Endothelin-1 in the human myocardium and circulating plasma: evaluation before, during and after correction of aortic stenosis with aortic valve replacement.
OBJECTIVE
Due to the pathological effects of endothelin-1 (ET-1) on cardiomyocytes and the extracellular matrix, ET-1 levels may impact on the prognosis of aortic stenosis (AS) patients operated with aortic valve replacement (AVR). We examined ET-1 levels in AS patients throughout the whole AVR process, thus exposing potential therapeutic windows of opportunity.


METHODS
Plasma ET-1 levels were measured before and 2 days, 6 and 12 months after AVR in 22 patients with AS. Myocardial ET-1 was measured in biopsies from 7 patients undergoing AVR. Peroperatively, plasma ET-1 was analyzed in the coronary sinus and radial artery before aortic cross-clamp and at 5 and 20 min of reperfusion, in a second group of 30 patients.


RESULTS
Circulating ET-1 levels were transiently increased 2.6-fold 2 days following AVR. Myocardial ET-1 protein was 2.1-fold higher in patients with AS compared to controls. Plasma levels of ET-1 correlated to echocardiographic markers of diastolic dysfunction postoperatively. There was no increase in plasma ET-1 during early reperfusion, but veno-arterial differences indicated potential cardiac ET-1 extraction.


CONCLUSIONS
Plasma ET-1 increases 2 days following AVR and myocardial ET-1 protein levels are increased in patients with AS before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.
Department of Cardiothoracic Surgery, Oslo University Hospital, Ullevål, Norway.
Peter
P
Majak
Johannes L
JL
Bjørnstad
Bjørn
B
Braathen
Ida G
IG
Lunde
Trygve
T
Husebye
Geir
G
Christensen
Theis
T
Tønnessen
D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D001024:Aortic Valve Stenosis / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D058385:Cardiac Valve Annuloplasty; D004452:Echocardiography; D004562:Electrocardiography; D019332:Endothelin-1 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies
D019332:Endothelin-1