This study had a number of important findings. Firstly, LAP was significantly decreased with amlodipine in dogs with MR. Secondly, LAP appeared to decrease according to the decreasing in SBP and MBP. Thirdly, stroke volume and cardiac output increased and systemic vascular resistance decreased after administration of amlodipine. Finally, the severity of mitral regurgitation appeared to decrease according to the reduction in ARJ/LAA.
In a previous report, amlodipine decreased left ventricular end-diastolic pressure (measured as a surrogate for LAP) in dogs with pacing-induced heart failure [13
]. However, there are few studies that the effect of amlodipine on left atrial pressure in dogs with MR. In the present study, LAP was significantly decreased and cardiac output was significantly increased by amlodipine in dogs with MR (Figure and ). Amlodipine is arterial vasodilators and used to reduce systemic vascular resistance in patients with cardiac heart failure [5
]. The reduction in systemic vascular resistance results in an increase in cardiac output. In dogs with MR, amlodipine increases cardiac out put, therefore, decreases the volume of regurgitation relatively across a mitral valve. So, our results suggest amlodipine has beneficial effect on LAP in dogs with MR. Also, in the present study, adverse effects of amlodipine were not observed but we feel this warrants further examination because there is a report that long-term administration of amlodipine to dogs with mitral regurgitation may cause gingival hyperplasia in a small percentage of patients [24
Both of the amlodipine and benazepril are classified of vasodilators based on mechanism of action. Amlodipine was more effective than ACE inhibitor in lowering blood pressure [25
]. In our previous report, an ACE inhibitor did not significantly decrease LAP despite a reduction in afterload [14
]. Conversely, in the present study, amlodipine significantly decreased LAP, as well as SVR (Figure ). This result suggests that strong reduction in afterload is associated with the decrease in LAP. Patients with heart failure need to maintain an adequate kidney perfusion and lowering the blood pressure per se can just induce renal failure (cardio-renal syndrome). So, while it is likely that amlodipine is an effective drug for helping the patients with acute onset of severe MR (i.e. rupture of chordae tendinae) or end stage patients were the LAP is likely to be elevated, the same cannot be true in patients stable chronic heart failure. It is thought that the positive long term benefits for patients treated with ACE inhibitor are related to their ability to block the Renin-Angiotensin-Aldosterone system (RAAS) more than to their vasodilation properties. On the other hand, indication of Amlodipine may be limited because the blood-pressure lowering effects of amlodipine can decrease renal perfusion and this can further activate the RAAS.
Amlodipine significantly decreased MBP and increased HR, although not statistically significant in previous reports [25
]. Similarly, in the present study, amlodipine decreased MBP but did not change HR. The published dosage data in dogs is from 0.05
] to 1
]. The high end of this range (approximately 1
mg/kg/day) was chosen in the previous report [25
]. However, in the present study, the dosage was 0.2
mg/kg q12h and HR might not have changed after administration of amlodipine. Further examination would be needed for the detailed information for the amlodipine dosage for dogs with MR.
There is a report on echocardiographic values of cats with systemic hypertension after administration of amlodipine [12
]. However, no difference was found in any of the echocardiographic measurements between the untreated and treated cats in the previous report. In the present study, only ARJ/LAA of the amlodipine group was significantly lower compared to baseline (Figure ). Other echocardiographic parameters did not change significantly. We previously have reported that E wave and E/Ea can be used for the evaluation of preload after administration of high doses of furosemide, and have monitored the reduction of LAP in the short-term [16
]. However, present study suggests that it is difficult to evaluate the reduction of LAP after administration of amlodipine by using E wave and E/Ea. E, E/A and E/Ea are influenced not only by preload but relaxation, compliance, and heart rate [27
]. Again it is the left atrial compliance that plays a major role in changing LAP. The echocardiographic indices might not have changed in this study because the left atrial compliance had been maintained despite the fluctuation of LAP. Conversely, ARJ/LAA, SBP and MBP may be useful to evaluation after administration of amlodipine.
Amlodipine is recommended at dosages of 0.05
mg/kg/day to 1
mg/kg/day for dogs [5
]. However, the optimal dosage for dogs with MR is not known. This study was not designed to evaluate the optimal dosage of amlodipine for dogs with MR. Therefore, it may have some adverse effects by dosage. Also, toxic effects are not known with longterm administration of amlodipine in asymptomatic dogs because this study is shortterm study using dogs with experimentally-induced MR. In the present study, five 2-year-old Beagle dogs were used and a 5-week period was defined as a subchronic period for experimentally-induced MR. In clinical situations, dogs with MR and cardiac dysfunction and myocardial tissue damage might differ from the model dogs in this study. Therefore, our model may more closely resemble acute MR and differ from naturally-occurring chronic MR. SV and CO were calculated by echocardiography. Therefore, it may differ from the value strictly measured with the catheter.
In the present study, the neurohormonal response to treatment was not studied. Therefore, if a pure vasodilator is used to decrease blood pressure, there is a risk of a deleterious neurohormonal activation leading for example in increased heart rate.