Vitamin E Attenuates Cardiomyopathy Via Alleviation of Autophagic Stress

Introduction: Vitamin E (Vit E) is well known antioxidant. Bisphenol A (BPA), widely used industrial chemical product, is associated with increased risk for cardiac diseases to identify the potential protective effect of Vit E on BPA induced cardiomyopathy by alleviation of oxidative and autophagic stress through its antioxidant effect. Materials and Methods: Twenty –four adult male rates were used in the study. They were randomly divided into 4 groups; negative control, vit E positive control, BPA, and vit E treated group. All chemicals were given orally via gastric gavage for 14 days. Rats were sacrificed and their hearts were dissected out. Serum, cardiac homogenates, and cardiac tissues were obtained for biochemical and histopathological evaluation. Results: There were significant increase in serum DH and CK-MB, tissue homogenates showed elevated levels of NO and MDA and decreased level of GSH in BPA group. Immunohistopathological evaluation of autophagic mediators showed significant increase in LC3 and P62 in BPA group. On Histological examination, there was pathological alteration in BPA group compared to normal group. Vit E administration showed significant improvement in cardiac enzymes and oxidative stress. Also, alleviation of autophagic process and restoration of the myocardial architecture with reduction of the fibrous tissue were observed with vit E administration. Conclusion: These results demonstrate that vitamin E exhibit substantial protective effects in BPA induced cardiotoxicity by attenuating inflammation, oxidative stress, and alleviation the autophagic process

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

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