Pathogenesis and treatment of septic cardiomyopathy_West China Medical Journal

Authors：

HU Qing ¹ , CAO Xiaoping ¹ , HUANG Zheng ¹ , XIE Mingxin ¹ , YU Renxuan ¹ ,  WANG Jiazhen ^1,2

1. Department of Emergency Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Department of Critical Care Medicine, Santai Hospital, North Sichuan Medical College, Santai, Sichuan 621100, P. R. China;

Corresponding?author：

WANG Jiazhen, Email: 398610290@qq.com

Keywords：

Sepsis; Cardiomyopathy; Pathogenesis; Treatment

DOI：

10.7507/1002-0179.201912091

Video：

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Sepsis is a common complication after severe trauma, infection, shock and major surgery. It has the characteristics of high morbidity, high mortality, and high hospitalization costs. Septic cardiomyopathy is one of the main causes of death in patients with sepsis. This article reviews the pathogenesis and treatment of septic cardiomyopathy. The pathogenesis includes hemodynamics and myocardial changes, mitochondrial fission, cardiomyocyte apoptosis and autophagy, calcium ion imbalance, inflammation mechanism and immune regulation mechanism. The treatment includes conventional treatment, β1 receptor blocker treatment, melatonin, serotonin 3 receptor antagonist, dexmedetomidine and traditional Chinese medicine treatment, etc., aiming to provide a reference for the diagnosis and treatment of septic cardiomyopathy.

Citation： HU Qing, CAO Xiaoping, HUANG Zheng, XIE Mingxin, YU Renxuan, WANG Jiazhen. Pathogenesis and treatment of septic cardiomyopathy. West China Medical Journal, 2020, 35(11): 1380-1385. doi: 10.7507/1002-0179.201912091 Copy

1.	中國醫師協會急診醫師分會, 中國研究型醫院學會休克與膿毒癥專業委員會. 中國膿毒癥/膿毒性休克急診治療指南 (2018). 感染、炎癥、修復, 2019, 20(1): 3-22.
2.	Flierl MA, Rittirsch D, Huber-Lang MS, et al. Molecular events in the cardiomyopathy of sepsis. Mol Med, 2008, 14(5/6): 327-336.
3.	江偉, 杜斌. 中國膿毒癥流行病學現狀. 醫學研究生學報, 2019, 32(1): 5-8.
4.	Vieillard-Baron A. Septic cardiomyopathy. Ann Intensive Care, 2011, 1(1): 6.
5.	Dalton A, Shahul S. Cardiac dysfunction in critical illness. Curr Opin Anaesthesiol, 2018, 31(2): 158-164.
6.	周芹, 王龍, 王晞, 等. 神經調節蛋白-1 對膿毒癥大鼠心臟功能及炎性介質的影響. 中華危重病急救醫學, 2018, 30(2): 140-144.
7.	Tan Y, Ouyang H, Xiao X, et al. Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones, 2019, 24(3): 595-608.
8.	Shang X, Li J, Yu R, et al. Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway. J Mol Histol, 2019, 50(2): 91-103.
9.	Li J, Shi W, Zhang J, et al. To explore the protective mechanism of PTEN-induced kinase 1 (PINK1)/Parkin mitophagy-mediated extract of periplaneta Americana on lipopolysaccharide-induced cardiomyocyte injury. Med Sci Monit, 2019, 25: 1383-1391.
10.	Cheng Mm W, Long Y, Wang H, et al. Role of the mTOR signalling pathway in human sepsis-induced myocardial dysfunction. Can J Cardiol, 2019, 35(7): 875-883.
11.	Shen YL, Shi YZ, Chen GG, et al. TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. Int J Mol Med, 2018, 41(4): 2317-2327.
12.	Hobai IA, Edgecomb J, LaBarge K, et al. Dysregulation of intracellular calcium transporters in animal models of sepsis-induced cardiomyopathy. Shock, 2015, 43(1): 3-15.
13.	Smeding L, Pl?tz FB, Groeneveld AB, et al. Structural changes of the heart during severe sepsis or septic shock. Shock, 2012, 37(5): 449-456.
14.	Zhang W, Tao A, Lan T, et al. Carbon monoxide releasing molecule-3 improves myocardial function in mice with sepsis by inhibiting NLRP3 inflammasome activation in cardiac fibroblasts. Basic Res Cardiol, 2017, 112(2): 16.
15.	Liu Z, Zeng Z, Wu C, et al. Tropisetron inhibits sepsis by repressing hyper-inflammation and regulating the cardiac action potential in rat models. Biomed Pharmacother, 2019, 110: 380-388.
16.	Giustina AD, Bonfante S, Zarbato GF, et al. Dimethyl fumarate modulates oxidative stress and inflammation in organs after sepsis in rats. Inflammation, 2018, 41(1): 315-327.
17.	Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA, 2011, 306(23): 2594-2605.
18.	陳欣, 周麗華, 黃志民, 等. 烏司他丁對內毒素心肌損傷大鼠 Toll 樣受體 4 表達的影響. 中國危重病急救醫學, 2012, 24(12): 763-765.
19.	Ouyang MZ, Zhou D, Zhu Y, et al. The inhibition of MyD88 and TRIF signaling serve equivalent roles in attenuating myocardial deterioration due to acute severe inflammation. Int J Mol Med, 2018, 41(1): 399-408.
20.	Zaky A, Deem S, Bendjelid K, et al. Characterization of cardiac dysfunction in sepsis: an ongoing challenge. Shock, 2014, 41(1): 12-24.
21.	Antonucci E, Fiaccadori E, Donadello K, et al. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care, 2014, 29(4): 500-511.
22.	Sanfilippo F, Corredor C, Fletcher N, et al. Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock:a systematic review and meta-analysis. Crit Care, 2018, 22(1): 183.
23.	Xu JY, Chen QH, Xie JF, et al. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials. Crit Care, 2014, 18(6): 702.
24.	Tigabu B, Davari M, Kebriaeezadeh A, et al. Is albumin-based resuscitation in severe sepsis and septic shock justifiable? An evidence from a cost-effectiveness evaluation. Ethiop J Health Sci, 2019, 29(1): 869-876.
25.	Thalji SZ, Kothari AN, Kuo PC, et al. Acute kidney injury in burn patients: clinically significant over the initial hospitalization and1 year after injury: an original retrospective cohort study. Ann Surg, 2017, 266(2): 376-382.
26.	王小明, 袁周, 陳齊紅, 等. 不同晶體液早期復蘇對感染性休克患者內環境的影響: 一項前瞻性隨機對照研究. 中華危重病急救醫學, 2018, 30(9): 824-829.
27.	Yamashita S, Suzuki T, Iguchi K, et al. Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis. Naunyn Schmiedebergs Arch Pharmacol, 2018, 391(9): 1021-1032.
28.	Meng JB, Hu MH, Lai ZZ, et al. Levosimendan versus dobutamine in myocardial injury patients with septic shock: a randomized controlled trial. Med Sci Monit, 2016, 22: 1486-1496.
29.	Chagnon F, Coquerel D, Salvail D, et al. Apelin compared with dobutamine exerts cardioprotection and extends survival in a rat model of endotoxin-induced myocardial dysfunction. Crit Care Med, 2017, 45(4): e391-e398.
30.	劉新強, 溫妙云, 李旭聲, 等. β1 受體阻滯劑通過 TLR4/NF-κB 信號通路抑制膿毒癥心肌炎癥反應. 中華危重病急救醫學, 2019, 31(2): 193-197.
31.	洪澄英, 陳懷生, 曹靜, 等. β 受體拮抗劑對膿毒癥大鼠心肌細胞線粒體損傷的保護作用. 中國醫科大學學報, 2018, 47(12): 1123-1127.
32.	陳曉. 艾司洛爾對老年膿毒癥心肌損傷的治療效果. 中國老年學雜志, 2017, 37(1): 179-181.
33.	Zhang WX, He BM, Wu Y, et al. Melatonin protects against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice. Life Sci, 2019, 217: 8-15.
34.	Zhong J, Tan Y, Lu J, et al. Therapeutic contribution of melatonin to the treatment of septic cardiomyopathy: A novel mechanism linking Ripk3-modified mitochondrial performance and endoplasmic reticulum function. Redox Biol, 2019, 26: 101287.
35.	湯龍信, 丁璐, 張在旺. 右美托咪定的藥效動力學、藥代動力學及臨床應用研究進展. 臨床誤診誤治, 2018, 31(11): 111-116.
36.	陳名智. 右美托咪定對早期膿毒癥患者心臟舒張功能的改善作用. 中國老年學雜志, 2017, 37(10): 2425-2427.
37.	Wang Y, Mao X, Chen H, et al. Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy. Int Immunopharmacol, 2019, 73: 471-481.
38.	Meng F, Lai H, Luo Z, et al. Effect of xuefu zhuyu decoction pretreatment on myocardium in sepsis rats. Evid Based Complement Alternat Med, 2018, 2018: 2939307.
39.	Zhou N, Zeng MN, Li K, et al. An integrated metabolomic strategy for the characterization of the effects of Chinese yam and its three active components on septic cardiomyopathy. Food Funct, 2018, 9(9): 4989-4997.
40.	張宏偉, 魏立友, 趙剛, 等. 血必凈注射液對老年膿毒癥患者心肌損傷的保護作用. 中國老年學雜志, 2017, 37(19): 4863-4865.
41.	Qian Y, Qian F, Zhang W, et al. Shengjiang Powder ameliorates myocardial injury in septic rats by downregulating the phosphorylation of P38-MAPK. J Biosci, 2019, 44(2): 40.
42.	Tan S, Long Z, Hou X, et al. H₂ protects against lipopolysaccharide-induced cardiac dysfunction via blocking TLR4-mediated cytokines expression. Front Pharmacol, 2019, 10: 865.
43.	Honda T, He Q, Wang F, et al. Acute and chronic remote ischemic conditioning attenuate septic cardiomyopathy, improve cardiac output, protect systemic organs, and improve mortality ina lipopolysaccharide-induced sepsis model. Basic Res Cardiol, 2019, 114(3): 15.

1. 中國醫師協會急診醫師分會, 中國研究型醫院學會休克與膿毒癥專業委員會. 中國膿毒癥/膿毒性休克急診治療指南 (2018). 感染、炎癥、修復, 2019, 20(1): 3-22.
2. Flierl MA, Rittirsch D, Huber-Lang MS, et al. Molecular events in the cardiomyopathy of sepsis. Mol Med, 2008, 14(5/6): 327-336.
3. 江偉, 杜斌. 中國膿毒癥流行病學現狀. 醫學研究生學報, 2019, 32(1): 5-8.
4. Vieillard-Baron A. Septic cardiomyopathy. Ann Intensive Care, 2011, 1(1): 6.
5. Dalton A, Shahul S. Cardiac dysfunction in critical illness. Curr Opin Anaesthesiol, 2018, 31(2): 158-164.
6. 周芹, 王龍, 王晞, 等. 神經調節蛋白-1 對膿毒癥大鼠心臟功能及炎性介質的影響. 中華危重病急救醫學, 2018, 30(2): 140-144.
7. Tan Y, Ouyang H, Xiao X, et al. Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell Stress Chaperones, 2019, 24(3): 595-608.
8. Shang X, Li J, Yu R, et al. Sepsis-related myocardial injury is associated with Mst1 upregulation, mitochondrial dysfunction and the Drp1/F-actin signaling pathway. J Mol Histol, 2019, 50(2): 91-103.
9. Li J, Shi W, Zhang J, et al. To explore the protective mechanism of PTEN-induced kinase 1 (PINK1)/Parkin mitophagy-mediated extract of periplaneta Americana on lipopolysaccharide-induced cardiomyocyte injury. Med Sci Monit, 2019, 25: 1383-1391.
10. Cheng Mm W, Long Y, Wang H, et al. Role of the mTOR signalling pathway in human sepsis-induced myocardial dysfunction. Can J Cardiol, 2019, 35(7): 875-883.
11. Shen YL, Shi YZ, Chen GG, et al. TNF-α induces Drp1-mediated mitochondrial fragmentation during inflammatory cardiomyocyte injury. Int J Mol Med, 2018, 41(4): 2317-2327.
12. Hobai IA, Edgecomb J, LaBarge K, et al. Dysregulation of intracellular calcium transporters in animal models of sepsis-induced cardiomyopathy. Shock, 2015, 43(1): 3-15.
13. Smeding L, Pl?tz FB, Groeneveld AB, et al. Structural changes of the heart during severe sepsis or septic shock. Shock, 2012, 37(5): 449-456.
14. Zhang W, Tao A, Lan T, et al. Carbon monoxide releasing molecule-3 improves myocardial function in mice with sepsis by inhibiting NLRP3 inflammasome activation in cardiac fibroblasts. Basic Res Cardiol, 2017, 112(2): 16.
15. Liu Z, Zeng Z, Wu C, et al. Tropisetron inhibits sepsis by repressing hyper-inflammation and regulating the cardiac action potential in rat models. Biomed Pharmacother, 2019, 110: 380-388.
16. Giustina AD, Bonfante S, Zarbato GF, et al. Dimethyl fumarate modulates oxidative stress and inflammation in organs after sepsis in rats. Inflammation, 2018, 41(1): 315-327.
17. Boomer JS, To K, Chang KC, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA, 2011, 306(23): 2594-2605.
18. 陳欣, 周麗華, 黃志民, 等. 烏司他丁對內毒素心肌損傷大鼠 Toll 樣受體 4 表達的影響. 中國危重病急救醫學, 2012, 24(12): 763-765.
19. Ouyang MZ, Zhou D, Zhu Y, et al. The inhibition of MyD88 and TRIF signaling serve equivalent roles in attenuating myocardial deterioration due to acute severe inflammation. Int J Mol Med, 2018, 41(1): 399-408.
20. Zaky A, Deem S, Bendjelid K, et al. Characterization of cardiac dysfunction in sepsis: an ongoing challenge. Shock, 2014, 41(1): 12-24.
21. Antonucci E, Fiaccadori E, Donadello K, et al. Myocardial depression in sepsis: from pathogenesis to clinical manifestations and treatment. J Crit Care, 2014, 29(4): 500-511.
22. Sanfilippo F, Corredor C, Fletcher N, et al. Left ventricular systolic function evaluated by strain echocardiography and relationship with mortality in patients with severe sepsis or septic shock:a systematic review and meta-analysis. Crit Care, 2018, 22(1): 183.
23. Xu JY, Chen QH, Xie JF, et al. Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials. Crit Care, 2014, 18(6): 702.
24. Tigabu B, Davari M, Kebriaeezadeh A, et al. Is albumin-based resuscitation in severe sepsis and septic shock justifiable? An evidence from a cost-effectiveness evaluation. Ethiop J Health Sci, 2019, 29(1): 869-876.
25. Thalji SZ, Kothari AN, Kuo PC, et al. Acute kidney injury in burn patients: clinically significant over the initial hospitalization and1 year after injury: an original retrospective cohort study. Ann Surg, 2017, 266(2): 376-382.
26. 王小明, 袁周, 陳齊紅, 等. 不同晶體液早期復蘇對感染性休克患者內環境的影響: 一項前瞻性隨機對照研究. 中華危重病急救醫學, 2018, 30(9): 824-829.
27. Yamashita S, Suzuki T, Iguchi K, et al. Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis. Naunyn Schmiedebergs Arch Pharmacol, 2018, 391(9): 1021-1032.
28. Meng JB, Hu MH, Lai ZZ, et al. Levosimendan versus dobutamine in myocardial injury patients with septic shock: a randomized controlled trial. Med Sci Monit, 2016, 22: 1486-1496.
29. Chagnon F, Coquerel D, Salvail D, et al. Apelin compared with dobutamine exerts cardioprotection and extends survival in a rat model of endotoxin-induced myocardial dysfunction. Crit Care Med, 2017, 45(4): e391-e398.
30. 劉新強, 溫妙云, 李旭聲, 等. β1 受體阻滯劑通過 TLR4/NF-κB 信號通路抑制膿毒癥心肌炎癥反應. 中華危重病急救醫學, 2019, 31(2): 193-197.
31. 洪澄英, 陳懷生, 曹靜, 等. β 受體拮抗劑對膿毒癥大鼠心肌細胞線粒體損傷的保護作用. 中國醫科大學學報, 2018, 47(12): 1123-1127.
32. 陳曉. 艾司洛爾對老年膿毒癥心肌損傷的治療效果. 中國老年學雜志, 2017, 37(1): 179-181.
33. Zhang WX, He BM, Wu Y, et al. Melatonin protects against sepsis-induced cardiac dysfunction by regulating apoptosis and autophagy via activation of SIRT1 in mice. Life Sci, 2019, 217: 8-15.
34. Zhong J, Tan Y, Lu J, et al. Therapeutic contribution of melatonin to the treatment of septic cardiomyopathy: A novel mechanism linking Ripk3-modified mitochondrial performance and endoplasmic reticulum function. Redox Biol, 2019, 26: 101287.
35. 湯龍信, 丁璐, 張在旺. 右美托咪定的藥效動力學、藥代動力學及臨床應用研究進展. 臨床誤診誤治, 2018, 31(11): 111-116.
36. 陳名智. 右美托咪定對早期膿毒癥患者心臟舒張功能的改善作用. 中國老年學雜志, 2017, 37(10): 2425-2427.
37. Wang Y, Mao X, Chen H, et al. Dexmedetomidine alleviates LPS-induced apoptosis and inflammation in macrophages by eliminating damaged mitochondria via PINK1 mediated mitophagy. Int Immunopharmacol, 2019, 73: 471-481.
38. Meng F, Lai H, Luo Z, et al. Effect of xuefu zhuyu decoction pretreatment on myocardium in sepsis rats. Evid Based Complement Alternat Med, 2018, 2018: 2939307.
39. Zhou N, Zeng MN, Li K, et al. An integrated metabolomic strategy for the characterization of the effects of Chinese yam and its three active components on septic cardiomyopathy. Food Funct, 2018, 9(9): 4989-4997.
40. 張宏偉, 魏立友, 趙剛, 等. 血必凈注射液對老年膿毒癥患者心肌損傷的保護作用. 中國老年學雜志, 2017, 37(19): 4863-4865.
41. Qian Y, Qian F, Zhang W, et al. Shengjiang Powder ameliorates myocardial injury in septic rats by downregulating the phosphorylation of P38-MAPK. J Biosci, 2019, 44(2): 40.
42. Tan S, Long Z, Hou X, et al. H₂ protects against lipopolysaccharide-induced cardiac dysfunction via blocking TLR4-mediated cytokines expression. Front Pharmacol, 2019, 10: 865.
43. Honda T, He Q, Wang F, et al. Acute and chronic remote ischemic conditioning attenuate septic cardiomyopathy, improve cardiac output, protect systemic organs, and improve mortality ina lipopolysaccharide-induced sepsis model. Basic Res Cardiol, 2019, 114(3): 15.

West China Medical Journal

Pathogenesis and treatment of septic cardiomyopathy

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