Novel cardioprotective strategy combining three different preconditioning methods to prevent ischemia/reperfusion injury in aged hearts in an improved rabbit model

摘要

The use of ischemic preconditioning (IPC) to protect the myocardium is usually not effective in elderly patients. The aim of the present study was to design new methods to achieve enhanced myocardial protection, based on the differential role of endogenous adenosine (ADO) and ADO receptors (ARs) in the effects of IPC on young and old animals. An improved New Zealand white rabbit model of ischemia/reperfusion was established based on the Langendorff model. Adult or elderly rabbit hearts, with or without exposure to IPC, were used in order to assess the roles of ADO and ARs in the different effects of IPC. Different protective methods were designed based on a combination of endogenous and exogenous interventions. Cardiac function, as well as biochemical, histopathological and apoptotic indices, were measured in the different intervention groups. The improved Langendorff model was stable, reliable and suitable for the undertaking of the experiments. The ADO levels in the aged rabbit hearts pre- and post-IPC were lower than those in the adult hearts, indicating that ADO levels may be an endogenous factor influencing IPC. A new protection strategy combining ADO-enhanced IPC, A1AR agonist 2-chloro-N(6)-cyclopentyladenosine preconditioning and cold crystalloid cardioplegia had a significant protective effect in aged hearts. The results of the present study suggested that endogenous ADO enhancement, A1AR agonist preconditioning and exogenous treatment yield an additive effect in aged rabbit hearts. The simultaneous application of these three types of intervention provided the most effective myocardial protection in the improved aged rabbit heart model.