Introduction: The conservative drug therapy of high-grade aortic regurgitation (AR) is often challenging. Higher heart rates to reduce the regurgitation fraction of AR via shortened diastole are generally recommended. On the other hand, a chronic reduction in heart rate with ivabradine can significantly improve the compliance of the aorta and thus also the total afterload of the heart with a possible decrease in the regurgitation fraction (RF). Therefore, we studied the influence of heart rate, aortic compliance and stroke volume  in an in vitro porcine model of severe AR.

Methods and Results: The experiments were performed on porcine ascending aorta and aortic valves (n=12). Compliance was varied by inserting a Dacron prosthesis just distal to the aortic valve. These tubing systems were connected to a left heart simulator that could vary heart rate (HR) (40, 50, 60, 80, 100, and 120 bpm) and stroke volume (SV) (40, 50, 60, 80, and 100 mL). AR was accomplished by punching a 0.3 cm² hole with a cannula in one of the aortic cusps. Flow, regurgitation volume and fraction, and aortic pressure were measured invasively in the various settings.  Aortic compliance was measured using transesophageal ultrasound probes placed in a water bath close to the ascending aorta. Compliance was defined as the difference in systolic and diastolic cross-sectional area of the aorta divided by the systolic aortic area times the pulse pressure. Aortic diastolic pressure was held constant at approximately 65 mmHg at each steady state and did not differ significantly while heart rate and stroke volume were varied.

The compliance of the aorta was significantly reduced in the experiments with the Dacron prosthesis (at HR of 60 bpm and SV of 60 ml, the compliance of the native aorta was 0.55 +/- 0.21%/mmHg vs. Dacron prosthesis (0.01 +/- 0.007% / mmHg, p<0.001). With increasing HR, RF was significantly reduced in each steady state (HR 40 bpm with RF = 88% +/- 7% vs. HR 120 bpm with RF 42% +/- 10%; p<0.001). Reduced aortic compliance did not significantly affect RF compared to native aorta (HF 40 bpm: RF Dacron 87+/-8%; p=0.79 vs. native aorta; HR 120 bpm: RF Dacron 42% +/-3%; p = 0.86 vs native aorta). Increasing stroke volume was also associated with a reduced RF (RF at SV 50ml: 81+/-11% vs. RF at SV 120ml: 44%+/-9; p<0.001), here, too, the stiffness of the Dacron prosthesis had no influence on this effect.

Conclusion: Aortic compliance does not affect aortic regurgitation in the in vitro porcine model of aortic regurgitation. RF is reduced with increasing heart rate due to the concomitant reduced diastolic period, as well as with increased stroke volume. The latter could be explained by the physical inertia of the blood moving away from the heart. These results suggest that negatively inotropic drugs and heart rate lowering agents such as beta-blockers and ivabradine should not be used to treat aortic regurgitation.