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Evaluation of time sequential changes in subendocardial arteioles in the hypertensive hypertrophic canine heart by using needle-lens CCD intravital microscope

针镜CCD活体显微镜评价高血压肥厚犬心脏内膜下小动脉随时间的变化

基本信息

批准号：
09480259
负责人：
KAJIYA Fumihiko
金额：
$ 6.46万
依托单位：
Kawasaki Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

Time sequential changes in endothelium-dependent and -independent vasodilator mechanisms on subendocardial arterioles (Emdo-A) were studied in hypertensive canine hearts (2-clip and 2-kidney model). The diameter of Endo-A and subepicardial (Epi-A) arterioles (<110 μm) was measured using a high-speed CCD intravital microscope. We also visualized the blood velocities in the subendocardial microcirculation with a light marker (niobium microsphere). Vascular responses to acetylcholine (Ach, 1μg/kg, ic) and papaverine (Papa, 1mg, ic) were compared in normotensive (N, left ventricular wall thickness : LVWT=9mm, n=7) and hypertensive (4w-HT, LVWT=12mm, m=8, p<0.01, vs N : 12w-HT, LVWT=14mm n=3, p<0.01, vs N) hearts. Percent increase of end-diastolic diameter of Endo-A in both 4w- and 12w-HT after Ach was smaller than that of N (4w, p<0.05 and 12w, p<0.001). The vasodilation of Endo-A after Papa was impaired in 12w-HT (p<0.01), but that of Epi-A was not. The blood velocity waveform in a subendocardial arteriole exhibited a forward flow exclusively during diastole and a twopeaked reverse flow during systole. This velocity waveform implies that a part of the diastolic forward flow moved back during systole and we called this wastful back and forth flow as "coronary slosh phenomenon" which increased in HT.In conclusion, in an early stage of HT (4w-HT), the endothelium-dependent response of Endo-A was impaired. In the later stage (12w-HT), both the endothelium-dependent and independent responses of Endo-A were impaired. These time sequential changes may be related with the degree of decreased subendocardial coronary flow reserve in progression of LVH. The coronary slosh phenomenon which increased in FIT may be important to understand the clinically well-known higher incidence of ischemia in the subendocardium.

在高血压犬心脏（2-夹和2-肾模型）上研究了内皮依赖性和非依赖性血管舒张机制（Emdo-A）的时间序列变化。用高速CCD活体显微镜测量心内膜A（Endo-A）和心外膜下（Epi-A）小动脉直径（<110 μm）。我们还用光标记物（铌微球）观察了血管内膜下微循环的血流速度。比较了正常血压（N，左室壁厚度：LVWT=9mm，n=7）和高血压（4 w-HT，LVWT= 12 mm，m=8，p<0.01，vs N：12 w-HT，LVWT= 14 mm，n=3，p<0.01，vs N）心脏对乙酰胆碱（Ach，1μg/kg，ic）和罂粟碱（Papa，1 mg，ic）的血管反应。Ach后4 w和12 w-HT的Endo-A舒张末期内径增加百分比均小于N组（4 w，p<0.05和12 w，p<0.001）。12 w-HT时，Pa后Endo-A的舒张功能受损（p<0.01），Epi-A的舒张功能无明显变化。内动脉下小动脉的血流速度波形在舒张期呈前向流，在收缩期呈双峰反向流。这种速度波形意味着舒张期前向流的一部分在收缩期向后移动，我们称这种浪费的来回流动为“冠状动脉晃动现象”，在HT中增加。总之，在HT的早期阶段（4 w-HT），内皮依赖性反应的Endo-A受损。在后期（12 w-HT），内皮依赖性和非依赖性内皮细胞反应均减弱。这些时序性变化可能与LVH进展过程中冠状动脉内膜下血流储备降低的程度有关。FIT中增加的冠状动脉晃动现象可能对理解临床上众所周知的内膜下缺血的高发生率很重要。