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Insulin Improves Isolated Perfused Heart and Cardiomyocyte Systolic-diastolic Functional Recovery Following Ischemia-reperfusion

Author: ZhangBo
Tutor: GaoFeng
School: Fourth Military Medical University
Course: Physiology
Keywords: Insulin Myocardial Ischemia / reperfusion Shrink Calcium transients Akt
CLC: R96
Type: Master's thesis
Year: 2003
Downloads: 87
Quote: 1
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Abstract

There are a large number of insulin receptors on the myocardial membrane, and is a typical insulin target cells. Absolute or relative insulin deficiency may induce coronary heart disease and other cardiovascular disorders. Studies have shown that insulin can reduce ischemia / reperfusion (ischemia / reperfusion, I / R) rat heart infarct size and to reduce neonatal rat I / R myocardial apoptosis occurred. The room before the stage of the study found that in all the circumstances, insulin signaling pathway by activating the phosphatidylinositol 3 - kinase - protein kinase B-endothelial nitric oxide synthase (PI3-kinase-Akt-eNOS) inhibition of I / R cardiomyocyte apoptosis, promote recovery of myocardial function in rabbits and rats after I / R. One of the direct consequences of myocardial ischemia / reperfusion lead to myocardial systolic / diastolic function weakened. Insulin can enhance the room had reported the rabbit cardiac contractile function in the body I / R, the Fourth Military Medical University Graduate Thesis ischemic heart has a protective effect, but whether it is the direct effect of insulin on myocardial its unclear . So far not been seen in insulin observed and reported on the direct effect of the k cardiomyocytes. The purpose of this study was to observe the insulin isolated rat cardiomyocytes g the Heart and k single systolic / diastolic function and calcium transients, and its relationship with myocardial PI3-lnase-A] t. Main method and experimental results: 1. Insulin Langendorff observed away from the heart perfusion model and left ventricular ischemia method of insulin on cardiac systolic function in vitro M away from the body I / R heart. Pulmonary vein inlet will be a water-filled bladders connected to a pressure sensor inserted into the left ventricle, the measurement of left ventricular pressure. Through a suture in the beginning part Zmm from the cardiac left anterior descending artery at alternate. Casing clipping blocked coronary perfusion resulting in ischemia of 20 min, and then release the sleeve to restore coronary blood flow reperfusion 40 min. Were before ischemia, ischemia 20 min, reperfusion instantly, 5,10,2000 min recording left ventricular systolic pressure (LVSP people left ventricular pressure changes in the maximum rate (soil LV dP / dtm.), Heart rate (HR) results found, the control group after reperfusion heart LVSP did not change significantly, insulin doors o'e-) reperfusion after cardiac LVSP soil LVdP with tm. Significantly enhanced role ... one, compared with the control group, P <0 knife 1> and the perfused heart * R slow down in -5, P <0 knife BU two. Insulin I / R cardiomyocytes adult rat cardiomyocytes isolated by conventional enzymatic method. Single cardiomyocytes motion edge detection effects of insulin on the rat the simulation M myocardial cells shrink / diastolic function and calcium transients. Myocardial cells in the 0,5 Hi, the the 5 ths waves wide electrical field stimulation Tyrode solution containing OZ perfusion 5 min, to be stable after reversing chemical missing O. 15 min perfusion during simulated ischemia. Role in chemical missing blood myocardial cell contraction amplitude gradually weakened to ischemia DqPa'''' 'e. 8% in mid-3o soil before t OfPhysl'otw 3 Fourth Military Medical University, Graduate Thesis before ischemia, P <0 knife 1> reperfusion, reversing the normal co-Q Tyrode solution analog shrink gradually restored of 9% to 85 before ischemia soil stability. High concentrations of insulin (5-10 IU / L) of normal Tyrode perfusion myocardial cells contraction slight positive effect, 10 IU / L insulin normal cardiac myocyte contraction amplitude enhancement 16 soil 5% (n = lo and plus drugs than before, P <0 knife 5h analog 1 from myocardial cells, insulin (0.off 0 IU / L), the positive inotropic effect was significantly enhanced, and a dose-dependent changes. IIU / L insulin to make a / R myocytes contraction amplitude enhancement of 62 soil 8% (n = 10, compared with before dosing, P <0 knife 1). reperfusion myocardial cell contraction amplitude 5 min after insulin by the control group 0l 3 ± 0 knife increased to 0.ZI soil 0.07 pm (11-10, P <0 knife 5) pm UR cardiomyocytes reperfusion 5 lin insulin disabilities cell contraction speed by the control group 4.31 1.58 llln / S increased 8.17 on 3.34 Bu ws ... a 10, P <0 knife 5), diastolic velocity shell. Knife with disabilities 1.14 BU the Ws increasing force 7.31 Guests 2.29 P ImS (n = 10, P <0 * 5). Intracellular calcium transients (convex of Cd fluorescence ratio luorescence ratio) while enhancing (0.13 ± 0.09 vs control group 0.09 Guests 0 knife n-10, P <0 knife 5 people and insulin reperfusion * / reached a peak when the process (TTPCaX diastolic C4 \kinase specific inhibitor of Qi u LY 294002 (50 v M) pre-treatment of myocardial cells, and found that to insulin the above positive inotropic effect almost completely blocked (insulin 10 LY 294002 0 * Guests knife 5 um vs the insulin group 0.21 soil 0 knife 7u m, P <0 knife 5) display of the myocardial cells Alct detection, insulin door IU / L) the myocardial cells phosphorylation lt India Akt) increased by 242% (compared with the control group, P Diao of people blocking with LY294002u0 uM) * 3-i deleted e, the same concentration of insulin the pob only increased by 43% (compared with the insulin group (P <0.05) \\ The results suggest that the insulin k myocardial cells positive inotropic effect, at least in part, dependent on the activation of Akt. Doparlnlent OfPhaiolegy Fourth Military Medical University Graduate Thesis Conclusion 1 during reperfusion administration of insulin can produce positive inotropic and negative chronotropic retired k heart, I / R cardiac systolic / diastolic function so as to promote recovery. insulin can directly enhance W myocyte contraction / relaxation and calcium transients, but resting on cell CaZ \OH activation.

Insulin Improves Isolated Perfused Heart and Cardiomyocyte Systolic-diastolic Functional Recovery Following Ischemia-reperfusion

Abstract

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