The Protective Effect of Target Temperature Management Combined with Prostaglandin E1 on Ischemia/reperfusion Injury of Cerebral Micro-vascular Endothelium of ROSC Rat

WEI Wei, LAI Shi-chao, XIE Yong. et al

Abstract

To investigate the protective effect of target temperature management (TTM) combined with prostaglandin E1 (PGE1) on ischemia/reperfusion (I/R) injury of cerebral micro-vascular endothelium cell (CMEC) in the return of spontaneous circulation (ROSC) rats with successful cardiopulmonary resuscitation. Methods Transoesophageal cardiac pacing with alternating current was used to induce ventricular fibrillation in rats. Five groups were set: Sham group (S group), ROSC group (R group), PGE1 group (P group), TTM group (T group) and PGE1/TTM group (PT group). Cell edema and micro-thrombus formation in cerebral tissue were evaluated through HE staining. I/R injury of CMEC was evaluated through CD34/TUNEL and vascular endothelial (VE)-cadherin/VE growth factor receptor double fluorescent immunohistochemistry staining. VE-cadherin mRNA and vascular cell adhesion molecule-1(VCAM-1) mRNA expression in cerebral tissue lysate was analyzed by fluorescence quantitative PCR. Results TTM, PGE1 and PGE1/TTM could significantly improve cerebral interstitial edema, micro-thrombus, and inflammatory cells infiltration in the brain tissue, and reduce the apoptosis and VE-cadherin protein loss of CMEC. PGE1/TTM showed better protective effect. These 3 interventions also inhibited the rapid elevation of VE-cadherin mRNA (0.5 h) and VCAM-1 mRNA (4 h and 8 h) expression (P1 and TTM could alleviate I/R injury of CMEC from ROSC rat after CPR separately, while PGE1/TTM combined intervention might have synergistic better effect.

 

Keywords: CPR CMEC Ischemic/reperfusion injury, TTM PGE1

 

Full Text:

PDF


References


CHALKIAS A, XANTHOS T. Post-cardiac arrest brain injury; pathophysiology and treatment. J Neurol Sci,2012, 315(1/2): 1-8.

ADAMS J A. Endothelium and cardiopulmonary resuscitation. Crit Care Med,2006,34(12 Suppl) ;S458-S165.

CALLAWAY CW, NNINO MW. FINK EL, et al. Part 8; Post-Cardiac Arrest Care. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation,2015,132(18 Suppl 2) :S465-S482.

LING L. ZHANG S, JI Z, et al. Therapeutic effects of lipo- prostaglandin K on angiogenesis and neurogenesis after ischemic stroke in rats. Int J Neurosci, 2016, 126 ( 5 ); 469- 477.

CHEN MH, LIU TW. XIE L, et al. Ventricular fibrillation induced by transoesophageal cardiac pacing: a new model of cardiac arrest in rats. Resuscitation,2007,74(3);546-551.

HARUKUNI I, BHARDWAJ A. Mechanisms of brain injury after global cerebral ischemia. Neurol Clin, 2006, 24 ( 1) : 1-21.

SECHER N, OSTERGARRD L, IVERSEN NK, et al. Preserved cerebral microcirculation after cardiac arrest in a rat model. Microcirculation.2015 ,22(6) :464-474.

ADAMS JA. Endothelium and cardiopulmonary resuscitation. Crit Care Med,2006,34( 12) ;S458-S465. GIANNOTTA M, TRANI M, DEJANA E. VE-Cadherin and endothelial adherens junctions: active guardians of vascular integrity. Dev Cell,2013,26(5):441-454.

CHEN F, KONDO N, SONOBE M. et al. Expression of endothelial cell-specific adhesion molecules in lungs after cardiac arrest. Interact Cardiovasc Thorac Surg. 2008, 7( 3): 437-440.

OSBORN L. HESSION C, TIZARD R, et al. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell, 1989,59(6): 1203-1211.

BISSCHOPS LL. VAN DER HOEVEN JG, MOLLNES ТЕ. et al. Seventy-two hours of mild hypothermia after cardiac arrest is associated with a lowered inflammatory response during rewarming in a prospective observational study. Crit Care,2014 ,18(5) ;546-553.

KIKUCHI S. SHINPO K. NIINO M. et al. Prostaglandin El protects cultured spinal neurons against the effects of nitric oxide toxicity. Neuropharmacology, 2002, 42 ( 5 ): 71 1- 723.

PERMAN SM, GOYAL M, NEUMAR RW, et al. Clinical applications of targeted temperature management. Chest, 2014,145(2) :386-393.

ZHOUJ, POLOYAC SM. The effect of therapeutic hypothermia on drug metabolism and drug response; cellular mechanisms to organ function. Expert Opin Drug Metab Toxicol,2011 ,7(7) :803-816.

CHIANG CH, WU K, YU CP, et al. Hypothermia and Prostaglandin El produce synergistic attenuation of ischemia- reperfusion lung injury. Am J Respir Crit Med, 1999, 160 (4):1319-1323.


Refbacks

  • There are currently no refbacks.