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Simvastatin Treatment Attenuates Increased Respiratory Variability and Apnea/Hypopnea Index in Rats with Congestive Heart Failure
Author(s) -
Marcus Noah J,
Haack Karla KV,
Zucker Irving H,
Schultz Harold D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb829
Subject(s) - medicine , heart failure , simvastatin , cardiology , hypercapnia , hypoxia (environmental) , statin , apnea–hypopnea index , nitric oxide , respiratory system , apnea , polysomnography , oxygen , chemistry , organic chemistry
Cheyne‐Stokes respiration (CSR) is associated with increased morbidity and mortality in patients with congestive heart failure (CHF). In CHF patients, enhanced carotid body chemoreflex (CBC) sensitivity is associated with CSR. Reduced carotid body nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC observed in CHF, and Simvastatin (SIM) treatment increases NOS expression. We hypothesized that, in a rodent model, development of CHF would be accompanied by enhanced CBC as well as increased respiratory variability (RV) and apnea/hypopnea index (AHI), and that SIM treatment would attenuate these changes. Using plethysmography, we measured ventilatory responses to hypoxia and hypercapnia, and calculated RV and AHI from measurements taken during resting breathing. Left ventricular (LV) function was quantified via echocardiography. We found that CHF was associated with enhanced ventilatory responses to hypoxia and hypercapnia and increased RV (sham vehicle SD1 0.07±0.12 vs. CHF vehicle SD1 0.133±.03) and AHI (sham vehicle 4±2 vs. CHF vehicle 14±1). SIM treatment prevented these increases (CHF statin SD1 0.07±0.01, and CHF statin AHI 6±2). Our findings demonstrate a relationship between increased CBC sensitivity and respiratory instability observed in CHF, and suggest that SIM may be an effective treatment for CSR in patient populations with high chemosensitivity.