Ischemic preconditioning in immature hearts: mechanism and compatibility with cardioplegia

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 traditional and effective cardioprotective measure in clinic, our study is also designed to probe the compatibility between IPC and cardioplegia.

New Zealand rabbits aged 14 - 21 days weighing 220 - 280 g were used. The animals were anesthetized and heparinized. The chest was opened and the heart was quickly 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(2)O (perfusion pressure). IPC consisted of 5 min global ischemia plus 10 min reperfusion. Glibenclamide was used as the K(ATP) channel blocker at a concentration of 10 micro mol/L before IPC. Cardiac arrest was induced with 4 degrees C St. Thomas cardioplegic solution, at which point the heart was made globally ischemic by withholding perfusion for 45 min followed by 40 min reperfusion. Thirty immature rabbit hearts were randomly divided 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 ischemia-reperfusion. Coronary flow (CF), HR, left ventricle developed pressure (LVDP), and +/- dp/dt(max) were monitored at equilibration (baseline value) and 5, 10, 20, 30 and 40 min after reperfusion. The values resulting from reperfusion were expressed as a percentage of their baseline values. Arrhythmia quantification, myocardial enzyme in the coronary effluent and myocardial energy metabolism were also determined.

The recovery of CF, HR, LVDP and +/- dp/dt(max) in preconditioned hearts was best among 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. Pretreatment with glibenclamide completely abolished the myocardial protection provided by IPC, but did not affect ischemia-reperfusion injury.

While applying cardioplegia, IPC provides significant cardioprotective effects. Activation of K(ATP) channels is involved in the mechanism of IPC-produced cardioprotection.