title: Does sustained epinephrine release trigger a hypoxia-neovascularization cascade?
abstract: BACKGROUND
  Recent data regarding the long-term local administration of epinephrine to soft tissues for the purpose of inducing prolonged vasoconstriction have yielded promising results. These studies postulated that long-term release of epinephrine by a microsphere/drug delivery system caused continuous vasoconstriction and subsequent vascular augmentation. The goal of this study was to test the hypothesis that epinephrine induces a hypoxia-neovascularization cascade and plays a primary role in vascular proliferation within soft tissues.
  
  
  METHODS
  Thirty male New Zealand White rabbits were randomly grouped as follows: group I, control (n = 10); group II, saline-loaded microsphere/drug delivery system injection (n = 10); and group III, epinephrine-loaded microsphere/drug delivery system injection (n = 10). A 2 x 1-cm rectangle was marked on the dorsal surface of the left ear of each rabbit. No solutions were injected in the control group, whereas 1 ml of saline-loaded and epinephrine-loaded microspheres was injected into groups II and III, respectively. A laser Doppler device was used to measure tissue blood volume and tissue blood flow.
  
  
  RESULTS
  Laser Doppler monitoring in tissue blood flow yielded a distinct difference between the epinephrine-loaded microsphere-injected group and the other two groups (p < 0.05).
  
  
  CONCLUSIONS
  The ability of epinephrine-loaded microspheres to augment the vascular network in vivo is the result of sustained vasoconstriction with consequent tissue hypoxia and subsequent neovascularization. Data extracted from the present study, first, might be applied to improve hemostasis for operations typically plagued by serious intraoperative blood loss. Second, the ability to intentionally augment the vascularity of certain flaps before elevation should result in their increased survival. Radiation-injured tissues may also derive great benefit from this treatment.
authors.affiliation: Division of Plastic Surgery, Brown University, School of Medicine, Rhode Island Hospital, Providence, RI, USA. drercanka@yahoo.com
authors.forename: Ercan
authors.initials: E
authors.lastname: Karacaoglu
authors.forename: Ismail
authors.initials: I
authors.lastname: Bayram
authors.forename: Bahattin
authors.initials: B
authors.lastname: Celiköz
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Zienowicz
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001810:Blood Volume; D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems; D004431:Ear, External / Q000098:blood supply; D004837:Epinephrine / Q000008:administration & dosage* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D017078:Laser-Doppler Flowmetry; D008297:Male; D008863:Microspheres; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow; D014661:Vasoconstriction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D004837:Epinephrine