PASSIVE ELECTRICAL-PROPERTIES, MECHANICAL-ACTIVITY, AND EXTRACELLULAR POTASSIUM IN ARTERIALLY PERFUSED AND ISCHEMIC RABBIT VENTRICULAR MUSCLE - EFFECTS OF CALCIUM ENTRY BLOCKADE OR HYPOCALCEMIA
PASSIVE ELECTRICAL-PROPERTIES, MECHANICAL-ACTIVITY, AND EXTRACELLULAR POTASSIUM IN ARTERIALLY PERFUSED AND ISCHEMIC RABBIT VENTRICULAR MUSCLE - EFFECTS OF CALCIUM ENTRY BLOCKADE OR HYPOCALCEMIA
复制标题
DOI：
10.1161/01.res.66.6.1461
复制
发表时间：
1990-06-01
影响因子：
20.1
通讯作者：
KLEBER, AG
中科院分区：
文献类型：
--
作者：
CASCIO, WE;YAN, GX;KLEBER, AG
在存在或不存在维拉帕米或降低细胞外 Ca2+ 浓度 [Ca2+]O 的情况下，在正常动脉灌注和无血流缺血期间，研究了离体兔乳头肌的被动电阻特性、纵向传导速度、细胞外钾浓度、[K+]0 和机械活动之间的关系。在正常动脉灌注期间，维拉帕米（0.5 μM，游离 [Ca2+]O = 1.0 mM）和低钙血液灌流液（游离 [Ca2+]O = 0.4 mM）使最大等长肌张力降低 48% 和 78%，使静息膜去极化 +3 和 +7 mV，使细胞外纵向阻力 (rO) 降低 15% 和26%，传导速度分别增加 4% 和 6%。这些干预期间传导速度的变化与线性电缆理论对观察到的 rO2 变化的预测一致（+3% 和 +9%）。相反，维拉帕米缩短，而[Ca2+]O减少则延长动作电位持续时间。缺血期间同时测量的纵向全组织阻力 (r1)、细胞内纵向阻力 (rt)、[K+]O 和静息张力的比较表明，突然的细胞间电解偶联、缺血性挛缩的发生和 [K+]O 的继发性升高之间存在密切关联，这些都在缺血约 15 分钟后开始发生。电池与电池之间的电解偶联在 15 分钟内完成。在存在维拉帕米的情况下，细胞间电解偶联的发生、[K+]O 的继发性升高和缺血中缺血性挛缩的发生之间的关系在性质上与不存在维拉帕米时相同。然而，这些事件被推迟了大约 10 分钟，挛缩发展和脱钩的速度也降低了。缺血12分钟后，传导速度从不存在维拉帕米时的54厘米/秒降低至36厘米/秒，以及在存在维拉帕米时从61厘米/秒降低至46厘米/秒。这种对脉冲传导的减慢效应不能归因于细胞间电耦合的变化，因为此时 ri 尚未增加。在 (Ca2+]o 减少的情况下，静息张力和 ri 几乎在缺血发生后立即增加。虽然静息张力在整个缺血过程中逐渐升高，但 ri 表现出双相增加，其特征是早期短暂增加，在 8 分钟时达到峰值 (+87%)，并在大约 12 分钟开始第二次不可逆的增加。细胞与细胞电解偶联的最终开始和继发性升高[K+]O 与正常 [Ca2+]O 的结果没有什么不同，传导速度的降低比正常 [Ca2+]O 的降低更大，并且缺血性传导阻滞发生得更早。 总之，我们的结果表明，细胞间电解偶联、缺血性挛缩和细胞外 K+ 积累的第二阶段密切相关，这表明它们是由可能涉及胞质游离增加的共同事件触发的。 [Ca2+]。相反，[Ca2+]O 减少导致细胞内阻力迅速增加，并导致可逆性缺血期间静息张力升高。Ca2+ 进入阻断和[Ca2+] 减少的效果之间的差异可能是由于它们在正常氧和缺血期间对膜电位的影响不同。从而影响Na+/Ca2+交换。
The relation among passive electrical resistive properties, longitudinal conduction velocity, extracellular potassium concentration, [K+]0, and mechanical activity was investigated in the isolated rabbit papillary muscle during normal arterial perfusion and no-flow ischemia in the presence and absence of verapamil, or a reduced extracellular Ca2+ concentration [Ca2+]O. During normal arterial perfusion, verapamil (0.5 .mu.M, free [Ca2+]O = 1.0 mM) and hypocalcemic blood perfusate (free [Ca2+]O = 0.4 mM) reduced the maximal isometric twitch tension by 48% and 78%, depolarized the resting membrane by +3 and +7 mV, decreased the extracellular longitudinal resistant (rO) by 15% and 26%, and increased conduction velocity by 4% and 6%, respectively. The changes in conduction velocity during these interventions were consistent with those predicted by linear cable theory (+3% and +9%) for the observed changes in rO. In contrast, verapamil shortened whereas a reduced [Ca2+]O lengthened action potential duration. Comparison of simultaneously measured longitudinal whole tissue resistant (r1), intracellular longitudinal resistant (rt), [K+]O, and resting tension during ischemia showed a close association between abrupt cell-to-cell electrical uncoupling, development of ischemic contracture, and the secondary rise of [K+]O, which all started to develop after approximately 15 minutes of ischemia. Electrical cell-to-cell uncoupling was completed within 15 minutes. In the presence of verapamil, the relation among the onset of electrial cell-to-cell uncoupling, secondary rise of [K+]O, and onset of ischemic contracture in ischemia was qualitatively the same as in its absence; however, these events were postponed by approximately 10 minutes, and the rates of contracture development and uncoupling were diminished. Conduction velocity decreased after 12 minutes of ischemia from 54 to 36 cm/sec in the absence of and from 61 to 46 cm/sec in the presence of verapamil. This slowing effect on impulse conduction could not be attributed to changes of electrical cell-to-cell coupling because at this time an increase in ri had not yet taken place. In the presence of a reduced (Ca2+]o, the resting tension and ri increased almost immediately after the onset of ischemia. Although the resting tension rose progressively throughout the course of ischemia, the ri showed a biphasic increase characterized by an early transient increase that reached a peak at 8 minutes (+87%) and a second, irreversible increase beginning at approximately 12 minutes. This final onset of electrical cell-to-cell uncoupling and the secondary rise of [K+]O were not different from the findings with a normal [Ca2+]O. The decrease of conduction velocity was greater with reduced than with normal [Ca2+]O, and ischemic conduction block occurred earlier. In conclusion, our results demonstrate that the abrupt onset of electrical cell-to-cell uncoupling, ischemic contracture, and the second phase of extracellular K+ accumulation are closely coupled, which suggests that they are triggered by a common event that probably involves an increase in cytosolic free [Ca2+]. Verapamil postpones the onset and slows the rate of development of the irreversible changes of electrical and mechanical function in ischemia. In contrast, reduced [Ca2+]O results in a rapid increase of intracellular resistance in associaton with a rise in resting tension during reversible ischemia. The differences between the effect of Ca2+ entry blockade and reduced [Ca2+] are likely to be explained by their different effects on membrane potential during normoxia and ischemia, and consequently on Na+/Ca2+ exchange.