Myocardial Protection Strategies Research Articles

Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.

Cardiovascular disease (CVD) is a prevalent non-communicable disease globally and holds the position of being the primary cause of mortality worldwide. Consequently, considerable focus has been directed towards the prevention and management of CVD. PCSK9, a frequently targeted element in the treatment and prevention of CVD, can reduce cardiovascular risk by effectively lowering lipid levels even in the context of statin therapy. It also exhibits substantial potential in the diagnosis and treatment of familial hypercholesterolemia from genetic aspects. This bibliometric study aims to analyze and visualize the global trends and emerging hotspots of PCSK9 and CVD researches and provide researchers with new perspectives in further studies. The data was obtained from the Web of Science Core Collection database. A total of 2,474 publications related to PCSK9 and CVD published between January 2006 and July 2023 were included. The VOSviewer was used to analyze most-cited references, co-authorship, co-citation, co-occurrence and generate a collaborative network map of authors, countries, and institutions. CiteSpace was used to analyze author and institution centroids, keyword bursts, and timeline graphs. A total of 2,474 articles related to CVD and PCSK9 were included. The number of articles and citations show an increasing trend from year to year. Publications were mainly from the United States. The most active institution was Amgen Inc. Watts, Gerald F. was the most prolific author. Atherosclerosis was the most published journal. Literature co-citation and keyword co-occurrence revealed that early studies focused on the lipid-lowering effects of PCSK9 inhibitors in the context of statins therapy, long-term efficacy, adverse effects, LDLR, diagnosis and treatment of familial hypercholesterolemia. In recent years, myocardial ischemic protection, CRISPR-based editing, and new therapeutic strategies for arteriosclerotic cardiovascular disease have gotten wide attention. The protein convertase, inflammation, beta-polyacetate, and inclisiran may be the important future research directions. This study analyses the current status and global trends in the CVD and PCSK9 studies comprehensively, which may provide researchers and policymakers with new and comprehensive perspectives on in this field of research.

Del Nido versus cold crystalloid cardioplegia for myocardial protection during ventricular septal defect repair in children under one year of age: a prospective randomized trial

Rationale: The choice of strategy for myocardial protection during procedures with cardiopulmonary bypass and cardioplegic arrest in children is not regulated by clinical guidelines due to insufficient data from clinical studies. The issue of methods to assess myocardial injury remains unresolved.
 Aim: To assess the frequency and specifics of the development of intraoperative myocardial injury syndrome in children of the first year of life with ventricular septal defect depending on the strategy for cardioplegia.
 Materials and methods: In a single center, prospective, randomized controlled trial we compared two cardioplegia strategies during surgical closure of ventricular septal defect in infants aged from 1 to 12 months: del Nido blood cardioplegia (n = 102) and cold crystalloid cardioplegia with Custodiol solution (n = 102). The primary endpoint was a persistent over 10-fold increase above the upper limit of the normal in the plasma concentration of high-sensitivity troponin I at 6 hours after surgery persisting after 24 hours. The secondary combined endpoint was myocardial damage verified by persistent increase in troponin I level more than 10-fold above the upper limit of the normal, persisting at 6 and 24 hours, accompanied by new pathological Q waves, acute complete left bundle branch block, abnormalities of the end part of the ventricular complex on the electrocardiography (ST segment elevation 1 mm or ST depression of 1 mm in more than 2 adjacent leads), and a decrease in the global longitudinal strain of the left ventricle by 50% from the initial value at 6 hours after surgery.
 Results: In 53/204 (26%) patients, the increase in troponin I persisted at 24 hours after the surgery and was associated with electrocardiography abnormalities, changes in the parameters of left ventricle longitudinal mechanics, and in some cases required greater inotropic support. By the end of the 1st postoperative 24 hours, the longitudinal strain of the left ventricle showed more negative changes over time in the Custodiol group compared to that in the del Nido group (-10 [-14.1; -6.27] versus -14.8 [- 16.5; -10]%; p 0.0001). The same was true for the left ventricle global strain rate (-0.71 [-0.9; -0.52] s-1 in the del Nido group and -0.57 [-0.760; - 0.44] s-1 in the Custodiol group; p = 0.0049). The primary endpoint was achieved by 21 (20.6%) and 55 (53.9%) patients in the del Nido and Custodiol groups, respectively (p = 0.032). The combined endpoint in the Custodiol group was achieved by 34 (33.3%) versus 19 (18.6%) patients in the del Nido group (p = 0.049, χ2 = 3.875, DF = 1, φ = 0.191).
 Conclusion: Del Nido blood cardioplegia compared to cold crystalloid cardioplegia with Custodiol has advantages in terms of preventing intraoperative myocardial damage and minimizing its severity. When assessing myocardial damage, such indicators as left ventricle global longitudinal strain and left ventricle global strain rate are informative, along with an increase in the troponin I level.

COMPARATIVE EVALUATION OF SEVOFLURANE AND ISOFLURANE IN FAST TRACK ANAESTHESIA FOR VALVULAR CARDIAC SURGERY: A RANDOMIZED STUDY

Objective: Contemporary valvular cardiac surgery has evolved with the adoption of expedited postoperative recovery, known as fast-tracking. This paradigm shift results from advancements in anaesthetic agents, surgical techniques, and myocardial protection strategies. Fast-track anaesthesia aims to reduce intensive care unit (ICU) stays and overall hospital length of stay (LOS), optimizing resource utilization. Cardioprotective properties of volatile anaesthetic agents, especially in mitigating ischemic myocardial damage, have garnered attention.
 Methods: A hospital-based, randomized, comparative study was conducted at the Department of Anaesthesiology, S. M. S Medical College, Jaipur. 70 undergoing valvular heart surgery under general anaesthesia, were randomly assigned to two groups: Group A (Sevoflurane) and Group B (Isoflurane). Inclusion criteria encompassed ASA grade II to IV patients aged 20 to 50 y, with a body weight of 30-65 kg, and willingness to provide written consent. Anaesthesia induction and maintenance involved the administration of Sevoflurane or Isoflurane based on group allocation. Hemodynamic parameters were recorded at various surgical stages.
 Results: Heart rate, systolic blood pressure, and cardiac output were statistically insignificant between groups at different surgical stages (p>0.05). Intraoperative variables demonstrated no significant differences, except for a transient decrease in systolic blood pressure post-induction in both groups.
 Conclusion: The study underscores the comparable efficacy of Sevoflurane and Isoflurane in valvular cardiac surgery, supported by similar hemodynamic profiles. Understanding the nuances of volatile anaesthetic agents is crucial for their optimal clinical application, considering challenges like beta-blocker usage and perioperative hyperglycemia.

Ferroptosis Exists in Ischemia Reperfusion Injury after Cardiac Surgery with Cardiopulmonary Bypass.

Ischemia-reperfusion (IR) injury commonly arises during cardiac surgery involving Cardiopulmonary Bypass (CPB), and it has relationship with ferroptosis in mice. However, the exact role of ferroptosis in the human cardiac damage caused by cardiac surgery remains unclear. Basic patient data and perioperative period information were collected, and clinic indicators related to cardiac function were detected to assess the extent of cardiac injury. Cardiac tissue samples were collected to determine histopathological changes, ultrastructure of mitochondrial and hallmarks of ferroptosis. 25 patients were involved in this study. In the present study, we observed a significant increase in the clinical indicator hs-cTnT, with levels rising more than 1393 ± 242 folds (P < 0.0001) following the cardiac surgery. Masson staining revealed a notable increase in fibrosis levels by 2.282 ± 0.259% (P = 0.0009). Furthermore, there was a significant elevation in lipid peroxidation, as evidenced by a 61.42 ± 17.33% increase in MDA (P = 0.0006). Additionally, we observed notable swelling, decreased mitochondrial crista, and even fragmented mitochondria. Notably, changes in the marker gene of ferroptosis were observed, with PTGS2 showing a 6.437 ± 0.81 folds increase (P < 0.0001). Furthermore, key regulators such as SLC7A11 and GPX4 proteins exhibited a reduction of 97.33 ± 25.78% (P = 0.0068) and 60.59 ± 14.93% (P = 0.0071), respectively, indicating the occurrence of ferroptosis following the surgery. Ferroptosis exists in myocardial IR injury caused by cardiac surgery with CPB, indicating that targeting ferroptosis could serve as a potential strategy for myocardial protection against CPB-induced IR injury. The trial has been registered in Chinese Clinical Trial Registry (ChiCTR, No. ChiCTR2200061995) on July 16th, 2022.

Myocardial protection in cardiac surgery-hindsight from the 2020s.

Myocardial protection and specifically cardioplegia have been extensively investigated in the beginnings of cardiac surgery. After cardiopulmonary bypass had become routine, more and more cardiac operations were possible, requiring reliable and reproducible protection for times of blood flow interruptions to the most energy-demanding organ of the body. The concepts of hypothermia and cardioplegia evolved as tools to extend cardiac ischaemia tolerance to a degree considered safe for the required operation. A plethora of different solutions and delivery techniques were developed achieving remarkable outcomes with cross-clamp times of up to 120 min and more. With the beginning of the new millennium, interest in myocardial protection research declined and, as a consequence, conventional cardiac surgery is currently performed using myocardial protection strategies that have not changed in decades. However, the context, in which cardiac surgery is currently performed, has changed during this time. Patients are now older and suffer from more comorbidities and, thus, other organs move more and more into the centre of risk assessment. Yet, systemic effects of cardioplegic solutions have never been in the focus of attention. They say hindsight is always 20-20. We therefore review the biochemical principles of ischaemia, reperfusion and cardioplegic extension of ischaemia tolerance and address the concepts of myocardial protection with 'hindsight from the 2020s'. In light of rising patient risk profiles, minimizing surgical trauma and improving perioperative morbidity management becomes key today. For cardioplegia, this means accounting not only for cardiac, but also for systemic effects of cardioplegic solutions.

Custodiol versus blood cardioplegia in pediatric cardiac surgery: a randomized controlled trial

BackgroundBlood-based cardioplegia is the standard myocardial protection strategy in pediatric cardiac surgery. Custadiol (histidine-tryptophan-ketoglutarate), an alternative, may have some advantages but is potentially less effective at myocardial protection. This study aimed to test whether custadiol is not inferior to blood-based cardioplegia in pediatric cardiac surgery.MethodsThe study was designed as a randomized controlled trial with a blinded outcome assessment. All pediatric patients undergoing cardiac surgery with cardiopulmonary bypass and cardioplegia, including neonates, were eligible. Emergency surgery was excluded. The primary outcome was a composite of death within 30 days, an ICU stay longer than 5 days, or arrhythmia requiring intervention. Secondary endpoints included total hospital stay, inotropic score, cardiac troponin levels, ventricular function, and extended survival postdischarge. The sample size was determined a priori for a noninferiority design with an expected primary outcome of 40% and a clinical significance difference of 20%.ResultsBetween January 2018 and January 2021, 226 patients, divided into the Custodiol cardioplegia (CC) group (n = 107) and the blood cardioplegia (BC) group (n = 119), completed the study protocol. There was no difference in the composite endpoint between the CC and BC groups, 65 (60.75%) vs. 71 (59.66%), respectively (P = 0.87). The total length of stay in the hospital was 14 (Q2–Q3: 10–19) days in the CC group vs. 13 (10–21) days in the BC group (P = 0.85). The inotropic score was not significantly different between the CC and BC groups, 5 (2.6–7.45) vs. 5 (2.6–7.5), respectively (P = 0.82). The cardiac troponin level and ventricular function did not differ significantly between the two groups (P = 0.34 and P = 0.85, respectively). The median duration of follow-up was 32.75 (Q2–Q3: 18.73–41.53) months, and there was no difference in survival between the two groups (log-rank P = 0.55).ConclusionsCustodial cardioplegia is not inferior to blood cardioplegia for myocardial protection in pediatric patients.Trial registration The trial was registered in Clinicaltrials.gov, and the ClinicalTrials.gov Identifier number is NCT03082716 Date: 17/03/2017

Berberine Alleviates Doxorubicin-Induced Myocardial Injury and Fibrosis by Eliminating Oxidative Stress and Mitochondrial Damage via Promoting Nrf-2 Pathway Activation.

Doxorubicin (DOX)-related cardiotoxicity has been recognized as a serious complication of cancer chemotherapy. Effective targeted strategies for myocardial protection in addition to DOX treatment are urgently needed. The purpose of this paper was to determine the therapeutic effect of berberine (Ber) on DOX-triggered cardiomyopathy and explore the underlying mechanism. Our data showed that Ber markedly prevented cardiac diastolic dysfunction and fibrosis, reduced cardiac malondialdehyde (MDA) level and increased antioxidant superoxide dismutase (SOD) activity in DOX-treated rats. Moreover, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts. This effect was mediated by increases in the nuclear accumulation of nuclear erythroid factor 2-related factor 2 (Nrf2) and levels of heme oxygenase-1 (HO-1) and mitochondrial transcription factor A (TFAM). We also found that Ber suppressed the differentiation of cardiac fibroblasts (CFs) into myofibroblasts, as indicated by decreased expression of α-smooth muscle actin (α-SMA), collagen I and collagen III in DOX-treated CFs. Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs. Further investigation indicated that the Nrf2 inhibitor trigonelline reversed the protective effect of Ber on both cardiomyocytes and CFs after DOX stimulation. Taken together, these findings demonstrated that Ber effectively alleviated DOX-induced oxidative stress and mitochondrial damage by activating the Nrf2-mediated pathway, thereby leading to the prevention of myocardial injury and fibrosis. The current study suggests that Ber is a potential therapeutic agent for DOX-induced cardiotoxicity that exerts its effects by activating Nrf2.

Effects of Remote Ischemic Preconditioning on Decreasing Troponin Release in Patients Not Taking Sulfonylureas After Cardiac Surgery - A Meta-Analysis.

Remote ischemic preconditioning (RIPC) is a new noninvasive myocardial protection strategy that uses blood pressure cuf inflation to simulate transient non-fatal ischemia to protect the myocardium and reduce ischemia-reperfusion injury. Sulfonylureas may mask the effects of RIPC due to their cardioprotec-tive effect. This meta-analysis aimed to evaluate whether RIPC, in the absence of sulfonylureas, reduces troponin release in patients undergoing cardiac surgery. We conducted a meta-analysis of randomized controlled clinical trials to determine whether RIPC can reduce postoperative troponin release in cardiac surgery patients undergoing cardiopulmonary bypass without treatment with sulfonylureas. The data were normalized to equivalent units prior to the analysis. A random-effects model was used to provide more conservative estimate of the effects in the presence of known or unknown heterogeneity. Six studies with a total of 570 participants were included. The analysis showed that troponin release was lower in the RIPC group than in the control group at six hours (test of standardized mean differences = 0, Z=3.64, P<0.001) and 48 hours (Z=2.72, P=0.007) postoperatively. When the mean of cross-clamping time was > 60 minutes, RIPC reduced troponin release at six hours (Z=2.84, P=0.005), 24 hours (Z=2.64, P=0.008), and 48 hours (Z=2.87, P=0.004) postoperatively. In cardiac surgery patients who are not taking sulfonylureas, RIPC can reduce troponin release at six and 48 hours postoperatively; hence, RIPC may serve significant benefits in certain cardiac surgery patients.

The Mitochondrial Unfolded Protein Response: A Novel Protective Pathway Targeting Cardiomyocytes.

Mitochondrial protein homeostasis in cardiomyocyte injury determines not only the normal operation of mitochondrial function but also the fate of mitochondria in cardiomyocytes. Studies of mitochondrial protein homeostasis have become an integral part of cardiovascular disease research. Modulation of the mitochondrial unfolded protein response (UPRmt), a protective factor for cardiomyocyte mitochondria, may in the future become an important treatment strategy for myocardial protection in cardiovascular disease. However, because of insufficient understanding of the UPRmt and inadequate elucidation of relevant mechanisms, few therapeutic drugs targeting the UPRmt have been developed. The UPRmt maintains a series of chaperone proteins and proteases and is activated when misfolded proteins accumulate in the mitochondria. Mitochondrial injury leads to metabolic dysfunction in cardiomyocytes. This paper reviews the relationship of the UPRmt and mitochondrial quality monitoring with cardiomyocyte protection. This review mainly introduces the regulatory mechanisms of the UPRmt elucidated in recent years and the relationship between the UPRmt and mitophagy, mitochondrial fusion/fission, mitochondrial biosynthesis, and mitochondrial energy metabolism homeostasis in order to generate new ideas for the study of the mitochondrial protein homeostasis mechanisms as well as to provide a reference for the targeted drug treatment of imbalances in mitochondrial protein homeostasis following cardiomyocyte injury.

Give Me a Shot of Holy Water: Critical Elements in Myocardial Protection during Cardiac Surgery.

There is a surprising paucity of information on myocardial protection during cardiac surgery in the popular techniques books on cardiac surgery. For instance, Khonsari's otherwise superb book, Cardiac Surgery: Safeguards and Pitfalls in Operative Technique, has only three of its 300 pages that address myocardial protection, while Cooley's book, Techniques in Cardiac Surgery, has none at all. Similarly, the major textbooks of cardiothoracic surgery (Kirklin & Barrett-Boyes, Sabiston & Spencer, and Cohn & Edmunds) all tend to dwell on basic science and pharmacology, while barely addressing the actual techniques and strategies of myocardial protection during cardiac surgical operations. [Khonsari, Cooley, Kouchoukos, Selke, Cohn].

Temperature-Related Effects of Myocardial Protection Strategies in Swine Hearts after Prolonged Warm Ischemia.

Insufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after circulatory death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitably longer period of unprotected warm ischemia between circulatory arrest and graft procurement. In this scenario, we aim to improve heart preservation after a warm ischemic period of 20 min by testing different settings of myocardial protective strategies. Pig hearts were collected from a slaughterhouse and assigned to one of the five experimental groups: baseline (BL), cold cardioplegia (CC), cold cardioplegia + adenosine (CC-ADN), normothermic cardioplegia (NtC + CC) or normothermic cardioplegia + cold cardioplegia + adenosine (NtC-ADN + CC). After treatment, tissue biopsies were taken to assess mitochondrial morphology, antioxidant enzyme activity, lipid peroxidation and cytokine and chemokine expressions. NtC + CC treatment significantly prevented mitochondria swelling and mitochondrial cristae loss. Moreover, the antioxidant enzyme activity was lower in this group, as was lipid peroxidation, and the pro-inflammatory chemokine GM-CSF was diminished. Finally, we demonstrated that normothermic cardioplegia preserved mitochondria morphology, thus preventing oxidative stress and the subsequent inflammatory response. Therefore, normothermic cardioplegia is a better approach to preserve the heart after a warm ischemia period, with respect to cold cardioplegia, before transplantation.

MiR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection

Exercise and its regulated molecules have myocardial protective effects against cardiac ischemia/reperfusion (I/R) injury. The muscle-enriched miR-486 was previously identified to be upregulated in the exercised heart, which prompted us to investigate the functional roles of miR-486 in cardiac I/R injury and to further explore its potential in contributing to exercise-induced protection against I/R injury. Our data showed that miR-486 was significantly downregulated in the heart upon cardiac I/R injury. Both preventive and therapeutic interventions of adeno-associated virus 9 (AAV9)-mediated miR-486 overexpression could reduce cardiac I/R injury. Using AAV9 expressing miR-486 with a cTnT promoter, we further demonstrated that cardiac muscle cell-targeted miR-486 overexpression was also sufficient to protect against cardiac I/R injury. Consistently, miR-486 was downregulated in oxygen-glucose deprivation/reperfusion (OGDR)-stressed cardiomyocytes, while upregulating miR-486 inhibited cardiomyocyte apoptosis through PTEN and FoxO1 inhibition and AKT/mTOR activation. Finally, we observed that miR-486 was necessary for exercise-induced protection against cardiac I/R injury. In conclusion, miR-486 is protective against cardiac I/R injury and myocardial apoptosis through targeting of PTEN and FoxO1 and activation of the AKT/mTOR pathway, and mediates the beneficial effect of exercise for myocardial protection. Increasing miR-486 might be a promising therapeutic strategy for myocardial protection.

EVOLUTION OF CARDIOPLEGIA- A BRIEF REVIEW

Cardiac surgery is one of the most commonly performed surgery nowadays - thanks to improved extracorporeal circulation technique , improved postoperative care as well as myocardial protection strategy . Cardioplegia solution was conceptualized to stop the heart for surgery as well as to protect the heart . Various modifications of cardioplegia solution had been made to make it more cardio-friendly. Following review article is a concise review of evolution of various cardioplegia solutions and their various components .

Urocortin Role in Ischemia Cardioprotection and the Adverse Cardiac Remodeling.

Despite the considerable progress in strategies of myocardial protection, ischemic heart diseases (IHD) and consequent heart failure (HF) remain the main cause of mortality worldwide. Several procedures are used routinely to guarantee the prompt and successful reestablishment of blood flow to preserve the myocardial viability of infarcted hearts from ischemia injuries. However, ischemic heart reperfusion/revascularization triggers additional damages that occur when oxygen-rich blood re-enters the vulnerable myocardial tissue, which is a phenomenon known as ischemia and reperfusion (I/R) syndrome. Complications of I/R injuries provoke the adverse cardiac remodeling, involving inflammation, mishandling of Ca2+ homeostasis, apoptotic genes activation, cardiac myocytes loss, etc., which often progress toward HF. Therefore, there is an urgent need to develop new cardioprotective therapies for IHD and HF. Compelling evidence from animal studies and pilot clinical trials in HF patients suggest that urocortin (Ucn) isoforms, which are peptides associated with stress and belonging to the corticotropin releasing factor family, have promising potential to improve cardiovascular functions by targeting many signaling pathways at different molecular levels. This review highlights the current knowledge on the role of urocortin isoforms in cardioprotection, focusing on its acute and long-term effects.

Cordycepin Decreases Ischemia/Reperfusion Injury in Diabetic Hearts via Upregulating AMPK/Mfn2-dependent Mitochondrial Fusion.

Diabetes mellitus is considered to be a major risk factor for cardiovascular disease, the most common cause of death in diabetes. However, therapeutic strategies for myocardial protection in patients with diabetes are still limited. Cordycepin is a traditional Tibetan medicine with a long history of widespread use, and exerts a wide range of anti-tumor, anti-inflammatory, and anti-oxidative effects. In recent years, although the therapeutic potential of cordycepin has attracted the attention of researchers, it remains unknown whether cordycepin plays a protective role in myocardial ischemia/reperfusion (MI/R) injury in diabetic patients. Here, using a diabetic mouse model, we found that cordycepin protected diabetic hearts from MI/R injury by promoting mitochondrial fusion and Mfn2 expression. Our in vitro results showed that cordycepin enhanced Mfn2-medicated mitochondrial fusion, improved mitochondrial function, and reduced cardiomyocyte apoptosis in high-glucose/high-fat cultured simulated ischemia/reperfusion cardiomyocytes. Furthermore, we found that knockout of Mfn2 significantly blocked the cardioprotective effects of cordycepin in diabetic mice. Finally, an AMPK-dependent pathway was found to upregulate Mfn2 expression upon cordycepin treatment, indicating that cordycepin protected diabetic hearts via AMPK/Mfn2-dependent mitochondrial fusion. Collectively, our study firstly demonstrated that cordycepin could be a potential cardioprotective agent for MI/R injury, and we established a novel mechanism by which upregulated AMPK/Mfn2-dependent mitochondrial fusion contributes to the cardioprotective role of cordycepin.

An Overview of Aortopulmonary Window

Aortopulmonary (AP) window is exactly a rare congenital anomaly that represents approximately 0.2 and 0.5% of all congenital heart abnormalities. It consists of communication between the aorta and the pulmonary artery or its branches. Although closely related to AP window, the pulmonary artery origin from the ascending aorta (also termed “hemitruncus”) is classified as a separate defect. AP window was first described by Elliotson in 1830 in an autopsy study. In 1948, Robert Gross successfully ligated an AP window in a patient undergoing a thoracotomy for closure of a patent ductus arteriosus (PDA). In 1957, Cooley and associates described the first successful repair of AP window using cardiopulmonary bypass. Aortopulmonary window occurs due to the abnormal development of the heart’s major blood vessels during early fetal growth. In most cases, this heart defect occurs by chance, with no clear reason. This condition can occur on its own or with other heart defects such as: 1. Tetralogy of Fallot, 2. Pulmonary atresia, 3. Truncus arteriosus, 4. Atrial septal defect, 5. Patent ductus arteriosus, 6. Interrupted aortic arch. Treatment for aortopulmonary window involves surgery to close the hole between the aorta and the pulmonary artery with a patch or device. This surgery is normally done as soon as possible after the diagnosis is made, usually when the child is a newborn. Associated lesions are usually repaired during the same surgery. Associated lesions are usually repaired during the same surgery. More complex repairs and myocardial protection strategies are required in patients with associated lesions, increasing the morbidity and mortality associated with the operation.

Cell programming to protect the ischemic heart and limb

New strategies for myocardial protection and regeneration after myocardial infarction are urgently needed to counter the heart failure pandemic. To address this unmet medical need, Kaur and colleagues (in this issue of Molecular Therapy)1 have identified in a preclinical proof-of-concept study a cocktail of modified RNA (modRNA) to endow stromal cells with angiogenic growth factor releasing activity (Figure 1). Sustained angiogenic programming was realized by lipid-nanoparticle (LNP) delivery, using formulations that have been employed safely and efficaciously in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations.

Investigation of myocardial protection during pediatric CPB: Practical experience in 100 Chinese hospitals.

Many measures have been proposed for myocardial protection in pediatric congenital heart surgeries, but little data is available for China. This study investigates myocardial protection strategies in pediatric cardiopulmonary bypass (CPB) throughout China. Online questionnaires were delivered to 100 hospitals in 27 provinces. The number of yearly on-pump pediatric cardiovascular surgeries in these hospitals varied greatly. About 91.0% of respondents believe that each surgery should have at least two perfusionists, while only 64.0% of hospitals actually met this requirement. For pediatric patients, crystalloid cardioplegia was more prevalent than blood-based cardioplegia. Histidine-tryptophan-ketoglutarate solution and St. Thomas crystalloid solution were dominant among crystalloid cardioplegia. Del Nido cardioplegia and St. Thomas blood-based cardioplegia ranked the top two in the popularity of blood-based cardioplegia. Dosages varied among different kinds of cardioplegia. In the choice of different cardioplegia, perfusionists mainly focused on myocardial protective effect and cost. Hypothermia of cardioplegia solution was maintained by ice buckets in 3/4 of the hospitals in this survey. In conclusion, the essence of myocardial protection management during pediatric CPB was cardiac arrest induced by cardioplegia under systemic hypothermia. However, there is no uniform standard for the type of cardioplegia, or dosages. Therefore, well-designed multicenter randomized controlled trials are warranted to provide tangible evidence for myocardial protection of cardioplegia in pediatric CPB.

Patient characteristics and surgical variables associated with intraoperative reduced right ventricular function.

Perioperative right ventricular function is a significant predictor of patient outcomes after cardiac surgery. This prospective study aimed to identify perioperative factors associated with reduced intraoperative right ventricular function. Right ventricular function was assessed at the beginning and end of surgery by standardized transesophageal echocardiographic measurements, including tricuspid annular plane systolic excursion, peak systolic longitudinal right ventricular strain, and fractional area change, in 109 adult patients undergoing cardiac surgery at Cleveland Clinic. Associations between right ventricular function and 33 patient characteristics and perioperative factors were analyzed by random forest machine learning. The relative importance of each variable in predicting right ventricular function at the end of surgery was determined. Longer aortic clamp duration and lower baseline right ventricular function were highly important variables for predicting worse right ventricular function measured by tricuspid annular plane systolic excursion, right ventricular strain, and fractional area change at the end of surgery. For example, right ventricular function after longer aortic clamp times of 100-120minutes was worse (median [Q1, Q3] tricuspid annular plane systolic excursion 1.0 [0.9, 1.1] cm) compared with right ventricular function after shorter aortic clamp times of 50 to 70minutes (tricuspid annular plane systolic excursion 1.5 [1.3, 1.7]; P=.001). Right ventricular strain at the end of surgery was reduced in patients with worse baseline right ventricular function compared with those with higher baseline right ventricular function (end of surgery right ventricular strain in lowest quartile -13.7 [-16.6, -12.4]% vs highest quartile -17.7 [-18.6, -15.3]% of baseline right ventricular function; P=.043). Intraoperative decline in right ventricular function is associated with longer aortic clamp time and worse baseline right ventricular function. Efforts to optimize these factors, including better myocardial protection strategies, may improve perioperative right ventricular function.

Role of Hydrogen Sulfide in Myocardial Ischemia-Reperfusion Injury.

Hydrogen sulfide (H2S), generally known as a new gas signal molecule after nitric oxide and carbon monoxide, has been found as an important endogenous gasotransmitter in the last few decades, and it plays a significant role in the cardiovascular system both pathologically and physiologically. In recent years, there is growing evidence that H2S provides myocardial protection against myocardial ischemia-reperfusion injury (MIRI), which resulted in an ongoing focus on the possible mechanisms of action accounting for the H2S cardioprotective effect. At present, lots of mechanisms of action have been verified through in vitro and in vivo models of I/R injury, such as S-sulfhydrated modification, antiapoptosis, effects on microRNA, bidirectional effect on autophagy, antioxidant stress, or interaction with NO and CO. With advances in understanding of the molecular pathogenesis of MIRI and pharmacology studies, the design, the development, and the pharmacological characterization of H2S donor drugs have made great important progress. This review summarizes the latest research progress on the role of H2S in MIRI, systematically explains the molecular mechanism of H2S affecting MIRI, and provides a new idea for the formulation of a myocardial protection strategy in the future.