Fazan Frederico, Colombari Débora Simões de Almeida, Menani José Vanderlei, Fazan Rubens, Colombari Eduardo
Araraquara School of Dentistry, São Paulo State University, Araraquara, São Paulo, Brazil.
Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Exp Physiol. 2021 May;106(5):1263-1271. doi: 10.1113/EP089356. Epub 2021 Mar 17.
What is the central question of this study? This study presents a new model for studying the rapid onset of severe, acute hyperkalaemia in rats with intact kidney function by administering an intragastric KCl load. What is the main finding and its importance? This new model of intragastric KCl load produces a reliable and reproducible model for studying the rapid onset of severe, acute hyperkalaemia in rats with intact kidney function. We report unprecedented rapid changes (30 min) in ECG, blood pressure and various arterial blood analyses with this new model, providing a solid foundation for future experiments in this field.
A variety of animal models have been proposed to study hyperkalaemia, but most of them have meaningful limitations when the goal is to study the effect of potassium overload on healthy kidneys. In this study, we aimed to introduce a new approach for induction of hyperkalaemia in a reliable and reproducible animal model. We used intragastric administration of potassium chloride [KCl 2.3 M, 10 ml/(kg body weight)] to male Holtzman rats (300-350 g) to induce hyperkalaemia. The results showed that this potassium load can temporarily overwhelm the renal and extrarenal handling of this ion, causing an acute and severe hyperkalaemia that can be useful to study the effect of potassium imbalance in a variety of scenarios. Severe hyperkalaemia (>8 meqiv/l) and very profound ECG alterations, characterized by lengthening waves and intervals, were seen as early as 30 min after intragastric administration of KCl in rats. In addition, a transient increase in arterial blood pressure and time-dependent bradycardia were also seen after the KCl administration. No metabolic acidosis was present in the animals, and the potassium ion did not increase proportionally to chloride ion in the blood, leading to an increased anion gap. In conclusion, the results suggest that intragastric KCl loading is a reliable model to promote rapid and severe hyperkalaemia that can be used for further research on this topic.
本研究的核心问题是什么？本研究提出了一种新模型，通过给具有完整肾功能的大鼠胃内给予氯化钾负荷，来研究严重急性高钾血症的快速发作。主要发现及其重要性是什么？这种胃内氯化钾负荷新模型为研究具有完整肾功能的大鼠严重急性高钾血症的快速发作提供了一个可靠且可重复的模型。我们报告了使用该新模型时心电图、血压及各种动脉血液分析出现了前所未有的快速变化（30分钟内），为该领域未来的实验奠定了坚实基础。
已经提出了多种动物模型来研究高钾血症，但当目标是研究钾过载对健康肾脏的影响时，它们大多存在显著局限性。在本研究中，我们旨在引入一种在可靠且可重复的动物模型中诱导高钾血症的新方法。我们给雄性霍尔兹曼大鼠（300 - 350克）胃内给予氯化钾[2.3 M，10毫升/（千克体重）]以诱导高钾血症。结果表明，这种钾负荷可暂时超过肾脏和肾外对该离子的处理能力，导致急性严重高钾血症，这对于研究各种情况下钾失衡的影响可能有用。在大鼠胃内给予氯化钾后30分钟内，即可观察到严重高钾血症（>8毫当量/升）以及非常明显的心电图改变，其特征为波和间期延长。此外，给予氯化钾后还出现了动脉血压短暂升高和随时间推移的心动过缓。动物未出现代谢性酸中毒，且血液中钾离子与氯离子不成比例增加，导致阴离子间隙增大。总之，结果表明胃内给予氯化钾负荷是促进快速严重高钾血症的可靠模型，可用于该主题的进一步研究。
