Hemodynamic effects of Enalapril and B‐type natriuretic peptide on the progression of pacing induced cardiac myopathy in conscious dogs

Purpose Enalapril and B‐type natriuretic peptide (BNP) are used in cardiovascular clinical practice as a common anti‐hypertensive drugs and a diagnostic marker of heart failure (HF). BNP is secreted from ventricular cardiomyocytes in response to high cardiac filling pressures and has anti‐hypertensive actions by stimulating natriuresis and diuresis. Typically, BNP is elevated in HF but studies suggest that a resistance to endogenous BNP causes this. Thus BNP could be potentially therapeutic as an exogenous source. Few studies have elucidated the changes in hemodynamics and echocardiographic parameters and the outcome on the pulmonary component during HF. Here we tested whether the above mentioned parameters could be favorably affected by Enalapril, BNP and the possible combined treatment resulting in slowing the progression or improving the tolerance to HF. Methods Twelve chronically instrumented dogs underwent left ventricular pacing at 210 beats/min for 3 weeks and at 240 beat/min thereafter. Starting at day 10 of pacing, the dogs were randomized into three groups to receive either Enalapril (1 mg/kg) orally, BNP (5–25 mg/kg) by sc injection, or placebo. The transitions from compensated dysfunction to HF occurred between the 3 rd and 4 th week of pacing, with end‐stage HF occurring at 28±1 days. Results We found that dP/dt max , LVEDP and arterial BP remained unchanged between the control and treated groups. However, Arterial PO2 was better preserved in the Enalapril group compared to the placebo group. Arterial P O2 typically falls during the decompensated stages of HF and is indicative of pulmonary edema. By week 4, arterial PO2 was significantly higher in the Enalapril group (88±2.8 mmHg) compared to the placebo group (78±3.0 mmHg, p<0.05). Echocardiography showed that EF was significantly maintained in the Enalapril group compared to the BNP (weeks 1, 3) and placebo (weeks 2, 3) groups indicating that, although small, the EF may be better maintained. At week 3, EF was 37±2.5% and 39±1.6% for the BNP and placebo groups, respectively, whereas the Enalapril group had an EF of 45±1.6% (p<0.05). In addition, end systolic diameters were significantly decreased with Enalapril compared to the placebo (weeks 2–4). No significant hemodynamic or echocardiographic changes were detected in comparison of compensated dysfunction and end stage heart failure of the groups. Conclusion Our data suggests that Enalapril and BNP treated dogs maintained a preserved cardiac systolic function and hemodynamic tolerance during end stage HF, as reflected by clinical parameters and blood values (P O2 ). Although the data did not reflect significant changes between BNP and placebo, it did not worsen the progression of HF and could be considered safe.