title: Acute remote ischemic preconditioning II: the role of nitric oxide.
abstract: The purpose of this study was to determine whether nitric oxide (NO) plays a role in the mechanism of acute "classic" as well as acute remote ischemic preconditioning (IP). Thirty-two male Wistar rats were divided into five experimental groups. The rat cremaster flap in vivo microscopy model was used for assessment of ischemia/reperfusion injury. In the control group (CG, n = 8), a 2-hr flap ischemia was induced after preparation of the cremaster muscle. The animals of group NO (n = 6) received 500 nmol/kg of the NO-donor spermine/nitric oxide complex (Sper/NO) intravenously 30 min prior to ischemia. The group LN + P (L-NAME + preclamping, n = 6) received 10 mg/kg Nomega-nitro-L-arginine methyl ester (L-NAME) intravenously before preclamping of the flap pedicle (10-min cycle length, 30-min reperfusion). L-NAME (10 mg/kg) was administered in group LN + T (L-NAME + tourniquet, n = 6) before ischemia of the right hindlimb was induced, using a tourniquet for 10 min after flap elevation. The limb was then reperfused for 30 min. Thereafter, flap ischemia was induced in each group as in group CG. In vivo microscopy was performed after 1 hr of flap reperfusion in each animal. Group NO demonstrated a significantly higher red blood cell velocity (RBV) in the first-order arterioles and capillaries, a higher capillary flow, and a decreased number of leukocytes adhering to the endothelium (stickers) of the postcapillary venules by comparison to all other groups (P < 0.05). The average capillary RBV and capillary flow were still higher in the CG than in the groups receiving L-NAME (P < 0.05). The data show that NO plays an important role in the mechanism of both acute "classic" as well as acute remote IP, since the administration of a NO-donor previous to ischemia simulates the effect of IP, whereas the nonspecific blocking of NO synthesis by L-NAME abolishes the protective effect of flap preconditioning.
authors.affiliation: Department of Plastic and Hand Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwig-Guttmann-Strasse 33, 67071 Ludwigshafen, Germany. markus.kuentscher@urz.uni-heidelberg.de
authors.forename: Markus V
authors.initials: MV
authors.lastname: Küntscher
authors.forename: Thomas
authors.initials: T
authors.lastname: Kastell
authors.forename: Jens
authors.initials: J
authors.lastname: Altmann
authors.forename: Henrik
authors.initials: H
authors.lastname: Menke
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Günter
authors.initials: G
authors.lastname: Germann
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005837:Genitalia, Male; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology*; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester