Comparative effects of amlodipine and benazepril on left atrial pressure in dogs with experimentally-induced mitral valve regurgitation

Abstract

Background: One of the purposes of treatment for dogs with mitral regurgitation (MR) is lowering left atrial pressure (LAP). There has been few study of the amlodipine in dogs with MR and amlodipine's effect on LAP has not been fully evaluated in a quantitative manner because of difficulties in directly measuring LAP. The objective of our study was to compare the short-term effects of amlodipine (0.2 mg/kg PO q12h) vs benazepril (0.5 mg/kg PO q12h), on LAP and echocardiographic parameters in five beagle dogs with experimentally-induced MR. LAP of eight dogs that has own control were measured using radiotelemetry system at baseline and again on days 1, 2, 3, 4, 5, 6, 7 of the drug administration.

Results: Mean LAP decreased significantly after amlodipine (11.20 ± 4.19 mmHg vs 14.61 ± 3.81 mmHg at baseline, p < .01) but not after benazepril treatment (13.19 ± 3.47 mmHg, p > .05). LAP was lower after 7 days of amlodipine treatment than after 7 days of benazepril treatment. Significant reduction was seen for the first time 4 days after the administration amlodipine. The rate of the maximal area of the regurgitant jet signals to the left atrium area (ARJ/LAA) of the amlodipine treatment was significantly lower (p < .05) after 7 days compared to baseline. Other echocardiographic parameters did not change significantly.

Conclusions: LAP was significantly decreased after amlodipine treatment in dogs with surgically-induced MR but not after benazepril treatment. Although this study did not focus on adverse effects, amlodipine may be an effective drug for helping the patients with acute onset of severe MR, such as rupture of chordae tendinae or end stage patients were the LAP is likely to be elevated. Additional studies in clinical patients with degenerative mitral valve disease and acute chordal rupture are warranted because the blood-pressure lowering effects of amlodipine can decrease renal perfusion and this can further activate the RAAS.

Figure 1

The scheme of left atrial pressure measurement by a radio telemetry system in this experiment. The digital signal of the data of the left atrial pressure from the transmitter was sensed by the receiver and sent to a data exchange matrix. An ambient pressure reference monitor was connected to the data exchange matrix to monitor correct atmospheric pressure and exclude all rocal environmental pressure fluctuations. Finally, the digital signal data was converted to an analog signal by the data exchange matrix and sent to a personal computer.

Figure 2

Left atrial pressure 7 days after administration of amlodipine. Left atrial pressure (LAP) 7 days after administration of amlodipine 0.2 mg/kg or benazepril 0.5 mg/kg q12h PO in 5 dogs with MR. Baseline values were those obtained before drug administration. The box and whiskers plot demonstrates the mean (+), the median (line), 5 and 95% confidence limits (box) and range (bars). ^*P < .05, ^**P < .01.

Figure 3

Temporal variation after administration of amlodipine. Temporal variation of Mean LAP and Systolic blood pressure after administration of amlodipine in 5 dogs with MR. ^*Significant differences (P < .05) compared with each baseline.

Figure 4

Systolic blood pressure Mean blood pressure and Heart rate 7 days after administration of amlodipine. Systolic blood pressure (SBP), Mean blood pressure (MBP) and Heart rate (HR) 7 days after administration of amlodipine 0.2 mg/kg or benazepril 0.5 mg/kg q12h PO in 5 dogs with MR. Baseline values were those obtained before drug administration. The box and whiskers plot demonstrates the mean (+), the median (line), 5 and 95% confidence limits (box) and range (bars). ^*P < .05, ^**P < .01.

Figure 5

ARJ/LAA 7 days after administration of amlodipine. The ratio of the maximum area of the regurgitant jet signals to the left atrium area (ARJ/LAA) 7 days after administration of amlodipine 0.2 mg/kg or benazepril 0.5 mg/kg q12h PO in 5 dogs with MR. Baseline values were those obtained before drug administration. The box and whiskers plot demonstrates the mean (+), the median (line), 5 and 95% confidence limits (box) and range (bars). ^*P < .05.

Figure 6

Stroke volume and Cardiac output 7 days after administration of amlodipine. Stroke volume (SV) and Cardiac output (CO) 7 days after administration of amlodipine 0.2 mg/kg or benazepril 0.5 mg/kg q12h PO in 5 dogs with MR. The box and whiskers plot demonstrates the mean (+), the median (line), 5 and 95% confidence limits (box) and range (bars). ^*P < .05.

Figure 7

Systemic vascular resistance 7 days after administration of amlodipine. Systemic vascular resistance (SVR) 7 days after administration of amlodipine 0.2 mg/kg or benazepril 0.5 mg/kg q12h PO in 5 dogs with MR. The box and whiskers plot demonstrates the mean (+), the median (line), 5 and 95% confidence limits (box) and range (bars). ^**P < .01.