Abstract P196: Effects of the Physiological Increase in Angiotensin-converting Enzyme in Acute Myocardial Infarction

Abstract

The angiotensin converting enzyme (ACE) act in the production of ANG II and degradation of bradykinin. It is believed that higher levels of ACE could modulate susceptibility to coronary occlusion. To investigate this possibility we used adult males mice genetically modified to express different concentrations of ACE similar to that found in humans. Animals (1, 2 or three copies of ACE gene; n = 6 each group) were subjected to acute myocardial infarction (AMI) and evaluated 7 days after. Systolic, diastolic, and mean blood pressure (BP), heart rate, heart rate variability (HRV) were evaluated as well as cardiac function by echocardiography. Regarding hemodynamic data, AMI induced no difference in systolic, diastolic and mean BP of diferente gene copies mice (ACE1: 74.02 ± 3.0; ACE2: 108.65 ± 2.8; ACE3: 102.07 ± 4.1mmHg). Regarding heart rate it was observed a reduction in 3 copies group (ACE1: 654.51 ± 26.34; ACE2: 668.22 ± 10; ACE3: 534.11 ± 33.4 BPM). The heart rate variability evaluated by SDNN (ACE1: 5.16 ± 0.93; ACE2: 5.84 ± 1:32; ACE3: 7.69 ± 1.4 ms), RMSSD (ACE1: 5.91 ± 0.69; ACE2: 5.7 ± 1:14; ACE3: 6.78 ± 1.2ms), and the total variance (ACE1: 30 ± 12.4; ACE2: 37 ± 13.8; ACE3: 69.9 ± 25.6 ms) was higher in the ACE 3 infarcted group. Regarding the spectral analysis of HRV a higher sympathetic modulation (ACE1: 5.14 ± 3; ACE2: 7.2 ± 2.8; ACE3: 12.9 ± 4.1ms 2 ) and a lower parasympathetic modulation (ACE1: 7 ± 2; ACE2: 8.6 ± 3.2; ACE3: 5.5 ± 2.8 ms 2 ) were observed in ACE 3 infarcted mice. The variability of the BP (ACE1: 18.7 ± 6.2; ACE2: 14.85 ± 1.6; ACE3: 13.76 ± 4.2 mmHg 2 ) and the sympathetic modulation component of the vessels were reduced in the ACE 3 AMI group (ACE1: 60.5 ± 6.2; ACE2: 54.6 ± 1.7; ACE3: 53 ± 3.3 mmHg 2 ). Echocardiographic data showed diastolic dysfunction expressed by E / A ratio (ACE1: 3.40 ± 0.67; ACE2: 3:02 ± 1:36; ACE3: 2.0 ± 0.75) and increase in FAC - Fractional Area Change (ACE1: 27.9 ± 4.5; ACE2: 26.4 ± 5.7; ACE3: 33.5 ± 1.3) in the ACE 3 group after AMI. Our data suggest that increasing the number of ACE gene copies may promote autonomic imbalance evidenced by increased sympathetic modulation and the reduction of parasympathetic modulation of the cardiovascular system as well as the impairment of the diastolic function.