BackgroundAortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR.MethodsAR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods.ResultsOM increased indices of global cardiac function (cardiac output, stroke volume), and increased systolic performance (fractional shortening, ejection fraction, left ventricular end systolic diameter) (all p < 0.05). These effects concurred with decreases in indices of LV preload (left atrial size, left ventricular end diastolic diameter) as well in the aortic pre-ejection period / left ventricular ejection time ratio (all p < 0.05). The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters.ConclusionThe cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR.

Locating the site of increased resistance within the vascular tree in pulmonary arterial hypertension could assist in both patient diagnosis and tailoring treatment. Wave intensity analysis (WIA) is a wave analysis method that may be capable of localizing the major site of reflection within a vascular system. We investigated the contribution of WIA to the analysis of the pulmonary circulation in a rabbit model with animals subjected to variable occlusive pulmonary disease. Animals were embolized with different sized microspheres for 6 wk ( n = 10) or underwent pulmonary artery (PA) ligation for 6 wk ( n = 3). These animals were compared with a control group ( n = 6) and acutely embolized animals ( n = 4). WIA was performed and compared with impedance-based methods to analyze wave reflections. The control group showed a relatively high extent of reflected waves (15.7 ± 10.6%); reflections had a net effect of pressure reduction during systole, suggesting an open-end reflector. The pattern of wave reflection was not different in the group with partial PA ligation (12.4 ± 4.1%). In the chronically embolized group, wave reflection was not observed (3.6 ± 1.5%). In the acute embolization group, wave reflection was more prominent (37.3 ± 12.6%), with the appearance of a novel wave increasing pressure, suggesting the appearance of a closed-end reflector. Wave reflections of an open-end type are present in the normal rabbit pulmonary circulation. However, the pattern and nature of reflections vary according to the extent of pulmonary vascular occlusion. NEW & NOTEWORTHY The study proposes an original framework of a complementary analysis of wave reflections in the time domain and in the frequency domain. The methodology was used in the pulmonary circulation with different forms of chronic obstructions. The results suggest that the pulmonary vascular tree generates a reflection pattern that could actually assist the heart during ejection, and chronic obstruction significantly modifies the pattern.