Olivari M T, Carlyle P F, Levine T B, Cohn J N
J Am Coll Cardiol. 1983 Nov;2(5):872-8. doi: 10.1016/s0735-1097(83)80234-4.
The hemodynamic and hormonal responses to nitroglycerin administered transdermally in a gel-like matrix were evaluated in nine patients with severe congestive heart failure and in nine normal subjects. In normal subjects, peripheral vasodilation was accompanied by reflex sympathetic stimulation as reflected by an increase in heart rate and plasma norepinephrine. In patients with heart failure, nitroglycerin produced sustained hemodynamic effects that began 30 minutes after the application and fully persisted for at least 6 hours. A significant decrease in right and left ventricular filling pressures was associated with an increase in stroke index and a significant decrease in forearm and pulmonary vascular resistances. There was no change in heart rate and systemic arterial pressure or in plasma norepinephrine or plasma renin activity. After 24 hours, pressures had partially returned to control levels, but mean pulmonary artery pressure was still significantly lower than in the control period. After removal of the nitroglycerin, each patient exhibited a decrease in cardiac index and an increase, above the control values, in pulmonary and systemic arterial pressures and pulmonary, systemic and forearm vascular resistances. This transient rebound appeared to be unrelated to stimulation of the sympathetic or renin-angiotensin systems. Thus, transdermal absorption of this new form of nitroglycerin appears to provide a nitrate vascular effect that is sustained for 24 hours, but an endogenous vasoconstrictor effect may influence the hemodynamic response over the first 24 hours.
在9例严重充血性心力衰竭患者和9名正常受试者中评估了经皮给予凝胶状基质硝酸甘油后的血流动力学和激素反应。在正常受试者中,外周血管舒张伴有反射性交感神经刺激,表现为心率和血浆去甲肾上腺素增加。在心力衰竭患者中,硝酸甘油产生持续的血流动力学效应,在用药后30分钟开始,至少持续6小时。右心室和左心室充盈压显著降低,同时每搏指数增加,前臂和肺血管阻力显著降低。心率、体动脉压、血浆去甲肾上腺素或血浆肾素活性无变化。24小时后,压力部分恢复到对照水平,但平均肺动脉压仍显著低于对照期。去除硝酸甘油后,每位患者的心指数均降低,肺和体动脉压以及肺、体和前臂血管阻力均高于对照值而增加。这种短暂的反跳似乎与交感神经或肾素-血管紧张素系统的刺激无关。因此,这种新型硝酸甘油的经皮吸收似乎提供了一种持续24小时的硝酸盐血管效应,但内源性血管收缩效应可能在最初24小时内影响血流动力学反应。