Beschreibung:
<jats:title>Summary</jats:title><jats:p><jats:bold>Objective: </jats:bold> 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).</jats:p><jats:p><jats:bold>Methods: </jats:bold> 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%.</jats:p><jats:p><jats:bold>Results: </jats:bold> At arterial GTN concentrations of 27·2 [10·0–57·8] nmol l<jats:sup>−1</jats:sup> in CHF and 2·8 [2·5–3·5] nmol l<jats:sup>−1</jats:sup> in HS [median (quartile range), <jats:italic>P<</jats:italic>0·05 between groups], MAP and mean capillary wedge pressures were reduced similarly in both groups (approx. 15% and 65%, respectively, <jats:italic>P = </jats:italic>NS <jats:italic>between groups</jats:italic>). 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), <jats:italic>P<</jats:italic>0·05], with a negative correlation between the 1,2‐GDN/1,3‐GDN ratio and the arterial GTN concentrations in the CHF patients (<jats:italic>R</jats:italic> = −0·8, <jats:italic>P<</jats:italic>0·05).</jats:p><jats:p><jats:bold>Conclusion: </jats:bold> 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.</jats:p>