Busselen P
Interdisciplinary Research Centre, K.U. Leuven, Belgium.
J Mol Cell Cardiol. 1991 Mar;23(3):237-47. doi: 10.1016/0022-2828(91)90060-y.
Polyamine levels were measured by means of high-performance liquid chromatography in Langendorff-perfused rat hearts subjected to the calcium paradox protocol. The concentrations of putrescine, spermidine and spermine did not change significantly during calcium-free perfusion but decreased when calcium was readmitted. This decrease was due to membrane disruption and release of the polyamines into the coronary effluent. The sum of released and remaining spermidine exceeded the concentration of spermidine in control hearts, but, for spermine, this sum was lower than the control level. The addition of 0.5 mM EGTA to the calcium-free solution raised the myocardial concentrations of putrescine and spermidine and enhanced the net increase of spermidine on calcium repletion. DL-alpha-Difluoromethylornithine (DFMO) inhibited these increases and lowered the putrescine level during all perfusion stages. External polyamines had a negative inotropic effect and inhibited the loss of myoglobin on calcium repletion (order of effectiveness: spermine greater than spermine greater than putrescine). Inhibition of contractions by the combined action of verapamil and ryanodine or by potassium depolarization did not prevent myoglobin loss. External polyamines had no effect on high K/low Na contractures, which were mediated mainly by Na-Ca exchange. Calcium-free perfusion in the presence of 0.5 to 1 mM EGTA improved the membrane protection by polyamines or by diamines and analogues, like ornithine, 1,3-diaminopropane, or DFMO, which, in the absence of EGTA, gave no clear protection. It is concluded that calcium depletion and repletion influences myocardiaal polyamine concentrations by (1) membrane disruption and release of polyamines into the coronary effluent, and (2) probably by a stimulation of ornithine decarboxylase activity. The changes in polyamine concentrations do not seem to have any causal role in calcium overload and cell death. Exogenous polyamines protect against membrane damage.
采用高效液相色谱法测定了经钙反常方案处理的Langendorff灌注大鼠心脏中的多胺水平。在无钙灌注期间，腐胺、亚精胺和精胺的浓度没有显著变化，但在重新加入钙后降低。这种降低是由于膜破坏以及多胺释放到冠状动脉流出液中。释放的亚精胺与剩余亚精胺之和超过了对照心脏中亚精胺的浓度，但对于精胺来说，这一总和低于对照水平。在无钙溶液中添加0.5 mM EGTA可提高心肌中腐胺和亚精胺的浓度，并增强钙再灌注时亚精胺的净增加量。DL-α-二氟甲基鸟氨酸（DFMO）抑制了这些增加，并在所有灌注阶段降低了腐胺水平。外源性多胺具有负性肌力作用，并抑制钙再灌注时肌红蛋白的丢失（有效性顺序：精胺＞亚精胺＞腐胺）。维拉帕米和ryanodine联合作用或钾去极化对收缩的抑制并不能阻止肌红蛋白的丢失。外源性多胺对主要由钠-钙交换介导的高钾/低钠挛缩没有影响。在存在0.5至1 mM EGTA的情况下进行无钙灌注可改善多胺或二胺及其类似物（如鸟氨酸、1,3-二氨基丙烷或DFMO）对膜的保护作用，而在没有EGTA的情况下，这些物质没有明显的保护作用。得出的结论是，钙耗竭和再灌注通过以下方式影响心肌多胺浓度：（1）膜破坏以及多胺释放到冠状动脉流出液中；（2）可能是通过刺激鸟氨酸脱羧酶活性。多胺浓度的变化似乎在钙超载和细胞死亡中没有任何因果作用。外源性多胺可防止膜损伤。
