Abstract 10974: OPC-28326, a Peripheral Vasodilator With Alpha2-Adrenergic Antagonist Property, Mitigates Postinfarction Cardiac Remodeling Through Angiogenic Action
Although OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl) piperidine hydrochloride monohydrate, was developed as a selective peripheral vasodilator with alpha2-adrenergic antagonist property, a recent study reported an additional angiogenic activity of OPC-28326 on ischemic legs. In the present study, we examined the effect of OPC-28326 on postinfarction cardiac remodeling and dysfunction. Myocardial infarction was created in male C3H/He mice (8-10 weeks of age) by ligating the left coronary artery and the mice were randomly assigned into the 2 groups after coronary artery ligation: a normal diet group; and a 0.05% OPC-28326-containing diet (OPC) group (n=18 each). The survival rate of mice 4 weeks postinfarction was significantly greater in the OPC group (82% vs. control: 44%, p<0.05) and the left ventricular remodeling and dysfunction were significantly mitigated in the OPC group. Histologically, the OPC group showed a significantly greater infarct wall thickness, compared with the control group, which contained abundant nonmyocytes including vessels (not only capillaries but also small arteries) and myofibroblasts. We next examined the hearts 5 days postinfarction (n=6 per each group). The Ki-67-positive proliferating cells in the granulation tissue were more abundant while the TUNEL-positive apoptotic nonmyocytes were fewer in the OPC group, accompanying activation of myocardial Akt and endothelial nitric oxide synthase. Hypoxia of the infarct issue assessed by Hypoxyprobe (pimonidazole HCl) staining was markedly attenuated in the OPC group. In conclusion, OPC-28326 increased cell proliferation while decreased apoptosis of the infarct tissue, thereby altering the infarct tissue dynamics via increasing proliferation and reducing apoptosis of granulation tissue cells to reduce the wall stress and attenuate postinfarction cardiac remodeling.
- © 2012 by American Heart Association, Inc.