Conclusions
MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.
Methods
One week after monocrotaline (MCT) injection, rats were randomly assigned to MAC (n=16), MAC combined with sildenafil (SIL) (MAC+SIL, n=16), or normal saline (MCT, n=16). Twelve sham rats (Sham) were included for comparison. Right ventricular (RV) systolic function was assessed via echocardiography as the RV fractional area change (RV-FAC). An invasive pressure-volume analysis using a Millar conductance catheter was performed 7 weeks after MCT injection. Rats were subsequently euthanized for histopathologic analysis.
Results
RV-right atrial pressure gradient on echocardiography was significantly increased 3 weeks after MCT injection, but was maintained in the Sham. RV-FAC was less deteriorated in the MAC, compared to that in the MCT (44±3% vs. 25±7%, p<0.05), and the co-administration of SIL showed no additional benefit (45±8%, p>0.05 vs. the MAC). On invasive hemodynamic analyses, RV end-systolic (196±78 μL) and end-diastolic volumes (310±86 μL), pulmonary artery systolic pressure (89±7.2 mmHg), and end-systolic pressure-volume relationship (-254±25.1) were significantly worse in the MCT vs. in the MAC (101±45 μL, 235±55 μL, 40±10.5 mmHg, and -145±42.1, respectively) and MAC+SIL (109±47 μL, 242±46 μL, 38±9.2 mmHg, and -151±39.2, respectively) (all p<0.05). However, the MAC and MAC+SIL did not differ (all p>0.05). On histopathology, both RV and lung fibrosis were significantly reduced in the MAC and MAC+SIL vs. in the MCT (all p<0.05); the 2 treatment groups did not differ. Conclusions: MAC treatment at an earlier stage significantly attenuated experimental PAH progression hemodynamically and histopathologically.