Are the cardiovascular effects of high dose insulin in calcium channel blockers and beta-blocker toxicity mediated by phopspholamban [abstract]? Abstract uri icon
Overview
abstract
  • Background : Phospholamban activation of SERCA is not the mechanism by which HDI produces its inotropic and lusiotropic effects in CCB and BB induced cardiovascular toxicity. : The mechanism of High Dose Insulin (HDI) effects in beta blocker (BB) and calcium channel blocker (CCB) induced cardiogenic shock is not defined. Phospholamban (PLB) is the primary mediator of calcium uptake into the sarcomplasmic reticulum (SR) viathe cardiac calcium pump (SERCA), enhancing diastolic relaxation which increases preload. PLB is regulated viabeta adrenergic stimulation of c-AMP dependent PKA or calmodulin.
    Objectives : Are the inotropic and lusiotropic effects of HDI in BB and CCB induced cardiogenic shock mediated by PLB activation?
    Methods : Swine myocardium specimens from 6 groups were obtained immediately and flash frozen upon death or sacrifice. Group 1 served as controls and did not receive any medications. Group 2 received only HDI. Group 3 was given propranolol until a predefined point of toxicity and resuscitated with saline. Group 4 was treated identical to group 3 and received HDI. Group 5 was given a verapamil infusion to the point of predefined toxicity and resuscitated with saline. Group 6 was treated identical to group 5 and received HDI. Resuscitation time was 4 hours. An isoproterenol infused pig was used as a positive control for its known PLB activation. Samples were analyzed by Western Blot analysis for phosphorylation of PLB. Antibodies to both serine 16 and threonine 17 activation sites on PLB determined ratios of phosphorylated to unphosphorylated PLB.
    Results : Three of 4 pigs treated with HDI survived thefull 4 hours after resuscitation. One of 4 pigs treated only with saline survived the full 4 hours after resuscitation. The isoproterenol positive control increased PLB activity as expected. There were no differences in PLB phosphorylation in cardiac tissue among controls, HDI alone, or CCB or BB toxic pigs resuscitated with saline or HDI.
    Conclusions

  • publication date
  • 2008
  • published in
    Research
    keywords
  • Adverse Effects
  • Animal Studies
  • Drugs and Drug Therapy
  • Emergency Medicine
  • Heart
  • Resuscitation
  • Additional Document Info
    volume
  • 15
  • issue
  • 5 Suppl 1