title: Chronic effects of ethanol on pharmacokinetics and left ventricular systolic function in rats.
abstract: BACKGROUND
  Observational clinical studies have demonstrated that there is a U-shaped relationship between ethanol consumption and all-cause mortality or risk of ischemic stroke. Although the exact cause of the U-shaped relationship is unclear, the pharmacokinetics of ethanol during the time course of chronic intake of ethanol may be involved, in relation to its cardiotoxic effects. The present study has assessed the cause of the U-shaped relationship between the ethanol consumption and left ventricular (LV) systolic dysfunction in a pharmacokinetic way.
  
  
  METHODS
  Male Wistar rats were paired, and either ethanol or control liquid diet was chronically administered for 7 weeks. Then, these rats were subdivided into 3 groups: control liquid-diet-fed rats [EtOH (-)], 3 g/dL ethanol liquid-diet-fed rats (3%EtOH), and 5 g/dL ethanol liquid-diet-fed rats (5%EtOH). Ethanol's cardiotoxicity on LV systolic function was investigated by echocardiography. Ethanol concentration in blood, ethanol pharmacokinetics, and hepatic alcohol dehydrogenase (ADH) activity were evaluated simultaneously.
  
  
  RESULTS
  The 5%EtOH group revealed LV systolic dysfunction, associated with a higher ethanol concentration in blood, and lower hepatic ADH activity than the EtOH (-) group; however, the 3%EtOH group did not show LV systolic dysfunction. During the acute ethanol stress, LV systolic dysfunction appeared in both EtOH (-) and 5%EtOH groups, with a higher ethanol concentration in blood and lower hepatic ADH activity than the 3%EtOH group. The 3%EtOH group showed a higher ethanol washout rate, less time-integral of ethanol concentration, and shorter mean residence time of ethanol in blood than the EtOH (-) or 5%EtOH group.
  
  
  CONCLUSIONS
  The U-shaped relationship between chronic ethanol consumption and LV systolic dysfunction may be closely related to the pharmacokinetic characteristics of ethanol in blood, which depends on the quantity of chronically drinking alcohol.
authors.affiliation: Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan. czhliu@yamaguchi-u.ac.jp
authors.forename: Jinyao
authors.initials: J
authors.lastname: Liu
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yano
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamoto
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Noma
authors.forename: Masunori
authors.initials: M
authors.lastname: Matsuzaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Fujimiya
mesh_terms: D000818:Animals; D000431:Ethanol / Q000009:adverse effects* / Q000493:pharmacokinetics; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
chemical_list: D000431:Ethanol