Magnesium potentiates imipramine toxicity in the isolated rat heart.
OBJECTIVE
To study the effect of magnesium on cardiac function and hemodynamics during imipramine toxicity.


METHODS
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.


METHODS
Animal research laboratory of a large, urban hospital.


METHODS
Heart rate, VDD, left ventricular pressure and +/- dP/dt, and coronary flow.


METHODS
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.


CONCLUSIONS
Magnesium potentiates IMIP-induced negative inotropic effects and cardiac conduction defects in isolated rat hearts.
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina.
J A
JA
Kline
A A
AA
DeStefano
J D
JD
Schroeder
R M
RM
Raymond
D000818:Animals; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007099:Imipramine / Q000633:toxicity*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D008274:Magnesium; D007099:Imipramine