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

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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.