Article ID: 18-226
The effect of DPP-4 inhibitor on the electrical and structural remodeling in myocardial injury has not been evaluated. We hypothesized that linagliptin, DPP-4 inhibitor, suppresses myocardial remodeling in the isoproterenol (ISP)-induced myocardial injury model.
Sprague-Dawley rats were assigned to 3 groups: 1) sham group, 2) ISP group (subcutaneous ISP injection of 70 mg/kg), and 3) ISP + linagliptin (ISP + Lin) (5 mg/kg/day, p.o.) group. Serum was sampled on day 1 (acute phase) and day 7 (sub-acute phase) to evaluate derivatives of reactive oxidative metabolites (d-ROMs). The electrophysiological study was performed in sub-acute phase for the evaluation of the ventricular effective refractory period (VERP) and monophasic action potential duration (MAPD). The VERP and MAPD were markedly prolonged in the ISP group in comparison with the sham (MAPD20: 14 ± 6 versus 11 ± 3 ms, MAPD90: 57 ± 8 versus 44 ± 7 ms, VERP: 74 ± 22 versus 38 ± 10 ms, P < 0.05). In contrast in the ISP + Lin group, such prolongations were suppressed, and the parameters were shorter than the ISP group (MAPD20: 9 ± 2 ms, MAPD90: 35 ± 6 ms, VERP: 52 ± 13 ms, P < 0.05). ISP treatment induced myocardial injury. The injured area was reduced in the ISP + Lin group in comparison with the ISP group (P < 0.05). Serum d-ROMs level in acute phase was higher in ISP group than the other 2 groups (sham: 214 ± 55 versus ISP: 404 ± 45 versus ISP + Lin: 337 ± 20 U.CARR, P < 0.05).
Linagliptin suppressed structural and electrical changes, possibly through the antioxidative effect, in this myocardial injury model.
