Exercise Pre-Conditioning Protects Right Ventricular Function And Increases Survival In MCT-induced PAH

Abstract

Pulmonary Arterial Hypertension (PAH) is characterized by progressive development of right ventricle (RV) hypertrophy, which is commonly followed by heart failure (HF) and premature death. The effect of exercise training in the natural history of PAH remains unknown. PURPOSE: we aimed to address if exercise pre-conditioning can modulate the RV response to PAH induced by Monocrotaline (MCT). METHODS: Male Wistar rats were distributed according to the following groups: i) sedentary injected with MCT (60 mg/kg, sc) or vehicle (SED+MCT and SED+V, respectively), ii) 4 week-moderate exercise training before MCT or vehicle injection (EX+MCT and EX+V). Hemodynamic bi-ventricular instrumentation with pressure catheters was assessed 4 weeks after MCT or vehicle injection. After cardiac instrumentation, the animals were sacrificed. The heart, lungs and gatrocnemius were collected for further analysis. RESULTS: When compared to SED+V, SED+MCT presented body (355±0.0 vs.276±0.0g) and gastrocnemius atrophy (2.15±0.2 vs. 1.80±0.1g), RV hypertrophy (0.18±0.0 vs. 0.29±0.1g), RV peak systolic pressure increase (RVPmax= 25.8±2.5 vs. 46.9±17.1mmHg), and RV relaxation disturbances (Tau= 10.2±2.8 vs. 17.3±2.9msec) (P<0.05). RV remodelling was also accompanied by significant collagen deposition (5.9±1.2 vs. 38.9±2.9%) (P<0.05). In comparison to SED+MCT, EX+MCT did not presented body (341±0.0 vs.276±0.0g) or muscular atrophy (2.21±0.1 vs. 1.80±0.1g), no relaxation disturbances (11.2±3.7 vs. 17.3±2.9msec) and no significant collagen deposition (4.0±0.9 vs. 38.9±2.9%) (P<0.05). These improvements were independent of cardiac overload, since no significant attenuation of RVPmax was observed in EX+MCT in relation to SED+MCT (38.8±6.6 vs. 46.8±17.1mmHg, respectively; P<0.05). Importantly, exercise pre-conditioning significantly reduced mortality rate (P<0.05). CONCLUSION: Exercise pre-conditioning seems to be an important preventive strategy in MCT model of PAH, with an important role in PAH development. Supported by Foundation for Science and Technology: SFRH/BD/33123/2007