Ischemic preconditioning in immature hearts: mechanism and compatibility with cardioplegia

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To investigate (1) whether ischemic preconditioning (IPC) could protect immature rabbit hearts against ischemia reperfusion injury and (2) the role of K ATP channel in the mechanism of myocardial protection Since cardioplegia is a t raditional and effective cardioprotective measure in clinic, our study is also d esigned to probe the compatibility between IPC and cardioplegia Methods New Zealand rabbits aged 14-21 days weighing 220-280 g were used The animals w ere anesthetized and heparinized The chest was opened and the heart was quickl y removed for connection of the aorta via Langendorff’s method within 30 s after excision All hearts were perfused with Krebs Henseleit buffer balanced with gas mixture (O 2∶CO 2=95%∶5%) at 60 cm H 2O (perfusion pressure) IPC cons isted of 5 min global ischemia plus 10 min reperfusion Glibenclamide was used as the K ATP channel blocker at a concentration of 10 μmol/L before IPC Cardiac arrest was induced with 4℃ St Thomas cardioplegic solution, at which point the heart was made globally ischemic by withholding perfusion for 45 min f ollowed by 40 min reperfusion Thirty immature rabbit hearts were randomly divi ded into four groups: CON (n=9) was subjected to ischemia reperfusion only; IPC ( n=9) underwent IPC and ischemia reperfusion; Gli (n=6) was given glibenclamide and ischemia reperfusion; and Gli+IPC (n=6) underwent glibenclamide, IPC and is chemia reperfusion Coronary flow (CF), HR, left ventricle developed pressure (LVDP), and ±dp/dt max were monitored at equilibration (baseline value) an d 5, 1 0, 20, 30 and 40 min after reperfusion The values resulting from reperfusion w ere expressed as a percentage of their baseline values Arrhythmia quantificati on, myocardial enzyme in the coronary effluent and myocardial energy metaboli sm were also determined Results The recovery of CF, HR, LVDP and ±dp/dt max in preconditioned hearts was b est am ong the four groups The incidence of arrhythmia was low and less CK MB leaked out in the IPC group Myocardial ATP content was better preserved by IPC Pre treatment with glibenclamide completely abolished the myocardial protection prov ided by IPC, but did not affect ischemia reperfusion injury Conclusions While applying cardioplegia, IPC provides significant cardioprotective effects Activation of K ATP channels is involved in the mechanism of IPC produced cardioprotection To investigate (1) whether ischemic preconditioning (IPC) could protect immature rabbit hearts against ischemia reperfusion injury and (2) the role of K ATP channel in the mechanism of myocardial protection Since cardioplegia is at raditional and effective cardioprotective measure in clinic, our study is also d esigned to probe the compatibility between IPC and cardioplegia Methods New Zealand rabbits aged 14-21 days weighing 220-280 g were used The animals w ere anesthetized and heparinized The chest was opened and the heart was quickl y removed for connection of the aorta via Langendorff’s method within 30 seconds after excision All hearts were perfused with Krebs Henseleit buffer balanced with gas mixture (O 2: CO 2 = 95%: 5%) at 60 cm H 2O (perfusion pressure) IPC cons isted of 5 min global ischemia plus 10 min reperfusion Glibenclamide was used as the K ATP channel blocker at a concentration of 10 μmol / L before IPC Cardiac arrest was induced with 4 ℃ St Thomas cardioplegic solution, at which point the heart was made globally ischemic by with perfusion perfusion for 45 min ollowed by 40 min reperfusion Thirty immature rabbit hearts were randomly dividized into four groups: CON (n = 9) was subjected to ischemia reperfusion Gli (n = 6) was given glibenclamide and ischemia reperfusion; and Gli + IPC (n = 6) underwent glibenclamide, IPC and is chemia reperfusion Coronary flow HR, left ventricle developed pressure (LVDP), and ± dp / dt max were monitored at equilibration (baseline value) an d 5, 1 0, 20, 30 and 40 min after reperfusion The values ​​resulting from reperfusion w ere expressed as a percentage of their baseline values ​​Arrhythmia quantificati on, myocardial enzyme in the coronary effluent and myocardial energy metaboli sm were also determined Results The recovery of CF, HR, LVDP and ± dp / dt max in preconditioned hearts was b est am ong the fou r groupsThe incidence of arrhythmia was low and less CK MB leaked out in the IPC group Myocardial ATP content was better preserved by IPC Pre treatment with glibenclamide completely abolished the myocardial protection prov ided by IPC, but did not affect ischemia reperfusion injury Conclusions While applying cardioplegia, IPC provides significant cardioprotective effects Activation of K ATP channels is involved in the mechanism of IPC produced cardioprotection
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