title: Malignant hyperthermia phenotype: hypotension induced by succinylcholine in susceptible swine.
abstract: BACKGROUND
  Succinylcholine causes immediate and severe arterial hypotension in swine with the malignant hyperthermia phenotype. The underlying mechanisms are unknown.
  
  
  METHODS
  Malignant hyperthermia-susceptible (MHS; n = 10) and normal swine (n = 5) were anesthetized with thiopental. The following were monitored: electrocardiogram; arterial blood pressure; pulmonary artery, central venous, and left and right ventricular pressure; cardiac output; end-tidal carbon dioxide; core temperature; peripheral-blood flows; and arterial blood gases. After a control period, 2 mg/kg succinylcholine was given intravenously. Three MHS animals received 1 mg/kg vecuronium and two MHS animals received 2.5 mg/kg dantrolene intravenously. The effects of succinylcholine on left and right ventricular pressure and contractility were analyzed in isolated hearts. The effects of 0.06 mm succinylcholine on isometric tension development were recorded in isolated femoral artery rings.
  
  
  RESULTS
  Succinylcholine caused an early, severe decrease in blood pressure, cardiac output, left ventricular pressure, and left ventricular contractility in MHS swine but not in normal swine; no significant differences were found in heart rate, right ventricular parameters, systemic vascular resistance, and preload (pulmonary diastolic pressure, central venous pressure). The succinylcholine-induced hypotension and associated effects were not prevented by dantrolene. However, pretreatment with high-dose vecuronium prevented not only the cardiovascular depression, but also MH. In addition, no phenotypic differences of succinylcholine on contractility or left ventricular pressure were observed in the isolated working hearts. Similary, succinylcholine did not cause a significantly different relaxation in rings in either phenotype.
  
  
  CONCLUSIONS
  Succinylcholine-induced hypotension occurred before muscle hypermetabolism in MHS swine. Succinylcholine had no differential physiologic effects on either the isolated heart or on isolated arteries. This hypotension could not be prevented by dantrolene but was prevented by pretreatment with high-dose vecuronium. Thus, an indirect mechanism such as the release of a cardiac depressant from skeletal muscle may have caused this hypotensive response.
authors.affiliation: Departments of Anesthesiology and Physiology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Sigg
authors.forename: P A
authors.initials: PA
authors.lastname: Iaizzo
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D066298:In Vitro Techniques; D008305:Malignant Hyperthermia / Q000235:genetics*; D008406:Masseter Muscle / Q000098:blood supply / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents / Q000009:adverse effects*; D010641:Phenotype; D012039:Regional Blood Flow / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D013390:Succinylcholine / Q000009:adverse effects*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D009467:Neuromuscular Depolarizing Agents; D019837:Ryanodine Receptor Calcium Release Channel; D013390:Succinylcholine