Harmful effects of inotropic agents on myocardial protection.
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.
Komai
H
H
Department of Cardiovascular Surgery, National Cardiovascular Center, Suita, Japan.
Yamamoto
F
F
Tanaka
K
K
Ichikawa
H
H
Shibata
T
T
Koide
A
A
Ohashi
T
T
Yamamoto
H
H
Nakashima
N
N
Kawashima
Y
Y
D000818:Animals; D001831:Body Temperature; D003994:Bucladesine / Q000633:toxicity; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000633:toxicity*; D003402:Creatine Kinase / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000633:toxicity; D008297:Male; D020105:Milrinone; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011728:Pyridones / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology
D002316:Cardiotonic Agents; D011728:Pyridones; D012433:Ryanodine; D003994:Bucladesine; D003402:Creatine Kinase; D004110:Diltiazem; D020105:Milrinone; D007545:Isoproterenol; D002118:Calcium