Effects of Methylprednisolone on Myocardial Function and Microcirculation in Post-resuscitation: A Rat Model

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2022 Jul 25

PMID 35872886

Authors

Changsheng Wang

Evelyne Bischof

Jing Xu

Qinyue Guo

Guanghui Zheng

Weiwei Ge

Juntao Hu

Elena Laura Georgescu Margarint

Jennifer L Bradley

Mary Ann Peberdy

Joseph P Ornato

Changqing Zhu

Wanchun Tang

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies have demonstrated that inflammation and impaired microcirculation are key factors in post-resuscitation syndromes. Here, we investigated whether methylprednisolone (MP) could improve myocardial function and microcirculation by suppressing the systemic inflammatory response following cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA).

Methods: Sprague-Dawley rats were randomly assigned to (1) sham, (2) control, and (3) drug groups. Ventricular fibrillation was induced and then followed by CPR. The rats were infused with either MP or vehicle at the start of CPR. Myocardial function and microcirculation were assessed at baseline and after the restoration of spontaneous circulation. Blood samples were drawn at baseline and 60-min post-resuscitation to assess serum cytokine (TNF-α, IL-1β, and IL-6) levels.

Results: Myocardial function [estimated by the ejection fraction (EF), myocardial performance index (MPI), and cardiac output (CO)] improved post-ROSC in the MP group compared with those in the control group ( < 0.05). MP decreased the levels of the aforementioned pro-inflammatory cytokines and alleviated cerebral, sublingual, and intestinal microcirculation compared with the control ( < 0.05). A negative correlation emerged between the cytokine profile and microcirculatory blood flow.

Conclusion: MP treatment reduced post-resuscitation myocardial dysfunction, inhibited pro-inflammatory cytokines, and improved microcirculation in the initial recovery phase in a CA and resuscitation animal model. Therefore, MP could be a potential clinical target for CA patients in the early phase after CPR to alleviate myocardial dysfunction and improve prognosis.

Citing Articles

Cardiac arrest and microcirculatory dysfunction: a narrative review.

Kravitz M, Lee J, Shapiro N Curr Opin Crit Care. 2024; 30(6):611-617.

PMID: 39377652 PMC: 11540727. DOI: 10.1097/MCC.0000000000001219.

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial.

Obling L, Beske R, Meyer M, Grand J, Wiberg S, Mohr T Crit Care. 2024; 28(1):28.

PMID: 38254130 PMC: 10801994. DOI: 10.1186/s13054-024-04808-3.

References

Qian J, Yang Z, Cahoon J, Xu J, Zhu C, Yang M . Post-resuscitation intestinal microcirculation: its relationship with sublingual microcirculation and the severity of post-resuscitation syndrome. Resuscitation. 2014; 85(6):833-9. DOI: 10.1016/j.resuscitation.2014.02.019. View

Varvarousi G, Stefaniotou A, Varvaroussis D, Xanthos T . Glucocorticoids as an emerging pharmacologic agent for cardiopulmonary resuscitation. Cardiovasc Drugs Ther. 2014; 28(5):477-88. PMC: 4163188. DOI: 10.1007/s10557-014-6547-4. View

Simon D, Borradori L, Simon H . Glucocorticoids in autoimmune bullous diseases: are neutrophils the key cellular target?. J Invest Dermatol. 2013; 133(10):2314-2315. DOI: 10.1038/jid.2013.205. View

Sitina M, Turek Z, Parizkova R, Cerny V . In situ assessment of the brain microcirculation in mechanically-ventilated rabbits using sidestream dark-field (SDF) imaging. Physiol Res. 2010; 60(1):75-81. DOI: 10.33549/physiolres.931937. View

Benjamin E, Virani S, Callaway C, Chamberlain A, Chang A, Cheng S . Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018; 137(12):e67-e492. DOI: 10.1161/CIR.0000000000000558. View

Ye S, Weng Y, Sun S, Chen W, Wu X, Li Z . Comparison of the durations of mild therapeutic hypothermia on outcome after cardiopulmonary resuscitation in the rat. Circulation. 2011; 125(1):123-9. DOI: 10.1161/CIRCULATIONAHA.111.062257. View

Omar Y, Massey M, Andersen L, Giberson T, Berg K, Cocchi M . Sublingual microcirculation is impaired in post-cardiac arrest patients. Resuscitation. 2013; 84(12):1717-22. PMC: 3864773. DOI: 10.1016/j.resuscitation.2013.07.012. View

Goldberger Z, Chan P, Berg R, Kronick S, Cooke C, Lu M . Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet. 2012; 380(9852):1473-81. PMC: 3535188. DOI: 10.1016/S0140-6736(12)60862-9. View

Bro-Jeppesen J, Kjaergaard J, Stammet P, Wise M, Hovdenes J, Aneman A . Predictive value of interleukin-6 in post-cardiac arrest patients treated with targeted temperature management at 33 °C or 36 °C. Resuscitation. 2015; 98:1-8. DOI: 10.1016/j.resuscitation.2015.10.009. View

10.

Chang W, Ma M, Chien K, Huang C, Tsai M, Shih F . Postresuscitation myocardial dysfunction: correlated factors and prognostic implications. Intensive Care Med. 2006; 33(1):88-95. DOI: 10.1007/s00134-006-0442-9. View

11.

Suehiro E, Ueda Y, Wei E, Kontos H, Povlishock J . Posttraumatic hypothermia followed by slow rewarming protects the cerebral microcirculation. J Neurotrauma. 2003; 20(4):381-90. DOI: 10.1089/089771503765172336. View

12.

Jentzer J, Chonde M, Dezfulian C . Myocardial Dysfunction and Shock after Cardiac Arrest. Biomed Res Int. 2015; 2015:314796. PMC: 4572400. DOI: 10.1155/2015/314796. View

13.

Ruiz-Bailen M, Aguayo de Hoyos E, Ruiz-Navarro S, Diaz-Castellanos M, Rucabado-Aguilar L, Gomez-Jimenez F . Reversible myocardial dysfunction after cardiopulmonary resuscitation. Resuscitation. 2005; 66(2):175-81. DOI: 10.1016/j.resuscitation.2005.01.012. View

14.

Hu Z, Chen Y, Ren Y . Methylprednisolone improves microcirculation in streptozotocin-induced diabetic rats after myocardial ischemia/reperfusion. Chin Med J (Engl). 2011; 124(6):923-9. View

15.

Jentzer J, Chonde M, Shafton A, Abu-Daya H, Chalhoub D, Althouse A . Echocardiographic left ventricular systolic dysfunction early after resuscitation from cardiac arrest does not predict mortality or vasopressor requirements. Resuscitation. 2016; 106:58-64. DOI: 10.1016/j.resuscitation.2016.06.028. View

16.

De Backer D, Hollenberg S, Boerma C, Goedhart P, Buchele G, Ospina-Tascon G . How to evaluate the microcirculation: report of a round table conference. Crit Care. 2007; 11(5):R101. PMC: 2556744. DOI: 10.1186/cc6118. View

17.

Yu H, Wang L, Zhang H, Wei W, Chen Y, Tang W . Effect of mild hypothermia on cerebral microcirculation in a murine cardiopulmonary resuscitation model. Microcirculation. 2019; 26(6):e12537. DOI: 10.1111/micc.12537. View

18.

Andersen L, Isbye D, Kjaergaard J, Kristensen C, Darling S, Zwisler S . Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021; 326(16):1586-1594. PMC: 8482303. DOI: 10.1001/jama.2021.16628. View

19.

Chalkias A, Xanthos T . Pathophysiology and pathogenesis of post-resuscitation myocardial stunning. Heart Fail Rev. 2011; 17(1):117-28. DOI: 10.1007/s10741-011-9255-1. View

20.

Belletti A, Benedetto U, Putzu A, Martino E, Biondi-Zoccai G, Angelini G . Vasopressors During Cardiopulmonary Resuscitation. A Network Meta-Analysis of Randomized Trials. Crit Care Med. 2018; 46(5):e443-e451. DOI: 10.1097/CCM.0000000000003049. View