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Published on: September 3, 2020
Therapeutical progress in sepsis-induced cardiomyopathy
Jinbo Zhang1,2, Shiying Sheng2, Weiwei Luo2
1Emergency Intensive Care Unit, The First People's Hospital of Wenling, Wenling, Zhejiang, China.
Insights
Sepsis-induced cardiomyopathy (SCM) involves complex mechanisms like inflammation and mitochondrial issues. This review highlights novel therapeutic strategies targeting these pathways for improved patient outcomes in sepsis.
Area of Science:
- Cardiology
- Critical Care Medicine
- Molecular Biology
Background:
- Sepsis-induced cardiomyopathy (SCM) is a severe complication of sepsis with high mortality.
- Understanding its complex pathogenesis is crucial for effective treatment.
Purpose of the Study:
- To provide a comprehensive review of SCM pathogenesis and therapeutic strategies.
- To propose an integrated mechanistic model for SCM reversibility.
- To categorize emerging therapies based on targeted pathological pathways.
Main Methods:
- Literature review of SCM pathogenesis, including inflammation, mitochondrial dysfunction, and calcium handling.
- Analysis of conventional and emerging treatment strategies.
- Categorization of therapies by targeted pathways (inflammation, mitochondria, calcium).
Main Results:
- SCM pathogenesis involves a multifaceted interplay of inflammatory, metabolic, and calcium-handling abnormalities.
- An integrated model highlights the energy metabolism-calcium handling axis in SCM reversibility.
- Emerging therapies include drug repurposing, traditional Chinese medicine, small molecules, and nanomedicine.
Conclusions:
- Targeting specific pathological pathways (inflammation, mitochondrial dysfunction, calcium dysregulation) offers promising therapeutic avenues for SCM.
- A phenotype-guided treatment framework and further clinical validation are essential.
- Precision medicine approaches hold potential for optimizing SCM patient outcomes.
Abstract:
Sepsis-induced cardiomyopathy (SCM) is a life-threatening complication of severe sepsis with a high mortality rate. This review comprehensively explores SCM. It details the multifaceted pathogenesis, including inflammatory storm, mitochondrial dysfunction, abnormal calcium handling, complement activation, and emerging mechanisms related to exosomes and non-coding RNAs. We propose an integrated mechanistic model centered on the "energy metabolism-calcium handling" axis to explain the unique reversibility of SCM. Conventional treatments like antibiotic therapy, fluid management, and the use of vasopressors and inotropic agents are discussed, along with their limitations. Promising strategies such as repurposing old drugs, applying traditional Chinese medicine, and new approaches are presented. To bridge the gap between mechanistic understanding and clinical application, we categorize these emerging therapies according to the primary pathological pathway they target: inflammation, mitochondrial dysfunction, or calcium dysregulation. Furthermore, we introduce a framework for phenotype-guided treatment and critically evaluate the level of clinical evidence for each intervention. Small active molecules and nanomedicine also show potential in SCM treatment. Future research should focus on large-scale clinical trials to validate these therapies and integrate precision medicine strategies for better patient outcomes.
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