The induction of heme oxygenase 1 decreases contractility in human internal thoracic artery and radial artery grafts.
OBJECTIVE
Spasm remains a potential problem encountered during the use of arterial grafts in coronary artery bypass surgery. Heme oxygenase plays a role in the control of arterial vasoreactivity. Heme oxygenase exists in 2 constitutive isoforms (heme oxygenase 2 and 3) and an inducible isoform (heme oxygenase 1). The aim of our study was to induce heme oxygenase 1 by using hemin in human internal thoracic and radial arteries and to evaluate the effect of this induction on the contractility of these arterial grafts.


METHODS
Segments of human arterial grafts obtained from patients undergoing isolated coronary artery bypass surgery were incubated in organ chambers for 4 hours in the presence of 10(-4) mol/L hemin. Concentration-response curves to norepinephrine were obtained in control and hemin-treated arterial rings. Heme oxygenase 1 expression was evaluated by using enzyme-linked immunosorbent assays and immunohistochemical staining.


RESULTS
The contractility of the arterial rings to norepinephrine was significantly reduced after incubation with hemin. Zinc protoporphyrin (an inhibitor of heme oxygenase) reversed the effect of hemin, whereas the inhibitor of nitric oxide synthase had no effect. The inhibitor of soluble guanylate cyclase blocked the decrease in contractility induced by hemin. Immunohistochemical staining revealed a large expression of heme oxygenase 1 in all vascular layers of hemin-treated internal thoracic artery and radial artery rings. Enzyme-linked immunosorbent assay studies showed a significant increase in heme oxygenase 1 levels in hemin-treated internal thoracic artery and radial artery rings.


CONCLUSIONS
Hemin caused in vitro induction of heme oxygenase 1 in human internal thoracic artery and radial artery grafts. This induction resulted in a reduced contractility to norepinephrine, partially through the cyclic guanosine monophosphate-dependent pathway. This effect was independent from nitric oxide synthesis.
Achouh
Paul
P
Department of Cardiovascular Surgery, European Hospital Georges Pompidou, Paris, France. paulachouh@softhome.net
Simonet
Serge
S
Badier-Commander
Cécile
C
Chardigny
Catherine
C
Vayssettes-Courchay
Christine
C
Zegdi
Rachid
R
Khabbaz
Ziad
Z
Fabiani
Jean-Noël
JN
Verbeuren
Tony J
TJ
D001026:Coronary Artery Bypass; D005260:Female; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000502:physiology* / Q000637:transplantation*; D008875:Middle Aged; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D017534:Radial Artery / Q000502:physiology* / Q000637:transplantation*
D051547:Heme Oxygenase-1