EARLY CHANGES IN ELECTRICAL PROPERTIES OF ISCHEMIC HEART WITH AND WITHOUT ECE INHIBITION: THREE-DIMENSIONAL ELECTROCARDIOGRAPHY STUDY: PP.13.488

Abstract

Little is known about the significance of ECE inhibition for modulation of electrical heart activity. The study aim was to assess three-dimensional electrocardiogram (ECG) changes during development of acute heart ischemia (AHI) due to global coronary arteries microembolization using 15 um microsphere with and without ECE inhibition. ECE inhibitor PP36 was used in current study. Two days before coronary embolization, male Wistar rats were randomized for treatment with PP36 (3.5 × 10–5 M/kg, AHI + PP36 group, n = 29) or with a vehicle (AHI group, n = 31 and sham control group, n = 15). Application of PP36 continued for two days post-embolization in AHI + PP36 group. Under anesthesia (sodium pentobarbital, 40 mg/kg), ECG were recorded with an orthogonal three-lead system before and after coronary vessels microembolization, and two days after global AHI induction. Data were analyzed with dedicated computer software. Invasively measured maximal left ventricular systolic pressure (LVSP) developed in response to aorta occlusion was similar between PP36 treated (261 + 5 mmHg) and untreated (261 + 4 mmHg) rats. Measured before induction of global heart ischemia magnitude of Q-wave and area under STT segment of controls and PP36 treated for two days rats were similar. ECG parameters of controls did not significantly change over time. However PP36 significantly reduced QRS-T angle after two days application. Immediately after induction of heart ischemia, LVSP was decreased by 26–27% and STT area was increased three-fold in AHI and AHI + PP36 groups. Differences between AHI and AHI + PP36 groups were reflected by depolarization changes in QRS-vector magnitude and repolarization changes in QRS- and T-axis orientation. In conclusion, three-dimensional ECG analysis appears to be very sensitive to early changes in ECE activity modulation. Induction of AHI with PP36 application is characterized by early ECG changes preceding left ventricular contractility changes compared to AHI group.