Background: Development of nitrate tolerance is a major problem which limits antianginal therapy. Subjective criterias are generally utilized to demonstrate the development of nitrate tolerance. The hypothesis that nitrate tolerance can be objectively demonstrated by tissue Doppler and forearm brachial artery diameter changes, was tested in the present study.

Methods: Eight healthy volunteers (5 men, 3 women; mean age 29±5; range 23 to 34 years) which were assessed with physical and laboratory examinations and concluded to be free of disease, in terms of internal disease and endothelial function were included in this study. Transdermal nitroglycerine, and transdermal placebo patchs, which were prepared by our pharmacy were applied to all cases every day on 7 consecutive days. Nitrate tolerance was developed in the transdermal nitroglycerin group by the application of sublingual nitroglycerin spray on the first day, and anytime after patch application on the third and seventh days. After a 10- day nitrate free interval following the seventh day, patches and sublingual nitroglycerin spray were applied again in the same manner. Tissue Doppler echocardiographic and brachial artery diameter measurements were obtained before and 3 minutes after every sublingual nitroglycerin spray. Tissue Doppler and brachial artery diameter changes were compared both in the placebo patch applied nitrate tolerance free interval and nitroglycerin patch and spray utilized nitrate tolerance positive interval of seven days.

Results: The tissue Doppler of mitral annulus E wave and brachial artery systolic diameter changes were most evident on the 1st day at 3rd and 9th hours before nitroglycerin spray (0.85±0.13, 0.72±0.12 m/sn, p=0.04; 4.1±0.2 ve 4.9±0.2 mm, p=0.03, respectively). There was a clear impact of sublingual nitroglycerin with respect to tissue Doppler and brachial artery diameter changes on the 1st day (0.75±0.11, 0.77±0.21 m/sn, p=0.04; 4.7±0.1 and 5.1±0.1 mm, p=0.04, respectively) but no hemodynamic response to additional sublingual nitroglycerin on the 3rd and 7th days in transdermal nitrate patch group (development of nitrate tolerance).

Conclusion: Tissue Doppler echocardiography and brachial artery diameter measurements, are safe and helpful laboratory parameters which can be utilized in the assessment of venous and arterial nitrate tolerance are also suitable for the selection and monitoring of the medical therapy.

Keywords : Brachial artery/ultrasonography; drug tolerance; mitral valve/ultrasonography; nitrates/administration & dosage; ultrasonography, Doppler