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Cardiovascular Research 1999 43(3):685-697; doi:10.1016/S0008-6363(99)00149-2
© 1999 by European Society of Cardiology
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Copyright © 1999, European Society of Cardiology

Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases

Christopher S.R. Bakera,*, Ornella Rimoldic, Paolo G. Camicic, Edward Barnesa, Matilde R. Chaconb, Tanya Y. Huehnsa, Dorian O. Haskarda, Julia M. Polakb and Roger J.C. Halla

aDepartment of Cardiology, Hammersmith Hospital, Imperial College School of Medicine, Du Cane Road, London W12 0HS, UK
bDepartment of Histochemistry, Hammersmith Hospital, Imperial College School of Medicine, London, UK
cMRC Cyclotron Unit, Hammersmith Hospital, Imperial College School of Medicine, London, UK

* Corresponding author. Tel.: +44-181-743-2030; fax +44-181-740-8373 cbaker{at}rpms.ac.uk

Objectives: Nitric oxide (NO) has complex effects on myocardial function particularly following ischaemia–reperfusion. The goal of this study was to examine the result of repetitive myocardial stunning on myocardial NO release and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. Methods and results: Propofol anaesthetised pigs underwent ten, 2-min episodes of circumflex artery occlusion (n=6) or acted as sham operated controls (n=4). Measurements of segment shortening demonstrated a fall in function in the ischaemic territory to 52.5±7.3% (mean±S.E.M.) of baseline shortening 30 min after the stunning stimulus, recovering to 92±8.7% 5.5 h later. Function remained stable in sham controls. The change in venous–arterial [NO] between baseline and 6 h reperfusion was found to be significantly different between the two groups (0.2±0.7 in stunned vs. –4.3±1.6 µM in shams; P<0.02). Western blotting and band optical density used to compare tissue from stunned territory (S), non-stunned territory (IC) and sham control animals (SC) demonstrated this was associated with an increase in the expression of both iNOS (S: 93±13.4, IC: 37±2.4 and SC: 25±4 [arbitrary units], P<0.01 and P=0.031) and eNOS (S: 104±7.4, IC; 62.5±7.4 and SC; 75.7±0.6, P<0.03 and P<0.01) in stunned myocardium. Immunocytochemistry localised iNOS reactivity to vascular smooth muscle cells and cardiomyocytes in stunned tissue and eNOS reactivity to endothelial cells. Conclusion: Recovery from repetitive myocardial stunning is associated with the increased expression of both iNOS and eNOS and would be compatible with a protective role for both these enzymes. This finding has possible relevance for both the late window of ischaemic preconditioning and myocardial hibernation.

KEYWORDS Nitric oxide; Stunning; Reperfusion injury; Preconditioning; Pig


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