Protección miocárdica

Chin J Nat Med. 2022 Dec;20(12):902-913. doi: 10.1016/S1875-5364(22)60213-9.

ABSTRACT

Curculigo orchioides (CUR) and Epimedium (EPI) are traditional Chinese medicines with estrogen-like biological activity, called Xianmao and Xianlingpi (Er-xian) in Chinese. However, whether Er-xian exerts protective effects on myocardial ischemia-reperfusion injury (MIRI) is unknown. This study aimed to investigate the cardioprotective effects of Er-xian preconditioning against MIRI and the underlying mechanisms. CUR or EPI was administered intragastrically to aged female rats as a monotherapy or combination therapy. 2 weeks later, a rat MIRI model was established. Myocardial infarction size, myocardial morphology, cTnT, cell apoptosis rate, intracellular calcium concentration, mitochondrial permeability transition pore (MPTP) opening and reperfusion injury salvage kinase (RISK) signaling pathway molecules were observed after the surgery. To evaluate the mechanisms of Er-xian, estrogen receptors antagonists ICI 182780 and G15 were used. In this study, Er-xian notably alleviated myocardial tissue damage, maintained mitochondrial morphology, reduced infarct size and cardiac markers, and increased sera levels of E2. Moreover, Er-xian inhibited calcium overload and mPTP opening, and decreased cardiomyocyte apoptosis. We found that the dual therapy of CUR and EPI elicited more noticeable results than CUR or EPI monotherapy. The significant protective effects of Er-xian on ischemia-reperfusion myocardium were attributed to the up-regulation of AKT, ERK1/2 and GSK-3β phosphorylation levels. The cardioprotective effects of Er-xian were significantly reduced after estrogen receptor blockade, especially GPER30. These results indicate that Er-xian attenuates MIRI through RISK signaling pathway and estrogen receptors are the critical mediators.

PMID:36549804 | DOI:10.1016/S1875-5364(22)60213-9

Eur J Pharmacol. 2022 Dec 19:175472. doi: 10.1016/j.ejphar.2022.175472. Online ahead of print.

ABSTRACT

This study aimed to investigate the alterations of myocardial succinate and fumarate levels with or without succinate dehydrogenase (SDH) inhibitor dimethyl malonate during 24 hours of lipopolysaccharides (LPS) challenge, as well as the effects of dimethyl malonate on the impaired cardiac tissue. Myocardial succinate and fumarate levels were increased in the initial 9 hours of LPS challenge. During this time, dimethyl malonate increased the succinate level, decreased the fumarate level, aggravated the cardiac dysfunction, reduced the oxidative stress, had little effect on interleukin-1β production, promoted interleukin-10 production and bothered the ATP production. Co-treatment with exogenous succinate significantly increased interleukin-1β production in this period. After 12 hours of LPS challenge, myocardial the succinate level increased sharply, while the fumarate level gradually decreased. During 12-24 hours of LPS challenge, dimethyl malonate effectively reduced the succinate level, increased the fumarate level, improved cardiac dysfunction, inhibited interleukin-1β production, and had little effect on oxidative stress, interleukin-10 production, and ATP production. LPS challenge also significantly increased the myocardial succinate receptor 1 expression and circulating succinate level. Inhibition of succinate receptor 1 significantly reduced the mRNA expression of interleukin-1β. In conclusion, the current study suggests that myocardial succinate accumulates during LPS challenge, and that SDH activity may be transformed (from forward to reversed) and involved in a line of stress response. Dimethyl malonate inhibits SDH and, depending on the time of treatment, reduces LPS-induced cardiac impairment. Furthermore, accumulated succinate exerts pro-inflammatory effects partly via succinate receptor 1 signaling.

PMID:36549501 | DOI:10.1016/j.ejphar.2022.175472

Diabetes Obes Metab. 2022 Dec 22. doi: 10.1111/dom.14950. Online ahead of print.

ABSTRACT

BACKGROUND: Hepatic steatosis is a recognised risk factor for cardiovascular disease (CVD). However, its effect on patient outcomes following acute myocardial infarction (AMI) remains poorly understood. This study examines the prevalence and prognosis of hepatic steatosis and fibrosis in post-AMI patients.

METHODS: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using hepatic steatosis index and fibrosis-4 index respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis.

RESULTS: Of 5,765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated BMI and increased metabolic burden of diabetes, hypertension and hyperlipidemia. Patients with hepatic steatosis (24.6% vs 20.9% mortality, p<0.001) and advanced fibrosis (45.6% vs 32.9% mortality, p<0.001) had higher all-cause mortality rates compared to their respective counterparts. Hepatic steatosis (aHR 1.364, 95%CI 1.145-1.625, p=0.001) was associated with all-cause mortality after adjustment for confounders. Survival curves demonstrated excess mortality in patients with hepatic steatosis compared to those without (p=0.002).

CONCLUSIONS: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors. This article is protected by copyright. All rights reserved.

PMID:36546614 | DOI:10.1111/dom.14950

Physiol Res. 2022 Dec 22. Online ahead of print.

ABSTRACT

Exercise can improve the cardiovascular health. However, the mechanism contributing to its beneficial effect on elderly patients with myocardial infarction is obscure. 20-month-old male Sprague-Dawley rats were used to establish myocardial infarction (MI) model by permanent ligation of the left anterior descending coronary artery (LAD) of the heart, followed by 4-week interval exercise training on a motor-driven rodent treadmill. The cardiac function, myocardial fibrosis, apoptosis, oxidative stress, and inflammatory responses were determined by using pressure transducer catheter, polygraph physiological data acquisition system, Masson's trichrome staining, and ELISA to evaluate the impact of post-MI exercise training on MI. Western blot were performed to detect the activation of AMPK/SIRT1/ PGC-1alpha signaling in the hearts of aged rats. Exercise training significantly improved cardiac function and reduced the cardiac fibrosis. In infarcted heart, the apoptosis, oxidative stress, and inflammation were significantly reduced after 4-week exercise training. Mechanistically, AMPK/SIRT1/PGC-1alpha pathway was activated in the myocardial infarction area after exercise training, which might participate in the protection of cardiac function. Exercise training improves cardiac function in MI rats through reduction of apoptosis, oxidative stress, and inflammation, which may mediate by the activation of AMPK/SIRT1/PGC-1alpha signaling pathway.

PMID:36545879

Cardiovasc Ther. 2022 Dec 5;2022:1652315. doi: 10.1155/2022/1652315. eCollection 2022.

ABSTRACT

OBJECTIVE: Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI.

METHODS: Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships.

RESULTS: SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia.

CONCLUSIONS: Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.

PMID:36545243 | PMC:PMC9744614 | DOI:10.1155/2022/1652315

Bone. 2022 Dec 18:116647. doi: 10.1016/j.bone.2022.116647. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular effects of osteoporosis medications have recently been highlighted. Although oral and intravenous bisphosphonates are assumed to have similar cardiovascular safety, few head-to-head comparisons exist. The cardiovascular safety of teriparatide is unknown. Aim We conducted a pharmacovigilance safety study of cardiac events using real-life adverse event reports from alendronate, zoledronic acid and teriparatide users.

METHODS: Adverse drug reactions were obtained from Vigibase, a WHO database of individual case safety reports (ICSRs) from 130 countries (1967-2020). ISCRs for atrial fibrillation (AF), angina pectoris, arteriosclerosis coronary artery (ACA), cardiac arrhythmias, coronary artery disease (CAD), thromboembolic events (TE), ischaemic heart disease (IHD), torsade de pointes/QT prolongation (TDP) associated with alendronate, zoledronic acid and teriparatide use were extracted. Data were included in a disproportionality analysis where the lower end of the 95 % credibility interval for the information component (IC025), showing a statistical association when >0. Head-to-head comparisons of ISCRs were estimated by age-adjusted odds ratios and 95 % confidence intervals.

RESULTS: 465 episodes of angina, 287 ACA, 13,385 arrhythmias, 792 CAD, 6743 TE, 3264 IHD, 1037 myocardial infarcts, and 3714 TDP events were recorded across 50,365 alendronate, 52,436 zoledronic acid and 137,629 teriparatide users. There was a significant association between alendronate and zoledronate with all outcomes except MI. Teriparatide use was associated with AF, arrythmias and angina only. In head-to-head comparisons, teriparatide use was associated with fewer ACA and CAD events than alendronate and fewer ACA than zoledronic acid.

DISCUSSION: Osteoporosis medication use is associated with adverse cardiac events, except for MI, and these appear to be more common with oral and intravenous bisphosphonates than teriparatide. Our data do not support differential effects of oral and intravenous bisphosphonates on cardiac events. Mechanisms whereby teriparatide may be cardio-protective warrant further investigation.

PMID:36543300 | DOI:10.1016/j.bone.2022.116647

Ann Thorac Cardiovasc Surg. 2022 Dec 22. doi: 10.5761/atcs.oa.22-00144. Online ahead of print.

ABSTRACT

PURPOSE: To compare the myocardial protective efficacy of del Nido cardioplegia (DNC) with St. Thomas blood cardioplegia (SBC) in adult cardiac surgery.

METHODS: From January to December 2021, all the patients who underwent elective cardiac operation were randomly divided into two cohorts based on the type of cardioplegia: DNC group and SBC group. Three categories of variables were compared: patient demographics, clinical variables, and laboratory variables.

RESULTS: A total of 133 patients were enrolled in this study: DNC group, n = 65; and SBC group, n = 68. Except that the volume of cardioplegia administration were obvious less in the DNC group (P <0.01), no significant difference was found in the other postoperative clinical variables (P >0.05). No statistical significance was proved (P >0.05) in postoperative troponin I, creatine kinase, and B-type natriuretic peptide. The malondialdehyde concentration was higher in the SBC group, whether it is at 4 hours (P <0.05) or 24 hours (P >0.05) after operation. At the same two points in time, the change in superoxide dismutase activity was more significant in the SBC group (P <0.05).

CONCLUSION: The DNC cardioplegia was safe and effective on adult myocardium protection. The potential antioxidant stress effect in DNC may provide a direction for further improvement on the formula of cardioplegic solution.

PMID:36543178 | DOI:10.5761/atcs.oa.22-00144

Pacing Clin Electrophysiol. 2022 Dec 21. doi: 10.1111/pace.14650. Online ahead of print.

ABSTRACT

Brugada Syndrome is a controversial disease whose pathophysiology is still far from being fully understood. Unlike other cardiological disorders, a definite etiology has not yet been established so that it could be summarized under two main chapters: "functional" or "organic", "repolarization" or "depolarization" disorder. Despite initial descriptions leaned towards the organic substrate and delayed depolarization features, functional and repolarization theories have attracted most of the Cardiological attention for many years. Data from electrocardiography, endocavitary tracings, electroanatomic mapping and histopathology, however, demonstrated that Brugada Syndrome is mainly characterized by structural myocardial changes mostly at the right ventricular outflow tract, but also at the right ventricle and by delayed conduction at the same sites. Conduction disorders at different levels may also be present and identify patients at high risk for major arrhythmic events. The aim of the present review is to provide the current state of art of the pathophysiology of BrS, focusing on electro-vectorcardiography and electrophysiological features, histopathology, echocardiography and cardiac magnetic resonance imaging. This article is protected by copyright. All rights reserved.

PMID:36542434 | DOI:10.1111/pace.14650

Function (Oxf). 2022 Nov 1;4(1):zqac055. doi: 10.1093/function/zqac055. eCollection 2023.

ABSTRACT

We aimed to determine the pathophysiological impact of heart rate (HR) slowing on cardiac function. We have recently developed a murine model in which it is possible to conditionally delete the stimulatory heterotrimeric G-protein (Gαs) in the sinoatrial (SA) node after the addition of tamoxifen using cre-loxP technology. The addition of tamoxifen leads to bradycardia. We used this approach to examine the physiological and pathophysiological effects of HR slowing. We first looked at the impact on exercise performance by running the mice on a treadmill. After the addition of tamoxifen, mice with conditional deletion of Gαs in the SA node ran a shorter distance at a slower speed. Littermate controls preserved their exercise capacity after tamoxifen. Results consistent with impaired cardiac capacity in the mutants were also obtained with a dobutamine echocardiographic stress test. We then examined if HR reduction influenced pathological cardiac hypertrophy using two models: ligation of the left anterior descending coronary artery for myocardial infarction and abdominal aortic banding for hypertensive heart disease. In littermate controls, both procedures resulted in cardiac hypertrophy. However, induction of HR reduction prior to surgical intervention significantly ameliorated the hypertrophy. In order to assess potential protein kinase pathways that may be activated in the left ventricle by relative bradycardia, we used a phospho-antibody array and this revealed selective activation of phosphoinositide-3 kinase. In conclusion, HR reduction protects against pathological cardiac hypertrophy but limits physiological exercise capacity.

PMID:36540889 | PMC:PMC9761894 | DOI:10.1093/function/zqac055

BMC Psychiatry. 2022 Dec 20;22(1):809. doi: 10.1186/s12888-022-04457-2.

ABSTRACT

BACKGROUND: Long-term psychological impacts of the COVID-19 pandemic on healthcare workers remain unknown. We aimed to determine the one-year progression of burnout and mental health since pandemic onset, and verify if protective factors against psychological distress at the beginning of the COVID-19 pandemic (Cyr et al. in Front Psychiatry; 2021) remained associated when assessed several months later.

METHODS: We used validated questionnaires (Maslach Burnout Inventory, Hospital Anxiety and Depression and posttraumatic stress disorder [PTSD] Checklist for DSM-5 scales) to assess burnout and psychological distress in 410 healthcare workers from Quebec, Canada, at three and 12 months after pandemic onset. We then performed multivariable regression analyses to identify protective factors of burnout and mental health at 12 months. As the equivalent regression analyses at three months post-pandemic onset had already been conducted in the previous paper, we could compare the protective factors at both time points.

RESULTS: Prevalence of burnout and anxiety were similar at three and 12 months (52% vs. 51%, p = 0.66; 23% vs. 23%, p = 0.91), while PTSD (23% vs. 11%, p < 0.0001) and depression (11% vs. 6%, p = 0.001) decreased significantly over time. Higher resilience was associated with a lower probability of all outcomes at both time points. Perceived organizational support remained significantly associated with a reduced risk of burnout at 12 months. Social support emerged as a protective factor against burnout at 12 months and persisted over time for studied PTSD, anxiety, and depression.

CONCLUSIONS: Healthcare workers' occupational and mental health stabilized or improved between three and 12 months after the pandemic onset. The predominant protective factors against burnout remained resilience and perceived organizational support. For PTSD, anxiety and depression, resilience and social support were important factors over time.

PMID:36539718 | PMC:PMC9763813 | DOI:10.1186/s12888-022-04457-2