非去极化心脏停跳液对缺血再灌注心肌的保护作用及其电生理机制
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摘要
目的：
1.观察St. Thomas液(ST液)、Histidine-Tryptophan-Ketoglutarate液(HTK液)和非去极化停跳液(Non-depolarizing cardioplegia, NDP液)对短时间(1小时)常温(24～26℃)和长时间(8小时)低温(4℃)缺血再灌注(Ischemia-reperfusion, I-R)离体心脏的心肌保护效果；
2.观察ST液、HTK液和NDP液对I-R乳鼠心肌细胞动作电位(Action Potential, AP)、快钠通道电流(Fast sodium current, INa)、L型钙通道电流(L-type calcium current,ICa-L)和瞬时外向钾通道电流(Transient outward potassium current,Ito)特性的影响；
3.观察ST液、HTK液和NDP液对乳鼠心肌细胞和线粒体钙离子代谢以及心肌细胞膜和线粒体膜电位的影响；
4.比较ST液、HTK液和NDP液对I-R心肌的保护效果及其电生理机制的异同。
方法：
1.SD大鼠64只,取其心脏建立Langendorff离体心脏灌注模型,用37℃氧饱和后的含钙KH缓冲液平衡15main后,随机分为8组,每组8只。(1)短时间常温心脏保存实验分组处理：对照组(Control, Con)、ST组、HTK组和NDP组分别在平衡后以室温(24-26℃)的无钙KH液、ST液、HTK液和NDP液灌注5min,在室温下相应的液体中保存1hr,再以37℃氧饱和的含钙KH液复灌lhr；(2)长时间低温心脏保存实验分组处理：Con组、ST组、HTK组和NDP组分别在平衡后以低温(4℃)的无钙KH液、ST液、HTK液和NDP液灌停5min,在4℃的相应液体中保存8hr后,分别以室温下的相应液体复温5main,再以37℃氧饱和的含钙KH液复灌1hr。比较各组再灌注后血流动力学、冠脉流出液中心脏肌钙蛋白I(Cardiac troponin I, cTnI)含量水平、心肌梗死面积、组织ATP和乳酸含量、心肌组织形态和超微结构。
2.原代培养出生1～2天的SD乳鼠心肌细胞。培养36hr后,分为5组。各组分别进行如下处理：(1)正常对照组(Normal Control, Con):不经缺血再灌注处理的正常心肌细胞；(2)缺血再灌注组(Ischemia/reperfusion, I/R):缺血缺氧处理3hr,再灌注lhr；(3)ST组：缺血缺氧处理3hr,再灌注lhr,期间加入ST液干预；(4)HTK组：缺血缺氧处理3hr,再灌注lhr,期间加入HTK液干预；(5)NDP组：缺血缺氧处理3hr,再灌注lhr,期间加入NDP液干预。使用全细胞膜片钳技术记录并比较各组心肌细胞AP、INa、ICa-L和Ito通道的特性。
3.原代培养出生1-2天的SD乳鼠心肌细胞。培养5天后,用荧光探针进行孵育,分为4组。各组分别进行如下处理：正常对照组(Con)：在激光共聚焦显微镜下持续观察35min; ST组、HTK组和NDP组观察5min后,分别加入ST液、HTK液和NDP液,再连续观察30min。
结果：
1.短时间常温心脏保存环境下：HTK组和NDP组I-R后心脏心功能的恢复水平优于ST组(P<0.05),两组差异无统计学意义；NDP组冠脉流量高于ST组和HTK组(P<0.05)；HTK组心梗面积、冠脉流出液中cTnI水平较ST组和NDP组降低(P<0.05)；各组心肌组织ATP和乳酸含量,心肌组织形态和超微结构无显著差异。
2.长时间低温心脏保存环境下：ST组心脏保存后心功能得不到有效恢复；NDP组再灌注后心功能和冠脉流量可恢复至平衡期的90%以上,显著高于Con组和HTK组(P<0.05)；HTK组和NDP组流出液中cTnI水平低于其他组(P<0.05)；NDP组心梗面积显著低于其他组(P<0.05),心肌组织ATP含量高于其他组(P<0.05),心脏超微结构损伤程度最轻；各组组织乳酸含量、光镜下形态结构的差异无统计学意义。
3.各组心肌细胞电生理特性的变化。(1)AP：I/R组动作电位幅度(Action Potential Amplifide, APA)和动作电位时程(Action Potential Duration, APD)较Con组显著降低,心肌细胞静息膜电位(Resting Membrane Potential, RMP)去极化,NDP液干预后RMP. APA和APD可恢复至接近正常水平,较ST组和HTK组增大(P<0.05);(2) INa:I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组INa峰值电流密度明显提升(P<0.05),失活曲线右移；(3)ICa-L：I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组峰值电流密度显著增高(P<0.05),失活曲线右移；(4)Ito：I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组峰值电流密度显著增高(P<0.05),失活曲线左移。
4.心肌细胞和线粒体钙代谢和膜电位的变化。加入停跳液后：(1)细胞内钙：NDP组停跳效果好,荧光强度基线水平较ST组和HTK组降低；(2)细胞膜电位：NDP组膜电位持续维持在超极化水平,ST组和HTK组膜电位持续维持在去极化水平,ST组去极化程度高于HTK组；(3)线粒体钙：ST组钙荧光强度基线水平较Con组和HTK组升高,NDP组较之降低；(4)线粒体膜电位：ST组膜电位去极化水平逐渐升高,NDP组和Con组膜电位具有超极化趋势。
结论：
1.对于短时间常温保存心脏而言,NDP液对冠脉血管舒张作用的保护优于ST液和HTK液；HTK液和NDP液促进I-R后心功能恢复的作用优于ST液；HTK液和NDP液心肌保护效果无明显差异。因此,NDP液在常规心脏外科手术心肌保护中的应用优势有待进一步探讨。
2.对于长时间低温保存心脏而言,ST液保存后心脏功能完全得不到恢复；NDP液保存后心脏功能基本可恢复至正常水平,与HTK液相比存在明显优势；NDP液的心肌保护效果最佳。从本研究结果来看,NDP液是一种较HTK液更为理想的体外心脏保存液。
3.停跳液的干预可不同程度的缓解MIRI引起的心肌细胞AP、INa、ICa-L和Ito通道特性的改变。NDP液对AP和各离子通道的恢复作用优于ST液和HTK液。
4.NDP液可有效诱导心脏停跳并使心肌细胞内和线粒体内的钙离子浓度持续维持在低水平。这有利于再灌注期间细胞内外钙离子梯度的维持,加快再灌注心脏功能的恢复,降低细胞内钙离子浓度升高引发心肌细胞损伤的风险；提高了线粒体对细胞质内钙离子的清除能力,增强心肌细胞抵御MIRI的作用。
5.NDP液可使心肌细胞膜电位稳定维持于超极化水平,亦可使得线粒体膜电位轻度超极化。这可以阻止细胞膜-钙离子-氧化应激-心肌损伤和炎性反应损伤的发生,减轻MIRI;同时有助于心肌细胞钙稳态和抗氧化损伤能力的维持。
Objective:
1. To investigate the cardioprotective effects of St. Thomas (ST) solution, Histidine-Tryptophan-Ketoglutarate (HTK) solution and Non-depolarizing (NDP) solution after preservation in the three solutions at room temperature and4℃, separately.
2. To investigate the effects of ST solution, HTK solution and NDP solution on the electrophysiological characteristics of action potential (AP), fast sodium current (INa), L-type calcium current (Ica-L and transient outward potassium current (Ito) from new-born rat cardiomyocytes.
3. To investigate the effects of ST solution, HTK solution and NDP solution on the cytoplasmic and mitochondrial calcium metabolism and their membrane potential migration.
4. Compare the cardioprotective and electrophysiological effects of ST solution, HTK solution and NDP solution.
Methods:
1. Sixty-four isolated SD rat hearts were perfused with37℃oxygen-saturated KH solution for15min and then divided into8groups,8for each group.(1) for the hearts preserved under room temperature:we used24～26℃calcium-free KH solution, ST solution, HTK solution and NDP solution for cardiac arrest and the1hour-preservation for the Con group, the ST group, the HTK group and the NDP group separately. After preservation, hearts were reperfused with37℃oxygen-saturated KH solution for lhr;(2) for the hearts preserved under icy temperature:we used4℃calcium-free KH solution, ST solution, HTK solution and NDP solution for cardiac arrest and the8hour-preservation for the Con group, the ST group, the HTK group and the NDP group separately. After preservation, hearts were rewarmed with each solution and reperfused with37℃oxygen-saturated KH solution for1hr. Heart function recovery, Cardiac troponin I (cTnI) level, myocardial infarction area, ATP and lactic acid (LA) content and morphology variations were compared between each group.
2. We cultured the new-born rat cardiomyocytes. Cells after36hours'culturation were usded for whole-cell patch clamp detection. Five groups were included:(1) the Control (Con) group:normal cardiomyocytes;(2) the ischemia/reperfusion (I/R) group:cells were treated with3-hour ischemia and1-hour-reperfusion;(3) the ST group, the HTK group and the NDP group:during the ischemia-reperfusion (I-R) treatment, ST solution, HTK solution and NDP solution were added in the culture medium separately. The characteristics of the AP, INa、ICa-L and Ito were compared between each group.
3. We cultured the new-born rat cardiomyocytes. Cells after5days'culturation were usded for laser confocal microscopy scanning. Cells were incubated with four different fluorochromes. Under each condition, four groups were included:the Con group were scanned for35min continuously; after5min scanning, the ST group, the HTK group and the NDP group were treated with ST solution, HTK solution and NDP solution separately, and then followed with30min continuous scanning.
Results:
1. Under the1-hour-room temperature condition:the heart function recovery in the HTK group and the NDP group were superior to the ST group (P<0.05); the coronary flow in the NDP group increased compared with the ST group and the HTK group (P<0.05); the infarction percentage and cTnI level in the HTK group were lower than the ST and NDP groups (P<0.05); there was no significant difference in the ATP and LA content among the three groups.
2. Under the8-hour-icy temperature condition:the heart function of the ST group could not effectively recover; the heart function of the NDP group could recover to the level of90%of the preischemic value; the cTnI levels of the HTK and NDP groups were lower than the ST group. Compared with the ST group and the HTK group, the infarction area of the NDP group decreased, and the ATP content increased. There was no significant difference in the LA content among the three groups.
3. The electrophysiological changes of each group were as follows.(1) AP:the action potential amplified (APA) and action potential duration (APD) of the I/R group decreased and the resting membrane potential (RMP) depolarized compared with the Con group. The RMP, APA, APD of the NDP group recovered almost to the normal level.(2) INa:the peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density increased (P<0.05), and the inactivation curve right-shifted.(3) ICa-L:the Peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density increased (P<0.05), and the inactivation curve right-shifted.(4) Ito:the peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density of the NDP group increased (P<0.05), and the inactivation curve left-shifted.
4. The calcium and membrane potential variations of each group were as follows. After the addition of each cardioplegia:(1) cytoplasmic calcium:the fluorescent intensity baseline in the NDP group kept staying at a lower level compared with the ST and the HTK groups.(2) cell membrane potential:the potential of the NDP group maintained at a hyperpolarization level, while of the ST and the HTK groups, the membrane potential kept at a depolarization level.(3) mitochondrial calcium:the fluorescent intensity in the ST group increased than the Con and the HTK groups, while the NDP group decreased.(4) mitochondrial membrane potential:the depolarization level of the ST group increased gradually, while the NDP and the Con groups tended to be more hyperpolarized.
Conclusion:
1. Under the1-hour-room temperature condition, the NDP solution could effectively protect the coronary function. The HTK solution and the NDP solution could improve the I-R heart function recovery, while there was no significant difference between the two groups. The result suggested that the application advantage of NDP solution in the regular cardiac surgery needed further studies.
2. Under the8-hour-icy temperature condition, the NDP solution could improve the heart function to an almost normal level. This result suggested, compared with the HTK solution, that the NDP solution was a more ideal preservation solution during the organ transferation process in heart transplantation.
3. The NDP solution could superiorly recover the electrophysiological characteristic changes caused by I-R injury.
4. The NDP solution could maintain the cytoplasm and the mitochondria calcium concentration at a continuous low level. These results indicated that the NDP solution could effectively reduce the risk of the intracellular calcium overload, and was beneficial for the mitochondrial calcium absorption function, which could intensify the myocardiual anti-I-R effects.
5. The NDP solution tended to induce the cell and the mitochondria membrane potential at hyperpolarization level, which could help maintain the cell calcium homeostatic and prevent the heart against oxidative damges during the I-R procedure.
1.观察St. Thomas液(ST液)、Histidine-Tryptophan-Ketoglutarate液(HTK液)和非去极化停跳液(Non-depolarizing cardioplegia, NDP液)对短时间(1小时)常温(24～26℃)和长时间(8小时)低温(4℃)缺血再灌注(Ischemia-reperfusion, I-R)离体心脏的心肌保护效果；
2.观察ST液、HTK液和NDP液对I-R乳鼠心肌细胞动作电位(Action Potential, AP)、快钠通道电流(Fast sodium current, INa)、L型钙通道电流(L-type calcium current,ICa-L)和瞬时外向钾通道电流(Transient outward potassium current,Ito)特性的影响；
3.观察ST液、HTK液和NDP液对乳鼠心肌细胞和线粒体钙离子代谢以及心肌细胞膜和线粒体膜电位的影响；
4.比较ST液、HTK液和NDP液对I-R心肌的保护效果及其电生理机制的异同。
方法：
1.SD大鼠64只,取其心脏建立Langendorff离体心脏灌注模型,用37℃氧饱和后的含钙KH缓冲液平衡15main后,随机分为8组,每组8只。(1)短时间常温心脏保存实验分组处理：对照组(Control, Con)、ST组、HTK组和NDP组分别在平衡后以室温(24-26℃)的无钙KH液、ST液、HTK液和NDP液灌注5min,在室温下相应的液体中保存1hr,再以37℃氧饱和的含钙KH液复灌lhr；(2)长时间低温心脏保存实验分组处理：Con组、ST组、HTK组和NDP组分别在平衡后以低温(4℃)的无钙KH液、ST液、HTK液和NDP液灌停5min,在4℃的相应液体中保存8hr后,分别以室温下的相应液体复温5main,再以37℃氧饱和的含钙KH液复灌1hr。比较各组再灌注后血流动力学、冠脉流出液中心脏肌钙蛋白I(Cardiac troponin I, cTnI)含量水平、心肌梗死面积、组织ATP和乳酸含量、心肌组织形态和超微结构。
2.原代培养出生1～2天的SD乳鼠心肌细胞。培养36hr后,分为5组。各组分别进行如下处理：(1)正常对照组(Normal Control, Con):不经缺血再灌注处理的正常心肌细胞；(2)缺血再灌注组(Ischemia/reperfusion, I/R):缺血缺氧处理3hr,再灌注lhr；(3)ST组：缺血缺氧处理3hr,再灌注lhr,期间加入ST液干预；(4)HTK组：缺血缺氧处理3hr,再灌注lhr,期间加入HTK液干预；(5)NDP组：缺血缺氧处理3hr,再灌注lhr,期间加入NDP液干预。使用全细胞膜片钳技术记录并比较各组心肌细胞AP、INa、ICa-L和Ito通道的特性。
3.原代培养出生1-2天的SD乳鼠心肌细胞。培养5天后,用荧光探针进行孵育,分为4组。各组分别进行如下处理：正常对照组(Con)：在激光共聚焦显微镜下持续观察35min; ST组、HTK组和NDP组观察5min后,分别加入ST液、HTK液和NDP液,再连续观察30min。
结果：
1.短时间常温心脏保存环境下：HTK组和NDP组I-R后心脏心功能的恢复水平优于ST组(P<0.05),两组差异无统计学意义；NDP组冠脉流量高于ST组和HTK组(P<0.05)；HTK组心梗面积、冠脉流出液中cTnI水平较ST组和NDP组降低(P<0.05)；各组心肌组织ATP和乳酸含量,心肌组织形态和超微结构无显著差异。
2.长时间低温心脏保存环境下：ST组心脏保存后心功能得不到有效恢复；NDP组再灌注后心功能和冠脉流量可恢复至平衡期的90%以上,显著高于Con组和HTK组(P<0.05)；HTK组和NDP组流出液中cTnI水平低于其他组(P<0.05)；NDP组心梗面积显著低于其他组(P<0.05),心肌组织ATP含量高于其他组(P<0.05),心脏超微结构损伤程度最轻；各组组织乳酸含量、光镜下形态结构的差异无统计学意义。
3.各组心肌细胞电生理特性的变化。(1)AP：I/R组动作电位幅度(Action Potential Amplifide, APA)和动作电位时程(Action Potential Duration, APD)较Con组显著降低,心肌细胞静息膜电位(Resting Membrane Potential, RMP)去极化,NDP液干预后RMP. APA和APD可恢复至接近正常水平,较ST组和HTK组增大(P<0.05);(2) INa:I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组INa峰值电流密度明显提升(P<0.05),失活曲线右移；(3)ICa-L：I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组峰值电流密度显著增高(P<0.05),失活曲线右移；(4)Ito：I/R组峰值电流密度较Con组显著降低,激活曲线右移,失活曲线左移,与I/R组、ST组和HTK组相比,NDP组峰值电流密度显著增高(P<0.05),失活曲线左移。
4.心肌细胞和线粒体钙代谢和膜电位的变化。加入停跳液后：(1)细胞内钙：NDP组停跳效果好,荧光强度基线水平较ST组和HTK组降低；(2)细胞膜电位：NDP组膜电位持续维持在超极化水平,ST组和HTK组膜电位持续维持在去极化水平,ST组去极化程度高于HTK组；(3)线粒体钙：ST组钙荧光强度基线水平较Con组和HTK组升高,NDP组较之降低；(4)线粒体膜电位：ST组膜电位去极化水平逐渐升高,NDP组和Con组膜电位具有超极化趋势。
结论：
1.对于短时间常温保存心脏而言,NDP液对冠脉血管舒张作用的保护优于ST液和HTK液；HTK液和NDP液促进I-R后心功能恢复的作用优于ST液；HTK液和NDP液心肌保护效果无明显差异。因此,NDP液在常规心脏外科手术心肌保护中的应用优势有待进一步探讨。
2.对于长时间低温保存心脏而言,ST液保存后心脏功能完全得不到恢复；NDP液保存后心脏功能基本可恢复至正常水平,与HTK液相比存在明显优势；NDP液的心肌保护效果最佳。从本研究结果来看,NDP液是一种较HTK液更为理想的体外心脏保存液。
3.停跳液的干预可不同程度的缓解MIRI引起的心肌细胞AP、INa、ICa-L和Ito通道特性的改变。NDP液对AP和各离子通道的恢复作用优于ST液和HTK液。
4.NDP液可有效诱导心脏停跳并使心肌细胞内和线粒体内的钙离子浓度持续维持在低水平。这有利于再灌注期间细胞内外钙离子梯度的维持,加快再灌注心脏功能的恢复,降低细胞内钙离子浓度升高引发心肌细胞损伤的风险；提高了线粒体对细胞质内钙离子的清除能力,增强心肌细胞抵御MIRI的作用。
5.NDP液可使心肌细胞膜电位稳定维持于超极化水平,亦可使得线粒体膜电位轻度超极化。这可以阻止细胞膜-钙离子-氧化应激-心肌损伤和炎性反应损伤的发生,减轻MIRI;同时有助于心肌细胞钙稳态和抗氧化损伤能力的维持。
Objective:
1. To investigate the cardioprotective effects of St. Thomas (ST) solution, Histidine-Tryptophan-Ketoglutarate (HTK) solution and Non-depolarizing (NDP) solution after preservation in the three solutions at room temperature and4℃, separately.
2. To investigate the effects of ST solution, HTK solution and NDP solution on the electrophysiological characteristics of action potential (AP), fast sodium current (INa), L-type calcium current (Ica-L and transient outward potassium current (Ito) from new-born rat cardiomyocytes.
3. To investigate the effects of ST solution, HTK solution and NDP solution on the cytoplasmic and mitochondrial calcium metabolism and their membrane potential migration.
4. Compare the cardioprotective and electrophysiological effects of ST solution, HTK solution and NDP solution.
Methods:
1. Sixty-four isolated SD rat hearts were perfused with37℃oxygen-saturated KH solution for15min and then divided into8groups,8for each group.(1) for the hearts preserved under room temperature:we used24～26℃calcium-free KH solution, ST solution, HTK solution and NDP solution for cardiac arrest and the1hour-preservation for the Con group, the ST group, the HTK group and the NDP group separately. After preservation, hearts were reperfused with37℃oxygen-saturated KH solution for lhr;(2) for the hearts preserved under icy temperature:we used4℃calcium-free KH solution, ST solution, HTK solution and NDP solution for cardiac arrest and the8hour-preservation for the Con group, the ST group, the HTK group and the NDP group separately. After preservation, hearts were rewarmed with each solution and reperfused with37℃oxygen-saturated KH solution for1hr. Heart function recovery, Cardiac troponin I (cTnI) level, myocardial infarction area, ATP and lactic acid (LA) content and morphology variations were compared between each group.
2. We cultured the new-born rat cardiomyocytes. Cells after36hours'culturation were usded for whole-cell patch clamp detection. Five groups were included:(1) the Control (Con) group:normal cardiomyocytes;(2) the ischemia/reperfusion (I/R) group:cells were treated with3-hour ischemia and1-hour-reperfusion;(3) the ST group, the HTK group and the NDP group:during the ischemia-reperfusion (I-R) treatment, ST solution, HTK solution and NDP solution were added in the culture medium separately. The characteristics of the AP, INa、ICa-L and Ito were compared between each group.
3. We cultured the new-born rat cardiomyocytes. Cells after5days'culturation were usded for laser confocal microscopy scanning. Cells were incubated with four different fluorochromes. Under each condition, four groups were included:the Con group were scanned for35min continuously; after5min scanning, the ST group, the HTK group and the NDP group were treated with ST solution, HTK solution and NDP solution separately, and then followed with30min continuous scanning.
Results:
1. Under the1-hour-room temperature condition:the heart function recovery in the HTK group and the NDP group were superior to the ST group (P<0.05); the coronary flow in the NDP group increased compared with the ST group and the HTK group (P<0.05); the infarction percentage and cTnI level in the HTK group were lower than the ST and NDP groups (P<0.05); there was no significant difference in the ATP and LA content among the three groups.
2. Under the8-hour-icy temperature condition:the heart function of the ST group could not effectively recover; the heart function of the NDP group could recover to the level of90%of the preischemic value; the cTnI levels of the HTK and NDP groups were lower than the ST group. Compared with the ST group and the HTK group, the infarction area of the NDP group decreased, and the ATP content increased. There was no significant difference in the LA content among the three groups.
3. The electrophysiological changes of each group were as follows.(1) AP:the action potential amplified (APA) and action potential duration (APD) of the I/R group decreased and the resting membrane potential (RMP) depolarized compared with the Con group. The RMP, APA, APD of the NDP group recovered almost to the normal level.(2) INa:the peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density increased (P<0.05), and the inactivation curve right-shifted.(3) ICa-L:the Peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density increased (P<0.05), and the inactivation curve right-shifted.(4) Ito:the peak current density of the I/R group decreased significantly than the Con group (P<0.05), the activation curve right-shifted and the inactivation curve left-shifted. Compared with the I/R, ST and the HTK groups, the peak current density of the NDP group increased (P<0.05), and the inactivation curve left-shifted.
4. The calcium and membrane potential variations of each group were as follows. After the addition of each cardioplegia:(1) cytoplasmic calcium:the fluorescent intensity baseline in the NDP group kept staying at a lower level compared with the ST and the HTK groups.(2) cell membrane potential:the potential of the NDP group maintained at a hyperpolarization level, while of the ST and the HTK groups, the membrane potential kept at a depolarization level.(3) mitochondrial calcium:the fluorescent intensity in the ST group increased than the Con and the HTK groups, while the NDP group decreased.(4) mitochondrial membrane potential:the depolarization level of the ST group increased gradually, while the NDP and the Con groups tended to be more hyperpolarized.
Conclusion:
1. Under the1-hour-room temperature condition, the NDP solution could effectively protect the coronary function. The HTK solution and the NDP solution could improve the I-R heart function recovery, while there was no significant difference between the two groups. The result suggested that the application advantage of NDP solution in the regular cardiac surgery needed further studies.
2. Under the8-hour-icy temperature condition, the NDP solution could improve the heart function to an almost normal level. This result suggested, compared with the HTK solution, that the NDP solution was a more ideal preservation solution during the organ transferation process in heart transplantation.
3. The NDP solution could superiorly recover the electrophysiological characteristic changes caused by I-R injury.
4. The NDP solution could maintain the cytoplasm and the mitochondria calcium concentration at a continuous low level. These results indicated that the NDP solution could effectively reduce the risk of the intracellular calcium overload, and was beneficial for the mitochondrial calcium absorption function, which could intensify the myocardiual anti-I-R effects.
5. The NDP solution tended to induce the cell and the mitochondria membrane potential at hyperpolarization level, which could help maintain the cell calcium homeostatic and prevent the heart against oxidative damges during the I-R procedure.
引文
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