title: Physiologically tolerable insulin reduces myocardial injury and improves cardiac functional recovery in myocardial ischemic/reperfused dogs.
abstract: This study was designed to examine whether physiologically tolerable insulin, which maintains lower blood glucose, can protect the myocardium against ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary blood flow) followed by 4 hours of reperfusion and treated with vehicle, glucose-insulin-potassium (GIK; glucose, 250 g/L; insulin, 60 U/L; potassium, 80 mmol/L), GK, or low-dose insulin (30 U/L) 10 minutes before reperfusion. Treatment with GIK exerted significant cardioprotective effects as evidenced by improved cardiac function, improved coronary blood flow, reduced infarct size, and myocardial apoptosis. In contrast, treatment with GK increased blood glucose level and aggravated myocardial I/R injury. It is interesting that treatment with insulin alone at the dose that reduced blood glucose to a clinically tolerable level exerted significant cardioprotective effects that were comparable to that seen in the GIK-treated group. This low-dose insulin had no effect on coronary blood flow after reperfusion but markedly reduced coronary reactive hyperemia and switched myocardial substrate uptake from fat to carbohydrate. Our results suggest that lower glucose supply to the ischemic myocardium at early reperfusion may create a "metabolic postconditioning" and thus reduce myocardial ischemia/reperfusion injury after prolonged reperfusion.
authors.affiliation: Department of Physiology and Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Hang-Xiang
authors.initials: HX
authors.lastname: Zhang
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Huo
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Liang
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Fan
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Guo
authors.forename: Hai-Chang
authors.initials: HC
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011188:Potassium / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; C030396:glucose-insulin-potassium cardioplegic solution; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D005947:Glucose; D011188:Potassium