[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

Effect of preinitiated glucose-insulin-potassium strategy for patients with undergoing planned percutaneous coronary intervention: a systematic review and meta-analysis.

OBJECTIVES: Whether the glucose-insulin-potassium (GIK) should be used as an adjuvant therapy for ischaemic myocardial disease remains controversial nowadays reperfusion era. This meta-analysis aimed to assess the effects of preinitiated GIK for patients undergoing planned percutaneous coronary intervention (PCI). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of science, MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov were searched through 27 November 2022. ELIGIBILITY CRITERIA: Only randomised controlled trials involving participants preinitiated with GIK or placebo before planned PCI were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers used standardised methods to search, screen and code included trials. Risk of bias was assessed with the Cochrane tool. Pooled analysis was conducted using random or effects models according to the heterogeneity. Subgroup analyses were carried out for dosage of GIK and if with ongoing myocardial ischaemia. RESULTS: 13 randomised controlled trials (RCTs) including 3754 participants were evaluated. We found patients preconditioned with GIK before PCI showed a significant increase in Thrombolysis in Myocardial Infarction 3 flow events after angioplasty (OR 1.59, 95% CI 1.03 to 2.46, p=0.04), also revealed improved in-hospital left ventricular ejection fraction (weighed mean difference, WMD 1.62, 95% CI 0.21 to 3.03, p=0.02) and myocardial salvage index (WMD 0.09, 95% CI 0.01 to 0.16, p=0.03). Nevertheless, no benefit was observed in all-cause mortality neither on 30-day (OR 0.81, 95% CI 0.59 to 1.11, p=0.18) nor 6 months (OR 1.02, 95% CI 0.42 to 2.46, p=0.97). Furthermore, GIK intervention was associated with higher occurrences of complications such as phlebitis (OR 10.13, 95% CI 1.74 to 59.00, p=0.01) and hypoglycaemia (OR 10.43, 95% CI 1.32 to 82.29, p=0.03), but not hyperkalaemia (OR 9.36, 95% CI 0.50 to 175.27, p=0.13), liquid overload (OR 1.02, 95% CI 0.25 to 4.13, p=0.98) or in-hospital heart failure (OR 0.42, 95% CI 0.06 to 2.96, p=0.39). CONCLUSIONS: Our study shows preconditioning GIK exhibits myocardial reperfusion and cardiac function benefits for patients planning to receive PCI intervention, while also some complications such as phlebitis and hypoglycaemia accompany. PROSPERO REGISTRATION NUMBER: CRD42022326334.

Rho A/ROCK1 signaling-mediated metabolic reprogramming of valvular interstitial cells toward Warburg effect accelerates aortic valve calcification via AMPK/RUNX2 axis.

The aberrant differentiation of valvular interstitial cells (VICs) to osteogenic lineages promotes calcified aortic valves disease (CAVD), partly activated by potentially destructive hemodynamic forces. These involve Rho A/ROCK1 signaling, a mechano-sensing pathway. However, how Rho A/ROCK1 signaling transduces mechanical signals into cellular responses and disrupts normal VIC homeostasis remain unclear. We examined Rho A/ROCK1 signaling in human aortic valves, and further detected how Rho A/ROCK1 signaling regulates mineralization in human VICs. Aortic valves (CAVD n = 22, normal control (NC) n = 12) from patients undergoing valve replacement were investigated. Immunostaining and western blotting analysis indicated that Rho A/ROCK1 signaling, as well as key transporters and enzymes involved in the Warburg effect, were markedly upregulated in human calcified aortic valves compared with those in the controls. In vitro, Rho A/ROCK1-induced calcification was confirmed as AMPK-dependent, via a mechanism involving metabolic reprogramming of human VICs to Warburg effect. Y-27632, a selective ROCK1 inhibitor, suppressed the Warburg effect, rescued AMPK activity and subsequently increased RUNX2 ubiquitin-proteasome degradation, leading to decreased RUNX2 protein accumulation in human VICs under pathological osteogenic stimulus. Rho A/ROCK1 signaling, which is elevated in human calcified aortic valves, plays a positive role in valvular calcification, partially through its ability to drive metabolic switching of VICs to the Warburg effect, leading to altered AMPK activity and RUNX2 protein accumulation. Thus, Rho A/ROCK1 signaling could be an important and unrecognized hub of destructive hemodynamics and cellular aerobic glycolysis that is essential to promote the CAVD process.

A ROCK1 Inhibitior Fasudil Alleviates Cardiomyocyte Apoptosis in Diabetic Cardiomyopathy by Inhibiting Mitochondrial Fission in a Type 2 Diabetes Mouse Model.

Diabetes mellitus (DM) often involves cardiovascular complications; however, treatment regimens are limited. ROCK1 (rho-associated coiled-coil containing protein kinase 1) serves as a pathological factor in several diabetic complications. Herein, we aimed to explore the effect of Fasudil (a ROCK1 inhibitor) on the progress of cardiac dysfunction in type 2 DM (T2DM), and to explore the possible mechanisms. Type II diabetic mice models were established by inducing insulin resistance through a high-fat diet combined with low-dose streptozotocin (STZ) injection. NMCMs (neonatal mouse ventricular cardiac myocytes) in the control group were treated with 5.5 mM glucose, while those in the High Glucose (HG) group were treated with 33 mM glucose and 10 nmol/L insulin. In vivo, we found that type 2 diabetes enhanced the expression and activation of ROCK1 (p < 0.05). The ROCK1 inhibitor, Fasudil, prevented cardiac dysfunction, fibrosis, oxidative stress and myocardial ultrastructural disorders (p < 0.05) in the diabetic mice. In vitro, ROCK1 was upregulated in HG-induced cardiomyocytes, and ROCK1 inhibition using Fasudil reversed the increased apoptosis, consistent with in vivo results. Mechanistically, ROCK1 inhibition abrogated apoptosis, relieved mitochondrial fission, and efficiently attenuated the escalated production of reactive oxygen species in vitro and in vivo. The content of Ser616-phosphorylated dynamin-related protein 1 (Drp1) increased while ROCK1 led to apoptosis in HG-treated cardiomyocytes, which could be partly neutralized by ROCK1 inhibition with Fasudil, consistent with the in vivo results. Fasudil attenuated the cardiac dysfunction in diabetes by decreasing excessive mitochondrial fission via inhibiting Drp1 phosphorylation at serine 616.

Pulmonary artery closure in combination with patch technique for treating congenital heart disease combined with large patent ductus arteriosus: A clinical study of 9 cases.

OBJECTIVE: To document clinical experience of treating congenital heart disease combined with large patent ductus arteriosus with pulmonary artery closure in combination with patch technique. METHODS: Thirty-six patients (8 males and 28 females) who suffered from congenital heart disease and underwent hybrid surgery in the First Affiliated Hospital of Zhengzhou University from October 2010 to February 2014 were selected for this study. They aged 14 to 39 years and weighed 32.20 to 61.50 kg. Diameter of arterial duct was between 10 mm and 13 mm; 28 cases were tube type, 4 cases were funnel type and four cases were window type. All patients had moderate or severe pulmonary arterial hypertension; besides, there were 28 cases of ventricular septal defect, 16 cases of atrial septal defect, eight cases of aortic insufficiency, four cases of mitral stenosis and insufficiency and four cases of infectious endocarditis. Cardz Pulmonary Bypass (CPB) was established after chest was opened along the middle line. With the help of Transesophageal echocardiography, large patent ductus arteriosus was blocked off through pulmonary artery. Pulmonary artery was cut apart after blocking of heart. Large patent ductus arteriosus on the side of pulmonary artery was strengthened with autologous pericardial patch. RESULTS: Of 36 patients, 32 patients had patent ductus arteriosus closure device and four patients had atrial septal defect closure device. Pulmonary arteries of 36 cases were all successfully closed. Systolic pressure declined after closure ((54.86±19.23) mmHg vs (96.05±23.07) mmHg, p<0.05); average pulmonary arterial pressure also declined after closure ((39.15±14.83) mmHg vs (72.88±15.76) mmHg, p<0.05). The patients were followed up for one to fifty one months (average 11.5 months). Compared to before surgery, left atrial diameter, left ventricular diameter and pulmonary artery diameter all narrowed after surgery. Besides, clinical symptoms were relieved and cardiac function of the patients also improved. CONCLUSION: Hybrid surgery is feasible and safe in treating patients with large patent ductus arteriosus and congenital heart disease, which decreases surgical problems, shortens surgical time and lowers the incidence of complications.