The effects of several pharmacologic agents upon postischemic recovery.
Using an isolated working rat heart model, the effects of DL-verapamil, ryanodine, gabexate mesilate (FOY), recombinant human superoxide dismutase (RH-SOD), and coenzyme Q10 upon myocardial protection were evaluated. Under conditions of normothermic ischemia, all these compounds, except RH-SOD, when added to the St. Thomas' cardioplegic solution at an optimal concentration, showed beneficial effects upon functional recovery and enzyme leakage. In contrast, the above compounds, except ryanodine and FOY, failed to improve the protective properties of the St. Thomas' cardioplegic solution under conditions of hypothermic ischemia. Our results indicate that calcium overload via the calcium channel and calcium-induced calcium release from sarcoplasmic reticulum (SR) may contribute to the onset of ischemic-reperfusion injury. However, under conditions of hypothermic ischemia, calcium-induced calcium release from SR plays a dominant role in calcium overload. Furthermore, intracellular calcium overload may activate proteases and result in the acceleration of myocardial injury.
Yamamoto
F
F
Dept. of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan.
Yamamoto
H
H
Yoshida
S
S
Ichikawa
H
H
Takahashi
A
A
Tanaka
K
K
Kosakai
Y
Y
Yagihara
T
T
Fujita
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions / Q000627:therapeutic use*; D003067:Coenzymes; D003402:Creatine Kinase / Q000187:drug effects; D016670:Gabexate; D006146:Guanidines / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D012433:Ryanodine / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000627:therapeutic use; D013696:Temperature; D014451:Ubiquinone / Q000627:therapeutic use / Q000031:analogs & derivatives; D014700:Verapamil / Q000627:therapeutic use
D002314:Cardioplegic Solutions; D003067:Coenzymes; D006146:Guanidines; D011994:Recombinant Proteins; D014451:Ubiquinone; D012433:Ryanodine; D016670:Gabexate; D014700:Verapamil; D013482:Superoxide Dismutase; D003402:Creatine Kinase; C024989:coenzyme Q10; D002118:Calcium