title: Postmortem acidification of blood/organs induces an increase in flecainide concentration in cardiac blood and the contribution of the lungs to this increase.
abstract: Postmortem acidification of blood and the contribution of this phenomenon to increased flecainide concentrations in cardiac blood were evaluated in rabbits. Flecainide was administered intravenously, antemortem peripheral blood was collected 15 min after administration, then rabbits were sacrificed. Blood and organs were collected immediately or 24 h after death, or immediately or 24 h after performance of cardiac massage. Postmortem left/right cardiac blood and organs showed lower pH than antemortem blood, and flecainide concentrations in all postmortem blood samples were higher than those in antemortem blood. Increased flecainide concentrations in cardiac blood were enhanced by postmortem cardiac massage and postmortem interval. In perfusion experiments using rabbit lung and heart, even if the flecainide concentration in inflow was kept constant, outflow concentrations were 2- to 3-fold higher than in inflow when inflow pH changed from 7.4 to 5.5. In contrast, flecainide concentration in outflow decreased immediately and then remained low when pH of perfusate changed from 5.5 to 7.4. These results demonstrate that flecainide accumulates in the lungs before death, and this accumulated flecainide releases into blood following postmortem acidification of blood/organs.
authors.affiliation: Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Yoshitome
authors.forename: Hideo
authors.initials: H
authors.lastname: Ishizu
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyaishi
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D003331:Coronary Vessels; D005424:Flecainide / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D053593:Forensic Toxicology / Q000379:methods; D006336:Heart Massage; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism*; D010477:Perfusion; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D005424:Flecainide