Pathogenesis and treatment strategies of sepsis-induced myocardial injury: modern and traditional medical perspectives

Abstract

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Myocardial injury is a common complication in sepsis patients, which accelerates the progression of sepsis, leading to multiple organ dysfunction and poor prognosis. However, there are still many uncertainties about the characteristics, pathogenesis, treatment, and prognosis of sepsis-induced myocardial injury. While modern medical approaches dominate current clinical management of sepsis-induced myocardial injury, emerging evidence highlights the growing therapeutic potential of traditional Chinese medicine in this field, driven by advances in biomedical research. The integration of these two paradigms holds promise for elucidating the pathophysiological mechanisms and identifying novel therapeutic targets for sepsis-induced myocardial injury, which may accelerate the development of innovative treatment strategies. Therefore, this review comprehensively summarizes the pathogenesis and therapeutic interventions of sepsis-induced myocardial injury from both modern medicine and traditional Chinese medicine perspectives, and critically analyzes the two aiming to provide a valuable reference for researchers' understanding of sepsis-induced myocardial injury.

Keywords: Modern medicine; Myocardial injury; Pathogenesis; Sepsis; Traditional Chinese medicine.

Figure 1

Summary of the pathogenesis and treatment strategies of sepsis-induced myocardial injury from the perspectives of modern medicine and traditional Chinese medicine.

Figure 2

Immune cell dysfunction in sepsis-induced myocardial injury. Infectious substances such as bacteria enter the circulation and activate various immune cells. Circulating monocytes are recruited into the myocardial tissue and mature into macrophages, releasing inflammatory cytokines such as IL-1β, IL-6, IL-12, IL-10, CXCL8, TNF-α, INFγ. Neutrophils trapped in blood vessels release NETs, activate platelets, promote fibrin formation, and induce thrombus formation. Activated NETs also stimulate endothelial cells to produce a large number of adhesion molecules, leading to increased permeability of endothelial cells. Neutrophils infiltrate myocardial tissue and release inflammatory cytokines such as IL-1β, IL-6, IL-17, G-Csf, and GM-Csf, and also release NETs and phagocytose pathogens. In addition to secreting inflammatory cytokines such as IL-12, IL-6, Csf3, TNF-α, INF-γ, activated NK cells also secrete cytotoxic proteins such as perforin and granzyme, which directly cause cell and even tissue necrosis.

Figure 3

Programmed cell death in sepsis-induced myocardial injury. In sepsis-induced myocardial injury, there are six kinds of programmed cell death: Caspase9 (Casp9) activated by mitochondrial pathway, Casp12 activated by endoplasmic reticulum stress pathway and Casp8 activated by death receptor pathway, all of which are involved in the the process of cardiomyocyte apoptosis. RIPK1-RIPK3 forms a heterologous complex that activates MLKL, and the activated MLKL translocates to the inner and cytoplasmic membranes, initiating Ca²⁺ influx, leading to cell swelling and membrane rupture, and necroptosis. Casp1 activates GSDMD, and the activated GSDMD interacts with phosphatidylinositol on the cell membrane to oligomerization, resulting in cell membrane pores and cell apoptosis. Whether Casp3/GSDME-mediated apoptosis is involved in sepsis-induced myocardial injury has not been investigated. SFXN1-mediated ferroptosis, LC3II and Beclin1-mediated autophagy, and ZBP1-mediated PANoptosis are involved in sepsis-induced myocardial injury.