1267 Either Cat: Cardiac Protection: from Basic Research to Translational

1267 either Cat: Cardiac Protection: From Basic Research to Translational

POTENTIAL EFFECT OF ALCOHOLIC EXTRACT OF LEAVES OF OCIMUM SANCTUM IN MONOCROTALINE-INDUCED PULMONARY ARTERY HYPERTENSION IN RATS H. Meghwani 1, P. Prabhakar1, S. Seth2, R. Ray3, M.P. Hote4, S.K. Maulik1, S. Banerjee5 1. Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India 2. Department of Cardiology, All India Institute of Medical Sciences (AIIMS), New Delhi, India 3. Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India 4. Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India 5. Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India

Background: Pulmonary hypertension is underdiagnosed and complex disease with features of mPAP above 25mm of Hg and vascular resistance above 3 WU resulting in high mortality if untreated. Cradioprotection using alternative medicine may provide hope. Objective: To evaluate the effect of ocimum sanctum in MCT-induced PH Methods: The study was approved by Institutional animal ethics committee, AIIMS, New Delhi, India. Baseline echocardiography was done in 30 rats (n=6). Control rats were injected 1ml/kg normal saline. PAH rats were administered monocrotaline (MCT) 50mg/kg.Sildenafil rats were administered with MCT 50mg/kg and sildenafil (175microg/kg/day) for 25 daysOS100 and OS200 rats were administered with MCT 50mg/kg sc and OS (100 and 200mg/kg/day) for 25 days. Echocardiography measures left ventricular ejection fraction (LVEF), ratio of right ventricular outflow tract to aortic diameter (RVoTD/AoD) and ratio of pulmonary artery acceleration time to ejection time (PAAT/ET). Cardiac catheterization to estimate right and left ventricular systolic pressure (RVSP, LVSP), end diastolic pressure (RVeDP). Heart and lungs were weighed. Lung was preserved for histopathology and western blot analysis for nicotinamide adenine dinucleotide phosphate oxidase (Nox-1). Right ventricular hypertrophy (RVH) and apoptotic markers (Bcl2/Bax). Results: Monocrotaline induce PAH through oxidative stress (increased TBARS, reduced GSH, SOD and catalase and increased Nox-1). It leads to initiation and progression of pulmonary artery smooth muscle cell proliferation and thus resulting in increased PVR (increased %MWT and decreased PAAT/ET), RV undergo compensatory hypertrophy (increased Fulton index, right ventricular systolic pressure, and RVoTD/AoD). If untreated the cardiac myocytes undergo apoptosis and failure (increased Bax expression and RVeDP). Sildenafil and OS both prevented increased RVSP, RVeDP, RVH, and RVoTD/AoD and apoptosis in right ventricle. Conclusion: The present study shows cardio protective property of ocimum sanctum in MCT model of PAH in rats, further validation is required through clinical research.