Diltiazem during reperfusion preserves high energy phosphates by protection of mitochondrial integrity
详细信息 查看全文
- 作者：Krö ; ner ; A. ; Seitelberger ; R. ; Schirnhofer ; J. ; Bernecker ; O. ; Mallinger ; R. ; Hallströ ; m ; S. ; et. al.
- 关键词：Reperfusion ; Mitochondria ; Diltiazem ; Isolated Working heart ; Rabbit
- 刊名：European Journal of Cardio-Thoracic Surgery
- 出版年：2002
- 出版时间：February, 2002
- 年：2002
- 卷：21
- 期：2
- 页码：224-231
- 全文大小：1.74 M
文摘
Objective: This study evaluates the effects of diltiazem administered during reperfusion on hemodynamic, metabolic, and ultrastructural postischemic outcome. Methods: Hearts of 38 adult White New Zealand rabbits underwent 60min of global cold ischemia followed by 40min of reperfusion in an erythrocyte perfused isolated working heart model. Hearts were randomly assigned to four groups and received diltiazem (0.1, 0.25, and 0.5μmol/l) during reperfusion only, or served as control. Results: The postischemic time courses of heart rate, aortic flow, and external stroke work clearly reflected the dose-dependent negative chronotropic and inotropic efficacy of diltiazem in the two higher concentrations. High energy phosphates (HEP) determined from myocardial biopsies taken after 40min of reperfusion were significantly better preserved in all treatment groups compared to control hearts. Similarly ultrastructural grading of mitochondria and myofilaments revealed a significant reduction of reperfusion injury in hearts that received diltiazem compared to control. Conclusions: Diltiazem protects mitochondrial integrity and function, thereby preserving myocardial HEP levels. Only low dose diltiazem (0.1μmol/l) during reperfusion combines both, optimal mitochondrial preservation with minimal changes in hemodynamics.