左心室机械卸载可恢复β2肾上腺素能受体mRNA表达，并降低衰竭心脏对缺血和再灌注的易感性。

Left ventricular mechanical unloading restores Beta-2-adrenergic receptor mRNA expression and decreases susceptibility to ischemia and reperfusion in the failing heart.

作者信息

Nakahara K, Horimoto H, Nakai Y, Mieno S, Nomura Y, Sasaki S

机构信息

Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan.

出版信息

Eur Surg Res. 2003 Mar-Apr;35(2):108-14. doi: 10.1159/000069396.

DOI:10.1159/000069396

PMID:12679621

Abstract

OBJECTIVES

Left ventricular (LV) mechanical unloading is known to reduce the hemodynamic demands of failing LV, resulting in improved myocyte contractility. This study was designed to examine effects of LV unloading on beta-adrenergic receptor (BAR) expression and ischemic susceptibility to ischemia reperfusion.

METHODS

Five groups were studied: group 1 [unloading myocardial infarction (MI), n = 6], MI hearts 2 weeks after coronary ligation subjected to LV unloading by heterotopic heart transplantation for 2 weeks; group 2 (2-week MI, n = 6), MI hearts left for 2 weeks without unloading; group 3 (4-week MI, n = 6), MI hearts left for 4 weeks without unloading; group 4 (control, n = 6), normal (non-MI) hearts as a control with no interventions, and group 5 (unloading control, n = 5), normal (non-MI) hearts subjected to LV unloading for 2 weeks. Then, all hearts were isolated and subjected to 20 min of global ischemia and 60 min of reperfusion on Langendorff apparatus. LV pressures and coronary flow were measured throughout the experiment. Either total BAR density or beta(2)-adrenergic receptor (B2AR) mRNA expression in the noninfarcted myocardium was determined by radioligand binding assays or real-time quantitative RT-PCR, respectively.

RESULTS

LV unloading improved postischemic functional recovery (unloading MI vs. 2-week MI vs. 4-week MI: 74 +/- 6 vs. 54 +/- 5 vs. 51 +/- 4%; p < 0.05 vs. unloading MI). LV unloading restored B2AR mRNA expression (unloading MI vs. 2-week MI vs. 4-week MI: 4.78 +/- 0.21 vs. 2.80 +/- 0.19 vs. 2.24 +/- 0.17 x 10(7) copy/microg total RNA; p < 0.05 vs. unloading MI).

CONCLUSION

LV mechanical unloading restored B2AR mRNA expression and improved postischemic functional recovery.

摘要

目的

已知左心室（LV）机械卸载可降低衰竭左心室的血流动力学需求，从而改善心肌细胞收缩力。本研究旨在探讨左心室卸载对β-肾上腺素能受体（BAR）表达及缺血再灌注缺血易感性的影响。

方法

研究分为五组：第1组[卸载心肌梗死（MI），n = 6]，冠状动脉结扎2周后的MI心脏，通过异位心脏移植进行左心室卸载2周；第2组（2周MI，n = 6），MI心脏未进行卸载，留置2周；第3组（4周MI，n = 6），MI心脏未进行卸载，留置4周；第4组（对照组，n = 6），正常（非MI）心脏作为对照，未进行干预，第5组（卸载对照组，n = 5），正常（非MI）心脏进行左心室卸载2周。然后，将所有心脏分离，在Langendorff装置上进行20分钟全心缺血和60分钟再灌注。在整个实验过程中测量左心室压力和冠状动脉血流。分别通过放射性配体结合试验或实时定量RT-PCR测定非梗死心肌中的总BAR密度或β2-肾上腺素能受体（B2AR）mRNA表达。

结果

左心室卸载改善了缺血后功能恢复（卸载MI组与2周MI组与4周MI组：74±6 vs. 54±5 vs. 51±4%；与卸载MI组相比，p < 0.05）。左心室卸载恢复了B2AR mRNA表达（卸载MI组与2周MI组与4周MI组：4.78±0.21 vs. 2.80±0.19 vs. 2.24±0.17×10⁷拷贝/μg总RNA；与卸载MI组相比，p < 0.05）。