[The effects of protease inhibitor upon the ischemia-reperfusion injury].
The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Shibata
T
T
Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan.
Yamamoto
F
F
Ohashi
T
T
Shimada
Y
Y
Nakajima
N
N
Kinoshita
H
H
Kawashima
Y
Y
D000818:Animals; D001550:Benzamidines; D001639:Bicarbonates / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002314:Cardioplegic Solutions; D006146:Guanidines / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011189:Potassium Chloride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000494:pharmacology
D001550:Benzamidines; D001639:Bicarbonates; D002314:Cardioplegic Solutions; D006146:Guanidines; D011480:Protease Inhibitors; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D008274:Magnesium; D002122:Calcium Chloride; C032855:nafamostat