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Acta Paediatr. 2022 Dec 25. doi: 10.1111/apa.16646. Online ahead of print.

ABSTRACT

AIM: Our aim was to evaluate cardiovascular risk profile in 42 children with kidney transplants (KT) at the Queen Silvia Children's Hospital, Gothenburg Sweden.

METHODS: Forty-two children (7.1-18 years) with KT, time from transplantation 3.5 (0.9-13) years, were examined at inclusion and annually for three consecutive years. Eighteen matched controls were examined once. Cardiovascular phenotyping included ultra-high frequency ultrasound (UHFUS), pulse wave velocity (PWV) and endothelial function.

RESULTS: Children with KT had higher body mass index (BMI) z-score and blood pressure (BP) z-score than healthy controls (BMI z-score: 0.4 ±1.0 and -0.2 ± 0.9, respectively, p=0.02; SBP z-score: 0.5 ± 0.9 and -0.8 ± 0.7; DBP z-score: 0.7 ± 0.7 and -0.3 ± 0.5, respectively, p<0.001). BP z-score decreased significantly over three years, other vascular markers remained unchanged. PWV and Carotid intima thickness (IT) was higher in children with KT compared to healthy controls. Children with preemptive KT had lower radial IT and dorsal pedal media thickness (MT) compared to children with preceding dialysis.

CONCLUSION: Children with KT show increased cardiovascular risk parameters, not increasing over time. Children on dialysis before KT have more pronounced vascular changes than those with preemptive KT, suggesting preemptive transplantation more beneficial for cardiovascular health.

PMID:36567640 | DOI:10.1111/apa.16646

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2022 Dec;34(12):1280-1284. doi: 10.3760/cma.j.cn121430-20220411-00355.

ABSTRACT

OBJECTIVE: To explore the effects and the possible mechanism of bone marrow mesenchymal stem cell (BMMSC) transplantation on apoptosis in rats cerebral cortex after cardiac arrest/cardiopulmonary resuscitation (CA/CPR).

METHODS: The BMMSC of 2 Sprague-Dawley (SD) rats aged 4-5weeks was extracted, and the 3rd passage was used in experimental study. Eighteen Sprague-Dawley (SD) rats were divided into sham group, model group (CA/CPR group) and intervention group (BMMSC group) according to random number table method, with 6 rats in each group. CPR was performed 6 minutes after asphyxia induced CA. In sham group, CA was not induced except performing general surgical procedure. At 1 hour after return of spontaneous circulation (ROSC), 0.5 mL phosphate buffered saline (PBS) was injected through tail vein in CA/CPR group. 2×109/L green fluorescence protein (GFP)-labeled BMMSC was injected through tail vein 1 hour after ROSC in BMMSC group. Neurological deficit score (NDS) were assessed in every group at 72 hours after CPR. Serum S100 calcium binding protein B (S100B) levels were assayed by enzyme linked immunosorbent assay (ELISA). Distribution of BMMSC in brain was observed under a fluorescent microscope. Apoptosis rate in cerebral cortex was assayed by TdT-mediated dUTP nick-end labeling (TUNEL). Western blotting was performed to measure the expression levels of active aspartic acid specific cysteine proteinase (caspase-8 and caspase-9) in cerebral cortex.

RESULTS: At 3 days after CPR, compared with sham group, the apoptosis of cerebral cortex cells was increased and brain damage was obvious, NDS score was decreased significantly (56.6±5.5 vs. 80.0±0.0, P < 0.05), and serum S100B was increased markedly (ng/L: 45.1±4.7 vs. 19.1±1.4, P < 0.05), apoptosis rate of cerebral cortex cells increased significantly [(52.9±11.8)% vs. (10.1±1.5)%, P < 0.05], the level of active caspase-8 expression in cerebral cortex was significantly higher (caspase-8/GAPDH: 0.689±0.047 vs. 0.330±0.108, P < 0.05), and there was no significant difference in active caspase-9 protein expression (caspase-9/GAPDH: 0.428±0.014 vs. 0.426±0.021, P > 0.05) in CA/CPR group. After BMMSC transplantation, GFP-labeled BMMSC were primarily detected in cerebral cortex, compared with CA/CPR group, the apoptosis of cerebral cortex cells and brain injury were significantly improved in BMMSC group, NDS score increased significantly (70.6±2.1 vs. 56.6±5.5, P < 0.05), serum S100B levels in BMMSC group were lower (ng/L: 32.0±3.2 vs. 45.1±4.7, P < 0.05), apoptosis rate of cerebral cortex cells decreased significantly [(31.1±3.4)% vs. (52.9±11.8)%, P < 0.05], and the active caspase-8 expression in cerebral cortex in BMMSC group was significantly decreased (caspase-8/GAPDH: 0.427±0.067 vs. 0.689±0.047, P < 0.05). The active caspase-9 expression in cerebral cortex in BMMSC group and CA/CPR group were not significantly different (caspase-9/GAPDH: 0.431±0.022 vs. 0.428±0.014, P > 0.05).

CONCLUSIONS: BMMSC transplantation can alleviate rat brain damage after CA/CPR possibly by inhibiting the death receptor mediated apoptotic pathway to inhibit the apoptosis of brain cells.

PMID:36567583 | DOI:10.3760/cma.j.cn121430-20220411-00355

Innovations (Phila). 2022 Dec 26:15569845221138268. doi: 10.1177/15569845221138268. Online ahead of print.

ABSTRACT

Single-ventricular cardiopathies are challenging conditions requiring multiple surgical interventions to hopefully achieve adulthood. In neonates, pulmonary artery banding allows ventricular adaptation and pulmonary vascular bed protection. Here we present a novel minimally invasive approach to pulmonary artery banding through a 1.5 cm left parasternal minithoracotomy. This technique not only allows for a less traumatic first procedure but also a less manipulated mediastinum and untouched sternum for the consequent surgeries to come. This technique is reproducible in experienced hands and shows favorable and promising results when performed properly.

PMID:36571265 | DOI:10.1177/15569845221138268

Cureus. 2022 Nov 21;14(11):e31747. doi: 10.7759/cureus.31747. eCollection 2022 Nov.

ABSTRACT

INTRODUCTION: Infective endocarditis (IE) is a rare disease with high mortality and morbidity. In recent years, an increase in the frequency of infective endocarditis has been observed due to the increase in the survival of cases with congenital heart diseases (CHDs) and the use of central catheters. In addition to revealing the incidence of IE in our clinic, this study aimed to evaluate the demographic characteristics, predisposing factors, clinical, laboratory, microbiological, and echocardiographic findings, and the complications of follow-up of our patients diagnosed with IE in light of the literature.

MATERIAL AND METHODS: Thirteen patients with IE who were hospitalized in Pediatric Cardiology Clinic, Pamukkale University Medical Faculty Hospital between January 2016 and August 2021 were retrospectively reviewed. The patients included in the study were evaluated in terms of demographic characteristics, predisposing factors, clinical, laboratory and microbiological findings, echocardiography data, surgical intervention needs, and complications. The incidence of IE in our clinic was defined as the rate of IE among patients admitted to the hospital and reported as the number of patients with IE per 100,000 hospital admissions.

RESULTS: The median age of these 13 patients was 11 (7-14) years, and the male/female ratio was 6/7. The five-year IE incidence in Pediatric Cardiology Clinic, Pamukkale University Medical Faculty Hospital, was found to be 2.5 in approximately 100,000 hospital admissions. A predisposing factor was detected in all patients. Six patients (46%) had CHDs, and four patients (31%) had acquired heart disease. The other three (23%) patients were receiving immunosuppressive therapy, and these patients had long-term port catheters. Eight (62%) patients had positive blood cultures. Streptococcus viridans, Streptococcus gordonii, Staphylococcus aureus, coagulase-negativeStaphylococcus, Brucella spp, and Candida albicans were isolated in the blood cultures of these patients. IE-related complications developed in seven (54%) patients. Five (38%) had heart failure, three patients (23%) had thromboembolic events, two (15%) had glomerulonephritis, and one (8%) had thrombophlebitis. Four patients were referred to early surgery. Two patients with recurrent IE attacks were referred to surgery after their treatment was completed.

CONCLUSION: The incidence of IE has shown an increase recently with increased rates of survival attributable to corrective surgeries performed for congenital heart diseases, increased prosthetic materials used in cardiac surgeries, and increased use of permanent catheters. In our study, the incidence of IE was found to be 2.5 in 100,000 hospital admissions. Our results have shown that rheumatic heart diseases, besides CHDs, are still an important risk factor for Turkey. Due to the low number of cases in IE studies in the pediatric population, there is a need for further studies to be conducted in large series in this field.

PMID:36569694 | PMC:PMC9770546 | DOI:10.7759/cureus.31747

Front Cell Dev Biol. 2022 Dec 7;10:1030587. doi: 10.3389/fcell.2022.1030587. eCollection 2022.

ABSTRACT

Congenital heart defects occur in almost 80% of patients with CHARGE syndrome, a sporadically occurring disease causing craniofacial and other abnormalities due to mutations in the CHD7 gene. Animal models have been generated to mimic CHARGE syndrome; however, heart defects are not extensively described in zebrafish disease models of CHARGE using morpholino injections or genetic mutants. Here, we describe the co-occurrence of craniofacial abnormalities and heart defects in zebrafish chd7 mutants. These mutant phenotypes are enhanced in the maternal zygotic mutant background. In the chd7 mutant fish, we found shortened craniofacial cartilages and extra cartilage formation. Furthermore, the length of the ventral aorta is altered in chd7 mutants. Many CHARGE patients have aortic arch anomalies. It should be noted that the aberrant branching of the first branchial arch artery is observed for the first time in chd7 fish mutants. To understand the cellular mechanism of CHARGE syndrome, neural crest cells (NCCs), that contribute to craniofacial and cardiovascular tissues, are examined using sox10:Cre lineage tracing. In contrast to its function in cranial NCCs, we found that the cardiac NCC-derived mural cells along the ventral aorta and aortic arch arteries are not affected in chd7 mutant fish. The chd7 fish mutants we generated recapitulate some of the craniofacial and cardiovascular phenotypes found in CHARGE patients and can be used to further determine the roles of CHD7.

PMID:36568983 | PMC:PMC9768498 | DOI:10.3389/fcell.2022.1030587

Front Pediatr. 2022 Dec 7;10:1040128. doi: 10.3389/fped.2022.1040128. eCollection 2022.

ABSTRACT

BACKGROUND: Although acquired von Willebrand syndrome (aVWS) has been described in congenital heart disease before, anatomical features leading to aVWS with characteristic reduction or loss of high molecular weight von Willebrand multimers (HMWM) are not well known. This study assesses the prevalence and effects of aVWS in infants with systemic-to-pulmonary shunts (SPS).

METHODS: This retrospective single-center study analyzes diagnostic data of infants with complex congenital heart defects requiring palliation with SPS. During the study period between 12/15-01/17 fifteen consecutive patients were eligible for analysis. Results of von Willebrand factor antigen (VWF:Ag), collagen binding activity (VWF:CB) and von Willebrand factor multimer analysis were included.

RESULTS: In all 15 patients with SPS an aVWS could be found. Blood samples were collected between 5 and 257 days after shunt implantation (median 64 days). None of the patients demonstrated increased bleeding in everyday life. However, 6 out of 15 patients (40%) showed postoperative bleeding complications after SPS implantation. Following shunt excision multimeric pattern normalized in 8 of 10 (80%) patients studied.

CONCLUSIONS: This study shows that in patients undergoing SPS implantation aVWS might emerge. Pathogenesis can be explained by shear stress resulting from turbulent flow within the shunt. Knowledge of aVWS existence is important for the consideration of replacement therapy with von Willebrand factor containing products and antifibrinolytic treatment in bleeding situations. Implementation of methods for rapid aVWS detection is required to achieve differentiated hemostatic therapy and reduce the risk of complications caused by empiric replacement therapy.

PMID:36568413 | PMC:PMC9768211 | DOI:10.3389/fped.2022.1040128

J Tehran Heart Cent. 2022 Apr;17(2):71-74. doi: 10.18502/jthc.v17i2.9842.

ABSTRACT

Congenital anomalous coronary arteries (CACAs) comprise an important variant of the coronary vasculature. They are benign in the vast majority of cases, whereas a small minority may be affected by serious consequences such as myocardial infarction, arrhythmia, cardiac arrest, and even death. We herein describe a 62-year-old man with sudden and severe substernal chest pain; Q waves in electrocardiographic leads II, III, and aVF; and positive serum troponin I enzyme. Left heart cardiac catheterization revealed triple coronary vessel disease with a 60% to 70% occlusion in the left main coronary artery (LMCA). The left anterior descending (LAD) and the left circumflex artery arose from the ostium of the right coronary artery. Additionally, a rudimentary type IV dual LAD originated from the LMCA. A coronary artery bypass graft surgery was performed using a left internal mammary artery graft for the LAD and a saphenous vein graft for the diagonal branches (I & II) of the LAD and the posterior descending artery. The patient was discharged after an uneventful 1-week hospital course.

PMID:36567935 | PMC:PMC9748230 | DOI:10.18502/jthc.v17i2.9842

Gac Med Mex. 2022;158(5):323-327. doi: 10.24875/GMM.M22000702.

ABSTRACT

Functional mitral regurgitation (FMR) is the result of three-dimensional structural disruption of the mitral valve due to left ventricular dysfunction. The "edge-to-edge" surgical technique has given rise to the percutaneous transcatheter edge-to-edge repair (TEER) technique to treat FMR; however, the lack of a mitral annuloplasty ring makes TEER only partially effective, with uncertain long-term results. The MITRA-FR and COAPT trials, on which current TEER recommendations are based, show conflicting results. COAPT results possible bias has influenced current recommendations issued by clinical practice guidelines in favor of TEER in FMR.

PMID:36572051 | DOI:10.24875/GMM.M22000702

Am Surg. 2022 Dec 26:31348221148357. doi: 10.1177/00031348221148357. Online ahead of print.

ABSTRACT

Structural cardiac injury after blunt trauma is uncommon but usually life-threatening. While tricuspid injury is very rare and potentially lethal, the right heart can accommodate larger volumes and higher pressures in acute tricuspid insufficiency and facilitate initial stabilization prior to definitive valvular repair. ECMO may be used to ameliorate resulting right heart failure. The traumatic force required to cause cardiac structural injury is also associated with pulmonary complications related to pneumothorax, hemothorax, effusion, acute pain secondary to rib fractures, and pulmonary contusions causing hypoxia. We present an unusual case of hypoxia in a trauma patient caused by acute tricuspid regurgitation with pre-existing patent foramen ovale.

PMID:36571144 | DOI:10.1177/00031348221148357

J Tehran Heart Cent. 2022 Apr;17(2):78-81. doi: 10.18502/jthc.v17i2.9845.

ABSTRACT

Injuries to the heart and great vessels should always be considered after blunt chest trauma. Valvular damage rarely occurs after blunt trauma, but symptoms may be delayed. A 58-year-old woman was referred to our hospital with exertional dyspnea (functional class III) and palpitations for elective transesophageal echocardiography. Her symptoms had exacerbated in the preceding 2 or 3 months. Physical examination showed holosystolic murmurs (IV/VI) at the lower sternal border with extension to the apex. Transesophageal echocardiography revealed avulsion of the base of the posterior mitral valve leaflet (P3) from the annulus. In the past medical history, there was a history of a motor vehicle accident 9 months earlier. The patient was recommended for mitral valve surgery. Mitral valve replacement was performed, and the diagnosis was confirmed by surgery. The patient was discharged without any complications.

PMID:36567937 | PMC:PMC9748236 | DOI:10.18502/jthc.v17i2.9845

Hellenic J Cardiol. 2022 Dec 22:S1109-9666(22)00182-8. doi: 10.1016/j.hjc.2022.12.008. Online ahead of print.

ABSTRACT

BACKGROUND: Myocardial perfusion scintigraphy (MPS) is an established diagnostic technique for inducible ischemia in patients with suspected chronic coronary syndrome (CCS). Some MPS findings, most notably an ischemia extent>10% of the left ventricle (LV), hold prognostic significance and support maximization of anti-ischemic treatment. We aimed to assess sex-specific associations of MPS findings with cardiovascular (CV) events in a population at high risk of CCS.

METHODS: In a prospective cohort study, 1,229 consecutive patients (age 70±9.5 years, 73.5% males) without known CCS were referred to stress-rest MPS. All patients were followed for a median of 4.6 years for CV events.

RESULTS: Men and women had comparable risk profile and incidence rate of CV events (6.6% vs 4.6% respectively, P=0.186). A summed stress score (SSS) >7 was associated with the primary endpoint including CV death and/or non-fatal myocardial infarction (MI) (adjusted hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.79-5.46; P=0.001), all-cause mortality (HR, 3.01; 95% CI, 1.31-6.93; P=0.01) and incidence of late revascularization (HR, 1.84; 95% CI, 1.22-2.78; P=0.004) in men but not women. Summed difference score (SDS) >6 was related to higher rate of the primary endpoint only in men (adjusted HR, 1.97; 95% CI, 1.18-3.30; P=0.009).

CONCLUSIONS: Among patients undergoing a diagnostic workup for suspected CCS, stress perfusion and reversible ischemia abnormalities may independently predict worse survival and more CV events in men. However, the obtained results indicated the need of sex-specific cut-offs to refine risk stratification and assist in clinical decisions on anti-ischemic therapy beyond coronary artery anatomy.

PMID:36566838 | DOI:10.1016/j.hjc.2022.12.008

J Ayub Med Coll Abbottabad. 2022 Oct-Dec;34(4):771-777. doi: 10.55519/JAMC-04-10733.

ABSTRACT

BACKGROUND: Contrast induced nephropathy (CIN) is a common complication seen after primary percutaneous coronary intervention (PCI) which can contribute to increased morbidity and mortality in patients of acute ST elevation myocardial infarction (STEMI). Aim of this study was to validate the TIMI Risk Index (TRI) for the risk stratification of CIN in patients undergone primary PCI.

METHODS: Consecutive patients of STEMI undergone primary PCI at a tertiary care cardiac center were included for this study. Patients in Killip class IV at presentation, patients with history of any PCI and chronic kidney diseases were excluded from this study. TRI was calculated using the formula " " and post-procedure serum creatinine level increase of either 25% or 0.5 mg/dL was taken as CIN.

RESULTS: A total of 507 patients were included in this study out of which 82.2% were males and 17.8% were females. In total 8.7% (44) patients developed CIN. In the receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) for TRI was found to be 0.717, [0.649-0.758] for the prediction of CIN. Sensitive, specificity, positive predictive value and negative predictive value of TRI >22.8 to predict the development of CIN were 59.09%, 76.69%, 19.55% and 95.19% respectively.

CONCLUSIONS: TIMI risk index is and easy to calculate and readily accessible score which has good predictive value to evaluate the risk of CIN in primary PCI setting.

PMID:36566397 | DOI:10.55519/JAMC-04-10733

Mol Cell Biochem. 2022 Dec 25. doi: 10.1007/s11010-022-04628-5. Online ahead of print.

ABSTRACT

Myocardial infarction (MI) damages cardiomyocytes permanently and compromises cardiac function. Mesenchymal stem cells (MSCs) with the potential to differentiate into multiple lineages are considered as one of the best options for the treatment of MI. However, aging affects their regeneration capability. With age, reactive oxygen species (ROS) accumulate in cells ultimately causing cell death. To successfully utilize these stem cells in clinic, novel strategies to improve their functional capability should be explored. In this study, we aimed to enhance the cardiac regeneration potential of bone marrow MSCs derived from aging rats by treating them with antioxidants, rutin or quercetagetin in separate in vivo experiments. Oxidative stress was induced by treating MSCs of young and aging rats with different concentrations of H2O2 which resulted in an increase in the ROS level. MSCs were treated with rutin or quercetagetin at varying concentrations and exposed to H2O2. It was observed that both antioxidants significantly (P < 0.001) suppressed H2O2-induced intracellular ROS accumulation in a dose-dependent manner. An optimized concentration of 10 µM rutin or quercetagetin was used for the in vivo experiments. MI models were developed in aging rats by ligation of left anterior descending artery and treated MSCs were transplanted in the MI models. Echocardiography was performed after 2 and 4 weeks of cell transplantation to evaluate the functional status of the infarcted heart and histological analysis was performed after 4 weeks to assess cardiac regeneration. Significant improvement was observed in cardiac parameters including LVEF% (P < 0.001), LVFS% (P < 0.01 and P < 0.001), LVIDd (P < 0.01 and P < 0.001), LVIDs (P < 0.001), LVEDV (P < 0.001) and LVESV (P < 0.001) in the treated young as well as aging MSCs. It is concluded from these findings that rutin and quercetagetin treatment enhance the regeneration efficiency of young and aging MSCs in vivo. These antioxidants can be effectively utilized to improve cellular therapy for myocardial infarction by suppressing ROS production.

PMID:36566485 | DOI:10.1007/s11010-022-04628-5

Adv Sci (Weinh). 2022 Dec 25:e2204999. doi: 10.1002/advs.202204999. Online ahead of print.

ABSTRACT

Myocardial infarction (MI) is the leading cause of death worldwide and can lead to the loss of cardiac function and heart failure. Reactive oxygen species (ROS) play a key role in the pathological progression of MI. The levels and effects of ROS are significantly different in three unique pathological stages of MI, and most antioxidants cannot make corresponding adjustments to eliminate ROS, which leads to a great compromise to treat MI with antioxidants. Herein, an innovative self-sustaining antioxidant strategy is developed to treat MI with self-sustaining selenium-embedded nanoparticles (SSSe NPs). SSSe NPs possess unique self-sustaining antioxidant effects at different pathological stages of MI. This strategy of on-demand ROS elimination during different pathological stages demonstrated excellent MI treatment efficacy and effectively reversed heart failure to normal heart function. The therapeutic mechanism of SSSe NPs is intensively investigated through a series of experiments and mainly involved five critical aspects of myocardial repair: protecting mitochondria, reducing cardiomyocyte apoptosis and ferroptosis, reducing inflammation and fibrosis, and promoting angiogenesis. This strategy not only provides a promising treatment option for MI but also offers inspiration for other ischemic diseases.

PMID:36567266 | DOI:10.1002/advs.202204999

J Electrocardiol. 2022 Dec 17;77:23-28. doi: 10.1016/j.jelectrocard.2022.11.010. Online ahead of print.

ABSTRACT

BACKGROUND: Several wearable, medical-grade consumer ECG devices are now available and integrated into consumer electronics like multi sensor fitness watches and scales. Specific consumer ECGs can also come in the form of patches or thin sensor plates in credit card or other shapes. Watches with ECG capabilities are often multi vital sign sensor devices. The majority of these devices are usually connected to a mobile smartphone. However, there are pros and cons to their use.

METHODS: We review here an exemplary selection of modern consumer ECG devices based on device type, recording method and the number of standard ECG channels derived.

RESULTS: Single-channel consumer ECG devices such as Smart Watches can be useful for detecting and monitoring atrial fibrillation and flutter and other arrhythmias, as well as ectopic complexes. However, they are currently limited with respect to recording duration and information content (a single-channel or limb‑lead ECG having less diagnostic information than a 12‑lead ECG). While some non watch-based consumer ECG devices can now record all 6 limb leads to yield increased information, no consumer ECG devices can currently reliably detect ST-segment deviations, potentially indicating myocardial infarction or ischemic episodes. Moreover, barriers to use still exist for at-risk elderly people. Finally, there currently is no universal data exchange format.

CONCLUSION: Consumer ECG devices, whether in fitness or fashionable design, allow for reliable detection of atrial fibrillation. Timely detection of atrial fibrillation and subsequent treatment might protect against stroke, especially in high-risk groups, yet prospective evidence is still lacking. Six-channel consumer ECG and longer data collection capabilities extend potential functionality, including for the monitoring of ST-segments and QT intervals. However, no currently available devices are sufficiently suitable for the detection of myocardial infarction or ischemia, which is why portable 12-channel technologies are desirable. For the reliable detection of a myocardial infarction, the determination of specific myocardial infarction blood markers and evaluation of patient medical history still is indispensable in addition to the 12 lead ECG.

PMID:36566580 | DOI:10.1016/j.jelectrocard.2022.11.010

Mol Cell Biochem. 2022 Dec 25. doi: 10.1007/s11010-022-04628-5. Online ahead of print.

ABSTRACT

Myocardial infarction (MI) damages cardiomyocytes permanently and compromises cardiac function. Mesenchymal stem cells (MSCs) with the potential to differentiate into multiple lineages are considered as one of the best options for the treatment of MI. However, aging affects their regeneration capability. With age, reactive oxygen species (ROS) accumulate in cells ultimately causing cell death. To successfully utilize these stem cells in clinic, novel strategies to improve their functional capability should be explored. In this study, we aimed to enhance the cardiac regeneration potential of bone marrow MSCs derived from aging rats by treating them with antioxidants, rutin or quercetagetin in separate in vivo experiments. Oxidative stress was induced by treating MSCs of young and aging rats with different concentrations of H2O2 which resulted in an increase in the ROS level. MSCs were treated with rutin or quercetagetin at varying concentrations and exposed to H2O2. It was observed that both antioxidants significantly (P < 0.001) suppressed H2O2-induced intracellular ROS accumulation in a dose-dependent manner. An optimized concentration of 10 µM rutin or quercetagetin was used for the in vivo experiments. MI models were developed in aging rats by ligation of left anterior descending artery and treated MSCs were transplanted in the MI models. Echocardiography was performed after 2 and 4 weeks of cell transplantation to evaluate the functional status of the infarcted heart and histological analysis was performed after 4 weeks to assess cardiac regeneration. Significant improvement was observed in cardiac parameters including LVEF% (P < 0.001), LVFS% (P < 0.01 and P < 0.001), LVIDd (P < 0.01 and P < 0.001), LVIDs (P < 0.001), LVEDV (P < 0.001) and LVESV (P < 0.001) in the treated young as well as aging MSCs. It is concluded from these findings that rutin and quercetagetin treatment enhance the regeneration efficiency of young and aging MSCs in vivo. These antioxidants can be effectively utilized to improve cellular therapy for myocardial infarction by suppressing ROS production.

PMID:36566485 | DOI:10.1007/s11010-022-04628-5

Cell Transplant. 2022 Jan-Dec;31:9636897221136787. doi: 10.1177/09636897221136787.

ABSTRACT

Myocardial infarctions affect approximately 735,000 people annually in the United States and have a substantial impact on quality of life. Neonates have an enhanced capability of repairing cardiovascular damage, while adults do not. The mechanistic basis for this age-dependent difference in regenerative capacity remains unknown. Recent studies have shown that microRNAs (miRNAs) play a significant role in regulating the regenerative ability of cardiovascular cells. This report defines the alterations in miRNA expression within the cardiovascular repair zone of infarcted sheep hearts following intracardiac injection of neonatal islet-1+ cardiovascular progenitor cells. Sheep were infarcted via left anterior descending coronary artery ligation. After 3 to 4 weeks of infarction, sheep neonatal islet-1+ cardiovascular progenitor cells were injected into the infarcted area for repair. Cell-treated sheep were euthanized 2 months following cell injection, and their hearts were harvested for the analysis of miRNA and gene expression within the cardiovascular repair zone. Ten miRNAs were differentially regulated in vivo, including miR-99, miR-100, miR-302a, miR-208a, miR-665, miR-1, miR-499a, miR-34a, miR-133a, and miR-199a. These miRNAs promote stemness, cell division, and survival. Several signaling pathways are regulated by these miRNAs, including Hippo, Wnt, and Erythroblastic Leukemia Viral Oncogene B (ERBB). Transcripts encoding Wnt, ERBB, and Neuregulin 1 (NRG1) were elevated in vivo in the infarct repair zone. Wnt5a signaling and ERBB/NRG1 transcripts contribute to activation of Yes-Associated Protein 1. MiRNAs that impact proliferation, cell survival, and signaling pathways that promote regeneration were induced during cardiovascular repair in the sheep model. This information can be used to design new approaches for the optimization of miRNA-based treatments for the heart.

PMID:36564913 | PMC:PMC9793054 | DOI:10.1177/09636897221136787

Med Phys. 2022 Dec 24. doi: 10.1002/mp.16186. Online ahead of print.

ABSTRACT

BACKGROUND: Non-invasive quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR) provides incremental benefit to relative myocardial perfusion imaging (MPI) to diagnose and manage heart disease. MBF can be measured with single-photon emission computed tomography (SPECT) but the uncertainty in the measured values is high. Standardization and optimization of protocols for SPECT MBF measurements will improve the consistency of this technique. One element of the processing protocol is the choice of kinetic model used to analyze the dynamic image series.

PURPOSE: This study evaluates if a net tracer retention model (RET) will provide a better fit to the acquired data and greater test-retest precision than a one-compartment model (1CM) for SPECT MBF, with (+MC) and without (-MC) manual motion correction.

METHODS: Data from previously acquired rest-stress MBF studies (31 SPECT-PET and 30 SPECT-SPECT) were reprocessed ±MC. Rate constants (K1) were extracted using 1CM and RET, +/-MC, and compared pairwise with standard PET MBF measurements using cross-validation to obtain calibration parameters for converting SPECT rate constants to MBF and to assess the goodness-of-fit of the calibration curves. Precision (coefficient of variation of test re-test relative differences, COV) of flow measurements was computed for 1CM and RET ±MC using data from the repeated SPECT MBF studies.

RESULTS: Both the RET model and MC improved the goodness-of-fit of the SPECT MBF calibration curves to PET. All models produced minimal bias compared with PET (mean bias < 0.6%). The SPECT-SPECT MBF COV significantly improved from 34% (1CM+MC) to 28% (RET+MC, p = 0.008).

CONCLUSION: The RET+MC model provides a better calibration of SPECT to PET and blood flow measurements with better precision than the 1CM, without loss of accuracy. This article is protected by copyright. All rights reserved.

PMID:36565461 | DOI:10.1002/mp.16186

Mol Biol Rep. 2022 Dec 24. doi: 10.1007/s11033-022-08115-4. Online ahead of print.

ABSTRACT

BACKGROUND: Sepsis-induced myocardial dysfunction is associated with worse clinical outcomes and high mortality, but no effective therapeutic intervention has been explored, reinforcing the urgent need to develop innovative strategies. Mitochondrial dysfunction underlies the pathogenesis of sepsis-induced myocardial dysfunction. Herein, we assessed the effect of mitochondrial transplantation on sepsis-induced myocardial dysfunction in a rat model of cecal ligation and puncture (CLP)-induced sepsis.

METHODS: Male Wistar rats (n = 80, 12 weeks old, 250-300 g) were divided into groups with/without CLP-induced sepsis receiving mitochondrial transplantation in single or two repetitive injections (1 h or 1 and 7 h post-CLP, respectively). Mitochondria were isolated from donor rats and injected intravenously (400 µl of mitochondrial suspension containing 7.5 × 106 mitochondria/ml of respiration buffer) in recipient groups. Twenty-four hours post-operation, LDH and cTn-I levels, mitochondrial functional endpoints, expression of mitochondrial biogenesis (SIRT-1 and PGC-1α) and fission/fusion (Drp1/Mfn1 and Mfn2) genes, and inflammatory cytokines (TNF-α, IL-1β, and IL-6) levels were evaluated. Survival was tested over 72 h post-operation.

RESULTS: Mitotherapy significantly improved 72-hours survival (P < .05) and decreased LDH and cTn-I levels (P < .01). It also restored mitochondrial function and expression of mitochondrial biogenesis and fusion genes, and decreased the expression of mitochondrial fission gene and the levels of inflammatory cytokines (P < .05 to P < .01). Mitotherapy with repetitive injections at 1 and 7 h post-CLP provided noticeable mitoprotection in comparison with the group receiving mitotherapy at single injection.

CONCLUSION: Mitotherapy improved mitochondrial function, biogenesis, and dynamic associated with SIRT-1/PGC-1α network and suppressed inflammatory response in CLP-induced sepsis model, therefore, offers a promising strategy to overcome life-threatening sepsis challenge.

PMID:36565415 | DOI:10.1007/s11033-022-08115-4

Eur J Haematol. 2022 Dec 24. doi: 10.1111/ejh.13919. Online ahead of print.

ABSTRACT

OBJECTIVES: Iron overload in patients with thalassemia represents a serious complication by affecting numerous organ systems. This meta-analysis aims to establish an evidence regarding the effect of amlodipine on cardiac iron overload in thalassemia patients.

METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Central, and EMBASE for all relevant randomized controlled trials (RCTs). The primary outcomes were cardiac T2* and myocardial iron concentration (MIC). Secondary outcomes were liver iron concentration (LIC), risk of G.I. upset and risk of lower limb edema. We used Hedges' g to pool continuous outcomes, while odds ratio was used for dichotomous outcomes.

RESULTS: Seven RCTs were eligible for this systematic review and meta-analysis, comprising of 233 patients included in the analysis. Amlodipine had a statistically significant lower MIC (Hedges' g = -0.82, 95% CI [-1.40, -0.24], p < 0.001) and higher cardiac T2* (Hedges' g = 0.36, 95% CI [0.10, 0.62], p = 0.03). Amlodipine was comparable to standard chelation therapy in terms of the risk of lower limb edema and GI upset.

CONCLUSION: Our meta-analysis found that amlodipine significantly increases cardiac T2* and decreases MIC, hence decreasing the incidence of cardiomyopathy-related iron overload in thalassemia patients. This article is protected by copyright. All rights reserved.

PMID:36565288 | DOI:10.1111/ejh.13919