Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers
Abstract
1. Introduction
2. Pathophysiology of Myocardial Injury in Polytrauma
3. Key Immunological Markers in Myocardial Injury Following Polytrauma
4. Clinical Relevance and Future Directions
5. Perspectives and Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Key Mechanism | Description | Clinical Implications | Early Detection & Diagnostics |
---|---|---|---|
Systemic Inflammation (SIRS) | Trauma triggers a massive inflammatory response with increased TNF-α, IL-6, and IL-1β, promoting endothelial dysfunction and myocardial apoptosis. | Increased risk of heart failure, prolonged inflammation, myocardial fibrosis, and remodeling. | Measurement of inflammatory biomarkers (IL-6, TNF-α, IL-1β), CRP levels, and echocardiography for early detection of myocardial dysfunction. |
Oxidative Stress | Hypoxia, ischemia-reperfusion injury, and immune activation lead to excessive ROS production, mitochondrial dysfunction, and cell death. | Cardiac remodeling, endothelial dysfunction, increased long-term cardiovascular risk. | Detection of oxidative stress markers (MPO, ROS levels), lipid peroxidation assays, and mitochondrial function tests. |
Neurohormonal Activation | Elevated catecholamines (epinephrine/norepinephrine) increase myocardial oxygen demand, causing contractile dysfunction, myocardial stunning, and arrhythmias. | Myocardial stunning, calcium overload, risk of Takotsubo cardiomyopathy in trauma patients. | Plasma catecholamine levels, HRV (heart rate variability) monitoring, echocardiography for myocardial function assessment. |
Endothelial Dysfunction | Upregulation of adhesion molecules (ICAM-1, VCAM-1) increases leukocyte infiltration, leading to microvascular thrombosis and myocardial inflammation. | Increased risk of myocardial infarction, thrombosis, organ failure, even without coronary artery disease. | Endothelial function testing (flow-mediated dilation), measurement of ICAM-1 and VCAM-1 levels, and D-dimer tests for thrombotic risk. |
Immune Dysregulation | Hyperinflammatory response (SIRS) is followed by compensatory immune suppression (CARS), delaying myocardial healing and increasing susceptibility to infections. | Persistent inflammation, fibrotic remodeling, risk of long-term cardiac complications. | Immune profiling (T-cell activation markers), cytokine level assays, and CRP monitoring for prolonged inflammation. |
Biomarkers & Diagnostics | IL-6, TNF-α, IL-1β, MPO, and adhesion molecules can help in early risk stratification. Advanced imaging (e.g., speckle-tracking echocardiography) can enhance early detection. | Early intervention, personalized treatment strategies, improved diagnostic accuracy. | High-sensitivity cardiac troponin, echocardiographic strain imaging, and biomarker-based risk assessment tools. |
Therapeutic Considerations | Anti-inflammatory therapies targeting IL-1β and TNF-α, oxidative stress inhibitors, endothelial stabilizers, and neurohormonal modulation are potential treatment options. | Reduction in cardiovascular complications, improved trauma-related cardiac outcomes, enhanced patient survival. | Serial biomarker tracking, cardiac imaging follow-ups, and therapeutic response monitoring using advanced analytics. |
Biomarker | Role in Myocardial Injury | Clinical Implications | Problems and Issues | Diagnosis and Treatment |
Interleukin-6 (IL-6) | Central mediator of systemic inflammation, promotes endothelial activation, increases vascular permeability, and facilitates immune cell infiltration into the myocardium. | Correlates with severity of systemic inflammatory response syndrome (SIRS), myocardial dysfunction, and multi-organ failure. | Lacks specificity for myocardial injury; elevated in various inflammatory conditions. | Can serve as an early indicator of myocardial stress, guiding risk stratification and potential anti-inflammatory interventions. |
Tumor Necrosis Factor-α (TNF-α) | Impairs cardiac contractility, increases endothelial permeability, induces apoptosis, and mitochondrial dysfunction. Upregulates ICAM-1 and VCAM-1, promoting leukocyte adhesion. | Contributes to myocardial fibrosis, endothelial dysfunction, and progression of heart failure. | Anti-TNF therapies have systemic effects and may suppress immune responses, increasing infection risk. | Targeting TNF-α with inhibitors may help reduce inflammation-driven myocardial damage. |
Interleukin-1 Beta (IL-1β) | Triggers cardiomyocyte hypertrophy, matrix remodeling, and fibrosis. Amplifies inflammatory signalling in myocardial injury. | Linked to prolonged hospital stays and increased mortality in trauma patients. | IL-1β inhibitors are costly and may not be widely available for trauma patients. | IL-1β inhibitors (e.g., Canakinumab) have shown promise in reducing cardiovascular complications. |
High-Sensitivity Troponin (hs-Tn) | Biomarker of myocardial stress; elevated in trauma patients due to immune-mediated myocardial injury rather than coronary occlusion. | Strong correlation with IL-6 and IL-1β levels; serves as a predictor of myocardial dysfunction. | May be elevated due to non-cardiac causes, including renal dysfunction and muscle damage. | Useful in differentiating trauma-induced cardiac stress from ischemic myocardial infarction. |
Myeloperoxidase (MPO) | Released by activated neutrophils, contributes to endothelial dysfunction, oxidative stress, and microvascular thrombosis. | Increases risk of long-term cardiac remodeling and heart failure. | Difficult to measure in routine clinical practice; oxidative stress is influenced by multiple factors. | MPO-targeting therapies may help mitigate oxidative damage and improve myocardial recovery. |
Suppression of Tumorigenicity 2 (sST2) | An indicator of myocardial strain and fibrosis, associated with poor cardiac recovery. | Predicts adverse cardiac outcomes in trauma patients. | Not yet widely adopted in clinical settings; limited availability of standardized testing. | Potential biomarker for early identification of high-risk trauma patients. |
Monocyte Chemoattractant Protein-1 (MCP-1) | Recruits monocytes and macrophages to injured myocardial tissue, exacerbating inflammation and fibrosis. | Linked to increased mortality in critically ill patients. | High variability in MCP-1 expression; influenced by multiple inflammatory pathways. | Could be a therapeutic target for reducing myocardial inflammation and fibrosis. |
Intercellular Adhesion Molecule-1 (ICAM-1) | Facilitates leukocyte adhesion and infiltration into the myocardium, worsening local inflammation. | Associated with persistent inflammation and prolonged myocardial dysfunction. | Lacks specificity; elevated in various conditions, including infections and autoimmune diseases. | Monitoring ICAM-1 levels may help assess the severity of inflammatory myocardial injury. |
Vascular Cell Adhesion Molecule-1 (VCAM-1) | Upregulated in response to TNF-α and IL-6, promoting leukocyte recruitment and endothelial dysfunction. | Contributes to chronic myocardial inflammation and heart failure progression. | Measurement of VCAM-1 levels is not routine; requires specialized laboratory testing. | May serve as a biomarker for assessing vascular inflammation in trauma patients. |
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Bekbossynova, M.; Saliev, T.; Mukarov, M.; Sugralimova, M.; Batpen, A.; Kozhakhmetova, A.; Zhanbolat, A. Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers. J. Cardiovasc. Dev. Dis. 2025, 12, 268. https://doi.org/10.3390/jcdd12070268
Bekbossynova M, Saliev T, Mukarov M, Sugralimova M, Batpen A, Kozhakhmetova A, Zhanbolat A. Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers. Journal of Cardiovascular Development and Disease. 2025; 12(7):268. https://doi.org/10.3390/jcdd12070268
Chicago/Turabian StyleBekbossynova, Makhabbat, Timur Saliev, Murat Mukarov, Madina Sugralimova, Arman Batpen, Anar Kozhakhmetova, and Aknur Zhanbolat. 2025. "Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers" Journal of Cardiovascular Development and Disease 12, no. 7: 268. https://doi.org/10.3390/jcdd12070268
APA StyleBekbossynova, M., Saliev, T., Mukarov, M., Sugralimova, M., Batpen, A., Kozhakhmetova, A., & Zhanbolat, A. (2025). Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers. Journal of Cardiovascular Development and Disease, 12(7), 268. https://doi.org/10.3390/jcdd12070268