Smooth muscle phenotypic modulation is an early event in aortic aneurysms Ailawadi, Gorav, MD; Moehle, Christopher W., BS; Pei, Hong, MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
12/2009, Letnik:
138, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Objectives Vascular smooth muscle cells can undergo profound changes in phenotype, defined by coordinated repression of smooth muscle cell marker genes and production of matrix metalloproteinases in ...response to injury. However, little is known of the role of smooth muscle cells in aortic aneurysms. We hypothesized that smooth muscle cells undergo phenotypic modulation early in the development of aortic aneurysms. Methods Abdominal aortas from C57B6 mice (n = 79) were perfused with elastase or saline (control) and harvested at 1, 3, 7, or 14 days. Aortas were analyzed by means of quantitative polymerase chain reaction and immunohistochemistry for smooth muscle cell marker genes, including SM22A, smooth muscle α-actin, and matrix metalloproteinases 2 and 9. In complimentary experiments human aneurysms (n = 10) and control aorta (n = 10) were harvested at the time of surgical intervention and analyzed. Results By 14 days, aortic diameter was larger after elastase perfusion compared with control diameter (100% ± 9.6% vs 59.5% ± 18.9%, P = .0002). At 7 days, elastase-perfused mice had a 78% and 85% reduction in SM22α and smooth muscle α-actin expression, respectively, compared with that seen in control animals well before aneurysms were present, and these values remained repressed at 14 days. Immunohistochemistry confirmed less SM22α and smooth muscle α-actin in experimental aneurysms at 14 days in concert with increased matrix metalloproteinase 2 and 9 expression at 7 and 14 days. Similarly, human aneurysms had less SM22α and smooth muscle α-actin and increased matrix metalloproteinase 2 and 9 staining, compared with control values, as determined by means of quantitative polymerase chain reaction. Conclusions Aneurysms demonstrate smooth muscle cell phenotypic modulation characterized by downregulation of smooth muscle cell marker genes and upregulation of matrix metalloproteinases. These events in experimental models occur before aneurysm formation. Targeting smooth muscle cells to a reparative phenotype might provide a novel therapy in the treatment of aortic aneurysms.
Background There is growing concern over the effect of starting non-emergent cardiac surgery later in the day on clinical outcomes and resource utilization. Our objective was to determine the ...differences in patient outcomes for starting non-emergent cardiac surgery after 3 pm. Methods All non-emergent cardiac operations performed at a single institution from July 2008 to 2013 were reviewed. Cases were stratified based on “early start” or “late start,” defined by incision time before or after 3 pm . Rates of observed and risk-adjusted mortality, major complications, and costs were compared on a univariate basis for all patients and by multivariable linear and logistic regression for patients with a valid The Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM). Results A total of 3,395 non-emergent cardiac operations were reviewed, including 368 late start cases. Compared with cases starting earlier, mortality was significantly higher for patients undergoing late operations (5.2% vs 3.5%, p = 0.046) despite similar preoperative risk (STS PROM 3.8% vs 3.3%) and major complication rates (18.2% vs 18.3%). Costs were 8% higher with late start cases ($51,576 vs $47,641, p < 0.001). After controlling for case type, surgeon, year, and risk, late cases resulted in higher mortality (odds ratio 2.04, p = 0.041) despite shorter operative duration (16 minutes, p < 0.001). Conclusions Starting non-emergent cardiac cases later in the day is associated with 2 times higher absolute and risk-adjusted mortality. These data should be carefully considered, not only by surgeons and patients but also in the context of the operating room system when scheduling non-emergent cardiac cases.
Objectives Ex vivo lung perfusion (EVLP) is a promising modality for the evaluation and treatment of marginal donor lungs. The optimal timing of EVLP initiation and the potential for rehabilitation ...of donor lungs with extended warm ischemic times is unknown. The present study compared the efficacy of different treatment strategies for uncontrolled non–heart-beating donor lungs. Methods Mature swine underwent hypoxic arrest, followed by 60 minutes of no-touch warm ischemia. The lungs were harvested and flushed with 4°C Perfadex. Three groups (n = 5/group) were stratified according to the preservation method: cold static preservation (CSP; 4 hours of 4°C storage), immediate EVLP (I-EVLP: 4 hours EVLP at 37°C), and delayed EVLP (D-EVLP; 4 hours of CSP followed by 4 hours of EVLP). The EVLP groups were perfused with Steen solution supplemented with heparin, methylprednisolone, cefazolin, and an adenosine 2A receptor agonist. The lungs then underwent allotransplantation and 4 hours of recipient reperfusion before allograft assessment for resultant ischemia–reperfusion injury. Results The donor blood oxygenation (partial pressure of oxygen/fraction of inspired oxygen ratio) before death was not different between the groups. The oxygenation after transplantation was significantly greater in the D-EVLP group than in the I-EVLP or CSP groups. The mean airway pressure, pulmonary artery pressure, and expression of interleukin-8, interleukin-1β, and tumor necrosis factor-α were all significantly reduced in the D-EVLP group. Post-transplant oxygenation exceeded the acceptable clinical levels only in the D-EVLP group. Conclusions Uncontrolled non–heart-beating donor lungs with extended warm ischemia can be reconditioned for successful transplantation. The combination of CSP and EVLP in the D-EVLP group was necessary to obtain optimal post-transplant function. This finding, if confirmed clinically, will allow expanded use of nonheart-beating donor lungs.
Abstract Objective Critical organ shortages have resulted in ex vivo lung perfusion gaining clinical acceptance for lung evaluation and rehabilitation to expand the use of donation after circulatory ...death organs for lung transplantation. We hypothesized that an innovative use of airway pressure release ventilation during ex vivo lung perfusion improves lung function after transplantation. Methods Two groups (n = 4 animals/group) of porcine donation after circulatory death donor lungs were procured after hypoxic cardiac arrest and a 2-hour period of warm ischemia, followed by a 4-hour period of ex vivo lung perfusion rehabilitation with standard conventional volume-based ventilation or pressure-based airway pressure release ventilation. Left lungs were subsequently transplanted into recipient animals and reperfused for 4 hours. Blood gases for partial pressure of oxygen/inspired oxygen fraction ratios, airway pressures for calculation of compliance, and percent wet weight gain during ex vivo lung perfusion and reperfusion were measured. Results Airway pressure release ventilation during ex vivo lung perfusion significantly improved left lung oxygenation at 2 hours (561.5 ± 83.9 mm Hg vs 341.1 ± 136.1 mm Hg) and 4 hours (569.1 ± 18.3 mm Hg vs 463.5 ± 78.4 mm Hg). Likewise, compliance was significantly higher at 2 hours (26.0 ± 5.2 mL/cm H2 O vs 15.0 ± 4.6 mL/cm H2 O) and 4 hours (30.6 ± 1.3 mL/cm H2 O vs 17.7 ± 5.9 mL/cm H2 O) after transplantation. Finally, airway pressure release ventilation significantly reduced lung edema development on ex vivo lung perfusion on the basis of percentage of weight gain (36.9% ± 14.6% vs 73.9% ± 4.9%). There was no difference in additional edema accumulation 4 hours after reperfusion. Conclusions Pressure-directed airway pressure release ventilation strategy during ex vivo lung perfusion improves the rehabilitation of severely injured donation after circulatory death lungs. After transplant, these lungs demonstrate superior lung-specific oxygenation and dynamic compliance compared with lungs ventilated with standard conventional ventilation. This strategy, if implemented into clinical ex vivo lung perfusion protocols, could advance the field of donation after circulatory death lung rehabilitation to expand the lung donor pool.
Abstract Objective Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also ...represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Methods Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pa o2 /F io2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Results Final Pa o2 /F io2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pa o2 /F io2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pa o2 /F io2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. Conclusions After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pa o2 /F io2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation.
Background Despite the critical need for donor lungs, logistic and geographic barriers hinder lung utilization. We hypothesized that lungs donated after circulatory death subjected to 6 hours of cold ...preservation after ex vivo lung perfusion (EVLP) would have similar outcomes after transplantation as lungs transplanted immediately after EVLP, and that both would perform superiorly compared with lungs transplanted immediately after procurement. Methods Donor porcine lungs were procured after circulatory death and 15 minutes of warm ischemia. Three groups (n = 5 per group) were randomized: immediate left lung transplantation (Immediate group), EVLP for 4 hours followed by transplantation (EVLP group), or EVLP for 4 hours followed by 6 hours of cold preservation followed by transplantation (EVLP+Cold group). Lungs were reperfused for 2 hours before obtaining pulmonary vein samples for partial pressure of oxygen/fraction of inspired oxygen ratio calculations, airway pressures for compliance measurements, and wet/dry weight ratios. Results The partial pressure of oxygen/fraction of inspired oxygen ratios in the EVLP and EVLP+Cold groups were significantly improved compared with those in the Immediate group (429.7 ± 51.8 and 436.7 ± 48.2 versus 117.4 ± 22.9 mm Hg, respectively). In addition, dynamic compliance was significantly improved in the EVLP and EVLP+Cold groups compared with immediate group (26.2 ± 4.2 and 27.9 ± 3.5 versus 11.1 ± 2.4 mL/cmH2 O, respectively). There were no differences in oxygenation capacity or dynamic compliance between the EVLP and EVLP+Cold groups. Inflammatory cytokine levels were significantly lower in the EVLP and EVLP+Cold groups. Conclusions Lungs donated after circulatory death can be successfully transplanted as much as 6 hours after EVLP. Cold preservation of lungs after ex vivo assessment and rehabilitation may improve organ allocation, even to distant recipients, without compromising allograft function.
Prospective study of giant paraesophageal hernia repair with 1-year follow-up Stringham, John R., MD; Phillips, Jennifer V., RN; McMurry, Timothy L., PhD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
08/2017, Letnik:
154, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract Objective Evaluating giant paraesophageal hernia (GPEH) repair requires long-term follow-up. GPEH repair can have associated high recurrence rates, yet this incidence depends on how ...recurrence is defined. Our objective was to prospectively evaluate patients undergoing GPEH repair with 1-year follow-up. Methods Patients undergoing elective GPEH repair between 2011 and 2014 were enrolled prospectively. Postoperatively, patients were evaluated at 1 month and 1 year. Radiographic recurrence was evaluated by barium swallow and defined as a gastroesophageal junction located above the hiatus. Quality of life was evaluated pre- and postoperatively with the use of a validated questionnaire. Results One-hundred six patients were enrolled. The majority of GPEH repairs were performed laparoscopically (80.2%), and 7.5% were redo repairs. At 1-year follow-up, 63.4% of patients were symptom free, and radiographic recurrence was 32.7%. Recurrence rate was 18.8% with standard definition (>2 cm of stomach above the diaphragm). Quality of life scores at 1 year were significantly better after operative repair, even in patients with radiographic recurrence (7.0 vs 22.5 all patients, 13.0 vs 22.5 with recurrence; P < .001). Patients with small radiographic recurrences have similar satisfaction and symptom severity to patients with >2 cm recurrences. Conclusions GPEH repair can be performed with low operative mortality and morbidity. The rate of recurrence at 1 year depends on the definition used. Patient satisfaction and symptom severity are similar between patients with radiographic and greater than 2 cm hernia recurrences. Longer follow-up and critical assessment of our results are needed to understand the true impact of this procedure and better inform perioperative decision making.
Background Chronic allograft vasculopathy (CAV) is a major cause of long-term complications and mortality after heart transplantation. Although recipient factors have been implicated, little is known ...of the role of donor factors in CAV development. We sought to identify donor factors associated with development of CAV after heart transplantation. Methods We reviewed the United Network for Organ Sharing heart transplant database from August 1987 to May 2008. Univariate and multivariate analyses were performed to assess the association between donor variables and the onset of CAV for adult recipients. Donor age was matched to recipient age and analyzed with respect to development of CAV. Results Of the 39,704 recipients, a total of 11,714 (29.5%) experienced CAV. Multivariate analysis demonstrated seven donor factors as independent predictors of CAV: age, ethnicity, sex, weight, history of diabetes, hypertension, and tobacco use. When matching young donors (0 to 19.9 years) and old donors (≥50 years) to each recipient age group, older donors (≥50 years) conferred a higher risk of developing CAV. Further modeling demonstrated that for each recipient group, older donor age (≥50 years) conferred a higher risk of CAV development compared with younger donor age (0 to 19.9 years; p < 0.0001). Conclusions Donor factors including sex, hypertension, diabetes, and tobacco use are independently associated with recipient CAV. Older donor age confers a greater risk of CAV development regardless of the age of the recipient. A heightened awareness for the development of CAV is warranted when using older donors in adult cardiac transplantation, in particular with recipients 40 years of age or older.
Background Policymakers have proposed risk-adjusted bundled payment as the single most promising method of linking reimbursement to value rather than to quantity of service. Our objective was to ...assess the relationship between risk and cost to develop a model for forecasting the costs of cardiac operations under a bundled payment scheme. Methods All patients undergoing adult cardiac operations for which there was a Society of Thoracic Surgeons (STS) risk score over a 5-year period (2008 to 2013) at a tertiary care, university hospital were reviewed. Patients were stratified into five groups based on preoperative risk as a basis for negotiating risk-adjusted bundles. A multivariable regression model was developed to analyze the relationship between risk and log-transformed costs. Monte Carlo simulation was performed to validate the model by comparing predicted with actual fiscal year 2013 costs. Results Among the 2,514 patients analyzed, preoperative risk was strongly correlated with costs ( p < 0.001) but was able to explain only 28% ( R 2 = 0.28) of the variation in costs between individual patients. The use of bundling to diffuse and adjust for risk improved prediction to only 33% ( R 2 = 0.33). Actual costs in 2013 were $21.6M compared with predicted costs of $19.3M (±$350K), which is well outside the forecast’s 95% confidence interval. Conclusions Even among the most routine cardiac operations and with use of the most widely validated surgical risk score available, much of the variation in costs cannot be explained by preoperative risk or surgeon. Consequently, policymakers should reexamine whether individual practices or insurers are best suited to manage the residual financial risk.
Objective For descending thoracic aortic aneurysms (TAAs), it is generally considered that thoracic endovascular aortic repairs (TEVARs) reduce operative morbidity and mortality compared with open ...surgical repair. However, long-term differences in survival of patients have not been demonstrated, and an increased need for aortic reintervention has been observed. Many assume that TEVAR becomes less cost-effective through time because of higher rates of reintervention and surveillance imaging. This study investigated midterm outcomes and hospital costs of TEVAR compared with open TAA repair. Methods This was a retrospective, single-institution review of elective TAA repairs between 2005 and 2012. Patient demographics, operative outcomes, reintervention rates, and hospital costs were assessed. The literature was also reviewed to determine commonly observed complication and reintervention rates for TEVAR and open repair. Monte Carlo simulation was used to model and to forecast hospital costs for TEVAR and open TAA repair up to 3 years after intervention. Results Our cohort consisted of 131 TEVARs and 27 open repairs. TEVAR patients were significantly older (67.2 vs 58.7 years old; P = .02) and trended toward a more severe comorbidity profile. Operative mortality for TEVAR and open repair was 5.3% and 3.7%, respectively ( P = 1.0). There was a trend toward more complications in the TEVAR group, although not statistically significant (all P > .05). In-hospital costs were significantly greater in the TEVAR group ($52,008 vs $37,172; P = .001). However, cost modeling by use of reported complication and reintervention rates from the literature overlaid with our cost data produced a higher cost for the open group in-hospital ($55,109 vs $48,006) and at 3 years ($58,426 vs $52,825). Interestingly, TEVAR hospital costs, not reintervention rates, were the most significant driver of cost in the TEVAR group. Conclusions Our institutional data showed a trend toward lower mortality and complication rates with open TAA repair, with significantly lower costs within this cohort compared with TEVAR. These findings were likely, at least in part, to be due to the milder comorbidity profile of these patients. In contrast, cost modeling by Monte Carlo simulation demonstrated lower costs with TEVAR compared with open repair at all time points up to 3 years after intervention. Our institutional data show that with appropriate selection of patients, open repair can be performed safely with low complication rates comparable to those of TEVAR. The cost model argues that despite the costs associated with more frequent surveillance imaging and reinterventions, TEVAR remains the more cost-effective option even years after TAA repair.
PDF
