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Thorac Cardiovasc Surg 2009; 57(7): 379-385
DOI: 10.1055/s-0029-1185873
Original Cardiovascular

© Georg Thieme Verlag KG Stuttgart · New York

Regulation of Endothelial Nitric Oxide Synthase (eNOS) in Myocardium Subjected to Cardioplegic Arrest

U. M. Fischer1 , O. Klass2 , C. S. Cox1 , U. Stock3 , A. Antonyan3 , K. Brixius4 , J. H. Fischer3 , U. Mehlhorn5 , W. Bloch4
  • 1Pediatric Surgery, University of Texas Medical School at Houston, Houston, Texas, United States
  • 2Radiology, University of Ulm, Ulm, Germany
  • 3Experimental Medicine, University of Cologne, Cologne, Germany
  • 4Molecular and Cellular Sport Medicine, German Sport University, Cologne, Germany
  • 5Thoracic and Cardiovascular Surgery, University of Mainz, Mainz, Germany
Further Information

Publication History

received February 20, 2008

Publication Date:
30 September 2009 (online)

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Abstract

Background: Nitric oxide (NO) production by both coronary endothelial cells and cardiomyocytes is thought to play a significant role in myocardial pathophysiology following ischemia/reperfusion (I/R). Methods: In thirteen pigs subjected to 1 hour cardioplegic arrest (CA) on CPB, left ventricular (LV) biopsies were collected prior to CPB (baseline), at 60 min CPA, at 15 and 30 min reperfusion on CPB, and at 120 min post CPB. LV specimens were immunocytochemically stained against phospho-eNOSSer1177, phospho-eNOSThr495, phosphorylated ERK1/2, and AKT/PKB. Four additional pigs without CA served as controls. Cardiomyocytes were quantitatively investigated using TV densitometry (gray units: U). Results: After 60 min CA phosphorylation of eNOSSer1177 increased significantly and remained elevated until 30 min of reperfusion. In contrast, eNOSThr495 phosphorylation remained unchanged during CA and throughout reperfusion. In control animals, eNOS phosphorylation remained unchanged. Akt/PKB activity significantly increased after 60 min CA and decreased thereafter. ERK1/2 activity remained unchanged during ischemia but increased during reperfusion. Conclusions: ENOS activation during ischemia occurs through phosphorylation at Ser1177 mediated by Akt/PKB. ERK1/2 does not seem to be involved in myocardial eNOS regulation especially not via phosphorylation at eNOSThr495.

Key words

myocardial protection - cardiovascular surgery - coronary bypass surgery

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MD Wilhelm Bloch

Department of Molecular and Cellular Sport Medicine
Institute of Cardiovascular Research
German Sport University Cologne

Carl-Diem-Weg 6

50933 Cologne

Germany

Phone: + 49 2 21 49 82 53 90

Fax: + 49 2 21 49 82 83 70

Email: W.Bloch@dshs-koeln.de

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