ALTERATIONS IN THE MYOCARDIAL CAPILLARY VASCULATURE ACCOMPANY TACHYCARDIA-INDUCED CARDIOMYOPATHY

Changes in capillary structure and distribution within the left ventricle (LV) occur with pressure and volume overload hypertrophy. These changes may cause an impairment in myocardial blood flow (MBF) and oxygen delivery resulting in myocyte injury and LV dysfunction. However, it is unknown whether changes in the capillary vasculature accompany the development of LV dysfunction in dilated cardiomyopathies. Accordingly, this study examined the relation between LV function, MBF and capillary architecture after the development of dilated cardiomyopathy in pigs produced by chronic supraventricular tachycardia (SVT). LV function was examined by echo-catheterization, and capillary morphometrics were computed using lectin histochemistry in two groups of pigs: sham controls (n = 8): and after 3 weeks of pacing-induced SVT (n = 8). Chronic SVT resulted in significantly increased LV end-diastolic dimension and pressure with a 50% reduction in LV fractional shortening compared to CON (p < 0.05). Although no significant change in capillary density (2180 +/- 164 vs 2402 +/- 147/mm2, p = 0.25) occurred in the SVT group compared to CON, a significant reduction in the volume fraction of capillaries (12.2 +/- 0.5 vs 9.9 +/- 0.7%, p < 0.05) and increased capillary diffusion distance (8.4 +/- 0.5 vs 7.5 +/- 0.3-mu-m, p < 0.05) was observed. Frequency distribution analysis revealed a higher percentage of smaller diameter capillaries with chronic SVT vs CON (p < 0.05). Ultrastructural examination revealed an increased capillary-myocyte distance with chronic SVT (0.95 +/- 0.08 vs 1.95 +/- 0.12-mu-m, p < 0.05). These changes were accompanied by ultrastructural evidence of significant subendocardial injury (p < 0.05). MBF was measured using microspheres in five additional conscious pigs in each group. MBF was significantly reduced and coronary vascular resistance increased in the SVT group compared to CON (p < 0.05). Chronic SVT caused significant remodeling of the capillary vasculature; these changes were associated with reduced MBF, myocyte injury, and LV dysfunction.