The Annals of Thoracic Surgery, Vol 52, 927-933, Copyright © 1991 by The Society of Thoracic Surgeons
Harmful effects of inotropic agents on myocardial protection
H Komai, F Yamamoto, K Tanaka, H Ichikawa, T Shibata, A Koide, T Ohashi, H Yamamoto, N Nakashima and Y Kawashima
Department of Cardiovascular Surgery, National Cardiovascular Center, Suita, Japan.
Using an isolated working rat heart model, the pretreatment effects of
positive inotropic agents on ischemia-reperfusion injury were investigated.
The experiment consisted of (1) working control perfusion; (2) working
perfusion with isoproterenol (I), milrinone (M), a combination of these
drugs (I + M) and dibutyl-cyclic adenosine monophosphate (DB) followed by
ischemic arrest for 33 minutes at 37 degrees C or 150 minutes at 20 degrees
C and Langendorff reperfusion; and (3) working perfusion. Under conditions
of normothermic ischemia, percent recoveries of postischemic cardiac output
(mean +/- standard error of the mean) in the I, M, I + M, and DB groups
were 37.8% +/- 12.7%, 61.3% +/- 3.1%, 0%, and 53.1% +/- 5.2%, respectively.
Under conditions of hypothermic ischemia, the percent recoveries in I + M
and DB groups were 10.9% +/- 7.9% and 29.8% +/- 9.5%; they were all
significantly lower than that in the control group. The addition of
diltiazem or ryanodine at several concentrations and lowering of the Ca2+
concentration in the St. Thomas' cardioplegic solution did not prevent I +
M-induced injury. Our data suggest that pretreatment by I + M aggravated
ischemia-reperfusion injury, and adjustments in Ca2+ concentration were not
sufficient to prevent that injury.
