title: Calcium paradox in an in vivo model of multidose cardioplegia and moderate hypothermia. Prevention with diltiazem or trace calcium levels.
abstract: The production and prevention of calcium paradox injury in myocardium was studied in a canine model of cardiopulmonary bypass with multidose, moderately hypothermic, crystalloid cardioplegic solution. During 4 1/2 hours of global ischemia, three groups of six dogs each received one of three histidine-buffered cardioplegic solutions (500 ml initially and 250 ml every 30 minutes) at 27 degrees C. Group 1 cardioplegic solution was calcium free, group 2 solution contained a trace amount of calcium chloride (70 mumols /L), and group 3 cardioplegic solution was calcium free but contained diltiazem (150 micrograms/kg body weight). Left ventricular function measured as percent control of developed pressure revealed significantly greater (p less than 0.05) recovery in groups 2 and 3. Triphenyltetrazolium chloride staining showed 35% +/- 9% (mean +/- standard error) of heart mass necrosis in group 1 versus 0% and 0.5% +/- 0.4% in groups 2 and 3, respectively (p less than 0.001). Electron microscopy revealed ultrastructural changes characteristic of calcium paradox injury in group 1 myocardium. Calcium paradox injury was produced in an in vivo model of global myocardial ischemia and multidose cardioplegia despite moderate hypothermia and non-coronary collateral flow. The addition of either trace levels of calcium or diltiazem to the cardioplegic solution was effective in preventing this injury.
authors.affiliation: Department of Surgery, Toronto General Hospital, Ontario, Canada.
authors.forename: I M
authors.initials: IM
authors.lastname: Rebeyka
authors.forename: R A
authors.initials: RA
authors.lastname: Axford-Gatley
authors.forename: B G
authors.initials: BG
authors.lastname: Bush
authors.forename: P J
authors.initials: PJ
authors.lastname: del Nido
authors.forename: D A
authors.initials: DA
authors.lastname: Mickle
authors.forename: A D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: G J
authors.initials: GJ
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000009:adverse effects* / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D003327:Coronary Disease / Q000503:physiopathology; D004110:Diltiazem / Q000627:therapeutic use*; D004285:Dogs; D006321:Heart / Q000503:physiopathology; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis
chemical_list: D004110:Diltiazem; D002118:Calcium