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Publisher Copyright: © 2022 The Authors Despite the development of device technology and operators' experience, access site vascular complications (VCs) remain one of the major concerns after transcatheter aortic valve implantation (TAVI). MANTA (Teleflex, Wayne, Pennsylvania) is a large-bore vascular closure device (VCD) with promising incidence of VC. Previously, we demonstrated that the ultrasound-guided MANTA (US-MANTA) technique further improved the outcomes compared with conventional MANTA (C-MANTA) without ultrasound guidance. The present study was established to prove the effectiveness of the technique in a larger population. In this study, we included 1,150 patients (335 patients with C-MANTA and 815 with US-MANTA) who received MANTA after TAVI from April 2017 to September 2021. The primary endpoint was MANTA-related VC. Overall VC, VCD failure, and bleeding complications were also assessed based on the Valve Academic Research Consortium 3 criteria. MANTA-related VC occurred in 12.5% in the C-MANTA group and 6.8% in the US-MANTA group (p = 0.001). VCD failure rate were 7.5% and 3.9%, respectively (p = 0.012). Valve Academic Research Consortium 3 major and minor VC were more frequent in C-MANTA group (major: 7.8% vs 4.4%, p = 0.023; minor: 8.1% vs 4.4%, p = 0.022). Multivariate analysis revealed US-MANTA as the negative predictor of MANTA-related VC (odds ratio 0.57, 95% confidence interval 0.36 to 0.89, p = 0.013). However, subgroup analysis showed the efficacy of the US-MANTA technique was limited to the patients without severely calcified puncture site (Pinteraction = 0.048). In conclusion, the US-MANTA technique was an effective strategy to reduce VC after transfemoral TAVI compared with C-MANTA. (c) 2022 The Authors. Published by Elsevier Inc.

Objectives: The authors aimed to investigate the impact of severe bleeding and use of red blood cell (RBC) transfusion on the development of postoperative stroke after surgical (SAVR) and transcatheter aortic valve replacement (TAVR), taken from the FinnValve registry. Design: Nationwide, retrospective observational study. Setting: Five Finnish university hospitals participated in the registry. Participants: A total of 6,463 patients who underwent SAVR (n = 4,333) or TAVR (n = 2,130). Interventions: Patients who underwent TAVR or SAVR with a bioprosthesis with or without coronary revascularization. Measurements and Main Results: The incidence of postoperative stroke after SAVR was 3.8%. In multivariate analysis, the number of trans-fused RBC units (odds ratio [OR], 1.098; 95% confidence interval [CI], 1.064-1.133) was one of the independent predictors of postoperative stroke. The incidence of stroke increased, along with the severity of perioperative bleeding, according to the European Coronary Artery Bypass Grafting (E-CABG) bleeding grades were as follows: grade 0, 2.2% (reference group); grade 1, 3.4% (adjusted OR, 1.841; 95% CI, 1.105-3.066); grade 2, 5.5% (adjusted OR, 3.282; 95% CI, 1.948-5.529); and grade 3, 14.8% (adjusted OR, 7.103; 95% CI, 3.612-13.966). The inci-dence of postoperative stroke after TAVR was 2.5%. The number of transfused RBC units was an independent predictor of stroke after TAVR (adjusted OR, 1.155; 95% CI, 1.058-1.261). The incidence of postoperative stroke increased, along with the severity of perioperative bleeding, as stratified by the E-CABG bleeding grades: E-CABG grade 0, 1.7%; grade 1, 5.3% (adjusted OR, 1.270; 95% CI, 0.532-3.035); grade 2, 10.0% (adjusted OR, 2.898; 95% CI, 1.101-7.627); and grade 3, 30.0% (adjusted OR, 10.706; 95% CI, 2.389-47.987). Conclusions: Perioperative bleeding requiring RBC transfusion and/or reoperation for intrathoracic bleeding is associated with an increased risk of postoperative stroke after SAVR and TAVR. Patient blood management and meticulous preprocedural planning and operative technique aiming to avoid significant perioperative bleeding may reduce the risk of cerebrovascular complications. (C) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

OBJECTIVES The aim of this study was to evaluate the incidence and prognostic impact of paravalvular regurgitation (PVR) on the outcome after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) for aortic stenosis. METHODS The nationwide FinnValve registry included data on 6463 consecutive patients who underwent TAVR (n = 2130) or SAVR (n = 4333) with a bioprosthesis for the treatment of aortic stenosis during 2008–2017. The impact of PVR at discharge after TAVR and SAVR on 4-year mortality was herein investigated. RESULTS The rate of mild PVR was 21.7% after TAVR and 5.2% after SAVR. The rate of moderate-to-severe PVR was 3.7% after TAVR and 0.7% after SAVR. After TAVR, 4-year survival was 69.0% in patients with none-to-trace PVR, 54.2% with mild PVR [adjusted hazard ratio (HR) 1.64, 95% confidence interval (CI) 1.35–1.99] and 48.9% with moderate-to-severe PVR (adjusted HR 1.61, 95% CI 1.10–2.35). Freedom from PVR-related reinterventions was 100% for none-to-mild PVR and 95.2% for moderate-to-severe PVR. After SAVR, mild PVR (4-year survival 78.9%; adjusted HR 1.29, 95% CI 0.93–1.78) and moderate-to-severe PVR (4-year survival 67.8%; adjusted HR 1.36, 95% CI 0.72–2.58) were associated with worse 4-year survival compared to none-to-trace PVR (4-year survival 83.7%), but the difference did not reach statistical significance in multivariable analysis. Freedom from PVR-related reinterventions was 99.5% for none-to-trace PVR patients, 97.9% for mild PVR patients and 77.0% for moderate-to-severe PVR patients. CONCLUSIONS This multicentre study showed that both mild and moderate-to-severe PVR were independent predictors of worse survival after TAVR. Mild and moderate-to-severe PVR are not frequent after SAVR, but tend to decrease survival also in these patients. Clinical trial registration number ClinicalTrials.gov Identifier: NCT03385915.

Background Recent surgical bovine pericardial prostheses are widely used despite limited data on their long-term durability. Methods This is a comparative analysis of the outcome of the Trifecta (Abbott, Abbott Park, IL) and Perimount Magna Ease (Edwards, Lifesciences Corp, Irvine, CA) bioprostheses from the FinnValve registry, a Finnish nationwide database including patients with aortic stenosis who underwent transcatheter or surgical aortic valve replacement with a bioprosthesis between 2008 and 2017. Results Overall 2216 patients (mean age, 74.1 ± 6.7 years; age Conclusions The Trifecta aortic bioprosthesis is associated with a higher occurrence of repeat aortic valve replacement for structural valve failure compared with the Perimount Magna Ease bioprosthesis. Further comparative studies with echocardiographic data on structural valve deterioration and longer follow-up are needed to confirm these findings.

Background: The aim of this study was to investigate the impact of anatomical site status and major vascular complication (MVC) severity on the outcome of transfemoral transcatheter aortic valve replacement (TF-TAVR). Methods and Results: The FinnValve registry enrolled consecutive TAVR patients from 2008 to 2017. MVC was divided into 2 groups: non-access site-related MVC (i.e., MVC in aorta, aortic valve annulus or left ventricle); and access site-related MVC (i.e., MVC in iliac or femoral arteries). Severity of access site-related MVC was measured as units of red blood cell (RBC) transfusion. Of 1,842 patients who underwent TF-TAVR, 174 had MVC (9.4%; non-access site related, n=29; access site related, n=145). Patients with MVC had a significantly higher 3-year mortality than those without MVC (40.8% vs. 24.3%; HR, 2.01; 95% CI: 1.16–3.62). Adjusted 3-year mortality risk was significantly increased in the non-access site-related MVC group (mortality, 77.8%; HR, 4.30; 95% CI: 2.63–7.02), but not in the access site-related MVC group (mortality, 32.6%; HR, 1.38; 95% CI: 0.86–2.15). In the access site-related MVC group, only those with RBC transfusion ≥4 units had a significantly increased 3-year mortality risk (mortality, 51.8%; HR, 2.18; 95% CI: 1.19–3.89). Conclusions: In patients undergoing TF-TAVR, MVC was associated with an increased 3-year mortality risk, incrementally correlating with anatomical site and bleeding severity.

Aims The aim of this study was to compare the risk of prosthetic valve endocarditis (PVE) in patients with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Methods and results The FinnValve registry included data from 6,463 consecutive patients who underwent TAVR (n=2,130) or SAVR (n=4,333) with a bioprosthesis from 2008 to 2017. PVE was defined according to the modified Duke criteria. In this study, the incidence of PVE was 3.4/1,000 person-years after TAVR, and 2.9/1,000 person-years after SAVR. In competing risk analysis there was no significant difference in the risk of PVE between patients with TAVR and SAVR over an eight-year observational period. Male gender (HR 1.73, 95% CI: 1.04-2.89) and deep sternal wound infection or vascular access-site infection (HR 5.45, 95% CI: 2.24-13.2) were positively associated with PVE, but not type of procedure (HR 1.09, 95% CI: 0.59-2.01) in multivariate analysis. The mortality rate was 37.7% at one month and increased to 52.5% at one year. Surgical treatment was independently associated with decreased in-hospital mortality (HR 0.34, 95% CI: 0.21-0.61). Conclusions PVE is rare, and its risk is similar after TAVR and SAVR. ClinicalTrials.gov Identifier: NCT03385915. https://clinicaltrials.gov/ct2/show/NCT03385915.

Objectives To compare the outcomes after surgical (SAVR) and transcatheter aortic valve replacement (TAVR) for severe stenosis of bicuspid aortic valve (BAV). Methods We evaluated the early and mid-term outcome of patients with stenotic BAV who underwent SAVR or TAVR for aortic stenosis from the nationwide FinnValve registry. Results The FinnValve registry included 6463 AS patients and 1023 (15.8%) of them had BAV. SAVR was performed in 920 patients and TAVR in 103 patients with BAV. In the overall series, device success after TAVR was comparable to SAVR (94.2% vs. 97.1%, p = 0.115). TAVR was associated with increased rate of mild-to-severe paravalvular regurgitation (PVR) (19.4% vs. 7.9%, p p = 0.053). When newer-generation TAVR devices were evaluated, mild-to-severe PVR (11.9% vs. 7.9%, p = 0.223) and moderate-to-severe PVR (0% vs. 0.7%, p = 1.000) were comparable to SAVR. Type 1 N-L and type 2 L-R/R-N were the BAV morphologies with higher incidence of mild-to-severe PVR (37.5% and 100%, adjusted for new-generation prostheses p = 0.025) compared to other types of BAVs. Among 75 propensity score-matched cohorts, 30-day mortality was 1.3% after TAVR and 5.3% after SAVR (p = 0.375), and 2-year mortality was 9.7% after TAVR and 18.7% after SAVR (p = 0.268) Conclusions In patients with stenotic BAV, TAVR seems to achieve early and mid-term results comparable to SAVR. Type 1 N-L and type 2 L-R/R-N BAV morphologies had higher incidence of PVR. Larger studies evaluating different phenotypes of BAV are needed to confirm these findings. Clinical trial registration ClinicalTrials.gov Identifier: NCT03385915. Graphic abstract

The case provided suggests that an ultrasound-navigated Manta device works well in closing percutaneously the peripheral arterial extracorporeal membrane oxygenation cannulation site. Ultrasonography use during extracorporeal membrane oxygenation decannulation can further diminish the possible device-related technical failures (toggle or collagen protrusion through the vessel wall, toggle stacking into calcifications, or delivery failure of the collagen pad) leading to bleeding and vascular complications. Further studies are needed on this topic.

Background. The impact of patient-prosthesis mismatch (PPM) on long-term outcome after surgical aortic valve replacement (SAVR) is controversial. We sought to investigate the incidence of PPM and its impact on survival and reinterventions in a Finnish nationwide cohort. Methods. In the context of the nationwide FinnValve registry, we identified 4097 patients who underwent SAVR with a stented bioprosthesis with or without myocardial revascularization. The indexed effective orifice areas (EOAs) of surgical bioprostheses were calculated using literature-derived EOAs. PPM was graded as moderate (EOA 0.65-0.85 cm(2)/m(2)) or severe (EOA Results. The incidence of PPM was 46.0%. PPM was moderate in 38.8% (n = 1579) patients and severe in 7.2% (n = 297) patients. Time-trend analysis showed that the proportion of PPM decreased significantly from 74% in 2009 to 18% in 2017 (P < .01). Severe PPM was associated with increased 5-year all-cause mortality (adjusted hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.07-2.76; P = .02). Severe PPM was not associated with an increased risk of repeat AVR (adjusted HR, 5.90; 95% CI, 0.95-36.5; P = .06). In a subanalysis of patients greater than or equal to 70 years of age, in comparison with no PPM, any PPM (adjusted HR, 1.23; 95% CI, 1.05-1.45; P = .01) and severe PPM (HR, 1.53; 95% CI, 1.17-2.00; P < 0.01) were associated with increased risk of 5-year mortality. Conclusions. Severe PPM after SAVR had a negative impact on survival. This study demonstrated that the effects of PPM should not be overlooked in elderly undergoing SAVR. (C) 2021 by The Society of Thoracic Surgeons

Background: The data on acute kidney injury (AKI) in patients without chronic kidney disease (CKD) after transcatheter aortic valve replacement (TAVR) are limited. The study sought to compare the incidence of AKI and its impact on 5-year mortality after TAVR and surgical aortic valve replacement (SAVR) in patients without CKD. Methods: This registry included data from 6463 consecutive patients who underwent TAVR or SAVR. CKD was defined as estimated glomerular filtration rate Results: The study included 4555 consecutive patients (TAVR, n = 1215 and SAVR, n = 3340) without CKD. Propensity-score matching identified 542 pairs. Patients who underwent TAVR had a significantly lower incidence of AKI in comparison to those who underwent SAVR (unmatched 4.7% vs 16.4%, P

Background. Patients with severe aortic stenosis and heart failure have poor prognosis, and their outcomes may be suboptimal even after transcatheter (TAVR) and surgical aortic valve replacement (SAVR). Methods. This is an analysis of the nationwide FinnValve registry, which included patients who underwent primary TAVR or SAVR with a bioprothesis for aortic stenosis. We evaluated the outcome of patients with acute heart failure (AHF) within 60 days prior to TAVR or SAVR. Results. The prevalence of recent AHF was 11.4% (484 of 4241 patients) in the SAVR cohort and 11.3% (210 of 1855 patients) in the TAVR cohort. In the SAVR cohort, AHF was associated with lower 30-day survival (91.3% vs 97.0%; adjusted odds ratio 1.801, 95% confidence interval [CI] 1.125-2.882) and 5-year survival (64.0% vs 81.2%; adjusted hazard ratio 1.482, 95% CI 1.207-1.821). SAVR patients with AHF had higher risk of major bleeding, need of mechanical circulatory support, acute kidney injury, prolonged hospital stay, and composite end-point (30-day mortality, stroke and/or acute kidney injury). Patients with AHF had a trend toward lower 30-day survival (crude rates 95.2% vs 97.9%; adjusted odds ratio 2.028, 95% CI 0.908-4.529) as well as significantly lower 5-year survival (crude rates 45.3% vs 58.5%; adjusted hazard ratio 1.530, 95% CI 1.185-1.976) also after TAVR. AHF increased the risk of acute kidney injury, prolonged hospital stay, and composite end-point after TAVR. Conclusions. Recent AHF is associated with increased risk of mortality and morbidity after SAVR and TAVR. These findings suggest that aortic stenosis patients should be referred for invasive treatment before the development of clinically evident heart failure.

Increasing data support transcatheter aortic valve implantation (TAVI) as a valid option over surgical aortic valve replacement (SAVR) in the treatment for severe aortic stenosis (AS) also in patients with low operative risk. However, limited data exist on the outcome of TAVI and SAVR in low-risk patients without coronary artery disease (CAD). The FinnValve registry included data on 6463 patients who underwent TAVI or SAVR with bioprosthesis between 2008 and 2017. Herein, we evaluated the outcome of low operative risk as defined by STS-PROM score3% and absence of CAD, previous stroke and other relevant co-morbidities. Only patients who underwent TAVI with third-generation prostheses and SAVR with Perimount Magna Ease or Trifecta prostheses were included in this analysis. The primary endpoints were 30-day and 3-year all-cause mortality. Overall, 1,006 patients (175 TAVI patients and 831 SAVR patients) met the inclusion criteria of this analysis. Propensity score matching resulted in 140 pairs with similar baseline characteristics. Among these matched pairs, 30-day mortality was 2.1% in both TAVI and SAVR cohorts (p = 1.00) and 3-year mortality was 17.0% after TAVI and 14.6% after SAVR (p = 0.805). Lower rates of bleeding and atrial fibrillation, and shorter hospital stay were observed after TAVI. The need of new permanent pacemaker implantation and the incidence of early stroke did not differ between groups. In conclusion, TAVI using third-generation prostheses achieved similar early and mid-term survival compared with SAVR in low-risk patients without CAD.

A new plug-based MANTA (Teleflex, Morrisville, North Carolina) vascular closure device was recently introduced. Although prospective studies of MANTA have reported promising results of a 2% to 4% rate of major vascular complications (VCs) in selected patients who underwent transfemoral transcatheter

Importance: Transcatheter aortic valve replacement (TAVR) has been shown to be a valid alternative to surgical aortic valve replacement (SAVR) in patients at high operative risk with severe aortic stenosis (AS). However, the evidence of the benefits and harms of TAVR in patients at low operative risk is still scarce. Objective: To compare the short-term and midterm outcomes after TAVR and SAVR in low-risk patients with AS. Design, Setting, and Participants: This retrospective comparative effectiveness cohort study used data from the Nationwide Finnish Registry of Transcatheter and Surgical Aortic Valve Replacement for Aortic Valve Stenosis of patients at low operative risk who underwent TAVR or SAVR with a bioprosthesis for severe AS from January 1, 2008, to November 30, 2017. Low operative risk was defined as a Society of Thoracic Surgeons Predicted Risk of Mortality score less than 3% without other comorbidities of clinical relevance. One-to-one propensity score matching was performed to adjust for baseline covariates between the TAVR and SAVR cohorts. Exposures: Primary TAVR or SAVR with a bioprosthesis for AS with or without associated coronary revascularization. Main Outcomes and Measures: The primary outcomes were 30-day and 3-year survival. Results: Overall, 2841 patients (mean [SD] age, 74.0 [6.2] years; 1560 [54.9%] men) fulfilled the inclusion criteria and were included in the analysis; TAVR was performed in 325 patients and SAVR in 2516 patients. Propensity score matching produced 304 pairs with similar baseline characteristics. Third-generation devices were used in 263 patients (86.5%) who underwent TAVR. Among these matched pairs, 30-day mortality was 1.3% after TAVR and 3.6% after SAVR (P = .12). Three-year survival was similar in the study cohorts (TAVR, 85.7%; SAVR, 87.7%; P = .45). Interaction tests found no differences in terms of 3-year survival between the study cohorts in patients younger than vs older than 80 years or in patients who received recent aortic valve prostheses vs those who did not. Conclusions and Relevance: Transcatheter aortic valve replacement using mostly third-generation devices achieved similar short- and mid-term survival compared with SAVR in low-risk patients. Further studies are needed to assess the long-term durability of TAVR prostheses before extending their use to low-risk patients.

Objective: To investigate the prognostic impact of red blood cell (RBC) transfusion on the outcome after transfemoral transcatheter aortic valve replacement (TAVR). Design: Nationwide, retrospective multicenter study. Setting: Five University Hospitals. Participants: The nationwide FinnValve registry included data from 2,130 patients who underwent TAVR for aortic stenosis from 2008 to 2017. After excluding patients who underwent TAVR through nontransfemoral accesses, 1,818 patients were selected for this analysis. Intervention: TAVR with or without coronary revascularization. Measurements and Main Results: RBCs were transfused in 293 patients (16.1%). Time-trend analysis showed that the rates of RBC transfusion decreased significantly from 27.5% in 2012 to 10.0% in 2017 (p

Nuss bars are increasingly used for minimally invasive correction of pectus excavatum and are usually removed within 3 years of insertion. Previously, several complications related to pectus bar removal have been reported with only 1 case report of aortic haemorrhage. Herein, we report a case with life-threatening aortic haemorrhage during late removal of displaced double Nuss bars.

Aim: We investigated the outcomes of transcatheter (TAVR) and surgical aortic valve replacement (SAVR) in Finland during the last decade. Methods: The nationwide FinnValve registry included data from 6463 patients who underwent TAVR or SAVR with a bioprosthesis for aortic stenosis from 2008 to 2017. Results: The annual number of treated patients increased three-fold during the study period. Thirty-day mortality declined from 4.8% to 1.2% for TAVR (p = .011) and from 4.1% to 1.8% for SAVR (p = .048). Two-year survival improved from 71.4% to 83.9% for TAVR (p

Cytokines initiate and modify systemic inflammatory response in early acute pancreatitis. The aim of this study was to analyze which cytokines are released from the pancreas to portal venous blood in the early phase of acute experimental necrotizing and oedematous pancreatitis and which of those cytokines are correlated with the more severe form of the disease.Fifteen pigs were randomized to develop mild oedematous pancreatitis (n = 5, saline infusion to pancreatic duct), severe necrotizing pancreatitis (n = 5, taurocholic acid infusion) along with a control group (n = 5). Arterial and venous blood samples were drawn and cytokine levels were measured from portal vein blood at 0, 120, 240 and 360 min after the induction of pancreatitis. Tissue samples from the pancreas were harvested at 0 and 360 min.White blood cell count increased in necrotizing pancreatitis and the control group. The amount of neutrophils increased (p0.001) and the lymphocyte and eosinophil counts decreased in all groups (p0.001, p0.001). The monocyte count, as well as PDGF and IL-6 concentrations, increased only in necrotizing pancreatitis. IL-8 and eotaxin increased both in oedematous and necrotizing pancreatitis. MCP-1 increased in all groups. IL-9, IL-4, MIP-1α, IFN- γ concentrations did not change. Eotaxin and MCP-1 plasma levels from a previous series between portal venous and pulmonary arterial blood were not significantly different.The initial inflammatory process was diverse in oedematous and necrotizing pancreatitis. Increased monocyte count in combination with elevated PDGF and IL-6 are characteristic of necrotizing pancreatitis in our model.

Bone marrow-derived mononuclear cell (BMMC) treatment in acute myocardial infarction (AMI) has been shown to have a beneficial effect. Our objective was to study in detail the histopathological process after the cell therapy after intramyocardial (IM) or intracoronary (IC) administration of BMMCs following experimental AMI.Twenty-fours pigs were randomized to the IM group (n=8), the IC group (n=8), and the control group (n=8).After 90 min of transient occlusion of the circumflex coronary artery, BMMCs were injected either intramyocardially or by a transfemoral catheter into the circumflex coronary artery. Echocardiography was performed preoperatively, postoperatively, and after a 21-day recovery period. The heart biopsies were examined histopathologically. Volumetric ex vivo CT scan was performed to evaluate calcification of the infarcted myocardium.The ejection fraction (EF) showed significant recovery in the IM group compared to the control group at Day 21 (P=.05). Despite beneficial histological changes in the infarction site in the IC group, compared to the control group, EF failed to recover. Reduction of collagen density that depicts scar formation was seen in both cell therapy groups compared to the control (P.001). The number of mitotic cells was higher in the control group compared to the cell therapy groups (P.001). The IC and IM groups differed significantly from each other in muscle-specific actin staining (P.001) and smooth muscle actin staining (P.004). The IM therapy group showed higher density for both stainings. Additionally, macrophage density was higher in the IC group compared to the IM and control groups (P.002). Both cell therapy regimens substantially diminished tissue calcification; due to the large variation, the effect was not statistically significant.BMMC therapy launches cellular changes that affect mostly the repair process in the granulation tissue. The cell transplantation method might have some effect on the magnitude of the effect.

Background Selective cerebral perfusion (SCP) is used for extending the period during which surgical procedures can be safely performed. We sought to determine the direct effects of pH management on cerebral microcirculation and metabolism during SCP. Methods An experimental SCP porcine model was created by selectively allowing cold perfusate only into the bicarotid brachiocephalic trunk during the SCP period. Twenty-four piglets (6 to 8 weeks; mean weight, 26.1 ± 4.1 kg) underwent 15-minute normothermic cardiopulmonary bypass, 45-minute cooling cardiopulmonary bypass, 60-minute SCP at 25°C, and 45-minute rewarming cardiopulmonary bypass with either α-stat or pH-stat perfusion strategy randomly assigned. A cranial window was created over the parietal cortex for visualization of the cerebral vessels with intravital microscopy. Rhodamine-stained leukocytes were observed in cerebral postcapillary venules for adhesion and rolling. Microdialysis analysis was used for determination of brain metabolism. Results Brain concentration of lactate was significantly higher in the α-stat group at 45 minutes of SCP, and at 15- and 45-minute rewarming intervals ( p = 0.03; p = 0.003; and p = 0.05; respectively), reaching borderline statistical significance when assessed throughout the experiment ( p = 0.06 for differences between groups). Further, at the end of cooling, the oxygen delivery tended to be higher in the pH-stat group ( p = 0.07), whereas at the 30-minute rewarming interval, the oxygen extraction tended to be higher in the α-stat group ( p = 0.06). There were no statistically significant differences between the groups in leukocyte–endothelial interaction, arterial diameter, or tissue oxygenation. Conclusions The higher concentration of brain lactate and the tendency to higher oxygen extraction levels during rewarming with α-stat strategy suggests anaerobic metabolism occurred during SCP. No major differences between pH management strategies in cerebral microcirculation could be shown during SCP.

Background. Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. Methods. Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. Results. There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower ( P = .015) and brain pyruvate levels ( P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA ( P = .049). Conclusion. The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

Background. Propofol is a widely used anesthetic in cardiac surgery. It has been shown to increase cerebrovascular resistance resulting in decreased cerebral blood flow. Efficient brain perfusion and tissue oxygenation during cardiopulmonary bypass (CPB) is essential in surgery requiring hypothermic circulatory arrest (HCA). The effects of propofol on brain metabolism are reported in a surviving porcine model of HCA.Methods. Twenty female juvenile pigs undergoing 75 minutes of HCA at a brain temperature of 18°C were assigned to either propofol- or isoflurane anesthesia combined with ?-stat perfusion strategy during CPB cooling and rewarming. Brain microdialysis analysis was used for determination of brain metabolism, and tissue oxygen partial pressure and intracranial pressures were also followed-up until 8 hours postoperatively.Results. Brain concentrations of glutamate and glycerol were significantly higher in the propofol group throughout the experiment (P < .01 and P < .01, respectively). The lactate/pyruvate ratio was significantly higher in the propofol group at 6-, 7-, and 8-hour intervals (P < .05, P < .01, and P < .05, respectively). The intracranial pressure was significantly higher at the 8-hour postoperative interval (P < .05) in the propofol group. A trend toward higher brain oxygen concentrations was observed in the isoflurane group.Conclusions. Anesthesia with propofol as compared with isoflurane is associated with impaired brain metabolism during experimental HCA.

Background There is some evidence of beneficial metabolic effects associated with the pH-stat than with α-stat perfusion strategy, but this is tempered by a likely increased risk of embolism to the brain, especially in adult patients. We investigated this possible adverse effect in an experimental model that combined hypothermic circulatory arrest (HCA) and embolic brain injury. Methods Twenty-four female juvenile pigs undergoing 25 minutes of HCA at a brain temperature of 18°C were assigned to either α-stat (n = 12) or pH-stat (n = 12) strategy during cardiopulmonary bypass. Before the initiation of HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250 to 750 μm in diameter) were injected into the isolated aortic arch in both groups. Results The 7-day survival rate was 75% in the pH-stat group and 50% in the α-stat group ( p = 0.40). The pH-stat group had significantly better behavioral scores on postoperative days 5 ( p = 0.03) and 6 ( p = 0.04). The pH-stat strategy was associated with better postoperative intracranial pressures and histopathologic scores, but such differences did not reach statistical significance. The α-stat group had lower brain glucose concentrations postoperatively as well as higher brain lactate/glucose and lactate/pyruvate ratios Conclusions These results suggest that pH-stat strategy does not cause any worse brain injury than the α-stat strategy. Indeed, the pH-stat strategy is associated with a slightly better outcome compared with the α-stat strategy, even in the setting of cerebral embolization. This observation suggests that the pH-stat strategy could also be used in adults during deep hypothermic cardiopulmonary bypass despite the increased risk of intraoperative cerebral embolization.

Because of current limitations in improving metabolic support to the brain during hypothermic circulatory arrest (HCA), attenuation of ischemia-reperfusion injury remains an area of therapeutic intervention of relevance. Apotransferrin (Apo-Tf), alpha 1-acid glycoprotein (AGP), and C1-esterase inhibitor (C1-INH) have been herein evaluated as potential beneficial agents in reducing the ischemia-reperfusion injury in a surviving model of HCA.Apo-Tf 100 mg/kg (n = 6), C1-INH 50 IU/kg (n = 6), AGP 100 mg/kg (n = 6), or NaCl 0.9% 2 ml/kg (n = 6) were randomly administered to 24 juvenile pigs after a 75-min period HCA at a brain temperature of 18 degrees C.Animals in the Apo-Tf group had a slightly better 7-day survival (66.7%) compared with the other study groups (50%), but such a difference was not statistically significant. Some favorable changes in the brain glucose metabolism parameters were observed in the AGP, C1-INH, and Apo-Tf groups, but these did not reach statistical significance. Semiquantitative analysis of the histopathological findings did not show any significant difference between the study groups. However, only two out of four surviving animals in the Apo-Tf group developed brain infarction, whereas all three survivors of the remaining study groups developed brain infarction.Although the small size of the study groups may affect the present findings, none of the metabolic and hemodynamic parameters as well as outcome endpoints indicate a substantial therapeutic efficacy of Apo-Tf, AGP, and C1-INH as neuroprotective agents after experimental HCA.

Background The superiority of the pH-stat to the α-stat acid-base strategy during cardiopulmonary bypass as a neuroprotective method during hypothermic circulatory arrest is still controversial. In the present study, brain metabolism and outcome have been evaluated in a surviving model of experimental hypothermic circulatory arrest. Methods Twenty pigs undergoing 75-minutes of hypothermic circulatory arrest at a brain temperature of 18°C were randomly assigned to the α-stat (n = 10) or pH-stat (n = 10) strategy during cardiopulmonary bypass. Results The 7-day survival rate was 90% (9 of 10) in the pH-stat group and 10% (1 of 10) in the α-stat group. At the end of cooling, pH-stat strategy was associated with significantly lower brain lactate and pyruvate concentrations and brain lactate-glucose ratio. After reperfusion, brain concentrations of glycerol, lactate, pyruvate, and lactate-glucose ratio were significantly lower in the pH-stat group. This strategy was associated with a faster rise of brain tissue temperature and reoxygenation on reperfusion, which is likely secondary to improved cerebral perfusion. Conclusions During cardiopulmonary bypass before and after a period of hypothermic circulatory arrest, acid-base management according to the pH-stat principles seemed to be associated with less derangements in cerebral metabolism, lower intracranial pressures, and excellent behavioral recovery and survival outcome. Because there is strong evidence of the beneficial metabolic effects related to this method, further studies using an experimental model of combined HCA and embolic brain injury are required to exclude a possible increased risk of cerebral embolism associated with the pH-stat strategy.

Cell homing optimisation after transplantation is critical in myocardial infarction (MI) cell therapy.Eight pigs were randomized to receiving autologous purified (111)indium-labeled bone marrow mononuclear cells (BMMCs) (10(8) cells/2 ml) by intramyocardial (IM) (n=4) or by intracoronary (IC) (n=4) transplantation after 90 minutes occlusion of the CX-coronary artery. Dual isotope SPECT imaging was performed 2 and 24 hours postoperatively. Two animals were additionally analyzed on the sixth postoperative day. Tissue samples from the major organs were analyzed.In SPECT imaging revealed that BMMCs administered using IM injection remained in the injured area. In contrast, minor proportion of IC transplanted cells remained in the myocardium, as most of the cells showed homing in the lungs. Analysis of the biopsies showed a seven-fold greater number of cells in the myocardium for the IM method and a 10-fold greater number of cells in the lungs in the IC group (p0.001).In producing persistently high cell homing at the infarction site, the IM transplantation is superior to the IC transplantation. However, the IC administration might be more specific in targeting injured capillaries and epithelial cells within the infarcted myocardium.

ObjectiveStem cell therapy in myocardial infarction is under intensive investigation; however, the mechanisms of recovery and the optimal transplantation technique remain controversial. The goal of this controlled and randomized study was to test the hypothesis that locally injected bone marrow–derived mononuclear cells can focus in on the damaged myocardium and improve cardiac function by means of active participation in remodeling.MethodsMyocardial infarction was introduced through occlusion of the circumflex coronary artery for 90 minutes in 14 piglets (24.0 ± 4.9 kg) that were randomized to a cell-therapy group (n = 7) and a control group (n = 7). At reperfusion, autologous purified prelabeled or unlabeled cells (108 cells/2 mL) or saline were injected into the myocardium. Cardiac function was measured by using echocardiography preoperatively and postoperatively and at 3 weeks, when hearts were collected for histopathologic examination.ResultsThe ejection fraction recovered in the cell-therapy group (P = .02) but failed to recover in the control group, and at 3 weeks, it remained at the lower level compared with that in the cell-therapy group (P = .067). The number of living cells in the necrotic area was significantly greater in the cell-therapy group (P < .001). Labeled cells were detected in the infarcted area, and they showed signs of myocyte differentiation. Furthermore, the proportional area of muscle actin-positive cells at the granulation area was higher in the cell-therapy group (P = .035).ConclusionsAutologous bone marrow–derived mononuclear cells at the infarcted area localize in the myocardium. The exact mechanism of recovery remains to be determined, but our findings may give new information concerning the cellular events that occur during cell therapy–enhanced recovery.

BACKGROUND Aprotinin is a serine protease inhibitor, which is usually used during cardiac surgery to reduce blood loss. There is evidence that aprotinin has neuroprotective effects during ischemia. We planned this study to evaluate its potential neuroprotective efficacy during hypothermic circulatory arrest (HCA). METHODS Twenty piglets with a median weight of 25.7 kg (interquartile range, 23.9-26.6) were randomly assigned to receive aprotinin or placebo prior to a 75-minute period of HCA at 18 degrees C. Brain microdialysis parameters and neurological and histological scores were the primary outcome measures. RESULTS Changes in brain metabolic parameters and histopathological findings were favorable in the aprotinin group. Brain lactate concentrations were significantly lower in the aprotinin group during the experiment (P = .02) along with blood lactate concentrations in the aprotinin group (P = .023). Brain glucose was significantly higher during the experiment (P = 0.02). Intracranial pressure tended to be higher in the control group. Two of 10 animals in the aprotinin group and 4 of 10 in the control group failed to reach full recovery on the seventh postoperative day. Four animals of 10 in the aprotinin group and 6 animals of 10 in the control group had brain infarction (P = .40). CONCLUSIONS The present data suggest that aprotinin mitigates cerebral damage and improves neurological outcome following a period of HCA.

Background Hypertonic saline dextran (HSD) has been shown to have neuroprotective properties. In the present study we have assessed its potential neuroprotective efficacy in the setting of hypothermic circulatory arrest in a surviving porcine model. Methods Twenty-four pigs were randomized to receive two 5-minute intravenous infusions (4 mL/kg) of either HSD (7.5 % saline, 6% dextran 70) or normal saline immediately after and 4 hours after a 75-minute period of hypothermic circulatory arrest at a brain temperature of 18°C. Results The 7-day survival was 75% in the HSD group and 66% in the control group ( p > 0.9). Brain total histopathologic score was lower in the HSD group ( p = 0.01). Postoperative behavioral scores were higher in the HSD group on the second day after surgery ( p = 0.03). Intracranial pressure was lower in the HSD group from 45 minutes to 8 hours after hypothermic circulatory arrest ( p = 0.03). Cerebral perfusion pressure was higher in the HSD group from 45 minutes to 3 hours after hypothermic circulatory arrest ( p = 0.06). Brain lactate concentration was lower in the HSD group when compared with controls ( p = 0.05). Furthermore, brain glucose levels tended to be higher and brain lactate-pyruvate ratio and lactate-glucose ratio were lower in the HSD group. Brain tissue oxygen partial pressures were somewhat higher in the HSD group ( p = 0.08). Conclusions The use of HSD in experimental hypothermic circulatory arrest is associated with significantly better neurologic recovery, better histopathology, lower intracranial pressure, higher cerebral perfusion pressure, and better preservation of brain metabolism.

Objective Cardiopulmonary bypass and hypothermic circulatory arrest induce a systemic inflammatory response, including a cascade of leukocyte and endothelial cell activity, during the postischemic reperfusion phase. Accumulation of leukocytes in the brain can lead to neurologic problems after cardiac surgery. The beneficial effects of a leukocyte-depleting filter have been documented, but because of contradictory results the underlying function of the filter remains unclear. Methods Twenty-two juvenile piglets (6 to 8 weeks) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter 60 minutes before and 60 minutes after a 75-minute hypothermic circulatory arrest at 18°C. The cerebral vessels were visualized with intravital microscopy through a cranial window placed over the parietal cortex. Rhodamine staining was used to observe adherent and rolling leukocytes in the cerebral postcapillary venules. The animals were electively killed 1 hour after weaning from cardiopulmonary bypass. Results There were no significant differences between the study groups regarding hemodynamic data. Numbers of adherent activated leukocytes were lower in the leukocyte filtration group, reaching borderline statistical significance when assessed throughout the experiment (between-groups P = .069) and actual statistical significance when assessed during the rewarming period (between-groups P = .029). Conclusion The leukocyte-depleting filter succeeded in reducing the number of adherent leukocytes during the reperfusion period in an experimental operation with deep hypothermic circulatory arrest. Such a filter thus could mitigate cerebral reperfusion injury after cardiac surgery.