Efficacy of methylene blue in a murine model of amlodipine overdose.

ABSTRACT

INTRODUCTION: Amlodipine overdoses have significant cardiac toxicity and are difficult to treat. Methylene blue has potential as a treatment for overdoses. METHODS: A randomized controlled study of methylene blue as a treatment for amlodipine toxicity was conducted in C57Bl/6 mice. A baseline echocardiography was followed by gavage administration of amlodipine (90 mg/kg). Five minutes after gavage, animals received either vehicle solution (controls) or methylene blue (20 mg/kg) by intra-peritoneal injection. Animals were continuously monitored, and cardiac parameters were acquired every 15 min up to two hours. RESULTS: Only 50% of control animals survived to the two-hour endpoint compared to 83% that received methylene blue. Amlodipine delivery induced significant reduction in left ventricular ejection fraction (EF), fractional shortening (FS), stroke volume (SV), and cardiac output (CO) in the vehicle treated animals relative to animals in the treatment group (p < 0.05 vehicle versus Methylene blue for EF, FS, SV, CO, and HR). DISCUSSION: The amlodipine dose induced cardiotoxicity that were effects were more pronounced in the untreated group. 50% vehicle controls quickly progressed into heart failure (within 90 min of exposure) and did not survive the two h observation endpoint. Distinctly, only one animal from the Methylene blue treatment group did not survive (83% survival) the study. Additionally, the surviving animals from the Methylene blue group displayed significantly higher ejection fraction, fractional shortening, stroke volume, and cardiac output compared to vehicle group, indicating that methylene blue preserved cardiac function. CONCLUSION: In this mouse model of amlodipine overdose, methylene blue decreased cardiac toxicity.