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Objective The aim of the present study was to construct a new drug delivery system for milrinone using microparticles. This novel technology enhances drug bioavailability and decreases toxicity, with future implications for the treatment of end-stage heart failure. Methods Polylactic-co-glycolic acid microparticles (PLGA-MPs) loaded with milrinone were prepared using a double emulsion-solvent evaporation technique. In vitro release kinetics was evaluated at physiologic conditions. A total of 24 female Lewis rats underwent left coronary artery ligation. One week after ligation, all rats were randomized to 1 of 3 groups (n = 8 per group). Group I received an intravenous injection of PLGA-MPs alone; group II, a bolus intravenous injection of milrinone; and group III an intravenous injection of milrinone-PLGA-MPs. All injections were administrated slowly by way of the tail vein over 10 minutes. Transthoracic echocardiography, noninvasive heart rate monitoring, and blood pressure measurements were performed at different predetermined intervals before and for 24 hours after the injection. All rats survived for 24 hours and were then killed by euthanasia. Serum plasma was taken for cytokine assays and determination of milrinone levels using high-performance liquid chromatography. Results Group III had a significantly greater left ventricular ejection fraction at 90 minutes and 3, 6, and 12 hours after treatment compared with the other groups. The milrinone plasma level was significantly greater in group III than in the other groups (group I, 0 ng/mL; group II, 1.7 ± 2.4 ng/mL; group III, 9.1 ± 2.2 ng/mL; P < .05). The intercellular adhesion molecule and cytokine-induced neutrophil chemoattractant-1 levels were significantly lower in group III than in the other 2 groups (P < .05). Conclusions Drug encapsulation using microparticles can prolong the effects of milrinone. We propose a new strategy for future drug delivery in patients with end-stage heart failure. [ABSTRACT FROM AUTHOR]

Abstract: Although the effects of insulin on glucose homeostasis are well recognized in surgical patients, its effect on perioperative protein metabolism has received little attention. The purpose of this study was to examine the effect of high-dose insulin therapy on the plasma concentrations of amino acids (AAs) in patients undergoing coronary artery bypass grafting surgery. We studied 20 nondiabetic patients scheduled for elective coronary artery bypass grafting surgery. Patients were randomly allocated to receive either standard metabolic care (target glycemia 6.0-10.0 mmol/L, control group, n = 10) or high-dose insulin therapy (insulin group, n = 10). Insulin was administered at 5 mU.kg−1.min−1 beginning at skin incision. Simultaneously, 20% dextrose was infused at a variable rate adjusted to maintain glycemia between 4.0 and 6.0 mmol/L. Plasma AAs, glucose, cortisol, and insulin were measured immediately before surgery and at sternal closure. Differences in mean values were assessed by Student t test. Plasma concentrations of all AAs decreased in the insulin group, with 15 of 22 AAs, including all branched-chain AAs, being significantly lower at sternal closure when compared with the control group. At the end of surgery, plasma glucose concentration was significantly lower in the insulin group (4.2 ± 0.6 vs 7.3 ± 1.0 mmol/L, P = .0001), whereas plasma cortisol levels did not show any difference between groups. High-dose insulin therapy resulted in a significant reduction in plasma AAs, particularly branched-chain AAs, during cardiac surgery. [Copyright &y& Elsevier]

The ability of mesenchymal stem cells to self-renew and differentiate into specialized cell lineages makes them promising tools for regenerative medicine. Local injection and use of scaffolds had been employed earlier to deliver these cells; yet, an optimal delivery system remains to be identified. Here, using genipin, which is a non-toxic natural cross linker for proteins, we prepared alginate-chitosan polymeric microcapsules (GCAC) to develop an efficient stem cell delivery system. We investigated the properties of this membrane along with the encapsulated adipose tissue-derived stem cells (ASCs) and compared that with the widely used alginate poly-lysine (APA) membranes. The GCAC membrane was able to support cell viability, augment cell growth, and showed better results under external rotational and osmotic pressures with about 30% of the ruptured capsules in comparison to 60% ruptured APA capsules. The membrane also provided immune-protection to the entrapped cells as demonstrated by the lymphocyte proliferation assay. The capsule also has potential for long-term storage. The encapsulated four million ASCs also showed steady secretion of approximately 4600 pg vascular endothelial growth factor (VEGF) over 15-day time period comparable to that of free cells. Furthermore, the encapsulated ASCs showed around 3.8-fold increase in VEGF secretion after 72 h hypoxic conditions in comparison to normoxic conditions. This increased VEGF expression resulted in improved angiogenic potential of the bioactive capsules as noted by enhanced endothelial cell growth. GCAC encapsulation also did not show any effect on their differentiation ability. Thus, because of these biocompatible and bioactive attributes, genipin cross-linked polymeric microcapsules can emerge as a potentially important tool for improved stem cell-based therapy and cell delivery applications. [ABSTRACT FROM AUTHOR]

During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC) therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM) can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptormediated survival pathways, inducing stemcell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy. [ABSTRACT FROM AUTHOR]

Background: The mechanism by which marrow stromal cells (MSCs) improve cardiac function after myocardial infarction (MI) is still unclear. Because MI patients with lower circulating proinflammatory/antiinflammatory cytokine ratios have been reported to have a better prognosis and in vitro studies showed that MSCs express antiinflammatory cytokines, we hypothesized that changes in cytokine ratios in the infarct microenvironment after MSC therapy may play a role in improving early cardiac function after MI. Methods: Sixty-three rats that survived left coronary artery ligations were injected with culture media (group M) or MSCs (group C). Cardiac functional changes were assessed with echocardiography. Cytokine gene expressions of interleukin (IL)-1β, IL-6, IL-8, (proinflammatory) and IL-10 (antiinflammatory) were quantified by real-time polymerase chain reaction. Extracellular matrix deposition, injury score, and the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 ratio were also analyzed. Results: The ratio of proinflammatory/antiinflammatory cytokine gene expression was decreased in group C at various times, particularly in the early postoperative period. In group C, the matrix metallopeptidase 2/tissue inhibitor of metallopeptidase 1 gene expression ratio was significantly lower than group M at the early phase (12 hours), which in group C was translated into significantly lower extracellular matrix deposition at 24 hours, 1, and 2 weeks. Functional recovery was also significantly better in cell therapy group C. Conclusions: Our data demonstrate that MSC therapy decreases the proinflammatory/antiinflammatory cytokine ratio in the microenvironment early after MI. This is associated with subsequent less scar formation and improved cardiac function. [Copyright &y& Elsevier]

Bone marrow derived mesenchymal stem cell (BMSCs) therapy can significantly improve cardiac ventricular function following ischemic injury. Their potential can be further enhanced by using genetically modified cells, overexpressing certain therapeutic biomolecules. However, such therapy is limited by low efficiency of transplantation of the cells, secreting inadequate therapeutic proteins. To address these issues, we developed recombinant baculoviruses to genetically modify the BMSCs and investigated the potential of using polyethylene glycol (PEG) integrated alginate–chitosan microcapsules (AC) for efficient myocardial transplantation. The data indicates that the cells encapsulated in AC–PEG microcapsules grew rapidly from 80 cells per capsule to above 100 cells per capsule within a week, reaching a confluency of average 110 cells by day 9 of encapsulation. The microcapsules proved superior to commonly used AC microcapsules in terms of immune protection. After 11 days of co-culture of the encapsulated cells with highly confluent lymphocytes, the viable cell population in AC–PEG microcapsules was reduced by only 20%, whereas in AC microcapsules it was reduced to more than 50%. AC–PEG microcapsules also had significantly higher mechanical (65 vs. 10%) and osmotic (92 vs. 52%) stability than commonly used AC microcapsules as seen after 2 h of external stresses. The entrapped genetically modified cells showed highest transgene expression on day 1, which was gradually reduced to 48% after 1 week and to 14% after 2 weeks. This expression pattern was also dependant on initial viral incubation time, with 8 h incubation being the optimum. The encapsulated cells, transduced with baculovirus, also retained their inherent potential to differentiate into multiple lineages. Because of the above characteristics, the baculovirus transduced microencapsulated BMSCs have immense potential in myocardial cell-based gene therapy, although preclinical studies are needed to be done to establish their functional benefits on myocardial implantation. [ABSTRACT FROM AUTHOR]

The potential of genetically modified cardiomyoblasts in treating damaged myocardium is well known. However, efficient delivery of these cells is of major concern during treatment. The limiting factors are the massive cell death that occurs soon after their intramyocardial transplantation into the beating heart. To address these problems, we generated recombinant baculoviruses (BacMam viruses) which efficiently transduced cardiomyoblast cells under optimized conditions. These genetically modified cells were then protected in a new polymeric microcapsule using poly-ethylene-glycol (PEG), alginate, and poly-L-lysine (PLL) polymers for efficient delivery. Results showed that microcapsules maintain cell viability and support cell proliferation for at least 30 days. The capsules exhibit strong immunoprotective potential and have high mechanical and osmotic stability with more than 70% intact capsules. The encased transduced cells showed a rapid transgene expression inside the capsule for at least 15 days. However, preclinical studies are needed to further explore its long-term functional benefits. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a promising approach for improving cardiac function after severe myocardial damage for which use of autologous donor cells have been preferred to avoid immune rejection. Recently however, rodent, porcine, and even human bone marrow stromal cells have been reported to be uniquely immune tolerant, both in the in vitro mixed lymphocyte co-culture studies and in the in vivo allo-transplant and xeno-transplant models. In this review, we explore the current understanding of the underlying immunologic mechanisms, which can facilitate the use of such cells as “universal donor cells” with fascinating therapeutic implications. [Copyright &y& Elsevier]

Background: Recently rodent and porcine bone marrow stromal cells (MSCs) have been reported to be uniquely immune tolerant. To confirm these findings in human cells, we tested whether human MSCs are also immune tolerant, such that they can be used as universal donor cells for myocardial regenerative therapy. Methods: Immunocompetent female rats underwent coronary ligations (n = 90). In group I, lacZ-labeled male human MSCs were implanted into the peri-infarcted area. In groups II, III, and IV, isogeneic rat MSCs, culture medium, or human fibroblasts were injected, respectively. Echocardiography was carried out to assess cardiac function, and the specimens were examined serially for up to 8 weeks with immunohistochemistry, fluorescent in situ hybridization, and polymerase chain reaction to examine MSCs survival and differentiation. Results: Human MSCs survived within the rat myocardium for more than 8 weeks without immunosuppression. Furthermore, the implanted MSCs significantly contributed to the improvement in ventricular function and attenuated left ventricular remodeling. No cellular infiltration characteristic of immune rejection was noted in contrast to group IV. Conclusions: Human MSCs survived within this xenogeneic environment, and contributed to the improvement in cardiac function. Our findings support the feasibility of using these cells as universal donor cells for xenogeneic or allogeneic cell therapy, as they can be prepared and stored well in advance for urgent use. Allogeneic MSCs from healthy donors may be particularly useful for severely ill or elderly patients whose own MSCs could be dysfunctional. [Copyright &y& Elsevier]

Objective: Direct intramyocardial injection is a common route of donor cell administration for myocardial cell therapy. Studies have demonstrated a significant and rapid loss of implanted cells, which is thought to be biologically caused. We hypothesized that mechanical loss of cells from the contracting myocardium might actually be the main culprit. Methods: Intramyocardial injections of fluorescent microspheres (10 μm) were carried out in both small and large animal models. The hearts of Lewis rats (250-350 g) received 3 × 106 microspheres injected into the left ventricular myocardium. Rats were divided evenly between two experienced operators. The nonbeating (n = 2) and beating (n = 5) hearts of piglets (7.5-7.8 kg) received 3 × 106 microspheres. The hearts were excised within 10 minutes, and the microspheres retained in the myocardium were quantified with fluorescent flow cytometry. Results: In the beating-heart rat model, the microsphere retention rates after a single injection were similar with and without purse-string occlusion of needle puncture sites and slightly lower than after multiple site injections (6.19% ± 4.05% vs 5.44% ± 5.66% vs 8.83% ± 3.29%). There were no significant operator-dependent differences. The retention rates in beating porcine hearts were higher than those in the rats (P < .05) but markedly lower than those in nonbeating porcine hearts (11.1% vs 67.4%). Conclusion: Mechanical leakage and washout may account for a major portion of cell loss after cell implantation, and efforts aimed at reducing mechanical loss in the beating heart may yield a greater benefit than those targeting biologic loss alone. [Copyright &y& Elsevier]

Objective: Marrow stromal cells (MSCs) contain multipotent cells, which may participate in the repair of damaged organs. We tested the hypothesis that MSCs are recruited to the heart upon myocardial infarction (MI), and play pathophysiological roles in the healing and adaptation process. Methods: Donor MSCs from isogenic Lewis rats were harvested, multiplied and labeled with Lac Z reporter gene. Ten million labeled cells were injected intravenously into the recipient rats (n=30). One week later, 10 rats were killed to examine the distribution of the labeled MSCs. Other rats underwent either coronary artery ligations (n=14) or sham operations (n=6). The hearts were removed at various time points (1–8 weeks) and stained for β-galactosidase activity. Phenotypes of labeled cells were identified with immunohistochemical stains. Results: In rats killed at 1 week, labeled cells had homed into the bone marrow of the recipients, and none found in their hearts. In the coronary ligated hearts, labeled cells were seen in and near the infarct at all time points studied (14/14), but none in the sham operated hearts (6/6). There was evidence for myogenic differentiation. Some of these labeled cells showed positive staining for cardiomyocyte specific troponin I-c at 4 weeks, while others appeared in the vascular walls expressing smooth muscle alpha-actin. Conclusions: Following myocardial infarction, MSC''s are signaled and recruited to the injured heart, where they undergo differentiation, and may participate in the pathophysiology of post-infarct remodeling, angiogenesis, and maturation of the scar. Therapeutic implantation of MSCs thus may further enhance such effects. [Copyright &y& Elsevier]

Objectives: The contact of cardiopulmonary bypass surface and patient''s blood activates systemic inflammatory response which aggravates ischemia-reperfusion injury. This study evaluates the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on cerebral protection using different steroid administration protocols. Methods: Eighteen (n=6/group) 4 week-old piglets were divided in three groups. Methylprednisolone (30 mg/kg) was administered intravenously 4 h prior to CPB in Group I, or added in pump prime in group II. Group III received no steroid. All animals were cooled to 15°C followed by 100 min of DHCA, then rewarmed over 40 min and sacrificed 6 h after CPB. Post-operative weight gain, bioelectrical impedance, colloid oncotic pressure (COP) and interleukin-6 (IL-6) were evaluated. Determination of cerebral trypan blue and immunohistochemical assays of transforming growth factor (TGF)-β1 and caspase-3 activities were performed. Results: Post-operative % weight gain (13.0±3.8 (I) versus 26.4±9.9 (II) versus 22.6±6.4 (III), P=0.02); % bioimpedance reduction (14.5±8.0 (I) versus 38.3±13.3 (II) versus 30.5±8.0 (III), P=0.003); mean COP (mmHg) (14.9±1.8 (I) versus 10.9±2.0 (II) versus 6.5±1.8 (III), P=0.0001) and systemic IL-6 levels (pg/ml) (208.2±353.0 (I) versus 1562.1±1111.4 (II) versus 1712.3±533.2 (III), P=0.01) were significantly different between the groups. Spectrophotometric analysis of cerebral trypan blue (ng/g dry weight) was significantly different between the groups (0.0053±0.0010 (I) versus 0.0096±0.0026 (II) versus 0.0090±0.0019 (III), P=0.004). TGF-β1 scores were 3.3±0.8 (I) versus 1.5±0.8 (II) versus 1.5±0.5 (III), P<0.05, groups I versus II and I versus III. Remarkable perivascular caspase-3 activity was observed in groups II and III. Conclusion: Different timing of steroid administration results in different inflammatory mediator response. Steroid in CPB prime is not significantly better than no steroid treatment, while systemic steroid pre-treatment significantly decreases systemic manifestation of inflammatory response and brain damage. [Copyright &y& Elsevier]

Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetics with a mean retention time of 123.7 min, half-life of 101.3 min, and clearance rate of 0.24 L/(kg*h). The targeted formulation also significantly improved ejection fraction and fractional shortening parameters thus improving cardiac function. This study demonstrates a new approach in delivering inotropic drugs such as milrinone for superior treatment of congestive heart failure. [ABSTRACT FROM AUTHOR]

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure–volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine. [ABSTRACT FROM AUTHOR]

Congestive heart failure, a prominent cardiovascular disease results primarily from myocardial infarction or ischemia. Milrinone (MRN), a widely used clinical drug for heart failure, improves myocardial contractility and cardiac function through its inotropic and vasodilatory effects. However, lacking target specificity, it exhibits low bioavailability and lower body retention time. Therefore, in this study, angiotensin II (AT1) peptide conjugated human serum albumin nanoparticles (AT1-HSA-MRN-NPs) have been synthesized for targeted delivery of MRN to the myocardium, overexpressing AT1 receptors under heart failure. The NPs were surface functionalized through a covalent conjugation reaction between HSA and AT1. Nanoparticle size was 215.2±4.7 nm and zeta potential -28.8±2.7 mV and cumulative release of MRN was ~72% over 24 hrs. The intracellular uptake of nanoparticles and cell viability was studied in H9c2 cells treated with AT1-MRN-HSA-NPs vs the control non-targeted drug, MRN Lactate under normal, hypoxic and hypertrophic conditions. The uptake of AT1-HSA-MRN-NPs in H9c2 cells was significantly higher as compared to non-targeted nanoparticles, and the viability of H9c2 cells treated with AT1-MRN-HSA-NPs vs MRN Lactate was 73.4±1.4% vs 44.9±1.4%, respectively. Therefore, AT1-HSA-MRN-NPs are safe for in vivo use and exhibit superior targeting and drug delivery characteristics for treatment of heart failure. [ABSTRACT FROM AUTHOR]

Introduction: Ventricular septal defect (VSD) is a mechanical complication of acute myocardial infarction (MI) with a very high mortality, despite advances in surgical and circulatory support. The tremendous hemodynamic disturbance and the severely fragile myocardium render surgical repair a great challenge. The optimal time of surgical repair with or without circulatory support is still controversial. Objective: The aim of this study is to review our experience with early surgical repair of post-MI VSD in a single major cardiac institution in China. Methods: From January 2013 to October 2020, 9consecutive patients presented to our emergency department with a diagnosis of post-MI VSD. Among them, 8 were male, and the mean age was 58 ± 7years. The mean VSD size was 22.5 ± 5.7 mm. In all patients, an intra-aortic balloon pump (IABP)was inserted immediately after admission to cardiac surgery service. All patients were operated at a mean of 3.3 ± 2.9 days, and 4 within 24 h of the rupture (range 1 to 9 days post-VSD). In 5 cases, the VSD was located superiorly, and 4 cases in the posterior septum. Results: The overall 30-day mortality was 11% (1/9). Coronary angiography was performed in all nine patients, four with single vessel disease had coronary stents implanted, and the other five received concomitant coronary artery bypass grafting during VSD repair surgery. There was no death in all 5 patients with anterior septal perforation. One patient with posterior septal perforation died in the operating room due to bleeding from the ventriculotomy site. Three survived patients were diagnosed with a small residual defect and mild left to right shunt post-repair. However, no further intervention was required, and patients remained asymptomatic (Killip II in 1 and III in 2). Conclusion: In our experience, immediate insertion of IABP and hemodynamic stabilization with early surgical intervention of VSD repair and concomitant coronary revascularization provided an 89% survival rate. [ABSTRACT FROM AUTHOR]

Nitric oxide synthase 3 (NOS3) eluting polyvinyl alcohol-based hydrogels have a large potential in medical applications and device coatings. NOS3 promotes nitric oxide and nitrate production and can effectively be delivered using insect cell viruses, termed baculoviruses. Nitric oxide is known for regulating cell proliferation, promoting blood vessel vasodilation, and inhibiting bacterial growth. The polyvinyl alcohol (PVA)-based hydrogels investigated here sustained baculovirus elution from five to 25 days, depending on the hydrogel composition. The quantity of viable baculovirus loaded significantly declined with each freeze-thaw from one to four (15.3 ± 2.9% vs. 0.9 ± 0.5%, respectively). The addition of gelatin to the hydrogels protected baculovirus viability during the freeze-thaw cycles, resulting in a loading capacity of 94.6 ± 1.2% with sustained elution over 23 days. Adding chitosan, PEG-8000, and gelatin to the hydrogels altered the properties of the hydrogel, including swelling, blood coagulation, and antimicrobial effects, beneficial for different therapeutic applications. Passive absorption of the baculovirus into PVA hydrogels exhibited the highest baculovirus loading (96.4 ± 0.6%) with elution over 25 days. The baculovirus-eluting hydrogels were hemocompatible and non-cytotoxic, with no cell proliferation or viability reduction after incubation. This PVA delivery system provides a method for high loading and sustained release of baculoviruses, sustaining nitric oxide gene delivery. This proof of concept has clinical applications as a medical device or stent coating by delivering therapeutic genes, improving blood compatibility, preventing thrombosis, and preventing infection. [ABSTRACT FROM AUTHOR]

Hydrogel wound dressings are effective in their ability to provide a wound-healing environment but are limited by their ability to promote later stages of revascularization. Here, a biosafe recombinant baculovirus expressing VEGFA tagged with EGFP is encapsulated in chitosan-coated alginate hydrogels using ionic cross-linking. The VEGFA, delivered by the baculovirus, significantly improves cell migration and angiogenesis to assist with the wound-healing process and revascularization. Moreover, the hydrogels have an encapsulation efficiency of 99.9%, no cytotoxicity, antimicrobial properties, good blood compatibility, promote hemostasis, and enable sustained delivery of baculoviruses over eight days. These hydrogels sustain baculovirus delivery and may have clinical implications in wound dressings or future gene therapy applications. [ABSTRACT FROM AUTHOR]

A 316L stainless steel (316L-SS) surface was electrochemically polished (EP) in an electrolyte of a new chemical composition at different cell voltages, with the aim of improving its corrosion resistance and biocompatibility. X-ray photoelectron spectroscopy results revealed that the EP-formed oxide films were characterized by a significantly higher atomic Cr/Fe ratio and film thickness, in comparison to the naturally-grown passive oxide film formed on the untreated (control) 316L-SS surface. As a result of the increase in the oxide film thickness and relative Cr enrichment, the EP-treated 316L-SS surfaces offered a notable improvement in general corrosion resistance and pitting potential. In addition, the attachment of endothelial cells (ECs) and smooth muscle cells (SMCs) to the 316L-SS surfaces revealed a positive effect of electropolishing on the preferential attachment of ECs, thus indicating that the EP surfaces could be endothelialized faster than the control (unmodified) 316L-SS surface. Furthermore, the EP surfaces showed a much lower degree of thrombogenicity in experiments with the platelet-rich plasma. Therefore, the use of the electrochemical polishing technique in treating a 316L-SS surface, under the conditions presented in this paper, indicates a significant improvement in the surface's performance as an implant material. [ABSTRACT FROM AUTHOR]

Abstract: This study report the development of a nanobiohybrid hydrogel based endovascular stent device capable of preventing postangioplasty in-stent restenosis (ISR) by promoting significant vascular endothelial recovery in a site-specific manner. The hydrogel is comprised of fibrin matrices, assembled layer-by-layer (LbL) on stent surface with alternate layers carrying endosomolytic Tat peptide/DNA nanoparticles (NPs) or NPs hybridized to polyacrylic acid (PAA) wrapped single-walled carbon nanotubes (NP–CNT). Here, the hydrogel works as a reservoir to carry, protect, and simultaneously deliver pro-angiogenic, vascular endothelial growth factor (Vegf) and Angiopoietin-1(Ang1), gene carrying NPs to the target site. In vitro results demonstrated that CNTs incorporated in the hydrogel layers play a major role in tuning the bioactivity of the stent. In addition, the developed stent formulation can significantly reduce the loss of therapeutics while traversing through the vessel and during deployment. In vivo experiments in balloon-injured canine femoral artery demonstrated that the NCS (+) group, carrying NPvegf+Ang1, can significantly enhance re-endothelialization of injured artery compared to control NCS (−), carrying NPNull, and bare metal stent (BMS) groups, attenuate stenosis (18.5±9.03% vs 39.56±13.8 vs 45.34±8.3%; n =8, p <0.05) and prevent neointima formation (1.53±0.36mm2 vs 2.51±0.27mm2 vs 2.66±0.14mm2; n =8, p <0.05) as analyzed angiography and histomorphometric analysis. These data collectively implicate that this new technology can be useful for stent and other biomedical devices through controlled delivery of multiple biotherapeutics. [Copyright &y& Elsevier]

This case report describes an initially stabilized transcatheter heart valve that embolized in the ascending aorta, leading to a postprocedural acute type A aortic dissection. [ABSTRACT FROM AUTHOR]

Background: The paracrine effects of multipotent mesenchymal stromal cells (MSCs) are mediated by their secretome composed by soluble factors (i.e., cytokines, growth factors, hormones) and extracellular vesicles (EVs). EVs promote intercellular communication, and the EV cargoes [e.g., proteins, soluble factors, microRNAs (miRNAs), messenger RNA (mRNA), DNA] reflect the molecular and functional characteristics of their parental cells. MSC-derived EVs (MSC-EVs) are currently evaluated as subcellular therapeutics. A key function of the MSC secretome is its ability to promote immune tolerance (i.e., immunopotency), a property that is enhanced by priming approaches (e.g., cytokines, hypoxia, chemicals) and inversely correlates with the age of the MSC donors. We evaluated mechanisms underlying MSC vesiculation and the effects of inflammation and aging on this process. Methods: We evaluated the effects of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) on human adipose-derived MSC: (a) vesiculation (custom RT2 Profiler PCR Array), (b) EV profiles (Nanoparticle Tracking Analysis and Nanoparticle Flow Cytometry), (c) EV cargo (proteomic analysis and Western blot analysis), and (d) immunopotency (standard MSC:CD4 T cell proliferation inhibition assay). We confirmed the role of RAB27B on MSC vesiculation (RAB27B siRNA) and assessed its differential contribution to vesiculation in adult and pediatric MSCs (qPCR). Results: Cytokine priming upregulated RAB27B in adipose-derived MSCs increasing their secretion of exosome-like small EVs (sEVs; < 200 nm) containing two key mediators of immunopotency: A20 and TSG-6. These EVs inhibited T cell proliferation in a dose-dependent manner. RAB27B siRNA inhibited MSC vesiculation. Adipose-derived MSCs isolated from pediatric donors exhibited higher RAB27B expression and secreted more sEVs than adult MSCs. Conclusions: Cytokine priming is a useful strategy to harvest anti-inflammatory MSC-sEVs for clinical applications. Of relevance, donor age should be considered in the selection of MSC-sEVs for clinical applications. [ABSTRACT FROM AUTHOR]

Highlights: [•] Ir/Ti-oxide coated surfaces are characterized by the so-called “cracked-mud” morphology. [•] 40% Ir in the coating material results in a morphologically uniform coating. [•] ECs and SMCs showed a desirable response to the Ir/Ti-oxide coated surfaces. [•] Ir/Ti-oxide coated surfaces are more bio/hemocompatible than the untreated 316L stainless steel. [ABSTRACT FROM AUTHOR]

Background and Aim With the advancement of percutaneous coronary interventions (PCIs), more patients with diffuse coronary artery disease are referred for coronary artery bypass graft (CABG) surgery. The use of coronary endarterectomy may be useful in such cases. We reviewed our experience with left anterior descending artery endarterectomy as an adjunct to conventional CABG. Methods Between June 2005 and 2011, 58 consecutive patients underwent left anterior descending artery endarterectomy as an adjunct to CABG. These were matched to 58 cases based on age, gender, and Parsonnet score. All data were collected prospectively in a departmental database. Postoperative complications and in-hospital mortality were analyzed. Survival curves were produced. Results There was one death in the endarterectomy group (1.7%) from liver failure. There was no significant difference in postoperative complications (especially perioperative myocardial infarction) between the two groups with similar hospital mortality. Computed tomography (CT) angiography was performed in 24 patients with endarterectomy (41%), which showed 100% patency of the left internal mammary artery graft to the left anterior descending artery. Survival and freedom from intervention at a mean follow-up of 4.2 years were similar. Conclusions In patients with diffuse disease, the use of endarterectomy is a safe technique with no increase in short-term morbidity or mortality. Mid-term results are similar to nonendarterectomized patients. This technique is useful in patients with diffuse coronary artery disease. doi: 10.1111/jocs.12230 (J Card Surg 2014;29:1-7) [ABSTRACT FROM AUTHOR]

Abstract: The study aims to design a new gene delivery method utilizing the complementary strengths of baculovirus, such as relatively high transduction efficiency and easy scale-up, and non-viral nanodelivery systems, such as low immunogenicity. This formulation was developed by generating a self assembled binary complex of negatively charged baculovirus (Bac) and positively charged endosomolytic histidine rich Tat peptide/DNA nanoparticles (NP). The synergistic effect of this hybrid (Bac-NP) system to induce myocardial angiogenesis in acute myocardial infarction (AMI) model has been explored in this study, using Angiopoietin-1 (Ang-1) as the transgene carried by both vector components. Under optimal transduction conditions, Bac-NPAng1 showed 1.75 times higher and sustained Ang-1 expression in cardiomyocytes than BacAng1, with significantly high angiogenic potential as confirmed by functional assays. For in vivo analysis, we intramyocardially delivered Bac-NPAng1 to AMI rat model. 3 weeks post AMI, data showed increase in capillary density (p < 0.01) and reduction in infarct sizes (p < 0.05) in Bac-NPAng1 compared to BacAng1, NPAng1 and control groups due to enhanced myocardial Ang-1 expression at peri-infarct regions (1.65 times higher than BacAng1). Furthermore, the Bac-NPAng1 group showed significantly higher cardiac performance in echocardiography than BacAng1 (44.2 ± 4.77% vs 37.46 ± 5.2%, p < 0.01), NPAng1 and the control group (32.26 ± 2.49% and 31.58 ± 2.26%). Collectively, this data demonstrates hybrid Bac-NP as a new and improved gene delivery system for therapeutic applications. [Copyright &y& Elsevier]

Objective(s): We conduct a comparative study that employs the use of multiple dynamic deep learning algorithms to develop predictive models with video-based echocardiographic images using sample size determination as a key variable to assess optimal performance metrics., Methods: Our study compares performance of 3D convolutional neural networks, video vision transformers, and hybrid convolutional neural networks and Long Short-Term Memory models within both supervised and semi-supervised domains using variable sample sizes., Results: For supervised learning, the ResNet3D model achieved the lowest Mean Absolute Error (MAE) and Root Mean Square Error (RMSE) across all training set sizes (200, 400, and 800-video datasets), with the best performance observed on the 800-video training set (MAE: 7.409, RMSE: 10.216). In the semi-supervised setting, both ResNet3D and ResNet+LSTM models benefited from the inclusion of unlabelled data, particularly at larger dataset sizes., Conclusions: Because semi-supervised models use both labelled and unlabelled data sets, our findings are significant in showing that performance of certain predictive models using mixtures of unlabelled and labelled data is comparable to those using only labelled data with similar sample sizes, thus obviating the need for large sample sizes of labelled data., (Copyright © 2025. Published by Elsevier Inc.)

One of the major challenges in vascular tissue regeneration is effective wound healing that can be resolved by an innovative targeted nanoshuttle that delivers growth factors to blood vessels. This study investigates the production and efficacy of transforming growth factor-β1 (TGFβ1) gene delivery using poly(lactic- co -glycolic acid) (PLGA) baculovirus (BV) nanoshuttles (NSs). They exhibited an encapsulation efficiency of 86.23% ± 0.65% and a negative zeta potential of -29.57 ± 1.27 mV. In vitro studies in human umbilical vein endothelial cells (HUVECs) revealed that a 12 h incubation period optimized virus transduction. The safety and superior intracellular uptake of NSs and BVs in HUVECs were observed. The NSs carrying 100 and 400 MOI exhibited the highest cell proliferation rates in HUVECs. These sustained-release NSs significantly improved vascular cell migration and wound closure compared to free TGFβ1 carrying BV and can be a groundbreaking find in regenerative medicine, cardiovascular diseases, and chronic ulcer conditions., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Coronary stents have saved millions of lives in the last three decades by treating atherosclerosis especially, by preventing plaque protrusion and subsequent aneurysms. They attenuate the vascular SMC proliferation and promote reconstruction of the endothelial bed to ensure superior revascularization. With the evolution of modern stent types, nanotechnology has become an integral part of stent technology. Nanocoating and nanosurface fabrication on metallic and polymeric stents have improved their drug loading capacity as well as other mechanical, physico-chemical, and biological properties. Nanofeatures can mimic the natural nanofeatures of vascular tissue and control drug-delivery. This review will highlight the role of nanotechnology in addressing the challenges of coronary stents and the recent advancements in the field of related medical devices. Different generations of stents carrying nanoparticle-based formulations like liposomes, lipid-polymer hybrid NPs, polymeric micelles, and dendrimers are discussed highlighting their roles in local drug delivery and anti-restenotic properties. Drug nanoparticles like Paclitaxel embedded in metal stents are discussed as a feature of first-generation drug-eluting stents. Customized precision stents ensure safe delivery of nanoparticle-mediated genes or concerted transfer of gene, drug, and/or bioactive molecules like antibodies, gene mimics via nanofabricated stents. Nanotechnology can aid such therapies for drug delivery successfully due to its easy scale-up possibilities. However, limitations of this technology such as their potential cytotoxic effects associated with nanoparticle delivery that can trigger hypersensitivity reactions have also been discussed in this review. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies., (© 2024 The Authors. WIREs Nanomedicine and Nanobiotechnology published by Wiley Periodicals LLC.)

Reduction of right ventricular (RV) function after cardiac surgery has been shown to impact outcomes. Conventional indices for right ventricular dysfunction are validated using transthoracic echocardiogram (TTE) which has limited use compared to transesophageal echocardiogram (TEE) in the perioperative settings. The aim of this study was to assess the agreement of RV systolic function assessment with TEE compared to TTE and assess the association of echocardiographic parameter with hemodynamic indices of RV dysfunction. This was a single center prospective observational study in an academic institution. Fifty adult patients undergoing elective cardiac surgery were included. TTE, TEE and stroke volume measurements pre-cardiopulmonary bypass (CPB) and post-CPB were performed. The variables of interest were anatomical M-mode tricuspid annular plane systolic excursion (AMM-TAPSE), fractional area change (FAC), tricuspid annular velocity (S') and myocardial performance index (MPI). FAC and AMM-TAPSE measured at the mid-esophageal 4 chamber view had substantial agreement with the TTE acquired parameters (Lin's concordance correlation coefficient (CCC) = 0.76, 95%CI 0.59-0.86 and CCC = 0.85, 95%CI 0.76-0.91). S' was significantly underestimated by TEE (CCC = 0.07, 95%CI 0.04-0.19) and MPI showed moderate agreement (CCC = 0.45 95%CI 0.19-0.65). Despite the significant changes in echocardiographic parameters, there were no corresponding changes in stroke volume (SV) or pulmonary artery pulsatility index at the post-CPB period. TEE acquired FAC and AMM-TAPSE had substantial agreement with pre-operative TTE values and no significant differences between the pre-CPB and post-CPB period. Systolic RV echocardiographic parameters decreased post-CPB but this was not accompanied by significant hemodynamic changes., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Although the field of cardiac regeneration is relatively young, it is progressing rapidly with technological advancements. Genome editing tools are allowing researchers to creatively influence signaling pathways to be able to shed light on them and are important for addressing certain issues and limitations associated with in vitro and in vivo aspects of cardiac regeneration, such as imaging and immune rejection. In this chapter, the pathways involved in cardiac regeneration will be highlighted, and the role of gene-editing tools in endogenous and exogenous approaches to regenerate injured myocardium is discussed., (© 2023. The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.)

Background: The management of anticoagulation for mechanical heart valves during pregnancy poses a unique challenge. Mechanical valve thrombosis is a devastating complication for which surgery is often the treatment of choice. However, cardiac surgery for prosthetic valve dysfunction in pregnant patients confers a high risk of maternofetal morbidity and mortality., Case Summary: A 39-year-old woman in her first pregnancy at 30 weeks gestation presented to hospital with a mechanical mitral valve thrombosis despite therapeutic anticoagulation with low-molecular-weight heparin. She underwent an emergent caesarean section followed immediately by a bioprosthetic mitral valve replacement. This occurred after careful planning and organization on the part of a large multidisciplinary team., Discussion: A proactive, rather than reactive, approach to the surgical management of a mechanical valve thrombosis in pregnancy will maximize the chances of successful maternal and fetal outcomes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: This study sought to compare characteristics and outcomes of patients who underwent surgical aortic valve replacement (SAVR) after being referred to a heart team (HT), to those of patients referred directly for SAVR., Methods: An analysis of patients who underwent SAVR from 2015 to 2020 was conducted. Patients were categorized into 3 groups, as follows: (i) H-HT: patients referred to the HT from 2015 to 2017 (historical cohort); (ii) C-HT: patients referred to the HT from 2018 to 2020 (contemporary cohort); and (iii) No-HT: patients referred directly to cardiac surgery from 2018 to 2020. Two subanalyses were performed: H-HT vs C-HT patients, and C-HT vs No-HT patients. The primary outcome was a composite of in-hospital mortality, prolonged intubation, reoperation, sternal wound infection, and stroke., Results: This study consisted of 288 patients, distributed as follows: H-HT (n = 45); C-HT (n = 51); and No-HT (n = 192). The mean ages of H-HT, C-HT, and No-HT patients was 76.3 ± 6.9 years, 73.3 ± 7.6 years, and 69.6 ± 9.7 years, respectively ( P  = 0.0001). H-HT, C-HT, and No-HT patients had average Society of Thoracic Surgeons scores of 4.8 ± 2.2, 3.2 ± 1.6, and 4.2 ± 2 ( P  = 0.002), respectively. The composite outcome rate was more than 5 times higher among H-HT patients compared to that among the C-HT patients (20.0 vs 3.9%, P  = 0.02), and was numerically higher in No-HT compared to C-HT patients (13.0 vs 3.9%, P  = 0.07)., Conclusions: Referral to an HT appears to be primarily driven by higher chronological age rather than overall risk profile. Patients assessed by the HT prior to undergoing SAVR have a low incidence of complications, comparable to that among patients referred directly to cardiac surgery., (© 2022 The Authors.)