Format

Send to

Choose Destination
J Cardiovasc Pharmacol. 2017 Jun;69(6):382-388. doi: 10.1097/FJC.0000000000000489.

Time Window Is Important for Adenosine Preventing Cold-induced Injury to the Endothelium.

Author information

1
*Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;†The Key Laboratory of Assisted Circulation, Ministry of Health, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;‡National and Guangdong Province Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;§Cardiovascular Medicine, The First Affiliated Hospital, Anhui Medical University, Hefei, China;¶Division of Hypertension and Vascular Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;‖Department of Pathophysiolgy, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China; and**Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China.

Abstract

Cold cardioplegia is used to induce heart arrest during cardiac surgery. However, endothelial function may be compromised after this procedure. Accordingly, interventions such as adenosine, that mimic the effects of preconditioning, may minimize endothelial injury. Herein, we investigated whether adenosine prevents cold-induced injury to the endothelium. Cultured human cardiac microvascular endothelial cells were treated with adenosine for different durations. Phosphorylation and expression of endothelial nitric oxide synthase (eNOS), p38MAPK, ERK1/2, and p70S6K6 were measured along with nitric oxide (NO) production using diaminofluorescein-2 diacetate (DAF-2DA) probe. Cold-induced injury by hypothermia to 4°C for 45 minutes to mimic conditions of cold cardioplegia during open heart surgery was induced in human cardiac microvascular endothelial cells. Under basal conditions, adenosine stimulated NO production, eNOS phosphorylation at serine 1177 from 5 minutes to 4 hours and inhibited eNOS phosphorylation at threonine 495 from 5 minutes to 6 hours, but increased phosphorylation of ERK1/2, p38MAPK, and p70S6K only after exposure for 5 minutes. Cold-induced injury inhibited NO production and the phosphorylation of the different enzymes. Importantly, adenosine prevented these effects of hypothermic injury. Our data demonstrated that adenosine prevents hypothermic injury to the endothelium by activating ERK1/2, eNOS, p70S6K, and p38MAPK signaling pathways at early time points. These findings also indicated that 5 minutes after administration of adenosine or release of adenosine is an important time window for cardioprotection during cardiac surgery.

PMID:
28581447
DOI:
10.1097/FJC.0000000000000489
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center