Abstract 4828: Effect of Atorvastatin on Pulmonary Hypertension and Lung Function and Remodeling in Heart Failure
Pulmonary hypertension (PH) and right ventricular (RV) dysfunction associated with congestive heart failure (CHF) carry a poor prognosis. Recent clinical trials have suggested some benefits of HMG-CoA reductase inhibitors in CHF, although the mechanisms remain uncertain. In this study, we evaluated the effect of Atorvastatin on lungs and RV function and remodeling in rats with CHF. Rats were submitted to myocardial infarction (MI) or sham surgery. Two weeks after MI, echocardiography was performed to determine infarct size. Medium to large MI rats (wall motion score index > 1.25) were randomized to Atorvastatin (20 mg kg−1 d−1, n=23) or no treatment (n=23) for 3 weeks and compared to the sham group (n=16). At 5 week we measured echocardiogarphic variables, lung function tests, hemodynamic parameters, infarct size, RVH, and pulmonary structural remodeling. Infarct size was similar in the MI group compared to the MI+Atorvastatin group at 2 weeks and 5 weeks by both echo and pathologic evaluations. CHF rats developed moderate PH associated with RV dysfunction and RVH, which were markedly improved by Atorvastatin treatment: RV systolic pressure was 42±5 versus 28±2 mmHg (P<0.01) and RV/LV +Septum was 40±4 versus 29±2% (P<0.05). There was minimal effect of therapy on left ventricular function. RV myocardial performance index was however greatly affected by CHF (32.8±6.8 versus 4.1±2.2%, P<0.01) and markedly improved by Atorvastatin (10.7±5.0%, P<0.01). CHF caused a restrictive lung syndrome with reduced dynamic compliance and a downward shift of the lungs P-V loop; both were greatly improved by Atorvastatin. Lung weight increased by about 62% with important interstitial collagen deposition: this was greatly reduced by Atorvastatin. HMG-CoA reductase inhibition with Atorvastatin reduces lung remodeling and dysfunction associated with CHF and also prevents RVH and PH despite similar infarct size. These effects should be considered in future clinical trials evaluating statins in CHF. The beneficial effects of statins in CHF could be on the lungs, not the heart.