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Magnesium potentiates imipramine toxicity in the isolated rat heart
J A Kline1, A A DeStefano, J D Schroeder
1Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina.
Study Objective:
To study the effect of magnesium on cardiac function and hemodynamics during imipramine toxicity.
Design:
After stabilization, isolated, beating rat hearts were perfused with Krebs-Henseleit bicarbonate buffer (KHB) solution containing 2.0 mg/L imipramine (IMIP) and 2.4 mEq [Mg2+] until toxicity, defined as 25% widening of the ventricular depolarization duration (VDD). Experiments were performed at either constant coronary perfusion pressure or flow.
Setting:
Animal research laboratory of a large, urban hospital.
Measurements:
Heart rate, VDD, left ventricular pressure and +/- dP/dt, and coronary flow.
Interventions:
On onset of toxicity, KHB+IMIP was switched to either control (KHB+IMIP), magnesium (KHB+IMIP+4.0 or 6.0 mEq/L [Mg2+]), or hypertonic alkaline treatment (165 mEq/L [Na+], pH 7.55).
Results:
At a constant coronary perfusion pressure of 100 mm Hg, magnesium at 6.0 mEq produced significant decreases in heart rate, left ventricular pressure, +dP/dt, and increase in VDD versus control. With coronary flow held constant, magnesium reduced left ventricular pressure and +dP/dt but not heart rate or VDD. Incidences of electromechanical dissociation and asystole were higher with magnesium versus control. Hypertonic alkaline treatment tended to improve all parameters in constant pressure and constant flow experiments.
Conclusion:
Magnesium potentiates IMIP-induced negative inotropic effects and cardiac conduction defects in isolated rat hearts.
Insights
Magnesium worsens imipramine (IMIP) toxicity in isolated rat hearts, increasing cardiac dysfunction and conduction problems. Hypertonic alkaline treatment showed potential benefits in mitigating these effects.
Area of Science:
- Cardiology
- Pharmacology
- Toxicology
Background:
- Imipramine (IMIP) is a tricyclic antidepressant with known cardiotoxic potential.
- Magnesium is often used to treat cardiac arrhythmias and toxicity.
- The interaction between magnesium and imipramine cardiotoxicity requires further investigation.
Purpose of the Study:
- To investigate the effect of magnesium on cardiac function and hemodynamics during imipramine-induced toxicity.
- To determine if magnesium exacerbates or ameliorates imipramine cardiotoxicity.
Main Methods:
- Isolated, beating rat hearts were perfused with imipramine (IMIP) and varying concentrations of magnesium (Mg2+).
- Cardiac function (heart rate, ventricular pressure, dP/dt) and electrophysiology (ventricular depolarization duration - VDD) were measured.
- Experiments were conducted under constant coronary perfusion pressure or constant coronary flow conditions.
Main Results:
- Magnesium (6.0 mEq/L) significantly decreased heart rate, left ventricular pressure, and +dP/dt, while increasing VDD at constant perfusion pressure.
- Under constant flow, magnesium reduced left ventricular pressure and +dP/dt but did not affect heart rate or VDD.
- Higher incidences of electromechanical dissociation and asystole were observed with magnesium treatment.
Conclusions:
- Magnesium potentiates the negative inotropic effects of imipramine.
- Magnesium exacerbates imipramine-induced cardiac conduction defects in isolated rat hearts.
- Hypertonic alkaline treatment demonstrated a trend towards improving cardiac parameters during imipramine toxicity.