title: Propofol protects the immature rabbit heart against ischemia and reperfusion injury: impact on functional recovery and histopathological changes.
abstract: The general anesthetic propofol protects the adult heart against ischemia and reperfusion injury; however, its efficacy has not been investigated in the immature heart. This work, for the first time, investigates the cardioprotective efficacy of propofol at clinically relevant concentrations in the immature heart. Langendorff perfused rabbit hearts (7-12 days old) were exposed to 30 minutes' global normothermic ischemia followed by 40 minutes' reperfusion. Left ventricular developed pressure (LVDP) and coronary flow were monitored throughout. Lactate release into coronary effluent was measured during reperfusion. Microscopic examinations of the myocardium were monitored at the end of reperfusion. Hearts were perfused with different propofol concentrations (1, 2, 4, and 10 μg/mL) or with cyclosporine A, prior to ischemic arrest and for 20 minutes during reperfusion. Propofol at 4 and 10 μg/mL caused a significant depression in LVDP prior to ischemia. Propofol at 2 μg/mL conferred significant and maximal protection with no protection at 10 μg/mL. This protection was associated with improved recovery in coronary flow, reduced lactate release, and preservation of cardiomyocyte ultrastructure. The efficacy of propofol at 2 μg/mL was similar to the effect of cyclosporine A. In conclusion, propofol at a clinically relevant concentration is cardioprotective in the immature heart.
authors.affiliation: Department of Cardiovascular Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: Department of Cardiovascular Surgery, Nippon Medical School Musashikosugi Hospital, 1-396 Kosugicho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Imura
authors.affiliation: Department of Cardiovascular Surgery, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nitta
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D019344:Lactic Acid / Q000032:analysis / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
chemical_list: D020011:Protective Agents; D019344:Lactic Acid; D016572:Cyclosporine; D015742:Propofol