Comparison of quantifiable electrocardiographic changes associated with severe hyperkalemia.

BACKGROUND: Hyperkalemia (HK) is a life-threatening condition that is frequently evaluated by electrocardiogram (ECG). ECG changes in severe HK (≥ 6.3 mEq/L) are not well-characterized. This study sought to compare and correlate ECG metrics in severe HK to baseline normokalemic ECGs and serum potassium. METHODS: A retrospective analysis of 340 severe HK encounters with corresponding normokalemic ECGs was performed. RESULTS: Various ECG metrics were analyzed. P wave amplitude in lead II, QRS duration, T wave slope, ratio of T wave amplitude: duration, and ratios of T wave: QRS amplitudes were significantly different between normokalemic and HK ECGs. P wave amplitude attenuation in lead II correlated better with serum potassium than in V1. T wave metrics that incorporated both T wave and QRS amplitudes correlated better than metrics utilizing T wave metrics alone. CONCLUSION: Multiple statistically significant and quantifiable differences among ECG metrics were observed between normokalemic and HK ECGs and correlated with increasing degrees of serum potassium and along the continuum of serum potassium. When incorporated into a logistic regression model, the ability to distinguish HK versus normokalemia on ECG improved significantly. These findings could be integrated into an ECG acquisition system that can more accurately identify severe HK.

Discovery of Lipophilic Bisphosphonates That Target Bacterial Cell Wall and Quinone Biosynthesis.

We report that alkyl-substituted bisphosphonates have activity against Bacillus anthracis Sterne (0.40 µg/mL), Mycobacterium smegmatis (1.4 µg/mL), Bacillus subtilis (1.0 µg/mL), and Staphylococcus aureus (13 µg/mL). In many cases, there is no effect of serum binding, as well as low activity against a human embryonic kidney cell line. Targeting of isoprenoid biosynthesis is involved with 74 having IC50 values of ∼100 nM against heptaprenyl diphosphate synthase and 200 nM against farnesyl diphosphate synthase. B. subtilis growth inhibition was rescued by addition of farnesyl diphosphate, menaquinone-4 (MK-4), or undecaprenyl phosphate (UP), and the combination of MK-4 and UP resulted in a 25× increase in ED50, indicating targeting of both quinone and cell wall biosynthesis. Clostridioides difficile was inhibited by 74, and since this organism does not synthesize quinones, cell wall biosynthesis is the likely target. We also solved three X-ray structures of inhibitors bound to octaprenyl diphosphate and/or undecaprenyl diphosphate synthases.