Effects on Large Arteries

NTG also has differential effects on other parts of the arterial tree. Because the central aortic walls have little in the way of smooth muscle, the effect of NTG in this part of the arterial tree is small [22, 23]. In the walls of the large peripheral arteries however, smooth muscle is abundant and NTG is not only

Normal Minimum Mild Moderate Severe Diseased segments

0-25 25-45 45-65 65-85 Control diameter stenosis (%)

Normal Minimum Mild Moderate Severe Diseased segments

0-25 25-45 45-65 65-85 Control diameter stenosis (%)

Fig. 4. Change in luminal cross-sectional area after sublingual GTN. The normal lumens are the relatively smooth segments proximal and distal to the stenosis. Narrowed segments are characterized as having minimum, mild, moderate or severe disease, depending on their percent diameter reduction (% stenosis). Each bar represents the average value of all luminal areas in each of the five groups, either before or after GTN. The percent changes reflect the average increase in area for all luminal areas in each of the five groups. x p < 0.05; * p < 0.01; + p < 0.005 [20].

effective in increasing their diameter but increases their compliance as well (fig. 6) [23, 24]. Therefore, in the central aorta there is little change in pulse wave velocity or stiffness, while in the periphery, pulse wave velocity is reduced and distensibility increased.

These changes in the behavior of the peripheral arterial walls alter the way in which the arterial pulse is transmitted and reflected. Studies in the frequency domain have shown no change in the impedance modulus of the aorta at zero frequency (systemic vascular resistance) from administered NTG, probably due to its lack of effect in the smallest resistance vessels. There was also no change in the characteristic impedance, as indicated above, but there were consistent decreases in the lowest frequency components of the impedance

Fig. 5. Aortic pressure («), retrograde flow (b) and calculated coronary collateral resistance (c) before (Base) and after GTN when aortic pressure decrease is mechanically prevented. In the absence of significant associated aortic pressure drop, GTN induced a uniform and a dramatic rise in retrograde flow and fall in collateral resistance (geometric mean decrease: 50%). Thus a decrease in aortic pressure was not requisite to demonstrate GTN-induced salutary effect on collateral function [21].

Fig. 5. Aortic pressure («), retrograde flow (b) and calculated coronary collateral resistance (c) before (Base) and after GTN when aortic pressure decrease is mechanically prevented. In the absence of significant associated aortic pressure drop, GTN induced a uniform and a dramatic rise in retrograde flow and fall in collateral resistance (geometric mean decrease: 50%). Thus a decrease in aortic pressure was not requisite to demonstrate GTN-induced salutary effect on collateral function [21].

modulus, indicating a reduction in the amplitude and delay in the timing of the reflected waves [25, 26]. The results of these changes can be easily seen on the aortic pulse wave itself (fig. 7) [25] where the reflected wave after NTG is of lower amplitude and peaks later in systole. This salutary effect of NTG on the aortic pulse may not be readily observed in the brachial artery pulse. Here, closer to the periphery, the reflected wave more markedly augments the primary systolic wave than it does in the aorta. The result is a higher brachial systolic blood pressure (SBP) than in the aorta (pulse amplification) and indicates to the clinician a smaller reduction in the SBP than that which has occurred centrally [23]. The functional effect of these changes in aortic pulse shape is to lower the SBP with little change in the mean blood pressure. Of the three major determinants of left ventricular afterload, systemic vascular resistance, aortic distensibility and reflected waves, NTG is able to lighten the load on the left ventricle by reducing the effect of reflected waves with little alteration in the other two. The explanation for the reduction in the reflected waves is speculative since the wave reflection sites are multiple and not well defined. If the primary waves are reflected from physiologically abrupt changes in small

40 50 60 70 80 90 100 Transmural pressure (mm Hg)

Fig. 6. Plot of calculated volume distensibility vs. transmural arterial pressure before and during nitroglycerin infusion [24].

Fig. 7. Effect of sublingual GTN (0.3 mg) on ascending aortic pressure. There is a 15 mm Hg reduction of peak systolic pressure due to a diminution of the late systolic pressure peak. Continuous line denotes control, broken line values after GTN [25].

Fig. 8. The proposed mechanism for reduction in peripheral reflection coefficient with GTN. The forward traveling wave is shown above, reflected at the peripheral arteri-oles indicated at right. The backward traveling reflected wave (dark arrow) is shown in the top panel under control conditions, and in the bottom panel after GTN. Wave reflection at peripheral arterioles is quite unchanged, but amplitude of the backward traveling reflected wave as observed centrally is decreased by negative ('open-ended') reflection at the junctions of parent artery with disproportionately dilated daughter branches [27].

Fig. 8. The proposed mechanism for reduction in peripheral reflection coefficient with GTN. The forward traveling wave is shown above, reflected at the peripheral arteri-oles indicated at right. The backward traveling reflected wave (dark arrow) is shown in the top panel under control conditions, and in the bottom panel after GTN. Wave reflection at peripheral arterioles is quite unchanged, but amplitude of the backward traveling reflected wave as observed centrally is decreased by negative ('open-ended') reflection at the junctions of parent artery with disproportionately dilated daughter branches [27].

arterial caliber, NTG-induced vasodilation could move those sites distally and help explain the time delay for the reflected wave to return to the central aorta (fig. 8) [27]. Reduced pulse wave velocity in the muscular arteries could also play a role. Relaxation of the larger arterioles (>200 ^m) could also reduce the reflection coefficient and thus the magnitude of the reflected wave. Whatever the explanation, NTG effectively reduces left ventricular afterload with little change in mean blood pressure.

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