title: Magnesium cardioplegia reduces cytosolic and nuclear calcium and DNA fragmentation in the senescent myocardium.
abstract: Previous reports have indicated that the senescent myocardium is less tolerant to surgically induced ischemia and that diminished functional recovery is associated with alterations in cytosolic calcium ([Ca2+]i) accumulation. Recently, increased [Ca2+]i has been suggested to alter nuclear calcium ([Ca2+]n) accumulation. To investigate the relation between [Ca2+]i and [Ca2+]n, we subjected mature and aged rabbit hearts to normothermic global ischemia, either without treatment or after treatment with potassium cardioplegia, magnesium cardioplegia, or a combination of potassium and magnesium cardioplegia. The relation between altered [Ca2+]n and DNA fragmentation was also investigated. Our results indicate that [Ca2+]i was increased during 30 minutes of normothermic global ischemia without treatment in both the mature and aged hearts (p < 0.05). Accumulation of [Ca2+]i during global ischemia was reduced with the use of potassium, magnesium, and a combination of potassium and magnesium cardioplegia (p < 0.05 versus untreated ischemia) in both the mature and aged hearts. Levels of [Ca2+]n were unaffected by global ischemia or cardioplegia in the mature myocardium; however, in the aged myocardium, [Ca2+]n was increased during global ischemia and with potassium cardioplegia and was associated with increased nuclear DNA fragmentation (p < 0.05). The use of magnesium and a combination of potassium and magnesium cardioplegia attenuated [Ca2+]n accumulation and nuclear DNA fragmentation (p < 0.05). Control of [Ca2+]i and [Ca2+]n was associated with enhanced functional recovery during reperfusion. These results indicate that during normothermic ischemia, there is increased [Ca2+]i and [Ca2+]n in the aged myocardium, and increased [Ca2+]n is associated with increased nuclear DNA fragmentation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, Ma 02215.
authors.forename: T
authors.initials: T
authors.lastname: Tsukube
authors.forename: J D
authors.initials: JD
authors.lastname: McCully
authors.forename: E A
authors.initials: EA
authors.lastname: Faulk
authors.forename: M
authors.initials: M
authors.lastname: Federman
authors.forename: J
authors.initials: J
authors.lastname: LoCicero
authors.forename: I B
authors.initials: IB
authors.lastname: Krukenkamp
authors.forename: S
authors.initials: S
authors.lastname: Levitsky
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004249:DNA Damage; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006324:Heart Arrest, Induced; D008278:Magnesium Sulfate / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D016277:Ventricular Function, Left
chemical_list: D011189:Potassium Chloride; D008278:Magnesium Sulfate; D002118:Calcium