title: Effects of early, late, and long-term nonselective β-blockade on left ventricular remodeling, function, and survival in chronic organic mitral regurgitation.
abstract: BACKGROUND
  Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined.
  
  
  RESULTS
  Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308 ± 25 versus 351 ± 31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2 ± 0.7 versus 1.59 ± 0.6 mL; P<0.001), end-systolic volumes (0.72 ± 0.42 versus 0.40 ± 0.19 mL; P<0.001), and mass index (2.40 ± 0.55 versus 2.06 ± 0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33 ± 7% versus 38 ± 7%; P<0.001) and ejection fraction (69 ± 11% versus 75 ± 7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114 ± 10 versus 93 ± 12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03).
  
  
  CONCLUSIONS
  Early and long-term nonselective β-blockade was associated with adverse left ventricular remodeling, systolic dysfunction, and a reduction in survival in the experimental rat model of organic MR.
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. mpu@wfubmc.edu
authors.forename: Min
authors.initials: M
authors.lastname: Pu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Gao
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Pu
authors.forename: William R
authors.initials: WR
authors.lastname: Davidson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D015150:Echocardiography, Doppler / Q000379:methods; D008944:Mitral Valve Insufficiency / Q000401:mortality* / Q000503:physiopathology*; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol
keywords: left ventricular function; left ventricular remodeling; mitral regurgitation; β-blocker