Changes in [Na(+)](i), compartmental [Ca(2+)], and NADH with dysfunction after global ischemia in intact hearts.
Changes in [Na(+)](i), compartmental [Ca(2+)], and NADH with dysfunction after global ischemia in intact hearts.
复制标题
完整心脏全缺血后 [Na( )](i)、室室 [Ca(2 )] 和 NADH 的变化以及功能障碍。
DOI：
10.1152/ajpheart.2001.280.1.h280
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发表时间：
2001
期刊：
影响因子：
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通讯作者：
Stowe,DF
中科院分区：
文献类型：
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作者：
Varadarajan,SG;An,J;Novalija,E;Smart,SC;Stowe,DF
我们测量了全脑缺血和再灌注对完整心脏细胞内Na+、NADH、胞浆和胞浆内Ca 2+、舒张、代谢、收缩和Ca 2+敏感性的影响。Langendorff制备的豚鼠心脏进行晶体灌注，左心室（LV）压力（LVP），LVP的一阶导数（LV dP/dt），冠状动脉流量，和O2提取和消耗之前，期间，和之后30分钟的全脑缺血和60分钟的再灌注进行了测量。在减去组织自发荧光（NADH）的变化后，分别使用吲哚1和苯并呋喃双甲酸钠通过发光分光光度法测量LV游离壁的Ca 2+、Na+和NADH。线粒体Ca 2+通过用MnCl 2淬灭胞浆indo 1来评估。在缺血再灌注前和缺血再灌注后，在细胞外[Ca 2 +]的范围内测试了对cytossolic-systolicsys，cytosolicdia和线粒体Ca 2+变化的机械反应。再灌注1 min时[Ca ~（2+）]和[Ca ~（2+）]均倍增，但在10 min内恢复到缺血前水平，而[Ca ~（2+）]线粒体在再灌注60 min内升高。再灌注30分钟时，与收缩功能有关的游离[Ca ~（2+）]_d和[Ca ~（2+）]_s系统，如LVPys_d和LVdP/dt（LVdP/dtmax）的上升被抑制1/3，LVdP/dt（LVdP/dtmin）的下降被抑制1/2，而LVPd仍明显升高。[Ca2 100%LV dP/dtmax时的[Ca ~（2+）]diaat 100%LV dP/dtmax和[Ca ~（2+）] mitat 100%LV dP/dtmax时的[Ca ~（2+）]diaat 100%LV dP/dtmax在再灌注后明显右移（ED_（50）分别为+36和+125 nM [Ca ~（2+）]），斜率无变化。NADH在缺血期间加倍，但在初始再灌注时恢复正常。细胞内[Na+]（[Na+]i）在缺血期间最低限度地增加，但在再灌注时增加一倍，并在再灌注60分钟时保持升高。因此，Na+和Ca ~（2+）在初始再灌注期间暂时积累，胞浆Ca ~（2+）恢复正常，而[Na+] i和[Ca ~（2+）]线粒体在后期再灌注时升高。Na+负荷可能导致再灌注过程中Ca 2+超载和收缩功能障碍。
We measured the effects of global ischemia and reperfusion on intracellular Na+, NADH, cytosolic and mitochondrialmitoCa2+, relaxation, metabolism, contractility, and Ca2+sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/dt), coronary flow, and O2extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca2+, Na+, and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca2+was assessed by quenching cytosolic indo 1 with MnCl2. Mechanical responses to changes in cytosolic-systolicsys, diastolicdia, and mitochondrial Ca2+were tested over a range of extracellular [Ca2+] before and after ischemia-reperfusion. Both [Ca2+]sysand [Ca2+]diadoubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca2+]mitowas elevated over 60-min reperfusion. Reperfusion dissociated [Ca2+]diaand [Ca2+]sysfrom contractile function as LVPsys-diaand the rise in LV dP/dt(LV dP/dtmax) were depressed by one-third and the fall in LV dP/dt(LV dP/dtmin) was depressed by one-half at 30-min reperfusion, whereas LVPdiaremained markedly elevated. [Ca2+]sys-diasensitivity at 100% LV dP/dtmaxwas not altered after reperfusion, but [Ca2+]diaat 100% LV dP/dtminand [Ca2+]mitoat 100% LV dP/dtmaxwere markedly shifted right on reperfusion (ED50+36 and +125 nM [Ca2+], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na+] ([Na+]i) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na+and Ca2+temporally accumulate during initial reperfusion, and cytosolic Ca2+returns toward normal, whereas [Na+]iand [Ca2+]mitoremain elevated on later reperfusion. Na+loading likely contributes to Ca2+overload and contractile dysfunction during reperfusion.