Bjørnstad H, Tande P M, Refsum H
Department of Medical Physiology, IMB, University of Tromsø, Norway.
Acta Physiol Scand. 1993 Jul;148(3):253-64. doi: 10.1111/j.1748-1716.1993.tb09556.x.
Lowering myocardial temperature increases contractile force, presumably by increasing intracellular calcium content. To study the mechanisms behind this, we compared the effects of some known inotropic interventions with hypothermia on mechanical restitution and post-rest contractile force in isolated guinea-pig papillary muscles. In four groups (n = 6 per group), the effects of: (1) reducing the ability for Na/Ca exchange to extrude Ca2+ (a) by increasing [Na+]i with ouabain or (b) by increasing [Ca2+]o; and (2) activation of calcium channels with Bay-K 8644, were compared with lowering temperature from 37 to 27 degrees C. Normally (at 37 degrees C and 2 mM CaCl2), mechanical restitution could be described by a rapid recovery phase with a time constant between 180 and 220 ms, followed by a slowly decaying phase with a time constant between 5000 and 8000 ms and post-rest contractions (1-10 min rest) were markedly depressed compared to steady-state contractions. Steady-state developed force was markedly increased at 27 degrees C, after 1 microM ouabain, 6 mM CaCl2 or 0.1 microM Bay-K 8644. At 27 degrees C the rapid recovery phase of restitution was delayed while the slowly decaying phase was not affected. Ouabain and increased [Ca2+]o caused elevation of the slowly decaying phase of restitution and markedly attenuated the post-rest depression of developed force, which may be attributed to a reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger. Hypothermia and Bay-K 8644 on the other hand, augmented this post-rest depression. Hence, this study suggests that increased Ca2+ influx due to delayed inactivation of calcium channels may account for the increased developed force during hypothermia rather than reduced diastolic extrusion of Ca2+ via the Na/Ca exchanger.
降低心肌温度可增加收缩力，这可能是通过增加细胞内钙含量来实现的。为了研究其背后的机制，我们比较了一些已知的正性肌力干预措施与低温对离体豚鼠乳头肌机械恢复和静息后收缩力的影响。在四组实验中（每组n = 6），比较了以下因素的影响：(1) 通过用哇巴因增加细胞内[Na⁺]或增加细胞外[Ca²⁺]来降低钠/钙交换体排出Ca²⁺的能力；(2) 用Bay-K 8644激活钙通道，并与将温度从37℃降至27℃进行对比。正常情况下（在37℃和2 mM CaCl₂时），机械恢复可描述为一个快速恢复阶段，时间常数在180至220毫秒之间，随后是一个缓慢衰减阶段，时间常数在5000至8000毫秒之间，与稳态收缩相比，静息后收缩（静息1 - 10分钟）明显受到抑制。在27℃、1 μM哇巴因、6 mM CaCl₂或0.1 μM Bay-K 8644作用后，稳态发展力明显增加。在27℃时，恢复的快速恢复阶段延迟，而缓慢衰减阶段不受影响。哇巴因和细胞外[Ca²⁺]增加导致恢复的缓慢衰减阶段升高，并明显减弱了静息后发展力的抑制，这可能归因于通过钠/钙交换体的Ca²⁺舒张期排出减少。另一方面，低温和Bay-K 8644增强了这种静息后抑制。因此，本研究表明，低温期间发展力增加可能是由于钙通道延迟失活导致Ca²⁺内流增加，而不是通过钠/钙交换体的Ca²⁺舒张期排出减少。
