Cascio W E, Yan G X, Kléber A G
Department of Physiology, University of Bern, Switzerland.
Circ Res. 1992 Feb;70(2):409-22. doi: 10.1161/01.res.70.2.409.
The role of local accumulation and diffusion of CO2 to modify cellular loss and extracellular accumulation of K+ during the initial, reversible phase of myocardial ischemia was investigated in isolated, cylindrical papillary muscles of the rabbit. The muscles were blood-perfused through their vascular tree and placed in a (permanently flowing) humidified gas mixture with predetermined partial pressures of N2, O2, and CO2. Ischemia was produced by total arrest of perfusion and O2 withdrawal from the gas mixture. With surface PCO2 kept constant during ischemia, [K+]o varied markedly with muscle geometry. After 10 minutes of ischemia, K+ accumulation was approximately 2.5 mM in muscles with a radius of 0.35 mm and approximately 14 mM in muscles with a radius of 0.9 mm, indicating that a large fraction of K+ accumulation was dependent on diffusion of a volatile metabolite. Computer simulation of CO2 accumulation and diffusion within a tissue cylinder suggested a close phenomenological relation between PCO2 and [K+]o in ischemia. This was confirmed by the finding that an increase of tissue PCO2 in small cylinders before or during ischemia by externally applied CO2 produced an increase in K+ accumulation. The importance of CO2 diffusion for local inhomogeneities in K+ within the same preparation was demonstrated by showing [K+]o gradients with simultaneous or consecutive measurements between the papillary muscle cylinders and the adjacent septum and within 300 microns from the surface of the papillary muscle cylinders. These gradients predict an inhomogeneity of impulse conduction that might contribute to the genesis of ventricular arrhythmias. Besides the demonstration that accumulation and diffusion introduce inhomogeneities of [K+]o in ischemia, our results suggest that a significant component of cellular ischemic K+ loss is associated with production and extrusion of metabolic acid. On the basis of previous measurements of pHo and pHi in identical conditions, possible mechanisms of ischemic cellular K+ loss are discussed.
在兔的离体圆柱形乳头肌中，研究了在心肌缺血初始可逆阶段，二氧化碳的局部积聚和扩散对改变细胞内钾离子丢失及细胞外钾离子积聚的作用。这些肌肉通过其血管树进行血液灌注，并置于含有预定氮气、氧气和二氧化碳分压的（持续流动）湿润气体混合物中。通过完全停止灌注和从气体混合物中撤出氧气来产生缺血。在缺血期间保持表面二氧化碳分压恒定，细胞外钾离子浓度随肌肉几何形状显著变化。缺血10分钟后，半径为0.35毫米的肌肉中钾离子积聚约为2.5毫摩尔，半径为0.9毫米的肌肉中约为14毫摩尔，这表明很大一部分钾离子积聚依赖于挥发性代谢产物的扩散。对组织圆柱体内二氧化碳积聚和扩散的计算机模拟表明，缺血时二氧化碳分压与细胞外钾离子浓度之间存在密切的现象学关系。这一点得到了以下发现的证实：在缺血前或缺血期间，通过外部施加二氧化碳增加小圆柱体组织中的二氧化碳分压会导致钾离子积聚增加。通过在乳头肌圆柱体与相邻隔膜之间以及距乳头肌圆柱体表面300微米内同时或连续测量细胞外钾离子浓度梯度，证明了二氧化碳扩散对同一制剂中钾离子局部不均匀性的重要性。这些梯度预示着冲动传导的不均匀性，这可能有助于室性心律失常的发生。除了证明积聚和扩散在缺血时会导致细胞外钾离子浓度不均匀外，我们的结果还表明，细胞缺血性钾离子丢失的一个重要组成部分与代谢性酸的产生和排出有关。基于先前在相同条件下对细胞外pH值和细胞内pH值的测量，讨论了缺血性细胞钾离子丢失的可能机制。
