The Annals of Thoracic Surgery, Vol 41, 542-546, Copyright © 1986 by The Society of Thoracic Surgeons
Myocardial protective effect of amiodarone in hypertrophied hearts during global ischemia
TJ Takach, JP Voigtlander, M Jones and RE Clark
The effect of amiodarone on the ischemic-reperfusion injury was tested in
an isolated working preparation, using hypertrophied rat heart at 37
degrees C. Constant filling and afterload pressures and similar heart rates
were used. Hearts from spontaneously hypertensive rats (N = 78) had thirty
minutes of ischemia. Each received a 12-ml injection, by aortic root
infusion, of amiodarone in normal saline or of normal saline alone at 37
degrees C at the onset of ischemia. Heart rate, aortic output, coronary
sinus output, atrial pressure, and aortic pressure were recorded before and
after global ischemia under steady- state conditions. Dose-response studies
were performed at concentrations of 0.01 to 1.0 mg/ml. At every dose
administered, amiodarone was found to significantly ameliorate the
deleterious effects of global ischemia. The maximal benefit of amiodarone
(70 +/- 4.6% recovery of function [mean +/- standard error of the mean], p
less than 0.01) was found to be 0.25 mg (0.021 mg/ml), or 0.11 mg/g wet
heart weight. Improvement in survival (return of aortic output and heart
rate following ischemia) with all doses of amiodarone was statistically
significant (p less than 0.002). Decreased recovery of function following
global ischemia when doses were greater than 0.25 mg may have been
secondary to the known negative inotropic effects of the drug. The
mechanisms for the protective effects of amiodarone may be coronary
vasodilatation, antiarrhythmic stabilization, or inhibition of calcium flux
at the slow channel.
