Systemic endothelial dysfunction in adults with cyanotic congenital heart disease.
BACKGROUND
Secondary erythrocytosis results in increased shear stress in cyanotic congenital heart disease (CCHD), which may modify the balance between vasodilators and vasoconstrictors and affect systemic endothelial function. Because no data are available on systemic vasomotion, systemic endothelial function and nitric oxide (NO) availability were investigated in CCHD patients.


RESULTS
Responses to arterial endothelium-dependent (acetylcholine [Ach]) and -independent (sodium nitroprusside [SNP]) vasodilation, NO synthase blockade (NG-monomethyl-L-arginine [L-NMMA]), endothelin-1 (ET-1), and ET-1 receptor blockade by BQ-123 in 11 CCHD patients (O2 saturation <90%; mean+/-SD, 79+/-1%; mean+/-SD age, 39+/-2 years) were compared with those in 10 age-matched healthy referents by using forearm venous occlusion plethysmography. Resting forearm blood flow (FBF) was lower in CCHD patients than in referents (2.4+/-0.2 versus 3.5+/-0.4 mL.min(-1).100 mL(-1) of forearm volume [FAV], P<0.05). Although the response to SNP was similar in both groups (CCHD, 2.0+/-0.3 to 8.3+/-1.0; referents, 3.6+/-0.7 to 11.9+/-1.2 mL.min(-1).100 mL(-1) of FAV; P>0.1), the response to Ach was markedly reduced in CCHD (maximal increase in FBF, 2.8+/-0.8 versus 37.5+/-4.4 mL.min(-1).100 mL(-1) of FAV; P<0.0001). l-NMMA was less effective in CCHD (decrease in FBF, 25+/-6% versus 40+/-4%; P<0.05). ET-1 caused less vasoconstriction in the CCHD group (-25+/-9% versus -51+/-7%, P<0.05), but the response to BQ-123 was similar in both groups (32+/-9% versus 27+/-9%).


CONCLUSIONS
Systemic endothelial dysfunction is evident in CCHD patients as shown by strikingly reduced endothelial vasodilation to Ach. The response to exogenous ET-1 is reduced, possibly because of elevated endogenous ET-1 levels, but the effects of endogenous ET-1 on arterial tone are not enhanced, as indicated by the similar response to ET-1 blockade.
Oechslin
Erwin
E
CardioVascular Center, Division of Cardiology, University Hospital, Zurich, Switzerland. erwin.oechslin@usz.ch
Kiowski
Wolfgang
W
Schindler
Ruth
R
Bernheim
Alain
A
Julius
Barbara
B
Brunner-La Rocca
Hans Peter
HP
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage; D003490:Cyanosis / Q000503:physiopathology*; D019332:Endothelin-1 / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006330:Heart Defects, Congenital / Q000503:physiopathology*; D006454:Hemoglobins; D006801:Humans; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000008:administration & dosage; D010100:Oxygen / Q000097:blood; D010456:Peptides, Cyclic / Q000008:administration & dosage; D011086:Polycythemia / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000959:Antihypertensive Agents; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D010456:Peptides, Cyclic; D014665:Vasodilator Agents; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D000109:Acetylcholine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D010100:Oxygen