Jones R M, Bagchi M, Das D K
Department of Surgery, University of Connecticut School of Medicine, Farmington.
Basic Res Cardiol. 1992 Nov-Dec;87(6):527-35. doi: 10.1007/BF00788663.
Recent studies indicate that preconditioning of the heart by repeated stunning protects it from subsequent ischemic injury. Such myocardial preservation is likely to be due to adaptive modification of lipid composition and dynamic structure of cellular membrane. To test this hypothesis, swine heart was subjected to four episodes of 5 min stunning by LAD occlusion, followed by 10 min of reperfusion after each stunning. The heart was then made regionally ischemic for 60 min by LAD occlusion, followed by 6 h reperfusion. A control heart was perfused for 60 min, followed by 60 min ischemia and 6 h reperfusion. Free fatty acids (FFA) accumulated in the control heart during ischemia, as expected, which was further enhanced by reperfusion. The FFA level was also enhanced during ischemia in stunned myocardium. However, this FFA level was almost restored during reperfusion. The levels of unsaturated fatty acids (UFA) such as oleate, linoleate, and arachidonate followed a similar pattern. Membrane fluidity, monitored by fluorescence polarization, was decreased during ischemia and reperfusion in the unstunned heart, with the corresponding increase in microviscosity. The increased microviscosity was significantly reduced by stunning. Since FFA are presumably generated from membrane phospholipids, these results suggest that stunning may cause the incorporation of a greater proportion of PUFA in membrane phospholipids, leading to preservation of membrane phospholipids and maintaining the membrane fluidity, which may be at least partially responsible for the attenuation of ischemic reperfusion injury.
近期研究表明,通过反复顿抑对心脏进行预处理可保护其免受随后的缺血性损伤。这种心肌保护作用可能归因于细胞膜脂质组成和动态结构的适应性改变。为验证这一假说,对猪心脏进行4次左前降支闭塞5分钟的顿抑,每次顿抑后再灌注10分钟。然后通过左前降支闭塞使心脏局部缺血60分钟,随后再灌注6小时。对照心脏灌注60分钟,然后缺血60分钟并再灌注6小时。正如预期的那样,对照心脏在缺血期间游离脂肪酸(FFA)蓄积,再灌注使其进一步增加。顿抑心肌在缺血期间FFA水平也升高。然而,再灌注期间该FFA水平几乎恢复正常。油酸、亚油酸和花生四烯酸等不饱和脂肪酸(UFA)水平呈现类似模式。通过荧光偏振监测的膜流动性在未顿抑心脏的缺血和再灌注期间降低,微粘度相应增加。顿抑可显著降低增加的微粘度。由于FFA可能由膜磷脂产生,这些结果表明,顿抑可能导致膜磷脂中多不饱和脂肪酸(PUFA)比例增加,从而保护膜磷脂并维持膜流动性,这可能至少部分解释了缺血再灌注损伤的减轻。