title: Extracellular calcium concentration affects susceptibility to global ischemic injury in newborn but not adult hearts.
abstract: BACKGROUND
  Whether immaturity in calcium handling, that persists for a time after birth, could increase sensitivity to extracellular calcium and affect the development of global ischemic injury in the newborn heart is unknown. To address this, the impact of alterations in extracellular calcium concentration on newborn vs. adult development of myocardial injury due to ischemia was studied.
  
  
  METHODS
  In Study 1, hearts of 3-day-old piglets and adult pigs were perfused with 1 of 3 different calcium concentrations: control (0.13 mmol/L); intermediate (2.23 mmol/L); high (4.44 mmol/L) before normothermic ischemia. In Study 2, newborn hearts were allocated to perfusion with or without the L-calcium channel antagonist verapamil before high (4.44 mmol/L) calcium exposure, followed by normothermic ischemia. Tolerance to ischemia was assessed by determining the time to irreversible injury in all hearts, and maximal intraventricular pressures at peak injury.
  
  
  RESULTS
  In adults, altering calcium did not significantly affect tolerance to ischemia. In newborns, increasing calcium exposure resulted in significantly greater intraventricular pressures at maximal injury when compared with the control (low) calcium group (p<.05). As well, newborns exposed to high calcium had a significantly shorter time to the development of ischemic injury compared with the other groups (p<.05). Those newborn hearts pretreated with an L-calcium channel antagonist before the high calcium exposure did not exhibit this increased susceptibility to ischemic injury (p<.05).
  
  
  CONCLUSIONS
  In contrast to adults, the development of ischemic injury in the newborn heart is affected by changes in extracellular calcium, that can be modified with an L-calcium channel antagonist. This information could be used to prolong the safe preservation time of newborn donor hearts harvested for transplantation, as well as to minimize postoperative ventricular dysfunction.
authors.affiliation: Department of Physiology, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wittnich
authors.forename: W J
authors.initials: WJ
authors.lastname: Wallen
authors.forename: M P
authors.initials: MP
authors.lastname: Belanger
authors.forename: J S
authors.initials: JS
authors.lastname: Ikonomidis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D011897:Random Allocation; D013552:Swine; D013997:Time Factors
chemical_list: D002118:Calcium