Beneficial effects of atorvastatin on lung structural remodeling and function in ischemic heart failure.
BACKGROUND
Studies have suggested some benefit of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors in congestive heart failure (CHF), although the mechanisms remain uncertain. We hypothesized that statins could improve pulmonary hypertension and right ventricular function in ischemic CHF by reducing lung remodeling.


RESULTS
Two weeks after myocardial infarct, rats received atorvastatin (n = 23) or no treatment (n = 23) for 3 weeks and were compared with a sham group (n = 16). Infarct size was similar by echocardiography and pathologic evaluations. Atorvastatin greatly reduced pulmonary hypertension and right ventricular hypertrophy: right ventricular systolic pressure 42 +/- 5 vs. 28 +/- 2 mm Hg (P < .01). Atorvastatin did not reduce left ventricular fibrosis and had minimal effects on left ventricular function. Right ventricular myocardial performance index was markedly improved by therapy (P < .01). CHF caused a restrictive lung syndrome with a downward shift of the respiratory pressure-volume loop, increased dry lung weight, and interstitial fibrosis that were greatly improved by atorvastatin. Reduced lung nitric oxide synthase expression was normalized by treatment. Atorvastatin also reduced isolated lung myofibroblasts proliferation after transforming growth factor-beta stimulation (-36 +/- 6%, P < 0.01).


CONCLUSIONS
3-hydroxy-3-methyl-glutaryl-CoA reductase inhibition reduces lung remodeling and dysfunction associated with heart failure with prevention of right ventricular hypertrophy and pulmonary hypertension.
Jiang
Bao Hua
BH
Research Center of the Montreal Heart Institute and Department of Medicine, Université de Montreal, Montreal, Quebec Canada.
Tardif
Jean-Claude
JC
Sauvageau
Stephanie
S
Ducharme
Anique
A
Shi
Yanfen
Y
Martin
James G
JG
Dupuis
Jocelyn
J
D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use*; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D058628:Myofibroblasts / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D012129:Respiratory Function Tests
D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin