Rich T L, Langer G A
Circ Res. 1982 Aug;51(2):131-41. doi: 10.1161/01.res.51.2.131.
The purpose of this study was to define further the basis of control of myocardial membrane permeability by further examination of the "calcium paradox." To this end, the protective effect of hypothermia and addition of micromolar amounts of divalent cations during the Ca-free perfusion period were studied. Damage during Ca++ repletion to the isolated arterially perfused, interventricular rabbit septum was assessed by contracture development, loss of developed tension, and loss of 42K and creatine kinase. Progressive hypothermia prolongs the time of Ca-free perfusion needed to cause similar 42K, creatine kinase and developed tension losses upon Ca++ repletion. Complete protection against the Ca-paradox after 30-60 minutes Ca-free perfusion is seen at 18 degree C. The inclusion of 50 microM Ca++ during 30 minutes "Ca-free" perfusion also provides complete protection during Ca++ repletion i.e., there was full mechanical recovery with no 42K or creatine kinase loss. Other divalent cations perfused in 50 microM concentrations during the Ca-free period exhibited variable ability to protect when Ca++ was reperfused. The order of effectiveness (Ca++ greater than Cd++ greater than Mn++ greater than Co++ greater than Mg++) was related to the crystal ionic radius, with those cations whose radii are closest to that of Ca++ (0.99 A) exerting the greatest protective effect. The cation sequence for effectiveness in Ca-paradox protection is the same sequence for potency of excitation-contraction uncoupling. The mechanism of hypothermic protection is likely a phase transition in the membrane lipids (from a more liquid to a less liquid state) which stabilizes membrane structure and preserves Ca++ permeability characteristics during the Ca-free period. The mechanism of protection via cation addition is perhaps a cation's ability to substitute for Ca++ (dependent on unhydrated crystal ionic radius) at critical sarcolemmal binding sites to preserve control of Ca++ permability during the Ca-free period.
本研究的目的是通过进一步研究“钙反常”来进一步确定心肌膜通透性的控制基础。为此，研究了低温以及在无钙灌注期添加微摩尔量二价阳离子的保护作用。通过挛缩发展、舒张期张力丧失以及42K和肌酸激酶丧失来评估在钙再灌注期间对离体动脉灌注的兔室间隔的损伤。逐渐降低温度可延长在钙再灌注时引起类似的42K、肌酸激酶和舒张期张力丧失所需的无钙灌注时间。在18℃时，无钙灌注30 - 60分钟后可完全防止钙反常。在30分钟“无钙”灌注期间加入50微摩尔的Ca++在钙再灌注期间也能提供完全保护，即机械功能完全恢复，42K或肌酸激酶无丧失。在无钙期以50微摩尔浓度灌注的其他二价阳离子在钙再灌注时表现出不同的保护能力。有效性顺序（Ca++＞Cd++＞Mn++＞Co++＞Mg++）与晶体离子半径有关，其半径最接近Ca++（0.99埃）的那些阳离子发挥最大保护作用。钙反常保护中有效性的阳离子序列与兴奋 - 收缩解偶联效力的序列相同。低温保护的机制可能是膜脂质的相变（从流动性较高的状态转变为流动性较低的状态），这在无钙期稳定了膜结构并保留了Ca++通透性特征。通过添加阳离子的保护机制可能是阳离子在关键肌膜结合位点替代Ca++的能力（取决于无水晶体离子半径），从而在无钙期保持对Ca++通透性的控制。
