Effect of Combined Etomidate-Ketamine Anesthesia on Perioperative Electrocardiogram and Postoperative Cognitive Dysfunction of Elderly Patients with Rheumatic Heart Valve Disease Undergoing Heart Valve Replacement

Objective. To explore the effect of combined etomidate-ketamine anesthesia on perioperative electrocardiogram (ECG) and postoperative cognitive dysfunction (POCD) of elderly patients with rheumatic heart valve disease (RHVD) undergoing heart valve replacement. Methods. The data of 100 elderly RHVD patients treated in our hospital from May 2019 to May 2020 were selected for the retrospective analysis, and by adopting the double-blind method, the patients were divided into the ketamine group (n = 50) and the combined group (n = 50) according to the anesthesia methods. During the induction of anesthesia, the patients of the two groups were given a small dose of ketamine (0.5 mg/kg) at 5 μg/kg/min continuously via pump injection until the end of surgery, and on this basis, with the same anesthesia measures, those in the combined group were given etomidate (0.3 mg/kg) additionally. The patients’ perioperative ECG indicators, POCD scores, and Numeric Rating Scale (NRS) scores were compared between the two groups. Results. Compared with the ketamine group, the combined group presented significantly lower incidence of ST-T wave changes after anesthesia induction and at the time of intubation and skin incision ( P < 0.05 ), significantly lower average magnitude of ST-segment depression after anesthesia induction ( P < 0.001 ), significantly lower average magnitude of ST-segment elevation after anesthesia induction and extubation ( P < 0.001 ), significantly lower POCD incidence (6.%, P < 0.05 ), and significantly better NRS score after surgery ( P < 0.001 ). Conclusion. Combined etomidate-ketamine anesthesia can stabilize the perioperative ECG indicators of elderly RHVD patients undergoing heart valve replacement, improve their postoperative cognitive function, and reduce their pain sensation, which should be promoted and applied in practice.

Rheumatic Heart Valve Disease Pathophysiology and Underlying Mechanisms

Rheumatic heart valve disease (RHVD) is a post-infectious sequel of acute rheumatic fever resulting from an abnormal immune response to a streptococcal pharyngitis that triggers valvular damage. RHVD is the leading cause of cardiovascular death in children and young adults, mainly in women from low and middle-income countries. It is known that long-term inflammation and high degree of fibrosis leads to valve dysfunction due to anatomic disruption of the valve apparatus. However, since public and private investments in RHVD studies are practically inexistent the number of publications is scarce. This disease shows different natural history and clinical presentations as compared to other degenerative heart valve diseases. Although more than five decades passed after the pioneering studies on the pathogenesis of RHVD, it is still unclear how self-tolerance mechanisms fail in this disease, and how humoral and cellular inflammatory responses are interconnected. Despite that pathological mechanisms have been already proposed for RHVD, none of them are able to explain the preferential involvement of the mitral valve. This review focuses on pathophysiology and underlying mechanisms of RHVD.

Abstract 13401: Prothymosin Alpha (Protα) Associates With Pathogenesis and Sex Predisposition in Rheumatic Heart Valve Disease

Introduction: Acute rheumatic fever (ARF) results from autoimmune responses to group A streptococcus. ARF can cause chronic rheumatic heart valve disease (RHVD), a major public health burden in low- and middle-income countries. Although ARF affects both sexes equally, females have a higher prevalence of RHVD. We identified a target protein, ProTα, that may contribute to pathophysiology of and gender predisposition in RHVD. Estradiol regulates ProTα, which influences transcriptional activity of the estrogen receptor (ER). Methods: Human heart valves (n=120) obtained from heart transplantation and valve replacement surgeries, including non-diseased mitral and aortic valves (NDMV and NDAV, n=17/group), rheumatic mitral and aortic valves (RMVD, n=45; RAVD, n=8) and calcifying valves from patients with calcific aortic valve disease (CAVD, n=33) underwent proteomic and network analyses, and immunohistochemical assessment of CD68, CD4, CD8 and ProTα. ProTα levels were measured in plasma and peripheral mononuclear cells (PBMCs) from RHVD patients and healthy donors (n=14/group) by ELISA and flow cytometry. Results: A comparison of proteomes from NDMV and NDAV established the baseline differences between valve types. 12 proteins were enriched (q<0.05) in NDMV that may indicate the mitral valve predisposition to RVHD. Proteome analysis of non-diseased and diseased valves (NDMV vs RMVD, NDAV vs RAVD) identified a total of 213 proteins enriched in RHVD (q<0.05). The expression of the 12 NDMV-enriched proteins were evaluated across the 213 proteins enriched in diseased valves, resulting in the identification of ProTα common to both the RMVD and RAVD proteomes, but absent in CAVD. Additional KEGG pathway enrichment analyses linked 6 among 213 proteins with the estrogen signaling pathway (p<0.05). Immunoreactive ProTα colocalized with T CD8 cells in RHVD. ProTα and ERα also correlated strongly in circulating T CD8 cells in RHVD (p<0.05). ProTα plasma levels were higher in RHVD patients than healthy individuals (2 fold, p<0.05). Conclusion: We propose that ProTα is a novel contributor to the immunopathogenesis of RHVD and may regulate sex predisposition in this disease.