Comparative effects of glyceryl trinitrate and amyl nitrite on pulse wave reflection and augmentation index

Abstract

Aims: The influence of vasodilators on augmentation index (AIx) offers a simple, rapid and noninvasive method of evaluating vascular function. Glyceryl trinitrate (GTN) is widely used as an endothelium-independent vasodilator, although other nitrates that are shorter acting may have advantages in clinical studies. The aim of this study was to compare the effects of two short-acting nitrates, GTN and amyl nitrite, which have differing pharmacodynamic profiles.

Methods: Twenty-one healthy volunteers (15 male; mean age 35 years, range 21-56 years) attended on three occasions and received sublingual GTN (0.5 mg for 3 min), inhaled amyl nitrite (0.2 ml inhaled for 30 s), or no treatment in a randomized cross-over design. Haemodynamic responses of AIx, blood pressure and thoracic bioimpedance (heart rate, cardiac index) were assessed by measurement at baseline, every 60 s for the first 5 min, and then every 5 min for a further 55 min.

Results: AIx was reduced by amyl nitrite (peak effect -9 +/- 2% at 1 min, P < 0.002) and GTN (peak effect -12 +/- 3% at 4 min, P < 0.05). Compared with amyl nitrite, the onset and offset of action of GTN was slower. Amyl nitrite initially increased heart rate by 27 +/- 4% (P < 0.001) and cardiac index by 13 +/- 3% (P < 0.001) whereas GTN had no significant effect (P > 0.05). Neither agent affected blood pressure.

Conclusions: GTN causes a slower and more sustained reduction in AIx than amyl nitrite. Although amyl nitrite causes a more rapid fall and recovery in AIx, it induces a reflex tachycardia that may limit interpretation of the initial (1 min) but not later (2 min) changes in AIx. The prolonged offset of GTN suggests that a sufficient washout period must be included when making repeated measures or when assessing the subsequent effects of other agents.

Figures

Figure 1

Schematic of the effect of arterial stiffness on the peripheral wave form. P1 represents the initial systolic pressure wave, travelling from the heart to the periphery. In compliant large arteries (as in healthy young subjects, Figure 1a), P2, composite of the forward wave and reflected pressure waves, arrive back at the central aorta in diastole, augmenting diastolic blood pressure and coronary filling. In stiff arteries (e.g. in age, with increasing cardiovascular risk, Figure 1b), wave reflection occurs earlier and thus the systolic peak is augmented. Augmentation index is calculated as the difference between P1 and P2 expressed as a percentage of the pulse pressure (PP)

Figure 2

Effect of amyl nitrite (closed triangle), GTN (closed square) and placebo (open rhomboid) on (a) augmentation index (b) heart rate (c) cardiac index and (d) mean arterial blood pressure. Placebo (◊), GTN (▪), Amyl Nitrite (▴)