Tfeb-Mediated Transcriptional Regulation of Autophagy Induces Autosis during Ischemia/Reperfusion in the Heart

Autosis is a unique form of cell death with characteristic morphological and biochemical features caused by dysregulated autophagy. Autosis is observed in the heart during the late phase of ischemia/reperfusion (I/R), when marked accumulation of autophagosomes is induced. We previously showed that the excessive accumulation of autophagosomes promotes autosis in cardiomyocytes. Although the inhibition of autophagic flux via the upregulation of Rubicon induces the accumulation of autophagosomes during I/R, it appears that additional mechanisms exacerbating autophagosome accumulation are required for the induction of autosis. Here, we show that Tfeb contributes to the induction of autosis during the late phase of I/R in the heart. During myocardial reperfusion, Tfeb is activated and translocated into the nucleus, which in turn upregulates genes involved in autophagy and lysosomal function. The overexpression of Tfeb enhanced cardiomyocyte death induced by a high dose of TAT-Beclin 1, an effect that was inhibited by the downregulation of Atg7. Conversely, the knockdown of Tfeb attenuated high-dose TAT-Beclin1-induced death in cardiomyocytes. Although the downregulation of Tfeb in the heart significantly decreased the number of autophagic vacuoles and inhibited autosis during I/R, the activation of Tfeb activity via 3,4-dimethoxychalcone, an activator of Tfeb, aggravated myocardial injury during I/R. These findings suggest that Tfeb promotes cardiomyocyte autosis during the late phase of reperfusion in the heart.

Effects of Levosimendan Preconditioning on Left Ventricular Remodeling after Myocardial Reperfusion in Acute Myocardial Infarction Patients Receiving Percutaneous Coronary Intervention

Objective: Levosimendan is a novel drug often used to treat heart failure. We aimed to explore the effects of levosimendan preconditioning on left ventricular remodeling (LVR) after myocardial reperfusion in acute myocardial infarction (AMI) patients receiving the percutaneous coronary intervention (PCI). Methods: A total of 258 AMI patients treated from January 2018 to September 2020 were randomly divided into control and observation groups. Based on conventional drug therapy, levosimendan was given 30 min before PCI for the observation group, and dobutamine was intravenously injected for the control group. Baseline data, thrombolysis in myocardial infarction (TIMI) blood flow grade, myocardial injury markers, and LVR indices were compared, and the influencing factors for LVR were analyzed. Results: After treatment, various degrees of blood perfusion were found, and the TIMI grade was better than that before treatment in both groups (P < .05). The levels of aspartate aminotransferase, creatine kinase-MB, cardiac troponin T, and brain natriuretic peptide (BNP) declined in both groups, more significantly in the observation group (P < .05). Left ventricular end-systolic diameter, left ventricular end-diastolic diameter and left ventricular end-diastolic volume declined, whereas left ventricular ejection fraction rose in both groups, more significantly in the observation group (P < .05). Age and BNP were risk factors for LVR, whereas levosimendan preconditioning was a protective factor (P < .05). Conclusion: Levosimendan preconditioning can protect cardiac function and promote the recovery of the left ventricular structure. Age and BNP are risk factors for LVR after myocardial reperfusion in AMI patients undergoing PCI, and levosimendan preconditioning is a protective factor.

Epidemiology of Post-Infarction Ventricular Septal Rupture in Patients Undergoing Surgical Repair at Different Times from the Development of Acute Myocardial Infarction

Introduction. The article is dedicated to the epidemiological aspects of the mechanical complication of acute myocardial infarction (AMI), particularly post-infarction ventricular septal rupture (VSR), problematic issues of its etiology and localization. Mortality of such patients is determined by rapid development of hemodynamic disorders and their severity, unpredictable clinical course, and the difficulty of early diagnosis. In addition, the high mortality rate of patients, especially when correcting the ventricular septal defect at the early stages after AMI, leaves open the question of the tactics of surgical treatment. The influence of certain risk factors of ischemic heart disease (IHD) on the development of post-infarction VSR is also considered. The aim. To study the epidemic features of post-infarction VSR in patients with different terms of surgical intervention after the development of AMI. Materials and methods. This study presents a retrospective analysis of 90 patients with coronary artery disease complicated by post-infarction VSR, who underwent surgical intervention for the period 2002-2019. The ages of hospitalized patients with post-infarction VSR ranged from 29 to 81 years. All the patients were divided into 3 groups depending on the time interval from AMI to surgical intervention. Results and discussion. It was found that post-infarction VSR is more common in men in the age range of 45-74 years after the manifestation of the first transmural AMI. More than a half of post-infarction VSR cases (56.7%) are associated with anterior localization of the ruptures in consequence of anterior AMI. Since the leading role in the treatment of AMI belongs to percutaneous coronary interventions (PCI), we analyzed the use of various reperfusion techniques to restore coronary blood flow in patients with post-infarction VSR. The analysis suggests that there are no statistically significant differences between the studied groups of patients with post-infarction VSR who underwent myocardial reperfusion (p = 0.103). Conclusions. The presence of chronic renal failure (CRF) in patients in the early post-infarction period can complicate the course of post-infarction VSR and affect perihospital mortality. The absence or untimeliness of myocardial reperfusion increases the risk of developing this complication of AMI. The ambiguous prognosis of treatment of post-infarction VSR makes a serious problem for clinicians.