Toxicokinetics of Arenobufagin and its Cardiotoxicity Mechanism Exploration Based on Lipidomics and Proteomics Approaches in Rats

Arenobufagin (ArBu), one of the main active bufadienolides of toad venom with cardiotonic effect, analgesic effect, and outstanding anti-tumor potentiality, is also a potential cardiotoxic component. In the present study, the cardiac effect of ArBu and its underlying mechanism were explored by integrating data such as heart rates, toxicokinetics, myocardial enzyme and brain natriuretic peptide (BNP) activity, pathological sections, lipidomics and proteomics. Under different doses, the cardiac effects turned out to be different. The oral dose of 60 mg/kg of ArBu sped up the heart rate. However, 120 mg/kg ArBu mainly reduced the heart rate. Over time, they all returned to normal, consisting of the trend of ArBu concentration-time curve. High concentrations of myocardial enzymes and BNP indicated that ArBu inhibited or impaired the cardiac function of rats. Pathological sections of hearts also showed that ArBu caused myocardial fiber disorder and rupture, in which the high-dose group was more serious. At the same time, serum and heart tissue lipidomics were used to explore the changes in body lipid metabolism under different doses. The data indicated a larger difference in the high-dose ArBu group. There were likewise many significant differences in the proteomics of the heart. Furthermore, a multi-layered network was used to integrate the above information to explore the potential mechanism. Finally, 4 proteins that were shown to be significantly and differentially expressed were validated by targeted proteomics using parallel reaction monitoring (PRM) analysis. Our findings indicated that ArBu behaved as a bidirectional regulation of the heart. The potential mechanism of cardiac action was revealed with the increased dose, which provided a useful reference for the safety of clinical application of ArBu.

In Depth Review of COVID-19 Effect on CVS

Corona virus disease 2019 (covid-19) is global pandemic affecting 185 countries and > 30,00,000 patient worldwide as of April 28,2020 COVID-19 is caused by severe acute respiratory syndrome corona virus. Which invades cells through the angiotensin – converting enzyme 2 receptor. Among patient with COVID-19, there is a high prevalence of cardiovascular disease and > 7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin – converting enzyme 2 serves as the portal for infection, the role of angiotensin – converting enzyme inhibitor or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection. Immunosuppression and posttransplant management. Primary cardiac manifestation includes acute myocarditis, myocardial infarction, arrhythmia and abnormal clotting. The disease does not discrimate but increasing age & the presence of comorbidities are associated with severe form of the disease and poor outcomes. While our knowledge of COVID-19 continues to rapidly expend, this review highlights recent advances in our understanding of the interaction between COVID-19 & the cardiovascular system. Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists and cardiologists. Clinical and diagnostic details of cardiovascular involvement in these patients a mostly limited to biochemical markers. Cardiovascular drugs the cardiac effect of therapeutic agent on the illness continue to be under investigation with an increasing number of patients newer promising therapies and ongoing clinical trials the exact mechanisms & extent to which this risk. Factors contribute to outcomes will be clearer in the future.

Effects of nifedipine on fetal cardiac function in preterm labor

ObjectivesTo evaluate the effects of nifedipine treatment on fetal hemodynamics and cardiac function during preterm labor. This prospective study assessed several quantitative parameters of fetal cardiac circulation and function, and found no significant changes at 48 h after nifedipine treatment. These findings suggest that tocolytic nifedipine may be safe for fetuses. It supports clinicians to use nifedipine treatment for tocolysis without any cardiac effect on the fetus.MethodsA prospective cohort study was conducted at a tertiary hospital between January 2016 and October 2017. A total of 45 pregnant women who required nifedipine for preterm labor were included in this study. Fetal Doppler ultrasound was performed and fetal systolic and diastolic function was measured prior to, and 48 h after, the first nifedipine treatment. Conventional Doppler parameters were used to evaluate fetal heart function and hemodynamic changes. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and the sphericity index were also evaluated to assess changes in fetal cardiac morphology.ResultsNo significant changes in fetal Doppler parameters were observed following nifedipine tocolysis. There was no significant difference in the fetal cardiac function parameters of both ventricles before vs. after nifedipine treatment. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, and sphericity index values were unchanged following nifedipine treatment.ConclusionsOral administration of nifedipine did not to alter fetal cardiac function or morphology. Fetal cardiac parameters and various Doppler indices were unchanged following nifedipine treatment. Maternal nifedipine treatment does not appear to have any significant effect on fetal cardiac function.

Preclinical cardiac organ damage during statin treatment in patients with inflammatory joint diseases: the RORA-AS statin intervention study

Objective Statin treatment has been associated with reduction in blood pressure and arterial stiffness in patients with inflammatory joint diseases (IJD). We tested whether statin treatment also was associated with regression of preclinical cardiac organ damage in IJD patients. Methods Echocardiography was performed in 84 IJD patients (52 RA, 20 ankylosing spondylitis, 12 psoriatric arthritis, mean age 61 (9) years, 63% women) without known cardiovascular disease before and after 18 months of rosuvastatin treatment. Preclinical cardiac organ damage was identified by echocardiography as presence of left ventricular (LV) hypertrophy, LV concentric geometry, increased LV chamber size and/or dilated left atrium. Results At baseline, hypertension was present in 63%, and 36% used biologic DMARDs (bDMARDs). Preclinical cardiac organ damage was not influenced by rosuvastatin treatment (44% at baseline vs 50% at follow-up, P = 0.42). In uni- and multivariable logistic regression analyses, risk of preclinical cardiac organ damage at follow-up was increased by higher baseline body mass index [odds ratio (OR) 1.3, 95% CI: 1.1, 1.5, P = 0.01] and presence of preclinical cardiac organ damage at baseline (OR 6.4, 95% CI: 2.2, 18.5, P = 0.001) and reduced by use of bDMARDs at follow-up (OR 0.3, 95% CI: 0.1, 0.9, P = 0.03). Conclusion Rosuvastatin treatment was not associated with a reduction in preclinical cardiac organ damage in IJD patients after 18 months of treatment. However, use of bDMARDS at follow-up was associated with lower risk of preclinical cardiac organ damage at study end, pointing to a possible protective cardiac effect of bDMARDs in IJD patients. ClinicalTrials.gov https://clinicaltrials.gov/NCT01389388

Delayed myocardial enhancement in children with different types of cardiomyopathy: a diagnostic and prognostic tool

Background The pattern of late gadolinium enhancement (LGE) in cardiomyopathy is quite different in children compared to adults. In addition, the data about LGE imaging in children are still restricted, so the goal was to study the role of cardiac magnetic resonance (CMR) with different techniques, including LGE images in diagnosis and evaluation of different types of cardiomyopathy in children. Results In group A (enhancement group), LVEDV 146.2 (144) ml, indexed LVEDV 81.8 (195) ml, LVESV 50 (357) ml, indexed LVESV 47.5 (243) ml, and LVEF 36% (64%), and a major adverse effect was found in 12 out of 15 cases (80%). However, in group B (non-enhancement group), the results were LVEDV 72 (303) ml, indexed LVEDV 75 (318) ml, LVESV 30 (220) ml, indexed LVESV 37.1 (189) ml, and LVEF 45.79% (65%), and a major adverse cardiac effect was found in 2 out of 16 cases (12.5%). The LVEF was lower, and LV volume indices including LVEDV and LVESV were higher in patients with LGE compared to those without LGE with a statistically significant difference (p value = 0.001, p value = 0.003, and p value = 0.005, respectively). Furthermore, it was also found that a major adverse effect occurs with higher incidence in enhancement cases (92%) as compared to non-enhancement cases (12.5%) with a statistically significant difference (p value ≤ 0.001). LGE was found in 15 cases out of 31 cases (48.4%); however, the remaining 13 cases had no contrast study. Conclusion Cardiac MRI can be considered as an important non-invasive imaging modality, not only for assessment but also for differentiation between ischemic and non-ischemic cardiomyopathy in the pediatric age group. Using its different techniques allows a better assessment of morphologic and functional parameters in cardiomyopathy. Moreover, the late gadolinium enhancement is regarded as a promising non-invasive tool in the detection and quantification of myocardial scars. That is considered of high importance in diagnosis, categorization, and detection of etiology in most cases of different types of cardiomyopathy, in addition to risk stratification that can be an essential step in patient management.