Abstract P163: Rescue of Preexisting Severe Pulmonary Hypertension and Right Ventricular Failure by Intralipid
Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure (RVF). Intralipid (ILP) is the first safe lipid emulsion for human use. Several constituents of ILP, like γ-linolenic acid and soy- phytoestrogens are protective for lungs and heart. Previously we showed that ILP prevents the development of PH. Here we test a more clinically relevant hypothesis if ILP can rescue pre-existing severe PH and RV dysfunction. To induce PH, male rats received single monocrotaline (MCT, 60mg/kg) injection. At day 21, when severe PH had been well-established (PH group, n=7), rats were given ILP (1mL of 20% ILP/day, i.p., n=7) from day 21-30. Other MCT rats were left untreated to develop RVF (RVF group, n=9) by day 30. Saline treated rats were control (CTRL, n=5). Serial echocardiography was done to monitor cardiopulmonary hemodynamics. Cardiac catheterisation was performed just before sacrifice to record RV pressure (RVP). CD31 staining for RV capillary density and smooth muscle actin staining for pulmonary arteriolar medial hypertrophy were performed. Rats developed severe PH and RV dysfunction 21 days after MCT in PH group [RVP=67±1 vs. 31±1mmHg in CTRL, RV-ejection fraction (RVEF)=39% vs. 65±1%; RV/(LV+IVS)=0.64±0.05 vs. 0.24±0.02; medial hypertrophy=2.8 fold vs. CTRL; all p<0.05]. Interestingly, we found that even 10-day ILP therapy not only prevented the progression of PH to RVF but also rescued pre-existing PH and RV dysfunction [RVP=44±1 mmHg vs. 70±2 mmHg in RVF; RVEF=53±1 vs. 30±1%; RV/(LV+IVS)=0.39±0.02 vs. 0.66±0.08; medial hypertrophy=3 fold less vs. RVF; all p<0.05]. ILP therapy resulted in 100% survival compared to only 25% survival in RVF. Next we investigated if ILP rescue was associated with stimulation of RV neoangiogenesis. We found that RV capillary density was decreased in PH (0.7±0.07 vs. 1±0.07 capillaries per myocyte in CTRL; p<0.05) and worsened in RVF (0.52±0.07 capillaries per myocyte; p<0.05 vs. CTRL). ILP therapy resulted in stimulation of neoangiogenesis (capillary density=0.98±0.01 capillaries per myocyte; p<0.05 vs. PH and RVF). ILP therapy rescues severe pre-existing PH and retards the development of RV failure possibly via stimulation of RV neoangiogenesis.
- © 2011 by American Heart Association, Inc.