Document Detail

Impaired nitroglycerin biotransformation in patients with chronic heart failure.
MedLine Citation:
PMID:  18384624     Owner:  NLM     Status:  MEDLINE    
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.
Magnus Petersson; Bengt Rundqvist; Brian M Bennett; Michael A Adams; Peter Friberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-01
Journal Detail:
Title:  Clinical physiology and functional imaging     Volume:  28     ISSN:  1475-0961     ISO Abbreviation:  Clin Physiol Funct Imaging     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-02     Completed Date:  2008-11-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137604     Medline TA:  Clin Physiol Funct Imaging     Country:  England    
Other Details:
Languages:  eng     Pagination:  229-34     Citation Subset:  IM    
Department of Cardiology, Sahlgrenska University Hospital, Göteborg, Sweden.
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MeSH Terms
Chronic Disease
Heart Failure / drug therapy,  metabolism*
Middle Aged
Nitroglycerin / analogs & derivatives,  chemistry,  pharmacokinetics*,  therapeutic use
Vasodilator Agents / chemistry,  pharmacokinetics*,  therapeutic use
Reg. No./Substance:
0/Vasodilator Agents; 27321-62-6/dinitroglycerol; 55-63-0/Nitroglycerin; 623-87-0/glyceryl-1,3-dinitrate

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