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Stromal cell-derived factor-1α (SDF-1α) mediated mobilization and homing of stem cells showed promising potential in stem cell based tissue engineering and regenerative medicine. However local and sustained release of SDF-1α is indispensable for stem cell mediated regenerative process due to its short half-life under inflammatory conditions. In this study, a gene activated collagen substrate (GAC) was formed via assembly of plasmid encoding SDF-1α into a collagen substrate to create a microenvironment favoring stem cell homing. Local release of SDF-1α from the transfected cells on GAC and its effect on CD117+ stem cell homing were investigated. Non-viral poly-ethyleneimine (25kDa PEI)/DNA complexes were mixed with rat tail collagen solution to form the GAC. Optimization of GAC was carried out based on collagen effects on the PEI/DNA complexes, viability and luciferase expression of COS7 cells on GAC. CD117+ stem cells homing in response to SDF-1α local expression from transfected cells on GAC were investigated in a flow chamber in vitro and in a mouse hind limb model in vivo. The gene expression, migration of CD117+ stem cells and the induced inflammation were investigated with immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and H&E staining. The optimized parameters for GAC were DNA dosage 10 μg/cm2, molar ratio of PEI nitrogen in primary amine to DNA phosphate (N/P ratio) 4 and mass ratio of collagen to DNA (C/D ratio) 1.0. It kept cell viability above 75% and transfection efficiency around 5.8 × 105 RLU/mg protein. GAC allowed the sustained gene release up to 60 days. GAC mediated SDF-1α gene release induced migration and homing of CD117+ stem cells in vitro and in vivo significantly, and the inflammation of GAC reduced significantly two weeks after transplantation. GAC is a promising stem cell based therapeutic strategy for regenerative medicine. [ABSTRACT FROM AUTHOR]

Copyright of Anatolian Journal of Cardiology / Anadolu Kardiyoloji Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To evaluate the effect of a miniaturized extracorporeal circulation system (MECC™System) compared to conventional extracorporeal circulation (ECC) regarding liver function in cardiac surgical patients. Methods: Double indicator dilution measurements were achieved by bolus injection of indocyanine green (ICG) for assessment of cardiac index (CI) and plasma disappearance rate of ICG (PDRig). Measurements were simultaneously performed preoperatively after induction of anaesthesia (T1), following admission on the ICU (T2) and 6 h postoperatively (T3). Results: CI and PDRig were markedly increased after cardiac surgery without significant differences between groups. The percentage increase in CI was significantly correlated to the percentage increase in PDRig in both groups. Conclusion: Liver function improved after cardiac surgery in both groups of patients, which may partly be explained by an increase in CI under mild inotrope support. Differences between the extracorporeal circuits with respect to PDRig appear to be minimal in a group of patients without pre-existing liver injury. [ABSTRACT FROM AUTHOR]

Objectives: Cell therapy may offer novel therapeutic options for chronic ischemic heart disease. In a clinical trial, we first assessed the feasibility and safety of intramyocardial CD133+ bone marrow cell injection together with coronary artery bypass grafting (CABG). We then tested the hypothesis that CABG plus CD133+ cell injection would result in better contractile function than CABG alone. Methods: Fifteen patients took part in the safety study, followed by 40 patients who underwent either CABG with cell therapy or CABG alone. Bone marrow was harvested from the iliac crest one day before surgery, and purified CD133+ progenitor cells were injected in the infarct border zone during the CABG operation. LV function was measured by echocardiography and myocardial perfusion by SPECT. Results: In the safety study, no procedure-related complications were observed for up to 3 years. LV injection fraction (LVEF) increased from 39.0% ± 8.7% preoperatively to 50.2% ± 8.5% at 6 months and 47.9% ± 6.0% at 18 months (F = 6.03, P = .012). In the efficacy study, LCEF rose form 37.4% ± 8.4% to 47.1% ± 8.3% at 6 months in the group with CABG and cell therapy (F = 24.16, P < .0001) but only from 37.9% ± 10.3% to 41.3% ± 9.1% in the CABG-only group (F = 7.72, P = .012). LVEF was significantly higher at 6 months in the group with CABG and cell therapy than in the CABG-only group (P = .03). Similarly, perfusion of the infarcted myocardium improved more in patients treated with CABG and cell therapy than in those treated with CABG alone. Conclusion: Intramyocardial delivery of purified bone marrow stem cells together with CABG surgery is safe and provides beneficial effects, though it remains to be seen whether thewe effects produce a lasting clinical advantage. [Copyright &y& Elsevier]

As intracardiac signal amplitudes fluctuate due to patient activity, drug intake, and other factors, it is imperative that an adequate sensing safety margin in an implanted pacemaker be used to compensate. We studied an investigational autosensing feature that automatically adjusts the device's sensitivity. Data were collected from 55 patients, with Intermedics model 292-03 or 294-03 .pacemakers, upon inclusion of the study (Visit 1); 1 month postinclusion (Visit 2); I month, 1 day postinclusion (Visit 3); then 1 month, 2 days postinclusion (Visit 4). Atrial (N = 45) and/or ventricular (N = 54) thresholds were assessed at each visit; during Visit 2, myopotential tests were performed at two sensitivity settings. Autosensing was activated following Visit 1, then programmed on randomly at Visit 2 or Visit 3. From Visit 2- Visit 4, patients were monitored during daily activities (D), exercise (E), and sleep (S) th 24-hour Halter. With Autosensing on, atrial undersensing episodes were D = 33 (p > 0.2), and S = 28 (p < 0.05); ventricular undersensing episodes were D = 6 (p > 0.5). Ventricular oversensing episodes were S = 2; atrial oversensing episodes were S = 34 (p > 0.5), D = 2, and E = 3. Comparing Autosensing adjusted sensitivity with the recommended 2:1 safety margin, 4 patients (p = 0.15) experienced atrial myopotential oversensing, and 2 patients (p = 0.15) ventricular. No unanticipated clinical events occurred. Compared with the recommended 2:1 sensing safety margin, the Autosensing feature performed equal to manual programming in preventing episodes of under/oversensing, and was better for atrial undersensing during sleep. Autosensing obviates the need for periodic reprogramming of a fixed sensitivity value. [ABSTRACT FROM AUTHOR]

We present a case of severe tricuspid valve insufficiency because of disruption of the anterior tricuspid leaflet with congenital absence of left thoracic pericardium. Findings suggest that tricuspid valve disruption was a result of distorted right ventricular geometry because of luxation of the heart into left thoracic cavity. Tricuspid valve could be repaired by reinsertion of anterior tricuspid leaflet and De-Vega annuloplasty. Normal hemodynamic was obtained and weaning from cardio pulmonary bypass was possible by lifting the heart in orthotopic position using increased positive end expiratory pressure. Postoperative course was uneventful. [Copyright &y& Elsevier]

Copyright of Herzschrittmachertherapie und Elektrophysiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care. [ABSTRACT FROM AUTHOR]

Background and Purpose: Endocannabinoids and opioids play a vital role in mediating pain-induced analgesia. The specific effects of these compounds within the orofacial region are largely unknown. In this study, we tried to determine whether an increase in cannabinoid and opioid concentration in the CSF affects impulse transmission between the motor centres localized in the vicinity of the third and fourth cerebral ventricles.Experimental Approach: The study objectives were realized on rats using a method that allows the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation. The amplitude of ETJ was a measure of the effect of neurotransmitters on neural structures.Key Results: Perfusion of cerebral ventricles with anandamide (AEA), endomorphin-2 (EM-2), URB597, an inhibitor of fatty acid amide hydrolase (FAAH) and JZL195, a dual inhibitor of FAAH and monoacylglycerol lipase (MAGL) reduced the ETJ amplitude. The antinociceptive effect of AEA, EM-2, URB597 and JZL195 was blocked by CB1 receptor antagonist, AM251 and by μ receptor-antagonist, β-funaltrexamine. In contrast to AEA, 2-arachidonoylglycerol alone did not decrease ETJ amplitude.Conclusions and Implications: We demonstrated that in the orofacial area, analgesic activity is modulated by AEA and that EM-2-induced antinociception was mediated by μ and CB1 receptors. The action of AEA and EM-2 is tightly regulated by FAAH and FAAH/MAGL, by preventing the breakdown of endogenous cannabinoids in regions where they are produced on demand. Therefore, the current findings support the therapeutic potential of FAAH and FAAH/MAGL inhibitors as novel pharmacotherapeutic agents for orofacial pain. [ABSTRACT FROM AUTHOR]

Background: Pulsatile extracorporeal circulation (ECC) may improve perfusion of critical organs during cardiac surgery. This study analyzed the influence of the components of a minimal invasive ECC (MiECC) on the transfer of pulsatile energy into the pseudo‐patient of a mock circulation. Methods: An aortic model with human‐like geometry and compliance was perfused by a diagonal pump. Surplus hemodynamic energy (SHE) was determined from flow and pressure data. Five adult‐size oxygenator models and three sizes of cannulas were compared. Pulsatile pump settings were optimized, and parallel dual‐pump configurations were evaluated. Results: Oxygenator models showed up to twofold differences in pressure gradients and influenced SHE at flow rates up to 2.0 L min−1. Adjustments of frequency, systole duration, and rotational speed gain significantly improved SHE compared with empirical settings, with SHE above 21% of mean arterial pressure at flow rates of 1.0 L min−1 to 1.5 L min−1 and SHE above 5% at 3.5 L min−1. Small diameter cannula (15 Fr) limited SHE compared with larger cannula (21 Fr and 23 Fr). Two diagonal pumps did not provide higher SHE than a single pump, but permitted additional control over pulse pressure and SHE by varying the total fraction of pulsatile flow and the fraction of flow bypassing the oxygenator. Conclusions: Proper selection of components and optimizations of pump settings significantly improved pulse pressure and SHE of pulsatile MiECC. Surplus hemodynamic energy depended on flow rate with a maximum at 1.0 L min−1–1.5 L min−1. Pulsatile MiECC may specifically assist organ perfusion during phases of low flow. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to elucidate long-term clinical and functional effects of intramyocardial stem cell transplant and to identify patients who will show sustained benefit. Methods: Long-term outcomes of 35 patients after intramyocardial CD133+ bone marrow stem cell transplant during coronary artery bypass grafting were compared with those of a control group of 20 patients after coronary artery bypass grafting alone. Clinical effects were assessed with the New York Heart Association classification system and the Minnesota Living With Heart Failure questionnaire. Electrocardiography, 24-hour Holter monitoring, echocardiography, myocardial perfusion scanning, magnetic resonance imaging, and computed tomography were performed. Logistic regression analyses were used to identify prognostic factors for improvement in long-term left ventricular ejection fraction after stem cell treatment. Results: The stem cell group revealed similar New York Heart Association and life quality scores to the control group. Myocardial perfusion score at the area of risk was significantly increased in the stem cell group after 36-month follow-up (P = .024 vs control). Multivariate logistic regression analysis revealed a 44-fold higher probability of at least 5% improvement in left ventricular ejection fraction for patients with preoperative left ventricular ejection fraction not greater than 40% than for patients with preoperative ejection fraction greater than 40% (P = .018). Furthermore, patients operated on between 7 and 12 weeks after myocardial infarction had a 56-fold higher chance of at least 5% improvement in left ventricular ejection fraction than patients treated later than 12 weeks after infarction (P = .023). Conclusions: Intramyocardial stem cell therapy was safe but lacked significant lasting benefits beyond 6 months in our study cohort with a limited number of patients. Preoperative left ventricular ejection fraction and time since myocardial infarction may be critical parameters for selection of patients who can benefit most from intramyocardial stem cell treatment during coronary artery bypass grafting. [ABSTRACT FROM AUTHOR]

The ultimate answer to the question whether minimal invasive extracorporeal circulation (MiECC) represents the optimal perfusion technique in contemporary clinical practice remains elusive. The present study is a real-world study that focuses on specific perfusion-related clinical outcomes after cardiac surgery that could potentially be favourably affected by MiECC and thereby influence the future clinical practice.The MiECS study is an international, multi-centre, two-arm randomized controlled trial. Patients undergoing elective or urgent coronary artery bypass grafting (CABG), aortic valve replacement (AVR) or combined procedure (CABG + AVR) using extracorporeal circulation will be randomized to MiECC or contemporary conventional cardiopulmonary bypass (cCPB). Use of optimized conventional circuits as controls is acceptable. The study design includes a range of features to prevent bias and is registered at clinicaltrials.gov (NCT05487612).The primary outcome is a composite of postoperative serious adverse events that could be related to perfusion technique occurring up to 30 days postoperatively. Secondary outcomes include use of blood products, ICU and hospital length of stay (30 days) as well as health-related quality of life (30 and 90 days).The MiECS trial has been designed to overcome perceived limitation of previous trials of MiECC. Results of the proposed study could affect current perfusion practice towards advancement of patient care. [ABSTRACT FROM AUTHOR]

The trial hypothesized that minimally invasive extra-corporeal circulation (MiECC) reduces the risk of serious adverse events (SAEs) after cardiac surgery operations requiring extra-corporeal circulation without circulatory arrest.This is a multicentre, international randomized controlled trial across fourteen cardiac surgery centres including patients aged ≥18 and <85 years undergoing elective or urgent isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR) surgery, or CABG + AVR surgery. Participants were randomized to MiECC or conventional extra-corporeal circulation (CECC), stratified by centre and operation. The primary outcome was a composite of 12 post-operative SAEs up to 30 days after surgery, the risk of which MiECC was hypothesized to reduce. Secondary outcomes comprised: other SAEs; all-cause mortality; transfusion of blood products; time to discharge from intensive care and hospital; health-related quality-of-life. Analyses were performed on a modified intention-to-treat basis.The trial terminated early due to the COVID-19 pandemic; 1071 participants (896 isolated CABG, 97 isolated AVR, 69 CABG + AVR) with median age 66 years and median EuroSCORE II 1.24 were randomized (535 to MiECC, 536 to CECC). Twenty-six participants withdrew after randomization, 22 before and four after intervention. Fifty of 517 (9.7%) randomized to MiECC and 69/522 (13.2%) randomized to CECC group experienced the primary outcome (risk ratio = 0.732, 95% confidence interval (95% CI) = 0.556 to 0.962, p = 0.025). The risk of any SAE not contributing to the primary outcome was similarly reduced (risk ratio = 0.791, 95% CI 0.530 to 1.179, p = 0.250).MiECC reduces the relative risk of primary outcome events by about 25%. The risk of other SAEs was similarly reduced. Because the trial terminated early without achieving the target sample size, these potential benefits of MiECC are uncertain. [ABSTRACT FROM AUTHOR]

Adequate differentiation of calcifications in contrast-enhanced CT scans remains difficult to assess TAVI parameters. The size of the aortic leaflets has not been taken into account so far in present studies. The aim of our study was to establish a new method for optimized quantification of the aortic valve calcification degree in contrast-enhanced CT scans for better preoperative prediction of postoperative paravalvular leak after TAVI.We retrospectively analyzed preoperative contrast-enhanced CT scans of patients who underwent TAVI in our institution between 2014 and 2017. Calcium volume was quantified by a method using contrast enhanced computer tomography (3mensio-Structural Heart-7.2 software) with different iodine contents for better discrimination of contrast agent from calcium and by an individually set Houndsfield Unit (HU) threshold with 50HU above the individually determined reference value. Calcium volume was correlated with surface area of each aortic cusp. Perioperative variables were analyzed. All patients (n = 150) with severe aortic stenosis were treated with TAVI implantation. Overall incidence of postoperative trace to moderate PVL was 37%. The amount of calcium correlated with the incidence of PVL. In a logistic regression analysis total volume of calcification (p = .032) as well as calcification of each aortic cusp (NC_p = .001; RC_p < .001; LC_p = .001) were independent predictors.Calcification degree as well as its correlation with the surface area of each aortic cusp significantly influence incidence of PVL. Our new method improves preoperative quantification of the calcification degree by use of contrast agents with different iodine contents and thereby helps to improve patients’ outcomes. [ABSTRACT FROM AUTHOR]