title: Minimally invasive monitoring of skeletal muscle hypermetabolism induced by the phosphodiesterase-III-inhibitor milrinone and sodium fluoride.
abstract: OBJECTIVE
  We hypothesized that the phosphodiesterase-III-inhibitor milrinone and the non-specific G-protein activator sodium fluoride increase the skeletal muscular lactate levels as a sign of a hypermetabolic response.
  
  
  METHODS
  With approval of the local animal care committee Sprague-Dawley rats were killed and artificially perfused either with Ringer's solution or sodium fluoride 110 mM, while milrinone 1.32 mM or Ringer's solution at 1 μl/min was applied via microdialysis probes in both hind limbs. Lactate was measured spectrophotometrically in the dialysate.
  
  
  RESULTS
  Baseline lactate levels before drug application did not differ between hind limbs. Local infusion of milrinone via microdialysis did not significantly increase intramuscular lactate concentrations compared with the Ringer control group. Muscular perfusion with sodium fluoride resulted in a significant increase of lactate and was potentiated by combination with local milrinone.
  
  
  CONCLUSIONS
  Phosphodiesterase-III-inhibition alone does not significantly influence the lactate levels in skeletal muscle of sacrificed rats. Sodium fluoride infusion leads to an intramuscular lactate increase, which was further potentiated by local inhibition of phosphodiesterase-III. The fluoride-mediated hypermetabolic response following sodium fluoride could be a possible explanation for the observed myotoxic adverse effects in individuals treated by fluoride-containing agents.
authors.affiliation: Department of Anaesthesia and Critical Care, University of Wuerzburg, Wuerzburg, Germany. schuster_f@klinik.uni-wuerzburg.de
authors.forename: Frank
authors.initials: F
authors.lastname: Schuster
authors.forename: Stephan
authors.initials: S
authors.lastname: Johannsen
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Martin
authors.initials: M
authors.lastname: Anetseder
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000819:agonists* / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000819:agonists*; D006614:Hindlimb; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D020105:Milrinone / Q000009:adverse effects / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D058987:Phosphodiesterase 3 Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000009:adverse effects / Q000819:agonists* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D058987:Phosphodiesterase 3 Inhibitors; D019344:Lactic Acid; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D020105:Milrinone