[Effect of phosphate diester linkage of vitamin E and vitamin C (EPC-K1) on myocardial ischemia reperfusion injury in the isolated working rat heart].
The myocardial protective effect of phosphate diester linkage of vitamin E and vitamin C (EPC-K1), a new hydroxyl radical scavenger, was investigated in an isolated working rat heart model. Initially, 0.25-3.0 micrograms/ml of EPC-K1 was given to non-ischemic heart to examine the effect of EPC-K1. Cardiac function did not change until 3.0 micrograms/ml EPC-K1 administration, however percent change of aortic flow prior to treatment (%AF) decreased significantly with 3.0 micrograms/ml and hearts were arrested with 5.0 micrograms/ml. Creatine kinase (CK) leakage did not change until 0.5 microgram/ml, however significantly increased over 1.0 microgram/ml. In the second protocol, EPC-K1 was applied before 15 min of ischemia at 37 degrees C. The %AF recovered significantly with 0.5 and 1.0 microgram/ml (81.2 +/- 3.1% and 75.2 +/- 4.1% vs. 57.2 +/- 3.1% in the control group), but hearts did not start to beat with 2.0 micrograms/ml. CK leakage was suppressed with 0.5 microgram/ml, although not significantly. In the third protocol, 0.5 microgram/ml of EPC-K1, which had the best protective effect before ischemia, was administered during reperfusion after 15 min of ischemia at 37 degrees C. The %AF (64.7 +/- 5.1%) was significantly higher than in the control group (57.2 +/- 3.1%), but was significantly less than in the pre-ischemic EPC-K1 group (81.2 +/- 3.0%). Thus, EPC-K1 had a myocardial protective effect at an appropriate dose, especially when given before ischemia. However, EPC-K1 showed myocardial toxicity at a high dose, therefore use of the correct dose will be important.
Inoue
M
M
Department of Cardiovascular Surgery, Okayama University Medical School, Japan.
D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016166:Free Radical Scavengers / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives*
D016166:Free Radical Scavengers; D014810:Vitamin E; C066638:potassium ascorbyl tocopheryl phosphate; D001205:Ascorbic Acid