Bone marrow cells contribute to seven different endothelial cell populations in the heart.

Understanding the mechanisms underlying vascular regeneration in the heart is crucial for developing novel therapeutic strategies for myocardial ischemia. This study investigates the contribution of bone marrow-derived cells to endothelial cell populations in the heart, and their role in cardiac function and coronary circulation following repetitive ischemia (RI). Chimeric rats were created by transplanting BM cells from GFP female rats into irradiated male recipients. After engraftment chimeras were subjected to RI for 17 days. Vascular growth was assessed from recovery of cardiac function and increases in myocardial blood flow during LAD occlusion. After sorting GFP+ BM cells from heart and bone of Control and RI rats, single-cell RNA sequencing was implemented to determine the fate of BM cells. Our in vivo RI model demonstrated an improvement in cardiac function and myocardial blood flow after 17 days of RI with increased capillary density in the rats subjected to RI compared to Controls. Single-cell RNA sequencing of bone marrow cells isolated from rats' hearts identified distinct endothelial cell (EC) subpopulations. These ECs exhibited heterogeneous gene expression profiles and were enriched for markers of capillary, artery, lymphatic, venous, and immune ECs. Furthermore, BM-derived ECs in the RI group showed an angiogenic profile, characterized by upregulated genes associated with blood vessel development and angiogenesis. This study elucidates the heterogeneity of bone marrow-derived endothelial cells in the heart and their response to repetitive ischemia, laying the groundwork for targeting specific subpopulations for therapeutic angiogenesis in myocardial ischemia.

Activation of PPAR-α attenuates myocardial ischemia/reperfusion injury by inhibiting ferroptosis and mitochondrial injury via upregulating 14-3-3η.

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.

Variant Coronary Arterial Collateral Ring.

A 74-year-old man presented with symptoms and noninvasive diagnostic studies suggestive of myocardial infarction. Coronary angiography revealed total occlusion of the distal right coronary artery with a unique accessory coronary ring that provided retrograde collateral flow to the left ventricle, demonstrating the importance of considering non-native vessels when identifying target lesions.

Skin sympathetic nerve activity and ST-segment depression in women.

Background: ST-segment depression (ST depression) on exercise electrocardiogram (ECG) and ambulatory ECG monitoring may occur without myocardial ischemia. The mechanisms of nonischemic ST depression remain poorly understood. Objective: The study sought to test the hypothesis that the magnitudes of skin sympathetic nerve activity (SKNA) correlate negatively with the ST-segment height (ST height) in ambulatory participants. Methods: We used neuECG (simultaneous recording of SKNA and ECG) to measure ambulatory ST height and average SKNA (aSKNA) in 19 healthy women, 6 women with a history of Takotsubo syndrome (TTS), and 4 women with ischemia and no obstructive coronary arteries (INOCA). Results: Baseline aSKNA was similar between healthy women, women with TTS, and women with INOCA (1.098 ± 0.291 µV, 0.980 ± 0.061 µV, and 0.919 ± 0.0397 µV, respectively; P = .22). The healthy women had only asymptomatic upsloping ST depression. All participants had a significant (P < .05) negative correlation between ST height and aSKNA. Ischemic episodes (n = 15) were identified in 2 TTS and 4 INOCA participants. The ischemic ST depression was associated with increased heart rate and elevated aSKNA compared with baseline. An analysis of SKNA burst patterns at similar heart rates revealed that SKNA total burst area was significantly higher during ischemic episodes than nonischemic episodes (0.301 ± 0.380 µV·s and 0.165 ± 0.205 µV·s; P = .023) in both the TTS and INOCA participants. Conclusion: Asymptomatic ST depression in ambulatory women is associated with elevated SKNA. Heightened aSKNA is also noted during ischemic ST depression in women with TTS and INOCA. These findings suggest that ST segment depression is a physiological response to heightened sympathetic tone but may be aggravated by myocardial ischemia.

AI-based Fully-Automated Stress Left Ventricular Ejection Fraction as a Prognostic Marker in Patients Undergoing Stress-CMR.

AIM: To determine in patients undergoing stress CMR whether fully automated stress artificial intelligence (AI)-based left ventricular ejection fraction (LVEFAI) can provide incremental prognostic value to predict death above traditional prognosticators. MATERIEL AND RESULTS: Between 2016 and 2018, we conducted a longitudinal study that included all consecutive patients referred for vasodilator stress CMR. LVEFAI was assessed using AI-algorithm combines multiple deep learning networks for LV segmentation. The primary outcome was all-cause death assessed using the French National Registry of Death. Cox regression was used to evaluate the association of stress LVEFAI with death after adjustment for traditional risk factors and CMR findings.In 9,712 patients (66±15 years, 67% men), there was an excellent correlation between stress LVEFAI and LVEF measured by expert (LVEFexpert) (r=0.94, p<0.001). Stress LVEFAI was associated with death (median [IQR] follow-up 4.5 [3.7-5.2] years) before and after adjustment for risk factors (adjusted hazard ratio [HR], 0.84 [95% CI, 0.82-0.87] per 5% increment, p<0.001). Stress LVEFAI had similar significant association with death occurrence compared with LVEFexpert. After adjustment, stress LVEFAI value showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.11; NRI=0.250; IDI=0.049, all p<0.001; LR-test p<0.001), with an incremental prognostic value over LVEFAI determined at rest. CONCLUSION: AI-based fully automated LVEF measured at stress is independently associated with the occurrence of death in patients undergoing stress CMR, with an additional prognostic value above traditional risk factors, inducible ischemia and LGE.

Impaired balance between coronary blood flow and myocardial metabolism in postpartum swine.

Understanding of the mechanisms contributing to the increased maternal susceptibility for major adverse cardiovascular events in the postpartum period remains poor. Accordingly, this study tested the hypothesis that the balance between coronary blood flow and myocardial metabolism is compromised during the puerperium period (35-45 days post-delivery) in swine. Systemic and coronary hemodynamic responses were assessed in anesthetized, open-chest control (nonpregnant) and puerperium/postpartum swine at baseline and in response to intravenous infusion of dobutamine (1-30 µg/kg/min). Blood pressure and heart rate were lower in postpartum swine at baseline and in response to dobutamine (P < 0.05). Coronary blood flow and myocardial oxygen delivery were significantly diminished at baseline in postpartum swine (P < 0.001), which corresponded with ∼35% reduction in myocardial oxygen consumption (MVO2) (P < 0.001). Postpartum swine displayed enhanced retrograde coronary flow, larger cardiomyocyte area (P < 0.01) and marked capillary rarefaction (P < 0.01). The relationship between coronary blood flow and heart rate (P < 0.05) or MVO2 (P < 0.001) was significantly diminished in postpartum swine as dobutamine increased MVO2 up to ∼135% in both groups. This reduction in myocardial perfusion was associated with decreases in myocardial lactate uptake (P < 0.001), increases in coronary venous PCO2 (P < 0.01) and decreased coronary venous pH (P < 0.01). These findings suggest an impaired balance between coronary blood flow and myocardial metabolism could contribute to the increased incidence of maternal myocardial ischemia and premature death in the postpartum period.

Insight into the cardioprotective effects of melatonin: shining a spotlight on intercellular Sirt signaling communication.

Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep-wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia-reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs.

Cardiac-derived extracellular vesicles improve mitochondrial function to protect the heart against ischemia/reperfusion injury by delivering ATP5a1.

BACKGROUND: Numerous studies have confirmed the involvement of extracellular vesicles (EVs) in various physiological processes, including cellular death and tissue damage. Recently, we reported that EVs derived from ischemia-reperfusion heart exacerbate cardiac injury. However, the role of EVs from healthy heart tissue (heart-derived EVs, or cEVs) on myocardial ischemia-reperfusion (MI/R) injury remains unclear. RESULTS: Here, we demonstrated that intramyocardial administration of cEVs significantly enhanced cardiac function and reduced cardiac damage in murine MI/R injury models. cEVs treatment effectively inhibited ferroptosis and maintained mitochondrial homeostasis in cardiomyocytes subjected to ischemia-reperfusion injury. Further results revealed that cEVs can transfer ATP5a1 into cardiomyocytes, thereby suppressing mitochondrial ROS production, alleviating mitochondrial damage, and inhibiting cardiomyocyte ferroptosis. Knockdown of ATP5a1 abolished the protective effects of cEVs. Furthermore, we found that the majority of cEVs are derived from cardiomyocytes, and ATP5a1 in cEVs primarily originates from cardiomyocytes of the healthy murine heart. Moreover, we demonstrated that adipose-derived stem cells (ADSC)-derived EVs with ATP5a1 overexpression showed much better efficacy on the therapy of MI/R injury compared to control ADSC-derived EVs. CONCLUSIONS: These findings emphasized the protective role of cEVs in cardiac injury and highlighted the therapeutic potential of targeting ATP5a1 as an important approach for managing myocardial damage induced by MI/R injury.

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

The factors of quality of life among patients after myocardial infarction in Poland: a cross-sectional study. The quality of life among patients after myocardial infarction.

The quality of life (QoL) is now recognised as a central indicator of the effectiveness of interventions especially in patients after myocardial infarction (MI). The QoL may be important predict poor outcomes in cardiac patients.The present work aims to increase knowledge of the level of QoL in patients after MI. Moreover, the paper analyses the QoL in relation to sociodemographic factors and the degree of functioning in chronic disease. The study was conducted among 231 patients who were hospitalized due to MI within the period of June 2021 to June 2022 in the Hospital in Racibórz in Poland. The WHO Quality of Life Questionnaire and the Chronic Disease Functioning Scale were used. The analysis showed a statistically significant correlation (coefficient value 0.5 <|r/rho|≤ 0.7) between general functioning in chronic disease and the average QoL (rho = 0.56; p < 0.001)and somatic QoL levels(rho = 0.52; p < 0.001), as well as a moderately strong positive correlation with the QoL level on the psychological domain (rho = 0.50; p < 0.001), social domain(rho = 0.48; p < 0.001) and environmental domain (rho = 0.43; p < 0.001). The results of this study suggested that healthcare workers adopts appropriate policies for the implementation of quality of life, which can reduce the number of repetitive referrals to the hospital and costs imposed on the health system.

Novel roles of κ-opioid receptor in myocardial ischemia-reperfusion injury.

Acute heart attack is the primary cause of cardiovascular-related death worldwide. A common treatment is reperfusion of ischemic tissue, which can cause irreversible damage to the myocardium. The number of mitochondria in cardiomyocytes is large, which generate adenosine triphosphate (ATP) to sustain proper cardiac contractile function, and mitochondrial dysfunction plays a crucial role in cell death during myocardial ischemia-reperfusion, leading to an increasing number of studies investigating the impact of mitochondria on ischemia-reperfusion injury. The disarray of mitochondrial dynamics, excessive Ca2+ accumulation, activation of mitochondrial permeable transition pores, swelling of mitochondria, ultimately the death of cardiomyocyte are the consequences of ischemia-reperfusion injury. κ-opioid receptors can alleviate mitochondrial dysfunction, regulate mitochondrial dynamics, mitigate myocardial ischemia-reperfusion injury, exert protective effects on myocardium. The mechanism of κ-OR activation during myocardial ischemia-reperfusion to regulate mitochondrial dynamics and reduce myocardial ischemia-reperfusion injury will be discussed, so as to provide theoretical basis for the protection of ischemic myocardium.

Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome: a Double-Blind, Randomized, Sham-Controlled Trial.

The CLIMACCS trial, a randomized, sham-controlled trial tested the CLinical efficacy of permanent internal mammary artery (IMA) device occlusion on symptoms in patients with chronic coronary syndrome (CCS), on coronary artery occlusive blood supply, and on myocardial ischemia. This was a prospective trial in 101 patients with CCS randomly allocated (1:1) to IMA device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study endpoint was the change in treadmill exercise time (ΔET in seconds, s) at 6 weeks after trial intervention. Secondary study endpoints were the changes in collateral flow index (CFI), and angina pectoris during a simultaneous 1-minute proximal balloon occlusion of a coronary artery. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. In the verum and placebo group, exercise time changed from 398±176s to 421±198s in the verum group (p=0.1745), and from 426±162s to 430±166s in the placebo group (p=0.55); DET amounted to +23±116s and +4±120s, respectively (p=0.44). CFI change during follow-up equalled +0.022±0.061 in the verum and-0.039±0.072 in the placebo group (p<0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20/48 patients of the verum, and in 9/47 patients of the placebo group (p=0.0242). In conclusion, permanent IMA device occlusion tends to augment treadmill exercise time in response to heightened coronary artery occlusive blood supply, the fact of which is reflected by mitigated symptoms and signs of myocardial ischemia.

Phytochemicals targeting ferroptosis in cardiovascular diseases: Recent advances and therapeutic perspectives.

Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

Fatal Outcome Due to Kounis Syndrome Following Fluorescein Retinal Angiography: A Case Report.

Kounis Syndrome (KS) is a clinical entity triggered by allergic or hypersensitivity reactions capable of inducing acute coronary events. Several causes can induce KS, including drugs and insect stings. Here, a rare case of post mortem assessment of fatal KS related to fluorescein retinal angiography has been reported. An 80-year-old man in follow-up for a retinal vein thrombosis underwent a retinal fluoroangiography. Approximately 30 min later, the patient complained of sweating and dizziness, and suddenly lost consciousness due to a cardiac arrest. Despite the immediate cardiopulmonary resuscitation, he died. The autopsy revealed foamy yellowish edema in the respiratory tract and coronary atherosclerosis with eccentric plaques partially obstructing the lumen. The routine histology highlighted lung emphysema and myocyte break-up with foci of contraction band necrosis at the myocardial tissue. Biochemistry showed increased serum tryptase, troponin, and p-BNP. Activated and degranulated (tryptase) mast cells were detected, using immunohistochemistry, in the larynx, lungs, spleen, and heart. Acute myocardial ischemia due to allergic coronary vasospasm related to fluorescein hypersensitivity has been assessed as cause of death. KS-related deaths are considered rare events, and the post mortem assessment of KS quite difficult. The integration of several investigations (gross and microscopic examination, biochemistry, immunohistochemistry) can provide useful findings to support the diagnosis, helping to reduce the unrecognized cases as much as possible.

Is ischemic stimulus involved for J wave augmentation during coronary angiography and intracoronary administration of normal saline?

BACKGROUND: J waves may be augmented by coronary angiography (CAG) or intracoronary drug administration but the underlying mechanism is unknown. PURPOSE: The effect of intracoronary normal saline (NS) on J waves were investigated. PATIENTS AND METHODS: After the standard CAG using iopamidol (IopamiroR Inj), NS was injected into the right coronary artery in 10 patients with and eight patients without J waves at the baseline. The 12-lead ECG was monitored, stored on a computer and retrieved later for measurement of the J wave amplitude before or during the coronary interventions. RESULTS: J waves in leads II, III and aVF at baseline increased significantly in each lead during the right CAG and NS injection into the right coronary artery. The J wave changes were similar between the two interventions and distinct similar alterations were observed in the QRS complex. We postulated that the ischemic myocardium that was induced during CAG or intracoronary NS administration slowed the conduction velocity of depolarization in the perfusion territory and delayed the timing of J waves to appear. Then, the delayed appearance of J waves would be less opposed by electromotive force from other areas resulting in augmentation. CONCLUSION: J wave augmentation was observed during CAG and intracoronary NS administration. As a mechanism of augmentation, we postulated that contrast media and NS induce myocardial ischemia and delay the timing of J waves to a point of less opposition by electromotive force from other areas. HIGHLIGHTS: J wave augmentation has been reported during intracoronary injection of contrast media or drugs. The present study confirmed that normal saline alone was able to augment J waves. Mechanistically, coronary interventions using anoxic solutions can cause regional myocardial ischemia and reduce the conduction velocity of depolarization. Then, delayed J waves are less opposed by the electromotive force from remote areas which leads to augmentation. When a drug is diluted in normal saline and given intracoronarily, changes in J waves can be due to normal saline. The pathophysiological and clinical significance of J waves augmented during coronary interventions need to be established.

Management of ROS and Regulatory Cell Death in Myocardial Ischemia-Reperfusion Injury.

Myocardial ischemia-reperfusion injury (MIRI) is fatal to patients, leading to cardiomyocyte death and myocardial remodeling. Reactive oxygen species (ROS) and oxidative stress play important roles in MIRI. There is a complex crosstalk between ROS and regulatory cell deaths (RCD) in cardiomyocytes, such as apoptosis, pyroptosis, autophagy, and ferroptosis. ROS is a double-edged sword. A reasonable level of ROS maintains the normal physiological activity of myocardial cells. However, during myocardial ischemia-reperfusion, excessive ROS generation accelerates myocardial damage through a variety of biological pathways. ROS regulates cardiomyocyte RCD through various molecular mechanisms. Targeting the removal of excess ROS has been considered an effective way to reverse myocardial damage. Many studies have applied antioxidant drugs or new advanced materials to reduce ROS levels to alleviate MIRI. Although the road from laboratory to clinic has been difficult, many scholars still persevere. This article reviews the molecular mechanisms of ROS inhibition to regulate cardiomyocyte RCD, with a view to providing new insights into prevention and treatment strategies for MIRI.

Comparative efficacy of sweated and non-sweated Salvia miltiorrhiza Bge. extracts on acute myocardial ischemia via regulating the PPARα/RXRα/NF-κB signaling pathway.

Salvia miltiorrhiza Bge. (S. miltiorrhiza) is a well-known traditional Chinese medicine for the treatment of cardiovascular diseases. The processing of S. miltiorrhiza requires the raw herbs to sweat first and then dry. The aim of this study was to investigate the anti-acute myocardial ischemia (AMI) of S. miltiorrhiza extracts (including tanshinones and phenolic acids) before and after sweating, and to further explore whether the "sweating" primary processing affected the efficacy of S. miltiorrhiza. The AMI animal model was established by subcutaneous injection of isoprenaline hydrochloride (ISO). After treatment, the cardiac function of rats was evaluated by electrocardiogram (ECG), biochemical, and histochemical analysis. Moreover, the regulation of S. miltiorrhiza extracts on the peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor α (RXRα)/nuclear transcription factor-kappa B (NF-κB) signaling pathway of rats was assessed by the Western blotting. The results showed that sweated and non-sweated S. miltiorrhiza extracts including tanshinones and phenolic acids significantly reduced ST-segment elevation in ECG and the myocardial infarction area in varying degrees. Meanwhile, sweated and non-sweated S. miltiorrhiza reversed the activities of aspartate transaminase (AST), lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB), and superoxide dismutase (SOD), as well as the levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in AMI rats. Concurrently, the results of Western blotting revealed that S. miltiorrhiza extracts regulated the PPARα/RXRα/NF-κB signaling pathway to exert an anti-inflammatory effect. Most importantly, sweated S. miltiorrhiza tanshinones extracts are more effective than the non-sweated S. miltiorrhiza, and the anti-inflammatory efficacy of tanshinones extract was also better than that of phenolic acid extract. Although phenolic acid extracts before and after sweating were effective in anti-AMI, there was no significant difference between them. In conclusion, both tanshinones and phenolic acids extracts of sweated and non-sweated S. miltiorrhiza promote anti-oxidative stress and anti-inflammatory against AMI via regulating the PPARα/RXRα/NF-κB signaling pathway. Further, the comparations between sweated and non-sweated S. miltiorrhiza extracts indicate that sweated S. miltiorrhiza tanshinones extracts have better therapeutic effects on AMI.

Myocardial Bridging in Patients Undergoing Coronary Angiography for Coronary Artery Disease.

Introduction Myocardial bridge is a rare, benign, normal anatomical variant of the coronary artery that puts the patient at risk for significant cardiac symptoms, resulting in myocardial ischemia, arrhythmia, and sudden cardiac death. The aim of the study was to assess the prevalence and characteristics of myocardial bridging (MB) in patients with chest pain undergoing coronary angiography. Methodology A total of 1301 patients presenting with chest pain suggestive of acute coronary syndrome with associated non-invasive supportive cardiac evaluation were subjected to coronary angiography by Philips Allura Xper FD10 Cath Lab (Philips Healthcare, Andover, MA) and evaluated. Results Out of 1301 patients, the mean age was 54.70 ± 11.41 years with a male-to-female ratio of 1.9:1. Tobacco use and diabetes mellitus were the most common associated risk factors (49% and 44%, respectively). MB was seen in 51 patients, making the prevalence 3.9%, with male predominance over females in the ratio of 3.9:1. The most common clinical presentation was unstable angina (UA) (n = 22, 43.1%), followed by stable angina (SA) (n = 11, 21.6%), non-ST-elevation myocardial infarction (NSTEMI) (n = 10, 19.6%), and ST-elevation myocardial infarction (STEMI) (n = 8, 15.7%). Myocardial bridges were more common among patients with stable coronary artery disease. The left anterior descending artery (n = 51, 3.9%) was involved in all the cases and the middle segment was affected in all patients with MB. Among patients with myocardial bridge, 26 patients (51%) had atherosclerosis and 25 patients had a normal artery. Among patients with myocardial bridge with atherosclerosis, 17 patients (65%) had atherosclerosis in the same artery in which the myocardial bridge was present. Among patients with myocardial bridge with atherosclerosis, nine patients (52%) had atherosclerosis proximal to the bridge, three patients (17%) had atherosclerosis distal to the bridge, and five patients (31%) had atherosclerosis both proximal and distal to the bridge. Conclusion The prevalence of MB in the Indian population is significantly lower than in the Western populations, and it is significantly higher in the male population with patients diagnosed as normal coronaries on coronary angiography.

Re-evaluation of the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria.

Ischemic heart disease, associated with high morbidity and mortality, represents a major challenge for the development of drug-based strategies to improve its prognosis. Results of pre-clinical studies suggest that agonists of cannabinoid CB2 receptors and multitarget cannabidiol might be potential cardioprotective strategies against ischemia-reperfusion injury. The aim of our study was to re-evaluate the cardioprotective effects of cannabinoids against ischemia-reperfusion injury according to the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria published recently by the European Union (EU) CARDIOPROTECTION COST ACTION. To meet the minimum criteria of those guidelines, experiments should be performed (i) on healthy small animals subjected to ischemia with reperfusion lasting for at least 2 hours and (ii) confirmed in small animals with comorbidities and co-medications and (iii) in large animals. Our analysis revealed that the publications regarding cardioprotective effects of CB2 receptor agonists and cannabidiol did not meet all three strict steps of IMPACT. Thus, additional experiments are needed to confirm the cardioprotective activities of (endo)cannabinoids mainly on small animals with comorbidities and on large animals. Moreover, our publication underlines the significance of the IMPACT criteria for a proper planning of preclinical experiments regarding cardiac ischemia-reperfusion injury.

A novel anti-inflammatory strategy for myocardial ischemia-reperfusion in rats with cinnamamide derivative compound 7.

Reperfusion after myocardial ischemia would aggravate myocardial structural and functional damage, known as myocardial ischemia-reperfusion (MI/R) injury. Cinnamamide derivatives have been reported to exert cardioprotective effects, and we have previously reported that compound 7 played a role in cardioprotection against MI/R via anti-inflammatory effect. However, exact mechanism underlying such beneficial action of compound 7 is still unclear. The protective effect of compound 7 was determined in H9c2 cells under H2O2 stimulation with or without nigerin (NLRP3 activator). Electrocardiogram, echocardiography, myocardial infarction size, histopathology and serum biochemical assay were performed in MI/R rats. Metabolomics in vivo and mRNA or protein levels of NLRP3, ASC, cleaved caspase-1 and its downstream IL-18 and IL-1ß were detected both in vitro and in vivo. Compound 7 significantly ameliorate H2O2-induced cardiomyocyte damage, which was supported by in vivo data determined by improved left ventricular systolic function and histopathological changes, reduced myocardial infarction area and cellular apoptosis in heart tissue. Cardiac differential metabolites demonstrated that compound 7 indeed altered the cardiac reprogramming of inflammation-related metabolites, which was evidenced by down-regulated cardiac inflammation by compound 7. Additionally, compound 7 alleviated myocardial injury by inhibiting the NLRP3 pathway rather than other members of the inflammasome both in vitro and in vivo, which was further evidenced by CETSA assay. Whereas, nigerin blocked the inhibitory activity of compound 7 against NLRP3. Cinnamamide derivative compound 7 ameliorated MI/R injury by inhibiting inflammation via NLRP3.