title: Harmful effects of inotropic agents on myocardial protection.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, National Cardiovascular Center, Suita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Komai
authors.forename: F
authors.initials: F
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: A
authors.initials: A
authors.lastname: Koide
authors.forename: T
authors.initials: T
authors.lastname: Ohashi
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: Y
authors.initials: Y
authors.lastname: Kawashima
mesh_terms: 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
chemical_list: D002316:Cardiotonic Agents; D011728:Pyridones; D012433:Ryanodine; D003994:Bucladesine; D003402:Creatine Kinase; D004110:Diltiazem; D020105:Milrinone; D007545:Isoproterenol; D002118:Calcium