Search Results (36)

Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article

Transseptal puncture (TSP) is an essential step for left heart procedures that allows access to the left atrium (LA) through the fossa ovalis (FO) of the interatrial septum (IS). Initially developed for diagnostic purposes, today, it is performed for procedures that require large-bore device delivery systems and complex three-dimensional navigation in the left atrium. TSP supports various interventions, including atrial fibrillation ablation, left atrial appendage closure, and transcatheter mitral valve repair and replacement. While traditionally performed with Brockenbrough needles under fluoroscopic guidance, the integration of transesophageal and intracardiac echocardiography (TEE/ICE) has significantly improved its safety and precision. Despite its generally high success rate, TSP poses challenges in complex anatomies or for less experienced operators, with complications such as cardiac tamponade, aortic root puncture, and embolic events. Anatomical variations, such as thickened or floppy septa, further complicate the procedure. Technological advancements, including radiofrequency-based systems and specialized guidewires, have enhanced safety in difficult cases. Effective training, including echocardiography and complication management, is vital for operator proficiency. This review outlines the procedural steps for safe TSP, emphasizing proper equipment selection, anatomical considerations, and vascular access techniques. Common complications are discussed alongside management strategies. Advanced tools and techniques for addressing challenging scenarios are highlighted. Full article

Background/Objectives: Sepsis remains one of the most serious and possibly fatal complications encountered in intensive care units. Considering the frequent use of narcotic analgesics in this setting, we investigated whether the cardiovascular and peripheral and central inflammatory features of sepsis could be modified by morphine. Methods: Rats were instrumented with femoral and intracisternal (i.c.) indwelling catheters and sepsis was induced by cecal ligation and puncture (CLP). Results: The i.v. administration of morphine (3 and 10 mg/kg) significantly and dose-dependently aggravated septic manifestations of hypotension and impaired cardiac autonomic activity, as reflected by the reductions in indices of heart rate variability (HRV). Cardiac contractility (dP/dtmax) was also reduced by morphine in septic rats. The morphine effects were mostly eliminated following (i) blockade of μ-opioid receptors by i.v. naloxone and (ii) inhibition of central PI3K, MAPK-ERK, MAPK-JNK, NADPH oxidase (NADPHox), or Rho-kinase (ROCK) by i.c. wortmannin, PD98059, SP600125, diphenyleneiodonium, and fasudil, respectively. Further, these pharmacologic interventions significantly reduced the heightened protein expression of toll-like receptor 4 (TLR4) and monocyte chemoattractant protein-1 (MCP1) in brainstem rostral ventrolateral medullary (RVLM), but not cardiac, tissues of CLP/morphine-treated rats. Conclusions: Morphine worsens cardiovascular and autonomic disturbances caused by sepsis through a mechanism mediated via μ-opioid receptors and upregulated central inflammatory, chemotactic, and oxidative signals. Clinical studies are warranted to re-affirm the adverse cardiovascular interaction between opioids and the septic challenge. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

Background and Objectives: Although transesophageal or intracardiac echocardiography and radiofrequency needles are employed to guide transseptal puncture, their routine utilization is associated with substantial expense. No reports have analyzed the use of the foramen ovale position to effectively guide transseptal punctures on chest X-rays or computed tomography scout views, which are more cost-effective approaches to safely and effectively guide the procedure. We aimed to find the foramen ovale position on chest computed tomography scout views to effectively guide percutaneous transseptal punctures. Materials and Methods: The study population included 31 patients treated with extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, 32 patients diagnosed with atrial fibrillation (AF) who underwent MDCT, and 197 patients who underwent MDCT for non-cardiac conditions. Vertebral body units, defined as the distance between two adjacent vertebral bodies (the sixth and seventh thoracic spines) inclusive of the intervertebral disk space, were used to express the distance from the carina to the foramen ovale on computed tomography scout views. Results: The mean vertebral body units, distance from the carina to the foramen ovale (carina–foramen ovale), and distance from the carina to the foramen ovale on chest computed tomography scout views (carina–foramen ovale vertebral body units⁻¹) were 2.3 ± 0.2 cm, 6.9 ± 0.9 cm, and 3.0 ± 0.3, respectively. Multivariate analysis showed significant correlations between the carina–foramen ovale vertebral body units⁻¹ and sex (β = 0.080; p = 0.028), body mass index (β = −0.020; p < 0.001), age (β = 0; p = 0.013), and the application of extracorporeal membrane oxygenation or the presence of atrial fibrillation (β = 0.130; p = 0.004). Conclusions: Although a three-dimensional approach was not employed, the foramen ovale position may serve as a radiologic guide in various clinical settings where transseptal punctures are required. This technique may be an effective aid in transseptal puncture procedures. Full article

Background: Sepsis-induced cardiomyopathy (SIC) is a life-threatening cardiac complication of sepsis with limited therapeutic options. Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has demonstrated cardioprotective effects in heart failure, but its role in mitigating sepsis-related cardiac dysfunction remains unclear. Methods: A retrospective cohort analysis was conducted to assess the impact of pre-hospital dapagliflozin use on major adverse cardiovascular events (MACEs) and survival in patients with SIC. Additionally, a murine SIC model was established using cecal ligation and puncture (CLP) to evaluate the effects of dapagliflozin on cardiac function, histopathology, and biomarkers of myocardial injury. Transcriptomic and metabolomic profiling, combined with multi-omics integration, was employed to elucidate the molecular mechanisms underlying dapagliflozin’s cardioprotective effects. Results: In the clinical cohort, pre-hospital dapagliflozin use was associated with a significant reduction in the risk of MACE and improved survival outcomes. In the murine SIC model, dapagliflozin restored cardiac function, reduced biomarkers of myocardial injury, and alleviated histological damage. Multi-omics analysis revealed that dapagliflozin modulates inflammatory responses, enhances autophagy, and regulates metabolic pathways such as AMPK signaling and lipid metabolism. Key regulatory genes and metabolites were identified, providing mechanistic insights into the underlying actions of dapagliflozin. Conclusions: Dapagliflozin significantly improves cardiac outcomes in sepsis-induced cardiomyopathy through the multi-level regulation of inflammation, energy metabolism, and cellular survival pathways. These findings establish dapagliflozin as a promising therapeutic strategy for SIC, offering translational insights into the treatment of sepsis-induced cardiac dysfunction. Full article

(1) Background: Ultrasound-guided axillary (USAX) vein puncture is a relatively new method to obtain venous access for the implantation of cardiac implantable electronic devices (CIED). However, its use is limited as most of the operators are not familiar with this technique. Our aim was to investigate the safety and efficacy of the USAX compared with the traditional cephalic vein dissection for venous access in CIED implantation. (2) Methods: This was a single-center, randomized, controlled, superiority trial. A total of 114 patients were randomized (1:1 ratio) to either USAX (u/s axillary group; 59 patients) or cephalic vein access (cephalic group; 55 patients). The primary study endpoint was defined as successful placement of all leads via the chosen access. Secondary study endpoints included time from local anesthetic injection to lead advancement in the SVC, total procedure time (skin to skin), procedure-related complications and pain perception. (3) Results: USAX was superior to cephalic access in terms of primary endpoint (OR: 4.3, 95% CI: 1.3, 14.0; p = 0.012). Total procedure duration was higher in the cephalic group (55.15 ± 16.62 vs. 48.35 ± 12.81 min, p = 0.017) but there was neither a significant difference in fluoroscopy time (p = 0.872) nor in total radiation dose (p = 0.815). The level of pain was higher in the cephalic group (p = 0.016), while the rates of complications were similar in both groups (p > 0.05). (4) Conclusion: USAX was superior to cephalic access regarding success rate, total procedure duration and level of pain, while having no difference in complication rates. Full article

Analysis of the white blood cell differential as part of a flow cytometry-based approach is a common routine diagnostic tool used in clinics and research. For human blood, the methodological approach, suitable markers, and gating strategies are well-established. However, there is a lack of information regarding the mouse blood count. In this article, we deliver a fast and easy protocol for reprocessing mouse blood for the purpose of flow cytometric analysis, as well as suitable markers and gating strategies. We also present two possible applications: for the analysis of the whole blood count, with blood from a cardiac puncture, and for the analysis of a certain leukocyte subset at multiple time points in the framework of a mouse experiment, using blood from the facial vein. Additionally, we provide orientation values by applying the method to 3-month-old and 24-month-old male and female C57BL/6J mice. Our analyses demonstrate differences in the leukocyte fractions depending on age and sex. We discuss the influencing factors and limitations that can affect the results and that, therefore, need to be considered when applying this method. The present study fills the gap in the knowledge related to the rare information on flow cytometric analysis of mouse blood and, thus, lays the foundation for further investigations in this area. Full article

Background: Percutaneous left-atrial appendage closure (LAAC) is an established method for preventing strokes in patients with atrial fibrillation, offering an alternative to oral anticoagulation. Various occluder devices have been developed to cater to individual anatomical needs and ensure a safe and effective procedure. In this retrospective, monocentric cohort study, we compare different LAAO devices with respect to clinical outcomes, LAA sealing properties, and device-related complications. Methods: We conducted a retrospective analysis of 270 patients who underwent percutaneous LAA closure in our center between 2009 and 2023. Patient data were extracted from medical records, including gender, age at implantation, indication, device type and size, laboratory values, LAA anatomy, periprocedural complications, ECG parameters, transthoracic and transesophageal echocardiography parameters (TTE and TEE), as well as medication at discharge. Moreover, fluoroscopy time and implantation duration, as well as post-implantation clinical events up to 1 year, were collected. Endpoints were bleeding events, recurrent stroke, thrombi on devices, and death. Results: The implanted devices were the Watchman 2.5, Watchman FLX, Amplatzer Cardiac Plug (ACP), and Amulet. The procedural success rate was 95.7% (n = 265), with cactus anatomy posing the most challenges across all devices. The mean patient age was 75.5 ± 7.7 years, with 64.5% being male. The median CHA2DS2-VASc score was 4.8 ± 1.5 and the median HAS-BLED score was 3.8 ± 1.0. Indications for LAA closure included past bleeding events and elevated bleeding risk. Periprocedural complications were most commonly bleeding at the puncture site, particularly after ACP implantation (p = 0.014). Significant peridevice leaks (PDL) were observed in 21.4% of simple sealing mechanism devices versus 0% in double sealing mechanism devices (p = 0.004). Thrombi were detected on devices in six patients, with no subsequent ischemic stroke or thromboembolic event. Comparative analysis revealed no significant differences in the occurrence of stroke, transient ischemic attack (TIA), thromboembolic events, device-related thrombi, or mortality among different device types. A 62.3% relative risk reduction in thromboembolic events and 38.6% in major bleedings could be observed over 568.2 patient years. Conclusions: In summary, our study highlights the efficacy and safety of LAA closure using various occluder devices despite anatomical challenges. Our long-term follow-up findings support LAA closure as a promising option for stroke prevention in selected patient cohorts. Further research is needed to refine patient selection criteria and optimize outcomes in LAA closure procedures. Full article

Background: Cephalic vein cutdown (CVC) and subclavian vein puncture (SVP) are the most commonly used access sites for transvenous lead placement of cardiac implantable electronic devices (CIEDs). Limited knowledge exists about the long-term patency of the vascular lumen housing the leads. Methods: Among the 2703 patients who underwent CIED procedures between 2005 and 2013, we evaluated the phlebographies of 162 patients scheduled for an elective CIED replacement (median of 6.4 years after the first operation). The phlebographies were divided into four stenosis types: Type I = 0%, Type II = 1–69%, Type III = 70–99%, and Type IV = occlusion. Due to the fact that no standardized stenosis categorization exists, experienced physicians in consensus with the involved team made the applied distribution. The primary endpoint was the occurrence of stenosis Type III or IV in the CVC group and in the SVP group. Results: In total, 162 patients with venography were enrolled in this study. The prevalence of high-degree stenosis was significantly lower in the CVC group (7/89, 7.8%) than in the SVP group (15/73, 20.5%, p = 0.023). In the CVC group, venographies showed a lower median stenosis (33%) than in the SVP group (median 42%). Conclusions: The present study showed that the long-term patency of the subclavian vein is higher after CVC than after SVP for venous access in patients with CIED. Full article

Targeted delivery of therapeutics specifically to cardiomyocytes would open up new frontiers for common conditions like heart failure. Our prior work using a phage display methodology identified a 12-amino-acid-long peptide that selectively targets cardiomyocytes after an intravenous injection in as little as 5 min and was hence termed a cardiac-targeting peptide (CTP: APWHLSSQYSRT). CTP has been used to deliver imaging agents, small drug molecules, photosensitizing nanoparticles, exosomes, and even miRNA to cardiomyocytes. As a natural extension to the development of CTP as a clinically viable cardiac vector, we now present toxicity studies performed with the peptide. In vitro viability studies were performed in a human left ventricular myocyte cell line with 10 µM of Cyanine-5.5-labeled CTP (CTP-Cy5.5). In vitro ion channel profiles were completed for CTP followed by extensive studies in stably transfected cell lines for several GPCR-coupled receptors. Positive data for GPCR-coupled receptors were interrogated further with RT-qPCRs performed on mouse heart tissue. In vivo studies consisted of pre- and post-blood pressure monitoring acutely after a single CTP (10 mg/Kg) injection. Further in vivo toxicity studies consisted of injecting CTP (150 µg/Kg) in 60, 6-week-old, wild-type CD1, male/female mice (1:1), with cohorts of mice euthanized on days 0, 1, 2, 7, and 14 with inhalational CO₂, followed by blood collection via cardiac puncture, complete blood count analysis, metabolic profiling, and finally, liver, renal, and thyroid studies. Lastly, mouse cardiac MRI was performed immediately before and after CTP (150 µg/Kg) injection to assess changes in cardiac size or function. Human left ventricular cardiomyocytes showed no decrease in viability after a 30 min incubation with CTP-Cy5.5. No significant activation or inhibition of any of seventy-eight protein channels was observed other than OPRM1 and COX2 at the highest tested concentration, neither of which were expressed in mouse heart tissue as assessed using RT-qPCR. CTP (10 mg/Kg) injections led to no change in blood pressure. Blood counts and chemistries showed no evidence of significant hematological, hepatic, or renal toxicities. Lastly, there was no difference in cardiac function, size, or mass acutely in response to CTP injections. Our studies with CTP showed no activation or inhibition of GPCR-associated receptors in vitro. We found no signals indicative of toxicity in vivo. Most importantly, cardiac functions remained unchanged acutely in response to CTP uptake. Further studies using good laboratory practices are needed with prolonged, chronic administration of CTP conjugated to a specific cargo of choice before human studies can be contemplated. Full article

Atrial septal defect (ASD) represents the most common congenital heart defect identified in adulthood. Atrial and ventricular geometric remodeling due to intracardiac shunt increase the risk of arrhythmias, especially atrial fibrillation (AF). Clinical, echocardiography, electrocardiogram, and device-related predictors may be used to assess the risk of atrial arrhythmias after ASD closure. The underlying mechanisms in these patients are complex and at least in part independent of the structural remodeling secondary to hemodynamic overload. Device closure of the ASD itself and its timing impact future arrhythmia risk, as well as posing a challenge for when transseptal puncture is required. Sudden cardiac death (SCD) risk is higher than in the general population and an implantable cardioverter-defibrillator (ICD) may be indicated in selected cases. Full article

Although ultrasound-guided axillary vein access (USGAVA) has proven to be a highly effective and safe method for cardiac electronic implantable device (CIED) lead placement, the collapsibility of the axillary vein (AV) during tidal breathing can lead to narrowing or complete collapse, posing a challenge for successful vein puncture and cannulation. We investigated the potential of the Valsalva maneuver (Vm) as a facilitating technique for USGAVA in this context. Out of 148 patients undergoing CIED implantation via USGAVA, 41 were asked to perform the Vm, because they were considered unsuitable for venipuncture due to a narrower AV diameter, as assessed by ultrasound (2.7 ± 1.7 mm vs. 9.1 ± 3.3 mm, p < 0.0001). Among them, 37 patients were able to perform the Vm correctly. Overall, the Vm resulted in an average increase in the AV diameter of 4.9 ± 3.4 mm (p < 0.001). USGAVA performed during the Vm was successful in 30 patients (81%), and no Vm-related complications were observed during the 30-day follow-up. In patients with unsuccessful USGAVA, the Vm resulted in a notably smaller increase in AV diameter (0.5 ± 0.3 mm vs. 6.0 ± 2.8 mm, p < 0.0001) compared to patients who achieved successful USGAVA, while performing the Vm. Therefore, the Vm is a feasible maneuver to enhance AV diameter and the success rate of USGAVA in most patients undergoing CIED implantation while maintaining safety. Full article

Polyherbal formulation (PHF) enhances therapeutic efficacy and minimizes side effects by reducing individual herb dosages. Allopolyherbal formulation (APHF) combines polyherbal extracts with allopathic medication, effectively reducing the latter’s required dose and mitigating associated adverse effects. The current study intends to assess the anti-diabetic effects of PHF and APHF in-vivo. Dried raw powders of Cassia auriculata leaf, Centella asiatica leaf, and Zingiber officinale rhizome were extracted by cold maceration process using 70% ethanol. These extracts were combined in three different ratios to make PHF. PHF was subjected to qualitative and quantitative phytochemical investigations. APHF has been prepared by combining a potent ratio of PHF with metformin in three different ratios. The compatibility of APHF has been confirmed by differential scanning calorimetry (DSC). In vivo activity was also evaluated in streptozotocin-induced diabetic albino rats. PHF (3 different ratios at a dose of 200–400 mg/kg b.w), APHF (combination of PHF and metformin in 3 different ratios, 200 + 22.5, 200 + 45, and 200 + 67.5 mg/kg b.w), and metformin (90 mg/kg b.w) were administered to albino rats for 21 consecutive days. Blood glucose levels were estimated on the 1st, 7th, 14th, and 21st days of treatment. On the 21st day, blood was collected by cardiac puncture for biochemical analysis. The liver and pancreas were isolated and subjected to histopathological analysis. PHF and APHF showed significant anti-diabetic and antihyperlipidemic efficacy. In comparison to PHF, APHF had the most promising action. The current study demonstrated that PHF and APHF are safe and efficacious drugs in the treatment of diabetes mellitus as they help to replace or lower the dose of metformin, thereby decreasing the risks of metformin. Full article

Leukocyte–platelet-rich fibrin (L-PRF) contains growth factors that stimulate bone regeneration. This study evaluated the bone repair in a tibia rat model around two implant surfaces in combination or not with L-PRF by assessing microtomographic and histomorphometric parameters. A total of 48 female rats were used in the study, in which 24 received implants with two types of surface treatments (dual acid etched—DAE or nanohydroxyapatite—nanoHA), and the other 24 received the same mini implants with L-PRF, which was collected by cardiac puncture, centrifugated, and inserted in the bone bed. The animals were euthanized 7 and 30 days after implant placement, and the retrieved samples were prepared for microtomographic and histomorphometric (bone-to-implant contact—BIC; and Bone Area Fraction Occupancy—BAFO) analyses. The adhesion of the nanoHA surface onto the implant surface was investigated by insertion and removal in simulated bone medium (Sawbones). The adhesion evaluation revealed that the loss of nanoHA after this procedure (as measured with SEM) from the implant surface was less than 1%. Overall, the nanoHA surface presented more bone in contact and in proximity to the implant, a higher bone surface/tissue volume fraction, a higher number of bone trabeculae, as well as trabecular separation relative to the DAE surface. Such results were more evident when the nanoHA surface was combined with L-PRF and after 30 days in vivo. The nanoHA surface presented higher BAFO when compared to DAE, with or without association with L-PRF. Therefore, implants with a nanoHA surface potentially benefit from the association to L-PRF. Full article