[Sarcoplasmic reticular calcium release and myocardial protection--effect of ryanodine on myocardial ischemia and reperfusion-induced injury].
Calcium release from sarcoplasmic reticulum (SR) may contribute to the intracellular calcium overload observed during myocardial ischemia and reperfusion. We have therefore investigated the ability of ryanodine to enhance myocardial protection when given before ischemia or during reperfusion in the isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer (Ca2+ = 2.4 mM). In the first series of studies, this was followed by a 3 min infusion of St Thomas' Hospital cardioplegic solution containing various concentrations of ryanodine. Hearts were then subjected to 38 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). The recoveries of aortic flow (%AF) were 50.3 +/- 2.5% in the ryanodine free controls versus 55.2 +/- 5.8, 72.0 +/- 1.3 (p < 0.05), 61.0 +/- 4.3, 51.8 +/- 5.1 and 32.1 +/- 5.0 (p < 0.05)% in the 0.88, 1.75, 2.13, 2.50 and 10.00 nM ryanodine groups, respectively. Creatine kinase (CK) leakage during Langendorff reperfusion was reduced in the 1.75 nM group but was similar to control in all other groups. In the second series of studies, 3 min of cardioplegia without ryanodine and 38 min of ischemia (37 degrees C) were followed by 15 min of Langendorff reperfusion with 0, 0.09, 0.18, 0.88 or 1.75 nM ryanodine, %AF was 59.3 +/- 3.3%, 54.7 +/- 3.3, 53.8 +/- 3.5, 38.4 +/- 8.9 (p < 0.05) and 33.3 +/- 5.8 (p < 0.05)% in the 0, 0.09, 0.18, 0.88 and 1.75 nM ryanodine groups, respectively. CK leakage tended to increase dose-dependently.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamamoto
H
H
Department of Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan.
Yamamoto
F
F
Ichikawa
H
H
Ohashi
T
T
Yoshida
S
S
Komai
H
H
Takahashi
A
A
Fujita
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions; D006324:Heart Arrest, Induced; D066298:In Vitro Techniques; D008297:Male; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D002314:Cardioplegic Solutions; D012433:Ryanodine; D002118:Calcium