Effects of chronic heparin administration on coronary vascular adaptation to hypertension and ventricular hypertrophy in sheep

Background-Hypertension decreases myocardial perfusion capacity in adults f or several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotio n. Heparin influences growth factors that promote angiogenesis and vasodila tion and inhibit arteriolar wall thickening. Methods and Results-Adult sheep were given heparin 200 U/kg body wt SC twic e daily throughout 6 weeks of LV and coronary hypertension from a progressi vely constricted ascending aortic band (n=14). They were compared with untr eated sheep with (n=13) and without (n=13) aortic stenosis. After 6 weeks, maximum myocardial perfusion was measured during adenosine infusion in the conscious state by the microsphere method. Sheep with aortic stenosis had l ess maximum coronary flow per gram, less conductance reserve, and thicker a rteriolar walls in the LV and nonhypertrophied right ventricle, Capillary d ensity decreased in the LV endomyocardium and remained unchanged in the rig ht ventricle. Heparin-treated sheep had significant partial normalization o f coronary conductance reserve and maximum perfusion in both ventricles and capillary density in the LV endomyocardium. Arteriolar wall thickness was unchanged. Compared with untreated sheep with aortic stenosis, in heparin-t reated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged. VEGF mRNA and protein increased 3-fold and 1.4-fold, respective ly, whereas TGF-beta(1) mRNA declined 3-fold. Conclusions-Heparin administration during LV hypertension increases heparin -binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decrea ses in LV perfusion capacity and capillary density.