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Background: Valvular heart disease remains common in both developed and developing countries, and it requires timely surgical treatment when necessary. However, the stability of hemodynamics during anesthesia induction in patients undergoing valve replacement surgery is difficult to maintain due to their impaired cardiac function. Remimazolam, a novel and ultrashort-acting intravenous sedative-hypnotic, may be beneficial to stable hemodynamics, but the evidence is limited. Therefore, this study aims to evaluate the effect of remimazolam induction on hemodynamics compared with midazolam and etomidate in patients undergoing valve replacement surgery. Methods: This is a prospective, multicenter randomized controlled trial (RCT). Three hundred and sixty-three non-obese adult patients aged 45 to 80 years old undergoing valve surgery with cardiopulmonary bypass will be randomly allocated to receive remimazolam tosilate, midazolam, or etomidate during anesthetic induction. The primary outcome is the incidence of hypotension within 20 min after the administration of investigated drugs. The hypotension is defined as systolic blood pressure (SBP) < 90 mmHg or a 30% reduction in SBP from baseline or the application of vasoactive drugs. Secondary outcomes include incidence of successful sedation, time to successful sedation, incidence of delirium and postoperative low cardiac output syndrome within 7 days after surgery, hospital mortality, mechanical ventilation time, ICU length of stay, and hospital length of stay. Discussion: To our knowledge, this is the first prospective RCT to investigate the efficacy and safety of remimazolam induction in adult cardiac surgery compared with midazolam and etomidate. This study will provide important information on the application of remimazolam in cardiac surgery in the future. Trial registration: Chinese Clinical Trial Registry chictr.org.cn ChiCTR2100050122. Registered on August 16, 2021. [ABSTRACT FROM AUTHOR]

Background: Ectopic angiogenesis within the intima and media is considered to be a hallmark of advanced vulnerable atherosclerotic lesions. Some studies have shown that specific matrix metalloproteinases (MMPs) might play different roles in angiogenesis. Therefore, we investigated the predominant effects of specific MMPs in intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. Methods and Results: New Zealand rabbits underwent balloon injury of the abdominal artery and ingestion of a high-cholesterol (1%) diet to establish an atherosclerotic animal model. At weeks 4, 6, 8, 10, and 12 after balloon injury, five rabbits were euthanized and the abdominal aorta was harvested. Blood lipid analysis, intravascular ultrasound imaging, pathologic and immunohistochemical expression studies, and western blotting were performed. From weeks 4 to 12, the expression of MMP-1, -2, -3, and -9 and vascular endothelial growth factor A (VEGF-A) increased with atherosclerotic plaque development in the abdominal aorta, while the expression of MMP-14 substantially decreased. The vulnerability index (VI) gradually increased over time. Intraplaque neovessels appeared at week 8. The microvessel density (MVD) was greater at week 12 than at week 8. The VI, MVD, and VEGF-A level were positively correlated with the MMP-1, -2,-3, and -9 levels within plaques. Negative correlations were noted between the MMP-14 level and the VI, MVD, and VEGF-A level. Conclusion: Upregulation of MMP-1, -2, -3, and -9 and downregulation of MMP-14 may contribute to intraplaque angiogenesis and plaque instability at the advanced stage of atherosclerosis in rabbits. [ABSTRACT FROM AUTHOR]