Effect of IQ-1 on the Infarct Size and the Parameters of Cardiodynamic Indicators in the Acute Period after Myocardial Ischemia/Reperfusion in Rats

The effect of a new JNK inhibitor IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was studied in male Wistar rats in a model of acute myocardial ischemia/reperfusion. Area at risk and myocardial infarct zones were studied in two series of experiments: 16 h after a single dose of IQ-1 (25 mg/kg intraperitoneally during cardiac ischemia) and on day 5 after its course administration (25 mg/kg intraperitoneally during cardiac ischemia and daily over 4 days). On day 5 after ischemia/reperfusion, cardiodynamic indicators were also studied: systolic, end-diastolic, and minimum pressure in the left ventricle, stress-time index, as well as the maximum rates of pressure rise and fall in the left ventricle (+dP/dt(max) and -dP/dt(max)). In 16 h after ischemia/reperfusion, the infarct area in the control was 24 +/- 2% of the total area of the sections, while after administration of IQ-1 this parameter was 14 +/- 1% (p<0.05). On day 5, the infarct area in the control group was 25 +/- 1% of the total area of myocardial sections. A course of IQ-1 administration led to a significant reduction in the infarct area to 10 +/- 2% of the total area of myocardial slices. Course administration of IQ-1 led to improvement in contractile function and weakening of the diastolic dysfunction of the left ventricle: systolic pressure in the left ventricle increased by 20%, +dP/dt(max) by 23%, voltage-time index by 12%, -dP/dt(max) by 43%, and the minimum pressure in the left ventricle decreased by 3.4 times.