Impaired nitroglycerin biotransformation in patients with chronic heart failure.
Clin Physiol Funct Imaging
; 28(4): 229-34, 2008 Jul.
Article
em En
| MEDLINE
| ID: mdl-18384624
ABSTRACT
OBJECTIVE:
Patients with chronic heart failure (CHF) often require higher doses of nitroglycerin (glyceryl trinitrate, GTN) than patients with normal cardiac function to achieve a given haemodynamic goal. Two pathways leading to biotransformation of GTN have been characterized; a high-affinity pathway operative in nanomolar concentration ranges yielding predominantly 1,2-glyceryl dinitrate (1,2-GDN), and a low-affinity pathway operative at higher, micromolar concentrations of GTN associated with a greater proportion of 1,3-GDN formation. We tested the hypothesis that, at a given GTN-induced blood pressure reduction, the CHF group would present with (i) higher concentrations of GTN; and (ii) decreased ratios of 1,2-GDN/GTN and 1,2-GDN/1,3-GDN compared with healthy subjects (HS).METHODS:
Twelve patients with CHF (left ventricular ejection fraction 20 +/- 5%, NYHA III) and nine HS were investigated during a right cardiac catheterization. GTN was titrated intravenously until mean arterial blood pressure (MAP) was reduced by 15%.RESULTS:
At arterial GTN concentrations of 27.2 [10.0-57.8] nmol l(-1) in CHF and 2.8 [2.5-3.5] nmol l(-1) in HS [median (quartile range), P<0.05 between groups], MAP and mean capillary wedge pressures were reduced similarly in both groups (approx. 15% and 65%, respectively, P = NS between groups). The ratios of 1,2-GDN/GTN and 1,2-GDN/1,3-GDN were lower in CHF (0.86 [0.28-1.58] and 5.8 [5.6-6.3]) compared with HS [1.91 (1.54-2.23) and 7.6 (7.2-10.2), P<0.05], with a negative correlation between the 1,2-GDN/1,3-GDN ratio and the arterial GTN concentrations in the CHF patients (R = -0.8, P<0.05).CONCLUSION:
Patients with CHF have attenuated GTN responsiveness and decreased relative formation of 1,2-GDN in comparison with HS, indicating an altered biotransformation of GTN.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vasodilatadores
/
Nitroglicerina
/
Insuficiência Cardíaca
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article