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

研究了高血压犬心脏（2夹和2肾模型）心内膜下小动脉（Emdo-A）内皮依赖性和非依赖性血管扩张机制的时间序列变化。采用高速CCD活体显微镜测量内径<110 μm的内、心外膜下（Epi-A）小动脉直径。我们还用轻标记物（铌微球）观察心内膜下微循环的血流速度。比较正常（N，左室壁厚度：LVWT=9mm, N =7）和高血压（4w-HT， LVWT=12mm, m=8, p<0.01, vs N: 12w-HT， LVWT=14mm, N =3, p<0.01, vs N）心脏对乙酰胆碱（Ach, 1μg/kg, ic）和罂粟碱（Papa, 1mg, ic）的血管反应。Ach后4w和12w- ht组Endo-A舒张末期内径增加百分比均小于N组（4w, p<0.05和12w， p<0.001）。12w-HT时，Papa后Endo-A的血管舒张功能受损（p<0.01），而Epi-A的血管舒张功能未受影响。心内膜下小动脉血流波形在舒张期表现为纯正向血流，在收缩期表现为双峰反向血流。这种速度波形表明，一部分舒张期前向血流在收缩期向后移动，我们称这种浪费的前后流动为“冠状动脉晃动现象”，这种现象在HT时增加。综上所述，在早期HT (4w-HT)， endoa的内皮依赖性反应受损。在后期（12w-HT），内皮依赖性和独立性的endoa反应都受到损害。这些时间顺序变化可能与LVH进展中心内膜下冠状动脉血流储备减少的程度有关。在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心内膜下缺血发生率较高的现象很重要。

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.