title: Glycemia and the cardioprotective effects of insulin pre-conditioning in the isolated rat heart.
abstract: While acute hyperglycemia has been shown to mitigate the beneficial effects of ischemic preconditioning, its effect on insulin-induced preconditioning remains unclear.
  
  
  
  The study was designed to test the hypothesis that acute hyperglycemia diminishes the cardioprotective effects following a 20-min pre-ischemic pre-conditioning with insulin in the isolated rat heart using the Langendorff system. Forty hearts were assigned to receive modified Krebs-Henseleit (KH) buffer containing 0.5 U/L insulin and 100 mg/dL glucose (InsG100, n = 10), KH buffer with 100 mg/dL glucose (G100, n = 10), KH buffer supplemented with 0.5 U/L insulin and 600 mg/dL glucose (InsG600, n = 10), or with 600 mg/dL glucose (G600, n = 10). To match the osmotic pressure of the InsG600 group, 27.5 mmol/L of mannitol was added to KH solution in the InsG100 and G100 group. The four groups were perfused with each solution for 20 min prior to 15 min of no-flow ischemia, and during 20 min of reperfusion. Only during the ischemic period the heart was paced at 222 beats/min. Measurements of heart rate, coronary flow and maximum of LV derivative of pressure development (dP/dt max) were recorded. Myocardial phospho-protein kinase B (p-Akt) and tumor necrosis factor-α (TNF-α) levels were assayed by enzyme-linked immunosorbent assay and sandwich ELISA, respectively following reperfusion.
  
  
  
  After reperfusion, LV dP/dt max and heart rate in the InsG100 group was significantly higher than that in the other three groups. The myocardial p-Akt level in the InsG100 group was significantly elevated when compared to the InsG600 group at the end of reperfusion. The p-Akt levels in the InsG600 and InsG100 group were significantly higher than in the corresponding non-insulin groups.
  
  
  
  Acute hyperglycemia diminishes the cardioprotective effects of insulin preconditioning in the isolated rat heart, possibly mediated through the suppression of myocardial Akt phosphorylation.
authors.affiliation: Department of Anesthesia, McGill University Health Centre Glen Site, Royal Victoria Hospital, 1001 Blvd, Decarie, Montreal, QC H4A 3J1, Canada. yosuke.nakadate@mail.mcgill.ca.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Nakadate
authors.affiliation: Department of Anesthesia, McGill University Health Centre Glen Site, Royal Victoria Hospital, 1001 Blvd, Decarie, Montreal, QC H4A 3J1, Canada.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Department of Anesthesiology, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Oguchi
authors.affiliation: Department of Anesthesia, McGill University Health Centre Glen Site, Royal Victoria Hospital, 1001 Blvd, Decarie, Montreal, QC H4A 3J1, Canada.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Operating Theater, Yamanashi University Hospital, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawakami
authors.affiliation: Operating Theater, Yamanashi University Hospital, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Ishiyama
authors.affiliation: Department of Anesthesiology, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Anesthesia, McGill University Health Centre Glen Site, Royal Victoria Hospital, 1001 Blvd, Decarie, Montreal, QC H4A 3J1, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schricker
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D038321:Glycemic Index / Q000187:drug effects* / Q000502:physiology; D006321:Heart; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006943:Hyperglycemia / Q000097:blood* / Q000139:chemically induced; D007328:Insulin / Q000494:pharmacology* / Q000633:toxicity; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: Acute hyperglycemia; Cardiac contractility; Insulin-induced cardioprotection; Isolated rat heart; Phospho-protein kinase B; Stunned myocardium; Tumor necrosis factor-α