Effects of pimobendan (UD-CG 115) on the contractile function of the normal and “Postischemic” canine myocardium

Pimobendan (UD-CG 115) is a long-acting positive inotropic drug with arterio- and venodilator properties. To determine to what extent this new agent is able to affect contractile function in previously ischemic areas of the left ventricle (LV), the effects of pimobendan on global and regional LV function were studied in eight conscious dogs, 2 days after a 2-h coronary occlusion followed by reperfusion. Before pimobendan, percentage of systolic shortening and mean velocity of shortening were lower in reperfused segments than in control areas (0.41 ± 0.17 vs. 0.93 ± 0.07 s^-1 and 7 ± 3 vs. 15 ± 1%, respectively; both p < 0.05). Infusion of 1 mg of pimobendan significantly improved peak + dP/dt (3202 ± 372 to 3848 ± 498 mm Hg/s; p < 0.05) and ejection time (166 ± 13 to 156 ± 15 ms; p < 0.05). Cumulative infusion up to 2.5 mg further improved these indexes to 5199 ± 934 mm Hg/s and to 125 ± 11 ms, (respectively; both p < 0.05) without affecting mean arterial pressure (91 ± 14 to 93 ± 22 mm Hg; NS). Mean velocity of shortening rose to 1.18 ± 0.09 s^-1 (p < 0.05) in control segments and to 0.62 ± 0.18 s^-1 (p < 0.05) in reperfused segments. The ratio between end-systolic pressure and length increased by 26 ± 9% (p < 0.05) in the reperfused segments and by 20 ± 8% (p < 0.05) in control areas. Coronary flow increased slightly in reperfused areas (endo, 111-149; epi, 78-100 ml/min/100 g; NS) as well as in control areas (endo, 126-155; epi, 92-122 ml/min/100 g; NS) during pimobendan infusion and the ratio (endo/epi) flow remained unchanged. No loss of benefit was seen in reperfused areas up to 5 h after pimobendan infusion. In conclusion, pimobendan improved global and regional indexes of contractility in postischemic myocardium. These results suggest that pimobendan might be useful to treat heart failure after reperfusion.