Sepsis‑induced cardiac dysfunction and pathogenetic mechanisms (Review)

Abstract

Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi‑organ failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.

Keywords: ferroptosis; metabolic change; mitochondrial dysfunction; sepsis; signaling pathway.

Figure 1.

Mitochondrial mechanisms in septic cardiomyopathy. Increased superoxide (O^2·−) and NO production can cause direct oxidative or nitrosative damage and inhibition of OXPHOS complexes, lead to decreased O₂ consumption and decreased Δψ. In addition, Δψ may drop due to increased (UCP)-mediated proton leak, increased Ca²⁺-induced mPTP opening and direct oxidative damage of the inner mitochondrial membrane. In addition, Ca²⁺ homeostasis was changed due to endoplasmic reticulum stress and LTCC damage. NO, nitric oxide; OXPHOS, oxidative phosphorylation; Δψ, proton motive force; UCP, uncoupling protein; mPTP, mitochondrial permeability transition pore; LTCC, L-type calcium channels; mtDNA, Mitochondrial DNA; F0F1, ATP synthase.

Figure 2.

Metabolic changes in septic cardiomyopathy. FA, fatty acids; FAO, fatty acid oxidation; KB, ketone bodies.

Figure 3.

Summary of HO-1 and Hepcidin action mechanism in septic cardiomyopathy. HO-1, heme oxygenase 1; Th1, T helper cell 1; Th2, T helper cell 2; FPN, Hepcidin ubiquitinates ferroportin.