title: Blood flow autoregulation in pedicled flaps.
abstract: BACKGROUND
  Clinical work on the blood perfusion in skin and muscle flaps has suggested that some degree of blood flow autoregulation exists in such flaps. An autoregulatory mechanism would enable the flap to protect itself from changes in the perfusion pressure. The purpose of the present study was to evaluate if, and to what extent, a tissue flap could compensate a reduction in blood flow due to an acute constriction of the feed artery. Further, we wanted to examine the possible role of smooth muscle L-type calcium channels in the autoregulatory mechanism by pharmacological intervention with the L-type calcium channel blocker nimodipine and the vasodilator papaverine.
  
  
  METHODS
  Pedicled flaps were raised in pigs. Flow in the pedicle was reduced by constriction of the feed artery (n=34). A transit time flow probe measured the effect on blood flow continuously. Following this, three different protocols were followed: (1) Time control (n=10): the procedure described above was repeated in the same flap to determine whether autoregulatory efficiency changed over time. (2) Nimodipine infusion (n=13): continuous intra-arterial infusion of nimodipine (0.2mg/ml, 0.5 ml/min) started when the flow had returned to the initial value. After stabilisation, the flow was reduced. When the flow had been stable for at least 5 min, the constriction was removed. (3) Nimodipine and papaverine (n=8): the infusion of nimodipine was followed by an intra-arterial bolus of papaverine (10mg). After stabilisation, the flow in the pedicle was reduced and the flow was recorded.
  
  
  RESULTS
  The flaps showed a strong autoregulatory response with complete compensation for flow reductions of up to 70-80%. Infusion of nimodipine caused a 28+/-10% increase in blood flow and removed the autoregulation. Papaverine caused a further increase in blood flow by 61+/-19%. The time control experiments proved that the experimental procedure was reproducible and stable over time.
  
  
  CONCLUSIONS
  A tissue flap can nearly completely compensate for repeated flow reductions of up to 70-80%. This is due to a decrease in the peripheral resistance, mediated by a local intrinsic mechanism. Nimodipine (a blocker of L-type voltage-activated calcium channels) abolishes the autoregulation, but a significant vasodilatory reserve exists, as an additional injection of papaverine (a smooth muscle relaxant) results in a further increase in the blood flow. This strongly suggests a direct role for voltage-activated calcium channels in the autoregulatory process.
authors.affiliation: Department of Plastic Surgery and Burns Unit, Center of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. ctbonde@gmail.com
authors.forename: Christian T
authors.initials: CT
authors.lastname: Bonde
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Elberg
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D003251:Constriction, Pathologic / Q000503:physiopathology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013524:Surgical Flaps / Q000098:blood supply*; D034421:Sus scrofa; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014665:Vasodilator Agents; D009553:Nimodipine; D010208:Papaverine