Emerging evidence has demonstrated the profound impact of the gut microbiome on cardiovascular diseases through the production of diverse metabolites. Using an animal model of myocardial ischemia-reperfusion (I/R) injury, we found that the prophylactic administration of a well-known probiotic, Bifidobacterium infantis (B. infantis), exhibited cardioprotective effects in terms of preserving cardiac contractile function and preventing adverse cardiac remodeling following I/R and that these cardioprotective effects were recapitulated by its metabolite inosine. Transcriptomic analysis further revealed that inosine mitigated I/R-induced cardiac inflammation and cell death. Mechanistic investigations elucidated that inosine suppressed the production of pro-inflammatory cytokines and reduced the numbers of dendritic cells and natural killer cells, achieved through the activation of the adenosine A2A receptor (A2AR) that when inhibited abrogated the cardioprotective effects of inosine. Additionally, in vitro studies using C2C12 myoblasts revealed that inosine attenuated cell death by serving as an alternative carbon source for adenosine triphosphate (ATP) generation through the purine salvage pathway when subjected to oxygen-glucose deprivation/reoxygenation that simulated myocardial I/R injury. Likewise, inosine reversed the I/R-induced decrease in ATP levels in mouse hearts. Taken together, our findings indicate that B. infantis or its metabolite inosine exerts cardioprotective effects against I/R by suppressing cardiac inflammation and attenuating cardiac cell death, suggesting prophylactic therapeutic options for acute ischemic cardiac injury.

Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk for heart failure, yet preventive cardiac care is suboptimal in this population. Pyridoxamine (PM), a vitamin B6 analog, has been shown to exert protective effects in metabolic and cardiovascular diseases. In this study, we aimed to investigate whether PM limits adverse cardiac remodeling and dysfunction in rats who develop T2DM. Male rats received a standard chow diet or Western diet (WD) for 18 weeks to induce prediabetes. One WD group received additional PM (1 g/L) via drinking water. Glucose tolerance was assessed with a 1 h oral glucose tolerance test. Cardiac function was evaluated using echocardiography and hemodynamic measurements. Histology on left ventricular (LV) tissue was performed. Treatment with PM prevented the increase in fasting plasma glucose levels compared to WD-fed rats (p < 0.05). LV cardiac dilation tended to be prevented using PM supplementation. In LV tissue, PM limited an increase in interstitial collagen deposition (p < 0.05) seen in WD-fed rats. PM tended to decrease 3-nitrotyrosine and significantly lowered 4-hydroxynonenal content compared to WD-fed rats. We conclude that PM alleviates interstitial fibrosis and oxidative stress in the hearts of WD-induced prediabetic rats.

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Perioperative myocardial injury is a common complication caused by major surgery. Many pharmacological and nonpharmacological studies have investigated perioperative cardioprotection. However, the methods are insufficient to meet the increasing clinical needs for cardioprotection. The application of Mesenchymal Stem Cell-Derived Exosomes (MSC-Exos) is a novel cell-free therapeutic strategy and has significantly benefitted patients suffering from various diseases. In this review, we comprehensively analyzed the application of MSC-Exos to prevent myocardial infarction/injury by regulating inflammatory reactions, inhibiting cardiomyocyte apoptosis and autophagy, promoting angiogenesis, and mediating cardiac remodeling. Finally, we assessed the therapeutic effects and the challenges associated with the application of MSC-Exos from a clinical perspective.

A variety of vegetable and fruit derived food oils are considered beneficial for human health due to their content of functional components including their positive effects in cardiovascular system. In addition to the favorable ratio of unsaturated versus saturated fatty acids, some of these oils include also other health beneficial compounds such as vitamins, minerals, pigments, enzymes and phenolic compounds. Particularly polyphenols have been documented to exert numerous positive effects in cardiovascular system including their anti-hypertensive, anti-atherogenic as well as cardio- and vasculo- protective effects in subjects suffering from various cardiovascular and cardiometabolic diseases, likely via their antioxidant, anti-inflammatory, anti-coagulant, anti-proliferative and anti-diabetic properties. However, it has not been proven so far whether the positive cardiovascular effects of polyphenol-rich food oils are, and to what measure, attributed to their phenolic content. Thus, the current review aims to summarize the main cardiovascular effects of major polyphenol-rich food oils including olive, flaxseed, soybean, sesame and coconut oils, and to uncover the role of their phenolic compounds in these effects.

UNASSIGNED: This study investigated the influence of volatile anesthesia (VA) on major complications and mortality in patients undergoing coronary artery bypass graft surgery (CABG).
UNASSIGNED: This post-hoc analysis included 1586 patients from the MYRIAD trial managed using the same perioperative protocol at a single institution. Patients were randomized to receive either volatile anesthesia (sevoflurane, isoflurane, or desflurane) or total intravenous anesthesia (TIVA). The assessed study outcomes were the rate of complications, including: myocardial infarction, stroke, acute kidney injury, prolonged ventilation ( > 24 h), receipt of high-dose inotropic support (inotropic score > 10), and need for mechanical circulatory support. The duration of intensive care unit (ICU) stay, length of hospitalization, hospital readmission during follow-up, 30-days and 1-year mortality were also analyzed.
UNASSIGNED: 1586 patients were enrolled between September 2014-September 2017 and randomly assigned to the volatile anesthesia group (n = 794) and the TIVA group (n = 792). The median patient age was 63 years, with a median ejection fraction of 60%. There were no significant differences in the rates of major complications, duration of ICU stay, and hospitalization between the groups. The median total dose of fentanyl was 12.0 mcg/kg in volatile group and 14.4 mcg/kg in TIVA group (p < 0.001). One-year mortality rates were 2.5% (n = 20) and 3.2% (n = 25) in the volatile and TIVA groups, respectively. Two patients were lost at the 30-day and 1-year follow-ups in the volatile group compared to four patients in TIVA group. Regression analysis showed that cardiopulmonary bypass (CPB) duration, fentanyl dose, and baseline serum creatinine level were associated with 30-days mortality, while ejection fraction was associated with 1-year mortality.
UNASSIGNED: The use of VA in patients undergoing CABG did not result in a reduction in major complications or mortality compared with TIVA. A higher dose of fentanyl was used in the TIVA group and was associated with an increase in the 30-days mortality. These findings warrant further investigation.
UNASSIGNED: ClinicalTrials.gov (NCT02105610).

(1) Background: Remote ischemic preconditioning (RIPC) is an intervention involving the application of brief episodes of ischemia and reperfusion to distant tissues to activate protective pathways in the heart. There is evidence suggesting the involvement of the autonomic nervous system (ANS) in RIPC-induced cardioprotection. This study aimed to investigate the immediate effects of RIPC on the ANS using a randomized controlled trial. (2) Methods: From March 2018 to November 2018, we conducted a single-blinded randomized controlled study involving 51 healthy volunteers (29 female, 24.9 [23.8, 26.4] years). Participants were placed in a supine position and heart rate variability was measured over 260 consecutive beats before they were randomized into either the intervention or the SHAM group. The intervention group underwent an RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the upper thigh. The SHAM group followed the same protocol but on the right upper arm, with just 40 mmHg of pressure inflation, resulting in no ischemic stimulus. Heart rate variability measures were reassessed afterward. (3) Results: The intervention group showed a significant increase in RMSSD, the possible marker of the parasympathetic nervous system (IG: 14.5 [5.4, 27.5] ms vs. CG: 7.0 [-4.3, 23.1 ms], p = 0.027), as well as a significant improvement in Alpha 1 levels compared to the control group (IG: -0.1 [-0.2, 0.1] vs. CG: 0.0 [-0.1, 0.2], p = 0.001). (4) Conclusions: Our results hint that RIPC increases the RMSSD and Alpha 1 parameters showing possible immediate parasympathetic modulations. RIPC could be favorable in promoting cardioprotective or/and cardiovascular effects by ameliorating ANS modulations.

The increasing trend of cardiac diseases is becoming a major threat globally. Cardiac activities are based on integrated action potential through electronic flux changes within intra- and extracellular molecular activities. Nicotinamide adenine dinucleotide (NAD) is a major electron carrier present in almost all living cells and creates gated potential by electron exchange from one chemical to another in terms of oxidation (NAD+) and reduction (NADH) reactions. NAD+ plays an important role directly or indirectly in protecting against various cardiovascular diseases, including heart failure, occlusion, ischemia-reperfusion (IR) injury, arrhythmia, myocardial infarction (MI), rhythmic disorder, and a higher order of cardiovascular complexity. Nicotinamide phosphoribosyl transferase (NAMPT) is well known as a rate-limiting enzyme in this pathway except for de-novo NAD synthesis and directly involved in the cardioprotective activity. There are two more enzymes - nicotinate phosphoribosyl transferase (NAPRT) and nicotinamide riboside kinase (NRK) - which also work as rate-limiting factors in the NAD+ synthesis pathway. This study concentrated on the role of NAMPT, NAPRT, and NRK in cardioprotective activity and prospective cardiac health.

OBJECTIVE: To evaluate the cardioprotective effects of Gynostemma pentaphyllum Makino in isoproterenol-induced myocardial infarction in rats and to evaluate the role of phosphatidylinositol 3-kinases (PI3K) in cardioprotection.
METHODS: The protective effect of the hydroalcoholic leaf extract of Gynostemma pentaphyllum (LEGP) on the heart was investigated against isoproterenol (ISO)-induced MI in rats. Preliminary phytochemical screening was performed followed by molecular docking. For the in vivo studies Wistar albino rats (Male) were divided among different groups. Different parameters were evaluated such as heart weight index, Electrocardiogram (ECG) analysis, triphenyl tetrazolium chloride assay, cardiac enzyme markers, oxidative stress, antioxidant enzymes, PI3K levels, and histopathology of cardiac tissue.
RESULTS: Results showed that LEGP improved the electrocardiogram, reduced infarct size, and decreased the levels of cardiac enzyme markers and oxidative stress, while antioxidant enzymes and PI3K levels were increased.
CONCLUSIONS: LEGP protected the heart against ISO-induced MI in rats by improving hemodynamic, biochemical and histological attributes. These protective effects were produced by the phytoconstituents of the LEGP through modulation of the PI3K signalling pathway.

This study aimed to explore the effects of peroxisome proliferator-activated receptor α (PPAR-α), a known inhibitor of ferroptosis, in Myocardial ischemia/reperfusion injury (MIRI) and its related mechanisms. In vivo and in vitro MIRI models were established. Our results showed that activation of PPAR-α decreased the size of the myocardial infarct, maintained cardiac function, and decreased the serum contents of creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and Fe2+ in ischemia/reperfusion (I/R)-treated mice. Additionally, the results of H&E staining, DHE staining, TUNEL staining, and transmission electron microscopy demonstrated that activation of PPAR-α inhibited MIRI-induced heart tissue and mitochondrial damage. It was also found that activation of PPAR-α attenuated MIRI-induced ferroptosis as shown by a reduction in malondialdehyde, total iron, and reactive oxygen species (ROS). In vitro experiments showed that intracellular contents of malondialdehyde, total iron, LDH, reactive oxygen species (ROS), lipid ROS, oxidized glutathione disulphide (GSSG), and Fe2+ were reduced by the activation of PPAR-α in H9c2 cells treated with anoxia/reoxygenation (A/R), while the cell viability and GSH were increased after PPAR-α activation. Additionally, changes in protein levels of the ferroptosis marker further confirmed the beneficial effects of PPAR-α activation on MIRI-induced ferroptosis. Moreover, the results of immunofluorescence and dual-luciferase reporter assay revealed that PPAR-α achieved its activity via binding to the 14-3-3η promoter, promoting its expression level. Moreover, the cardioprotective effects of PPAR-α could be canceled by pAd/14-3-3η-shRNA or Compound C11 (14-3-3η inhibitor). In conclusion, our results indicated that ferroptosis plays a key role in aggravating MIRI, and PPAR-α/14-3-3η pathway-mediated ferroptosis and mitochondrial injury might be an effective therapeutic target against MIRI.