扩张剂-收缩剂给药顺序会影响狭窄血流动力学反应。
The order of dilator-constrictor administration affects stenotic hemodynamic responses.
作者信息
Li K S, Ferdinand F D, Tulenko T N, Corin W J, Santamore W P
机构信息
Philadelphia Heart Institute, Presbyterian Medical Center, PA 19104.
出版信息
Am J Med Sci. 1993 Jun;305(6):354-64. doi: 10.1097/00000441-199306000-00002.
This study tested the hypothesis that, due to intraluminal pressure changes, the order of constrictor-dilator administration alters stenotic hemodynamic responses. Canine carotid arteries were perfused with a physiologic salt solution under constant pressure (100 mm Hg). An intraluminal stenosis partially obstructed the arteries. Pressures proximal and distal to the artery and the flow were continually recorded as norepinephrine (10(-9)-10(-6) M) was added to the perfusate. Adding diltiazem (10(-7) M) before norepinephrine shifted the effective half maximum dose (ED50) of the norepinephrine flow curve from 7.35 +/- 0.66 X 10(-8) M to 6.39 +/- 0.72 X 10(-7) M (p < 0.05). More important, adding 10(-7) M diltiazem after norepinephrine-induced constriction did not reestablish stenotic pressure or flow: A 30-fold increase in diltiazem concentration (3.16 X 10(-6)M) was required to reestablish stenotic pressure (62.6 +/- 4.4 mm Hg) and flow (25.4 +/- 3.2 ml/min). Similarly, adding nitroglycerin (10(-7) M) before norepinephrine shifted the ED50 from 7.21 +/- 0.58 X 10(-8) to 5.94 +/- 0.78 X 10(-6) (p < 0.05). Adding 10(-7) M nitroglycerin after norepinephrine did not reestablish stenotic pressure or flow: 3.16 X 10(-6) M nitroglycerin was required to reestablish stenotic pressure (59.2 +/- 4.8 mm Hg) and flow (23.2 +/- 2.7 mL/min). This constrictor-dilation history did not occur in isolated arterial rings (norepinephrine + nitroglycerin = 38.1 +/- 13.9 g/cm2; nitroglycerin + norepinephrine = 42.2 +/- 9.4 g/cm2; p = not significant [NS]) or in normal arteries (norepinephrine + nitroglycerin = 4.89 +/- 0.14 mm [external diameter]; nitroglycerin + norepinephrine = 4.92 +/- 0.23 mm; p = NS). In stenotic arteries, intraluminal pressure influenced the order of constrictor-dilator administration on hemodynamic response, which was not observed in isolated arterial rings or in normal arteries. This pressure-dependent sensitivity affects vasomotor tone and may be important in the pathophysiology of ischemia.
本研究检验了以下假设
由于管腔内压力变化，缩血管药与扩血管药给药顺序会改变狭窄处的血流动力学反应。在恒定压力（100 mmHg）下用生理盐溶液灌注犬的颈动脉。管腔内狭窄部分阻塞动脉。在向灌注液中添加去甲肾上腺素（10⁻⁹ - 10⁻⁶ M）时，持续记录动脉近端和远端的压力以及血流量。在去甲肾上腺素之前添加地尔硫䓬（10⁻⁷ M）使去甲肾上腺素流量曲线的有效半数最大剂量（ED50）从7.35 ± 0.66×10⁻⁸ M 变为6.39 ± 0.72×10⁻⁷ M（p < 0.05）。更重要的是，在去甲肾上腺素引起收缩后添加10⁻⁷ M地尔硫䓬并不能恢复狭窄处的压力或血流：需要将地尔硫䓬浓度增加30倍（3.16×10⁻⁶ M）才能恢复狭窄处压力（62.6 ± 4.4 mmHg）和血流（25.4 ± 3.2 ml/min）。同样，在去甲肾上腺素之前添加硝酸甘油（10⁻⁷ M）使ED50从7.21 ± 0.58×10⁻⁸变为5.94 ± 0.78×10⁻⁶（p < 0.05）。在去甲肾上腺素之后添加10⁻⁷ M硝酸甘油不能恢复狭窄处压力或血流：需要3.16×10⁻⁶ M硝酸甘油才能恢复狭窄处压力（59.2 ± 4.8 mmHg）和血流（23.2 ± 2.7 mL/min）。这种缩血管 - 扩血管给药顺序的情况在离体动脉环中未出现（去甲肾上腺素 + 硝酸甘油 = 38.1 ± 13.9 g/cm²；硝酸甘油 + 去甲肾上腺素 = 42.2 ± 9.4 g/cm²；p = 无显著差异[NS]），在正常动脉中也未出现（去甲肾上腺素 + 硝酸甘油 = 4.89 ± 0.14 mm[外径]；硝酸甘油 + 去甲肾上腺素 = 4.92 ± 0.23 mm；p = NS）。在狭窄动脉中，管腔内压力影响缩血管药与扩血管药给药顺序对血流动力学反应的影响，这在离体动脉环或正常动脉中未观察到。这种压力依赖性敏感性影响血管运动张力，可能在缺血的病理生理学中起重要作用。
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