钙传递与时间：大鼠心脏钙反常过程中影响细胞损伤进展的因素

Calcium delivery and time: factors affecting the progression of cellular damage during the calcium paradox in the rat heart.

作者信息

Baker J E, Kemmenoe B H, Hearse D J, Bullock G R

出版信息

Cardiovasc Res. 1984 Jun;18(6):361-70. doi: 10.1093/cvr/18.6.361.

DOI:10.1093/cvr/18.6.361

Abstract

Using an isolated rat heart preparation we have investigated the influence of calcium delivery and time upon the induction of cellular injury during the calcium paradox. Hearts were subjected to 10 min of calcium depletion. This was followed by calcium repletion for up to 20 min during which time the calcium concentration in the perfusate was varied between 0.025 and 1.00 mmol X litre-1. For the lowest calcium repletion concentration, cumulative leakage of creatine kinase activity was small and linear with time over the 20 min repletion period, and relatively few damaged cells were observed, these being situated around coronary vessels. For calcium concentrations of 0.05 mmol X litre-1 and above the progression of structural injury was dependent on both increasing calcium concentration and time. After 1 min of repletion with 0.10 mmol calcium X litre-1 the percentage damaged cells was 2%, this sharply increased to 95% after 10 min of repletion but without a parallel increase in the profile for creatine kinase leakage. For calcium repletion at 0.05 mmol X litre-1 morphological injury was shown to be highly heterogeneous both within and between hearts. Uniform cellular damage (ie greater than 95%) in the concentration range 0.25 to 1.00 mmol calcium X litre-1 was only seen after 10 min of calcium readmission. Maximal cumulative creatine kinase activity only occurred after 15 to 20 min of repletion with 0.50 and 1.00 mmol calcium X litre-1. Our results show calcium delivery and time can both modulate the progression of cellular injury and allow a dissociation between indices of tissue damage.

摘要

利用离体大鼠心脏标本，我们研究了钙供应和时间对钙反常过程中细胞损伤诱导的影响。心脏先经历10分钟的钙缺失。随后进行长达20分钟的钙再灌注，在此期间灌注液中的钙浓度在0.025至1.00 mmol·L⁻¹之间变化。对于最低的钙再灌注浓度，在20分钟的再灌注期内，肌酸激酶活性的累积泄漏量较小且与时间呈线性关系，并且观察到相对较少的受损细胞，这些细胞位于冠状血管周围。对于0.05 mmol·L⁻¹及以上的钙浓度，结构损伤的进展取决于钙浓度的增加和时间。用0.10 mmol·L⁻¹钙再灌注1分钟后，受损细胞百分比为2%，再灌注10分钟后急剧增加到95%，但肌酸激酶泄漏曲线没有相应增加。对于0.05 mmol·L⁻¹的钙再灌注，形态学损伤在心脏内部和心脏之间均表现出高度异质性。仅在钙重新进入10分钟后，才在0.25至1.00 mmol·L⁻¹钙浓度范围内观察到均匀的细胞损伤（即大于95%）。最大累积肌酸激酶活性仅在用0.50和1.00 mmol·L⁻¹钙再灌注15至20分钟后出现。我们的结果表明，钙供应和时间均可调节细胞损伤的进展，并使组织损伤指标之间出现分离。