Abstract 19022: Intralipid Therapy for Prevention of Pulmonary Hypertension-induced Right Ventricular Failure
Introduction: Intralipid (ILP) is an effective treatment for local anesthetic-induced cardiac arrest and is widely used as parenteral nutrition for patients. Some of its constituents are known precursors of pulmonary vasodilator prostaglandins. Pulmonary hypertension (PH) is a lung disorder that leads to right ventricular (RV) hypertrophy and failure. We hypothesized that ILP can prevent monocrotaline (MCT)-induced PH.
Methods: To induce PH, male rats were treated with a s.c. dose (60 mg/kg) of MCT (n=5) or MCT together with daily ILP treatment (1 mL of 20% ILP/day) for 30 days (n=8). Saline treated rats served as control (CTRL, n=5). Serial echocardiography was performed to monitor RV function. At day 30, RV systolic pressure (RVSP) was recorded with a catheter right before sacrifice. Immunohistochemistry, confocal microscopy and RT PCR were performed. P<0.05 was considered significant. Values were mean±SE.
Results: MCT group developed PH; RVSP increased from 30±2 mmHg in CTRL to 70±5 mmHg, RV hypertrophy index (RV/(LV+IVS)) increased from 0.24±0.06 in CTRL to 0.68±0.1, RV ejection fraction (RVEF) decreased from 64±1% in CTRL to 32±3 %, and lung weight increased from 1.36±0.1 g in CTRL to 2.38±0.2g (all p<0.05 vs. CTRL). ILP prevented PH by fully restoring the RVSP to 34±2 mmHg and RVEF to (63±1.5%), and by partially reversing RV hypertrophy (RV/(LV+IVS)=0.33±0.04), and lung weight to 1.8±0.06 g (all p<0.05 vs. MCT). Lung histology revealed that ILP prevented arteriolar medial hypertrophy induced by MCT. RV sections double labelled with CD31 and wheat germ agglutinin showed significantly reduced capillary density in MCT (0.7±0.1 micro vessels per cell in MCT vs. 1±0.1 in CTRL). ILP significantly increased capillary density ∼ 2 fold (1.5±0.1). RT PCR showed a significant increase in IL-6 transcripts in lungs ∼ 25 fold in MCT and ILP significantly reduced IL-6 compared to MCT. Lung sections stained with macrophage marker ED1 showed a significant increase in inflammatory cells in MCT. ILP prevented this increase (from 70±6 cells per field in MCT to19±3 cells in MCT+ILP which was similar to 14±2 cells in CTRL).
Conclusion: ILP prevents PH and RV failure by ameliorating inflammation, preventing RV hypertrophy, improving RV function and enhancing capillary density.
- © 2010 by American Heart Association, Inc.