoptotic signaling, was elevated in the ischemic myocardium from DM. Collateral dependent perfusion was impaired in DM. CONCLUSION: Impaired VEGF-induced proliferation response in EPC as well as an increase in negative myocardial protein expression for cell proliferation and proapoptotic signaling via VEGF could be a therapeutic target to enhance the effects of proangiogenesis therapies in DM and other chronic illnesses.
Assuntos
Proliferação de Células/efeitos dos fármacos , Isquemia Miocárdica/cirurgia , Células-Tronco/metabolismo , Fatores de Crescimento do Endotélio Vascular/farmacologia , Aloxano , Animais , Western Blotting , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular , Transplante de Células/métodos , Células Cultivadas , Diabetes Mellitus Experimental/tratamento farmacológico , Modelos Animais de Doenças , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Insulina/farmacologia , Distribuição Aleatória , Valores de Referência , Estatísticas não Paramétricas , Células-Tronco/citologia , Suínos , Porco Miniatura , Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Cardiopulmonary bypass may be associated with postoperative neurocognitive dysfunction; however, risk factors have not been clearly identified. We hypothesize that lower hematocrit levels are correlated with postoperative neurocognitive dysfunction. METHODS: A total of 30 patients underwent cardiac operations utilizing cardiopulmonary bypass and screening for neurocognitive dysfunction preoperatively and on postoperative day 4. Patients were analyzed according to hematocrit preoperatively, 6 hours postoperatively, and on postoperative day 4, and whether they received intra or postoperative transfusions of packed red blood cells. Neurocognitive data is presented as a difference in Repeatable Battery for the Assessment of Neuropsychological Status standardized score from baseline to postoperative day 4 and analyzed by unpaired two-tailed Spearman test and unpaired Mann-Whitney U test. RESULTS: There was a significant correlation between patients with lower hematocrit before surgery and a decline in neurocognitive function at postoperative day 4 (P < .05). All patients experienced a decrease in hematocrit during their hospital stay, but the hematocrit 6 hours postoperatively and postoperative day 4 did not impact cognition. Receiving a transfusion was also not associated with neurocognitive dysfunction. Patients with low hematocrit preoperatively had a consistently lower hematocrit throughout their stay. Prolonged total length of stay was also significantly associated with neurocognitive decline. CONCLUSION: A lower preoperative hematocrit and prolonged length of hospital stay are correlated with neurocognitive decline after cardiac surgery utilizing cardiopulmonary bypass.
Assuntos
Anemia/complicações , Ponte Cardiopulmonar/efeitos adversos , Transtornos Neurocognitivos/etiologia , Complicações Pós-Operatórias/etiologia , Idoso , Transfusão de Sangue Autóloga , Procedimentos Cirúrgicos Cardíacos , Feminino , Hematócrito , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Despite advances in left ventricular assist device (LVAD) technology, right ventricular failure (RVF) continues to be a complication after implantation. Most patients undergoing LVAD implantation have underlying right ventricular (RV) dysfunction (either as a result of prolonged LV failure or systemic disorders) that becomes decompensated post-implantation. Additional insults include intra-operative factors or a sudden increase in preload in the setting of increased cardiac output. The current literature estimates post-LVAD RVF from 3.9% to 53% using a diverse set of definitions. A few of the risk factors that have been identified include markers of cardiogenic shock (e.g., dependence on inotropes and Interagency Registry for Mechanically Assisted Circulatory Support profiles) as well as evidence of cardiorenal or cardiohepatic syndromes. Several studies have devised multivariable risk scores; however, their performance has been limited. A new functional assessment of RVF and a novel hepatic marker that describe cholestatic properties of congestive hepatopathy may provide additional predictive value. Furthermore, future studies can help better understand the relationship between pulmonary hypertension and post-LVAD RVF. To achieve our ultimate goal-to prevent and effectively manage RVF post-LVAD-we must start with a better understanding of the risk factors and pathophysiology. Future research on the different etiologies of RVF-ranging from acute post-surgical complication to late-onset RV cardiomyopathy-will help standardize definitions and tailor therapies appropriately.
Assuntos
Coração Auxiliar/efeitos adversos , Disfunção Ventricular Direita/epidemiologia , Disfunção Ventricular Direita/etiologia , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: Diabetic (DM) inactivation of small conductance calcium-activated potassium (SK) channels contributes to coronary endothelial dysfunction. However, the mechanisms responsible for this down-regulation of endothelial SK channels are poorly understood. Thus, we hypothesized that the altered metabolic signaling in diabetes regulates endothelial SK channels and human coronary microvascular function. METHODS: Human atrial tissue, coronary arterioles and coronary artery endothelial cells (HCAECs) obtained from DM and non-diabetic (ND) patients (n = 12/group) undergoing cardiac surgery were used to analyze metabolic alterations, endothelial SK channel function, coronary microvascular reactivity and SK gene/protein expression/localization. RESULTS: The relaxation response of DM coronary arterioles to the selective SK channel activator SKA-31 and calcium ionophore A23187 was significantly decreased compared to that of ND arterioles (p < 0.05). Diabetes increases the level of NADH and the NADH/NAD+ ratio in human myocardium and HCAECs (p < 0.05). Increase in intracellular NADH (100 µM) in the HCAECs caused a significant decrease in endothelial SK channel currents (p < 0.05), whereas, intracellular application of NAD+ (500 µM) increased the endothelial SK channel currents (p < 0.05). Mitochondrial reactive oxygen species (mROS) of HCAECs and NADPH oxidase (NOX) and PKC protein expression in the human myocardium and coronary microvasculature were increased respectively (p < 0.05). CONCLUSIONS: Diabetes is associated with metabolic changes in the human myocardium, coronary microvasculature and HCAECs. Endothelial SK channel function is regulated by the metabolite pyridine nucleotides, NADH and NAD+, suggesting that metabolic regulation of endothelial SK channels may contribute to coronary endothelial dysfunction in the DM patients with diabetes.
Assuntos
Diabetes Mellitus , Células Endoteliais , Arteríolas , Vasos Coronários/diagnóstico por imagem , Coração , HumanosRESUMO
BACKGROUND: Mesenchymal stem cell-derived extracellular vesicles (EVs) appear to be a very exciting treatment option for heart disease. Here, we used a swine model of chronic myocardial ischemia to evaluate the efficacy of a less-invasive method of injection of EVs via a peripheral intravenous route. METHODS: Sixteen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex (LCx) artery at age 11 weeks to induce chronic myocardial ischemia. Two weeks later, they were divided into two groups: control (CON; n = 8), and intravenous injection of EVs (EVIV; n = 8). At 18 weeks of age, animals underwent final analysis and euthanasia. The chronically ischemic myocardium (LCx territory) was harvested for analysis. RESULTS: Intravenous injection (IV) of EVs induced several pro-angiogenic markers such as MAPK, JNK but not Akt. Whereas IV injections of EVs decreased VEGFR2 expression and inhibited apoptotic signaling (caspase 3), they increased expression of VEGFR1 that is believed to be anti-angiogenic. Injection of EVs did not result in an increase in vessel density and blood flow when compared to the control group. CONCLUSIONS: Although IV injection of EVs upregulated several pro-angiogenic signaling pathways, it failed to induce changes in vascular density in the chronically ischemic myocardium. Thus, a lack of increase in vascular density at the doses tested failed to elicit a functional response in ischemic myocardium.