title: Remote ischemic preconditioning with--but not without--metabolic support protects the neonatal porcine heart against ischemia-reperfusion injury.
abstract: BACKGROUND
  While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo.
  
  
  RESULTS
  32 newborn piglets were randomized into 4 groups: control, GI, GI+rIPC and rIPC. GI and GI+rIPC groups received GI infusion continuously from 40 min prior to ischemia. rIPC and GI+rIPC groups underwent four cycles of 5 min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the left anterior descending artery followed by 2 h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dt(max) as % of baseline) after 2 h reperfusion was 68.5±13.8% in control, 53.7±11.2% in rIPC (p<0.05), and improved in GI (83.6±18.8%, p<0.05) and GI+rIPC (87.0±15.7%, p<0.01).
  
  
  CONCLUSIONS
  rIPC+GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark. Electronic address: Michael.rahbek@ki.au.dk.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schmidt
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Nicolaj B
authors.initials: NB
authors.lastname: Støttrup
authors.affiliation: Department of Cardiology, The John Radcliffe, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom.
authors.forename: Hussain
authors.initials: H
authors.lastname: Contractor
authors.affiliation: Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Janus A
authors.initials: JA
authors.lastname: Hyldebrandt
authors.affiliation: Department of Forensic Medicine, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Mogens
authors.initials: M
authors.lastname: Johannsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Pedersen
authors.affiliation: Department of Forensic Medicine, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Birkler
authors.affiliation: Department of Cardiology, The John Radcliffe, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom.
authors.forename: Houman
authors.initials: H
authors.lastname: Ashrafian
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Keld E
authors.initials: KE
authors.lastname: Sørensen
authors.affiliation: Department of Cardiology, The John Radcliffe, Headley Way, Headington, Oxford, OX3 9DU, United Kingdom.
authors.forename: Rajesh K
authors.initials: RK
authors.lastname: Kharbanda
authors.affiliation: Division of Cardiology, Hospital for Sick Children, Toronto, M5G 1X8, Canada.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Redington
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Skejby, Brendstrupgaardsvej, Aarhus N, DK-8200, Denmark.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Bøtker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005947:Glucose / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007288:Inosine / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D019194:Ischemic Preconditioning / Q000379:methods*; D019344:Lactic Acid / Q000378:metabolism; D017551:Microdialysis; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D007288:Inosine; D005947:Glucose
keywords: Insulin; Ischemia-reperfusion injury; Metabolism; Pediatric; Preconditioning