Electrocardiographic changes in the acute hyperkalaemia produced by intragastric KCl load in rats

Abstract

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.

HSD2 neurons are evolutionarily conserved and required for aldosterone-induced salt appetite

“…To determine the high end of endogenous production, we adapted a human protocol that combined dietary sodium deprivation with potassium supplementation, followed by acute potassium infusion (55). Supplementing dietary potassium in sodium-deprived mice, followed by potassium gavage (56), produced higher concentrations of endogenous aldosterone in blood plasma (ranging 313 to 990 ng/dL, Figure 5A ) and in CSF (ranging 48 to 74 ng/dL, Figure 5B ).…”

“…For dietary sodium deprivation plus potassium supplementation, we modeled our approach after a similar dietary protocol followed by acute infusion of potassium chloride (KCl) in human subjects (55). However, instead of intravenous infusion at the end of our protocol, we gave a bolus of potassium by gavage (3M KCl, 0.1 mL per 10 g), similar to previous rodent experiments (56). Also, after pilot experiments testing a range of concentrations, we found that mice show no aversion to 1.5% or less KCl in drinking water (they consumed this solution at the same daily volumes as dH 2 O).…”

Moderate Hyperkalemia Regulates Autophagy to Reduce Cerebral Ischemia-Reperfusion Injury in a CA/CPR Rat Model

“…However, the optimal levels of high serum (K + ) and the standard of optimal levels are undefined. Potassium (K + ) is among the most abundant cations in cells, which can cause alterations in the resting membrane potential, nerve and muscle excitability, and cardiac electrical activity [ 46 ]. Elevated serum (K + ) leads to changes in the electrical activity of the heart, which are reflected in the ECG and changes in the ECG can provide crucial insights into myocardial function in turn [ 47 ].…”

“…As serum (K + ) levels continue to increase, it can lead to heart block, asystole and ventricular tachycardia (VT)/ventricular fibrillation (VF), and a significant decrease in MAP. In contrast to humans, the rats failed to observe significant “high and sharp” T-waves on the ECG during the increased serum (K + ) levels but were able to observe complete changes in the P waves and QRS complexes [ 46 ]. Therefore, we selected the P and QRS waves with significant changes as the grouping criteria: a decrease in P wave amplitude to 1/2 the basal value was used as the low-dose group (P group), and a widening of the QRS complex to three times the basal value was used as the high-dose group (Q group).…”