Prognostic value of the SYNTAX score on myocardial injury and salvage in STEMI patients after primary percutaneous coronary intervention: a single-center retrospective observational study.

BACKGROUND: SYNTAX score (SS) was shown to positively correlate with postprocedural myocardial injury in patients after elective coronary artery intervention, but evidence about the association of SS with myocardial salvage in ST-segment elevation myocardial infarction (STEMI) patients is still needed. This study aimed to evaluate the prognostic value of SS for myocardial injury and salvage assessed by cardiac magnetic resonance (CMR) after primary percutaneous coronary intervention (PCI) in STEMI patients. METHODS: This single-center retrospective study consecutively enrolled STEMI patients who had undergone primary PCI within 12 h from symptom onset. Both angiography and CMR were performed during hospitalization, and patients were divided into low SS (SS ≤ 22), mediate-high SS (SS > 22) groups. Correlation and multivariable analyses were performed. RESULTS: A total of 149 STEMI patients (96 low SS, 53 mediate-high SS) were included. In terms of myocardial injury parameters, there was a positive correlation (p < 0.001, Spearman r = 0.292) between SS and infarct size (IS), and a negative correlation (p < 0.001, Spearman r = - 0.314) between SS and myocardial salvage index (MSI). In the multivariable model, SS (> 22 as categorical variable, OR = 2.245, 95% CI [1.002-5.053], p = 0.048; as continuous variable, OR = 1.053, 95% CI [1.014-1.095], p = 0.008) was significantly associated with high IS (≥ mean 35.43). The areas under the receiver operating characteristic (ROC) curves of SS for high IS and low MSI (≤ median 28.01) were 0.664 and 0.610. CONCLUSIONS: In STEMI patients undergoing primary PCI, SYNTAX score positively correlated with infarct size and negatively with myocardial salvage, indicating an independent predictive value of the myocardial injury.

Impact of Compound Hypertonic Saline Solution on Decompensated Heart Failure.

The aim of the present study was to evaluate the effects of hypertonic saline solution (C-HSS) with high dose furosemide on hospitalization time, readmission, and mortality in patients with New York Heart Association (NYHA) class III heart failure.Decompensated heart failure patients (NYHA III) with chronic ischemic or nonischemic cardiomyopathy and ejection fraction < 40% were divided into 2 groups in an open-label random manner: the first group received a 1-hour intravenous infusion of furosemide (100 mg) plus compound C-HSS (100 mL) twice daily and underwent serious water restriction (500 mL/day); the second group received furosemide intravenous bolus (100 mg) twice a day and water restriction (500 mL/day), without C-HSS. Both groups had normal sodium (120 mmol sodium) intake. After discharge, the two groups continued to receive 120 mmol Na/day and 500-1000 mL water/day.The first group (132 C-HSS patients) had an increase in urination, a reduction in hospitalization time (4 ± 2 versus 7 ± 2 days, P < 0.01), and a reduction in hospitalization costs (2210 RMB versus 3506 RMB, P < 0.01) compared with the second group (132 without C-HSS patients). During the follow-up period (36 ± 12 months), the first group had a significantly higher average readmission time (31.84 ± 7.58 months versus 15.60 ± 6.25 months, P < 0.01) and lower mortality rate (16.5% versus 31.9%, P < 0.01).The results suggest that periodical C-HSS administration, combined with serious water restriction and a normal sodium diet, significantly reduces the hospitalization time, readmission rate, and mortality in patients with NYHA class III HF.

Effects of Rosuvastatin and MiR-126 on Myocardial Injury Induced by Acute Myocardial Infarction in Rats: Role of Vascular Endothelial Growth Factor A (VEGF-A).

BACKGROUND The present study investigated the effects of VEGF-A targeted by miR-126 on myocardial injury after acute myocardial infarction (AMI) in rats, along with the contributions of rosuvastatin to the synergic effect. MATERIAL AND METHODS SD rats were obtained to construct AMI models by ligating their left anterior descending coronary arteries (LAD). We conducted echocardiography to check the 6 involved indexes: left ventricular ejection fractions (LVEF), fractional shortening (FS), left ventricular end-systolic volume (LVV), left ventricular end-diastolic volume (LVVd), cardiac output (CO), and heart rate (HR). Moreover, antibody sandwich enzyme-linked immunosorbent assay was carried out to determine MI markers: creatine kinase (CK), CK Isoenzyme (CK-MB), and Troponin I (cTn I). Dual-Luciferase Reporter Assay was performed to confirm the targeting of miR-126 and VEGF-A. MTT assay provided insight into the proliferation of myocardial fibroblasts. Finally, RT-RCR and Western blot were used for the detection of miR-126 and VEGF-A expressions in vivo and in vitro. RESULTS Luciferase activity assay showed that miR-126 transfection significantly decreased the relative luciferase activity in HEK293T cells when it was bound to normal 3' UTR of VEGF-A (P<0.05). In comparison to the control group, rats in the AMI model group had significantly lower LVEF, FS, and CO, and substantially higher LVVs, LVVd, HR, CK/U, CK-MB/U, and cTn-1/U (all P<0.05). Down-regulated miR-126 and up-regulated VEGF-A were also observed in MI models (P<0.05). CONCLUSIONS miR-126 and rosuvastatin have protective effects on AMI risk, and VEGF-A antagonizes effects on AMI is imposed by.

MELATONIN ATTENUATES RENAL ISCHEMIA-REPERFUSION INJURY BY REGULATING MITOCHONDRIAL DYNAMICS AND AUTOPHAGY THROUGH AMPK/DRP1.

ABSTRACT: Ischemia-reperfusion injury (IRI) often stems from an imbalance between mitochondrial dynamics and autophagy. Melatonin mitigates IRI by regulating mitochondrial dynamics. However, the precise molecular mechanism underlying the role of melatonin in reducing IRI through modulating mitochondrial dynamics remains elusive. The objective of this study was to investigate whether pretreatment with melatonin before IRI confers protective effects by modulating mitochondrial dynamics and mitophagy. Melatonin pretreatment was administered to HK-2 cells and live rats before subjecting them to hypoxia-reoxygenation or IRI, respectively. Cells and rat kidney models were evaluated for markers of oxidative stress, autophagy, mitochondrial dynamics, and the expression of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and phospho-AMPKα (P-AMPK). After renal IRI, increased mitochondrial fission and autophagy were observed, accompanied by exacerbated cellular oxidative stress injury and aggravated mitochondrial dysfunction. Nevertheless, melatonin pretreatment inhibited mitochondrial fission, promoted mitochondrial fusion, and attenuated autophagy levels. This intervention was correlated with a notable reduction in oxidative stress injury and remarkable restoration of mitochondrial functionality. Ischemia-reperfusion injury led to a decline in P-AMPK levels, whereas melatonin pretreatment increased the level of P-AMPK levels. Silencing AMPK with small interfering RNA exacerbated mitochondrial damage, and in this context, melatonin pretreatment did not alleviate mitochondrial fission or autophagy levels but resulted in sustained oxidative stress damage. Collectively, these findings indicate that melatonin pretreatment shields the kidneys from IRI by mitigating excessive mitochondrial fission, moderating autophagy levels, and preserving appropriate mitochondrial fission, all in an AMPK-dependent manner.

Naringenin promotes angiogenesis of ischemic myocardium after myocardial infarction through miR-223-3p/IGF1R axis.

Introduction: Naringenin exerts a protective effect on myocardial ischemia and reperfusion. It has been reported that miR-223-3p is a potential target for the treatment of myocardial infarction (MI). In view of the unreported correlation between Naringenin and miR-223-3p, this study was designed to confirm that the ameliorative effects of Naringenin on MI is directly related to the regulation of miR-223-3p. Methods: Through electrocardiogram detection, Masson pathological staining and immunohistochemistry of angiogenesis-related factors, alleviative effects of Naringenin on heart function, myocardial injury and angiogenesis in MI mice were observed individually. Hypoxic HUVECs were selected in the in vitro experimental model. The cell viability, angiogenesis and migration ability were analyzed to fathom out the pro-angiogenesis potential of Naringenin. The effect of Naringenin on miR-223-3p, as well as the downstream molecular mechanism was verified through bioinformatics analysis and rescue experiments. Results: Naringenin improved heart functions of MI mice, reduced degree of myocardial fibrosis, stimulated expressions of angiogenic factors and down-regulated level of miR-223-3p in myocardial tissue. In in vitro experiments, Naringenin increased the viability of hypoxic HUVECs, as well as the abilities of tube formation and migration, and further inhibited the expression of miR-223-3p. In the rescue trial, miR-223-3p mimic reversed the therapeutic effect of Naringenin. Type 1 insulin-like growth factor receptor (IGF1R), as a downstream target gene of miR-223-3p, partially offset the cellular regulatory effects of miR-223-3p after overexpression of IGF1R. Conclusions: Naringenin improves the angiogenesis of hypoxic HUVECs by regulating the miR-223-3p/IGF1R axis, and has the potential to promote myocardial angiogenesis in MI mice.

Different Changing Patterns of Three NOS-NO System Activities after Ischemia-Reperfusion in Rabbit with AMI.

NOS-NO system activity is closely correlated with ischemia-reperfusion injury (IRI) and NOS subtypes were suggested to play different roles in IRI. In this work, the activity of serum NOS, NO levels, and ischemic necrosis after reperfusion in rabbit with AMI at different time was studied. We also explored the NOS-NO system activity changes and its correlation with myocardial ischemia and necrosis. It shows that after reperfusion in rabbits with AMI, NO-NOS system activities present different changes at each time point due to inactivation of NO and iNOS activation, and different experimental animals, ischemia-reperfusion degree, and length of time will also lead to different research results. Therefore, it is necessary to conduct dynamic observation on animals from different species at multi-temporal point under the state of NOS-NO system activities, and simultaneously detect inflammatory factor, MDA, and SOD indexes. Therefore, it is a must to conduct relevant drug research studies to make NOS-NO system activities maintain the level in favor of ideal myocardial ischemia reperfusion.

Homocysteine induces mitochondrial dysfunction and oxidative stress in myocardial ischemia/reperfusion injury through stimulating ROS production and the ERK1/2 signaling pathway.

Acute oxidative stress and mitochondrial dysfunction are crucial for acute myocardial ischemia-reperfusion (AMI/R) injury, which may induce cell or mitochondrial membrane rupture and myocardial infarction. Plasma homocysteine (Hcy) expression levels are positively associated with risk of cardiovascular disease, and ERK1/2 exert anti-apoptotic and cardioprotective effects on AMI/R injury. However, the precise molecular mechanism of action underlying the effects of Hcy and the ERK1/2 signaling pathway on mitochondrial dysfunction and oxidative stress in AMI/R injury remains unclear. In the present study, AMI/R injury models were established in an animal model treated with Hcy and in H9C2 cells that were treated with hypoxia-reoxygenation. Mitochondrial function and oxidative stress were evaluated. The results demonstrated that Hcy enhanced ERK1/2 protein expression levels and oxidative stress, induced cytochrome c translocation and mitochondria dysfunction, and caused cardiac dysfunction in rats with AMI/R injury. However, an ERK1/2 inhibitor effectively protected AMI/R injury rats from Hcy-induced cardiac dysfunction and oxidative stress. In conclusion, Hcy induced mitochondrial dysfunction and oxidative stress in AMI/R injury through stimulating ROS production and the ERK1/2 signaling pathway. An ERK1/2 inhibitor may be an effective new therapeutic method for treating Hcy-induced cardiac dysfunction in patients with AMI/R injury.